FN Clarivate Analytics Web of Science VR 1.0 PT J AU Chen, H Chen, SY Huang, HX Chen, K Wan, HM Zhang, RF Wu, LY Wu, QF Tong, HB Xu, G AF Chen, Han Chen, Shuying Huang, Haixia Chen, Kai Wan, Huimin Zhang, Ruifen Wu, Linya Wu, Qifang Tong, Haibin Xu, Gang TI Kaempferol reprograms pro-inflammatory macrophage polarization by targeting the PTGS2-PGE2 axis: A multi-omics deconvolution of a traditional anti-inflammatory herb pair SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Metabolic dysfunction; associatedsteatohepatitis (MASH); Macrophage polarization; Chaihu-Baishao; Kaempferol; PTGS2 (COX-2); Network pharmacology ID NONALCOHOLIC STEATOHEPATITIS; LIVER; HOMEOSTASIS AB Metabolic dysfunction-associated steatohepatitis (MASH), a progressive liver disease driven by pro-inflammatory (M1) macrophage polarization, lacks effective pharmacotherapies. While the Chaihu-Baishao (CB) herb pair is a traditional remedy for liver disorders, its molecular mechanism is unknown. This study aimed to deconstruct CB's mechanism and validate its core bioactive component for MASH therapy. We employed an integrative strategy from multi-omics to in vivo validation. Transcriptomic analysis identified M1-polarized macrophages as central drivers of MASH. We then demonstrated that the CB extract ameliorates MASH pathology in a dietinduced mouse model. To elucidate the underlying mechanism, network pharmacology predicted kaempferol as the core bioactive compound and PTGS2 (COX-2) as its primary target. A direct kaempferol-PTGS2 interaction was rigorously confirmed by a suite of biophysical assays (CETSA, DARTS, MST), yielding a dissociation constant (Kd) of 5.16 & micro;M. Functionally, kaempferol suppressed M1 macrophage polarization in vitro by inhibiting PTGS2mediated prostaglandin E2 (PGE2) production, an effect reversed in a PGE2 rescue experiment. Crucially, in vivo administration of kaempferol alone recapitulated the therapeutic benefits of the full CB extract, significantly improving liver pathology and suppressing hepatic PGE2 levels. Our study provides a multi-scale validation, identifying kaempferol as the principal bioactive component of the CB herb pair. Kaempferol ameliorates MASH by directly targeting the PTGS2-PGE2 axis to reprogram macrophage polarization, presenting a promising, mechanism-defined therapeutic lead with clear translational potential. C1 [Chen, Han; Chen, Shuying; Huang, Haixia; Xu, Gang] Wenzhou Med Univ, Affiliated Hosp 1, Dept Clin Lab, Key Lab Clin Lab Diag & Translat Res Zhejiang Prov, Wenzhou 325000, Peoples R China. [Chen, Kai] Zhejiang Univ, Sch Med, Womens Hosp, Dept Gynecol, Hangzhou 310006, Peoples R China. [Wan, Huimin] Zhejiang Univ, Sch Med, Womans Hosp, Dept Obstet, Hangzhou 310006, Peoples R China. [Zhang, Ruifen; Wu, Linya; Wu, Qifang; Tong, Haibin] Wenzhou Univ, Coll Life & Environm Sci, Wenzhou 325035, Peoples R China. [Tong, Haibin] State Key Lab Qual Ensurance & Sustainable Use Dao, Beijing 100700, Peoples R China. C3 Wenzhou Medical University; Zhejiang University; Zhejiang University; Wenzhou University RP Xu, G (corresponding author), Wenzhou Med Univ, Affiliated Hosp 1, Dept Clin Lab, Key Lab Clin Lab Diag & Translat Res Zhejiang Prov, Wenzhou 325000, Peoples R China.; Tong, HB (corresponding author), Wenzhou Univ, Coll Life & Environm Sci, Wenzhou 325035, Peoples R China.; Tong, HB (corresponding author), State Key Lab Qual Ensurance & Sustainable Use Dao, Beijing 100700, Peoples R China. EM tonghb@wzu.edu.cn; xugang217@163.com FU Zhejiang Province Medical and Health Science and Technology Plan Project [2024KY1265]; Wenzhou Municipal Basic Public Welfare Research Project [Y2023096]; Key Laboratory of Clinical Laboratory Diag-nosis and Translational Research of Zhejiang Province [2022E10022, 2060302]; Chronic Disease Management Research Project of National Health Commission Capacity Building and Continuing Education Center [GWJJMB202510024127] FX This work was financially supported by the Zhejiang Province Medical and Health Science and Technology Plan Project (2024KY1265) , the Wenzhou Municipal Basic Public Welfare Research Project (Y2023096) , the Key Laboratory of Clinical Laboratory Diag-nosis and Translational Research of Zhejiang Province (2022E10022) , the Key Project at Central Government Level: The Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources (2060302) , and the Chronic Disease Management Research Project of National Health Commission Capacity Building and Continuing Education Center (GWJJMB202510024127) . 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PD JUN PY 2026 VL 248 AR 117865 DI 10.1016/j.bcp.2026.117865 PG 21 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA FB9TY UT WOS:001715117400001 PM 41794261 DA 2026-03-26 ER PT J AU Hong, LL Sun, YB Hou, HH Zhang, JJ Shi, WW Yang, YJ Fan, XS Zhu, JF AF Hong, Lingling Sun, Yubo Hou, Haihui Zhang, Jingjing Shi, Weiwei Yang, Yaojing Fan, Xinsheng Zhu, Jinfeng TI Study on the anti-pulmonary fibrosis mechanism of Renshen Pingfei formula by inhibiting M2 macrophage polarization and regulating TGF-(3/SMAD signaling pathway SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Renshen pingfei formula; Macrophage polarization; Pulmonary fibrosis; TGF-(3; SMAD ID ACID AB Ethnopharmacological relevance: Renshen Pingfei formula (RSPF), a traditional Chinese medicine (TCM) formulation,has been historically prescribed in China for treating "Fei Bi" (pulmonary stagnation syndrome), which symptoms and pathogenesis aligns with those of idiopathic pulmonary fibrosis (IPF). Aim of study: This study aimed to investigate the effects of RSPF on bleomycin-induced pulmonary fibrosis in mice and explore its regulatory effects on the TGF-(3/SMAD signaling pathway and M2 macrophages polarization. Materials and methods: LC-MS/MS was used to detect and identify the main active components of RSPF. In vivo studies were conducted using forty-eight C57BL/6 mice divided into six groups (n = 8): control, BLM, low, medium, or high RSPF dose (8.8, 17.5, or 35 g/kg, respectively), and Nintedanib (60 mg/kg/d). A pulmonary fibrosis mouse model was established by intratracheal instillation of bleomycin at 5 mg kg-1. Histopathological changes in the lung tissue were assessed using hematoxylin-eosin (HE), Masson, and Sirius red staining. Enzyme-linked immunosorbent assay (ELISA) was employed to measure IL-1(3 and TNF-alpha levels in bronchoalveolar lavage fluid (BALF). Immunofluorescence analysis was performed to determine the expression levels of Arg-1+/F4/80+ and CD206+/F4/80+ cells. Flow cytometry was used to detect the expression of CD206 in interstitial macrophages (IMs) and alveolar macrophages (AMs). Furthermore, in vitro studies were employed using RSPF applied to IL-4-stimulated bone marrow-derived macrophages (BMDMs), co-cultured with alveolar epithelial cells. Flow cytometry was used to quantify M1 (CD86) and M2 (CD206) polarization. RT-qPCR, Western blot, and immunofluorescence were used to evaluate the fibrosis/EMT markers (E-cadherin, Vimentin, alpha-smooth muscle actin [alpha-SMA], fibronectin [FN], type I collagen [Collagen I], TGF-(31, and Smad2/3 phosphorylation). Results: Seventy-eight active components were identified in RSPF. In vivo studies, RSPF increased the body weight of mice, improved collagen deposition and fibrosis in IPF, upregulated E-cadherin protein levels, and downregulated the expression of fibrosis-related markers such as Vimentin, alpha-SMA, FN, and Collagen I. Additionally, RSPF inhibited IL-1(3 and TNF-alpha levels in BALF and suppressed the protein expression levels of TGF-(3, p-Smad2/Smad2, and p-Smad3/Smad3. Further mechanistic studies indicated that RSPF downregulated the expression of Arg-1+/F4/80+ and CD206+/F4/80+ and decreased CD206 expression in IMs. In vitro studies, RSPF suppressed M2 polarization (CD206, Arg1), downregulated fibrotic markers (Collagen 1 alpha 1, alpha-SMA), and inhibited TGF-(31/Smad signaling. Conclusion: RSPF alleviated pathological damage and fibrosis in the lung tissue of IPF mice, thereby delaying the progression of IPF. Its anti-fibrotic mechanism involved dual suppression of TGF-(31/Smad signaling and M2 macrophage polarization. C1 [Hong, Lingling; Sun, Yubo; Hou, Haihui; Zhang, Jingjing; Shi, Weiwei; Yang, Yaojing; Fan, Xinsheng] Nanjing Univ Chinese Med, Sch Tradit Chinese Med, Nanjing 210023, Peoples R China. [Hong, Lingling; Hou, Haihui; Zhang, Jingjing; Shi, Weiwei; Zhu, Jinfeng] Nanjing Univ Chinese Med, Dept Resp, Nantong TCM Hosp, Nantong 226000, Jiangsu, Peoples R China. C3 Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine RP Fan, XS (corresponding author), Nanjing Univ Chinese Med, 138 Xianlin Ave, Nanjing 210023, Peoples R China. EM shshfan@njucm.edu.cn FU National Natural Science Foundation of China [82174258]; Key Project of the Collaborative Innovation Center for the Industrialization of Traditional Chinese Medicine Resources in Jiangsu Province [ZDXM-2020-22]; NATCM's Project of High-level Construction of Key TCM Disciplines [GSPZDXK]; Nantong Traditional Chinese Medicine Alliance Project [TZYK202310] FX This work was supported by the National Natural Science Foundation of China (Grant No. 82174258) , the Key Project of the Collaborative Innovation Center for the Industrialization of Traditional Chinese Medicine Resources in Jiangsu Province (Grant no. ZDXM-2020-22) , and NATCM's Project of High-level Construction of Key TCM Disciplines (GSPZDXK) . It also partially supported by the Nantong Traditional Chinese Medicine Alliance Project (TZYK202310) . 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Ethnopharmacol. PD MAY 23 PY 2026 VL 363 AR 121465 DI 10.1016/j.jep.2026.121465 PG 17 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA ES8OC UT WOS:001708918800001 PM 41780616 DA 2026-03-26 ER PT J AU Wang, Y Guo, JX Zhou, L Yuan, JF Huang, RX Xing, TT Chang, LP Wu, ZB Li, J Huang, M AF Wang, Yu Guo, Jianxin Zhou, Lu Yuan, Jianfeng Huang, Ruixue Xing, Tiantian Chang, Liping Wu, Zhongbing Li, Jing Huang, Ming TI Zuoguiyin modulates M2 macrophage polarization to inhibit glycolysis in esophageal squamous cell carcinoma SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Esophageal squamous cell carcinoma; Zuoguiyin; M2 macrophages; Glycolysis ID NORHARMANE AB Ethnopharmacological relevance: Zuoguiyin (ZGY), a traditional Chinese medicine formula used to nourish Yin and replenish vital essence, possesses tonifying properties that are conceptually aligned with modern strategies aiming to modulate the immunosuppressive tumor microenvironment (TME). In esophageal squamous cell carcinoma (ESCC), M2 macrophages are pivotal components that drive tumor progression. Therefore, therapeutic strategies targeting M2 macrophages may offer a beneficial approach. Aim of the study: This study aimed to explore whether ZGY suppresses ESCC by disrupting the pro-tumorigenic interactions between M2 macrophages and cancer cells, with a specific focus on the immunometabolic axis. Materials and methods: A co-culture system of ESCC cells and macrophages was employed to investigate cellular interactions. An in vivo ESCC mouse model induced by a 4-nitroquinoline-1-oxide (4-NQO) was employed for validation. Proteomic analysis, Seahorse metabolic analysis, flow cytometry, Western blotting, molecular docking, and molecular dynamics simulations were conducted to elucidate the underlying mechanisms and identify active components. Results: IL-4 secreted by ESCC cells bound to the IL-4 receptor on macrophages, activating the JAK/STAT6 signaling pathway and driving M2 polarization. These M2 macrophages, in turn, enhanced glycolytic metabolism in ESCC cells. ZGY treatment did not directly affect the cancer cells but effectively inhibited M2 polarization by blocking JAK2/STAT6 phosphorylation. This led to a reversal of the M2-driven enhancement of tumor glycolysis and a reduction in tumor growth in vivo. Isoferulic acid and norharman, key bioactive components of ZGY, were identified as stable binders of JAK2. Conclusions: This study elucidates the mechanism through which IL-4/JAK2/STAT6-mediated M2 macrophages promote glycolysis in ESCC and demonstrates that ZGY disrupts this pathway by targeting JAK2 in macrophages. These findings provide a mechanistic foundation for developing ZGY as a promising tumor microenvironmentmodifying therapy for ESCC. C1 [Wang, Yu; Guo, Jianxin; Zhou, Lu; Yuan, Jianfeng; Huang, Ruixue; Xing, Tiantian; Wu, Zhongbing; Li, Jing; Huang, Ming] Hebei Med Univ, Coll Integrated Chinese & Western Med, Shijiazhuang 050017, Peoples R China. [Chang, Liping] Natl Key Lab Innovat & Transformat Luobing Theory, Shijiazhuang 050035, Peoples R China. [Li, Jing] Hebei Med Univ, Hosp 4, 12 Jiankang Rd, Shijiazhuang 050011, Peoples R China. C3 Hebei Medical University; Hebei Medical University RP Wu, ZB; Li, J; Huang, M (corresponding author), Hebei Med Univ, Coll Integrated Chinese & Western Med, Shijiazhuang 050017, Peoples R China.; Li, J (corresponding author), Hebei Med Univ, Hosp 4, 12 Jiankang Rd, Shijiazhuang 050011, Peoples R China. EM 23031100064@stu.hebmu.edu.cn; 25031100110@stu.hebmu.edu.cn; 24031100100@stu.hebmu.edu.cn; 23033100266@stu.hebmu.edu.cn; 24033100325@stu.hebmu.edu.cn; 24033100323@stu.hebmu.edu.cn; 22031100077@stu.hebmu.edu.cn; 19001631@hebmu.edu.cn; lijing@hebmu.edu.cn; 19701907@hebmu.edu.cn FU National Natural Science Foundation of China [82274593]; Natural Science Foundation of Hebei Province [H2023206137]; Hebei Education Science Research Project [BJK2024113]; Hebei Traditional Chinese Medicine Science Research Project [Z2026009] FX This work was supported by grants from the National Natural Science Foundation of China (No. 82274593) ; Natural Science Foundation of Hebei Province (H2023206137) ; Hebei Education Science Research Project (BJK2024113) ; and Hebei Traditional Chinese Medicine Science Research Project (Z2026009) . 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PD MAY 10 PY 2026 VL 362 AR 121404 DI 10.1016/j.jep.2026.121404 PG 21 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA EE3CT UT WOS:001699042000001 PM 41720415 OA hybrid DA 2026-03-26 ER PT J AU He, L Zhong, ZT Liu, FB Wen, ST AF He, Long Zhong, Zhuotai Liu, Fengbin Wen, Shuting TI Berberine alleviates DSS-induced colitis by modulating macrophage phenotype via PPAR-γ/ mTOR/HIF-1α signaling pathway SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Berberine; M2 macrophage; Peroxisome proliferator activated receptor gamma; Oxidative phosphorylation AB Ethnopharmacological relevance: Berberine (BBR), an isoquinoline alkaloid derived from Chinese herbal drugs of Coptis chinensis Franch. and Phellodendron chinense C.K. Schneid., has been traditionally extensively utilized in treating acute or chronic diarrhea and distension. In modern medical practice, BBR has also been developed to remit diarrhea of ulcerative colitis (UC). However, the potential mechanism remains not been fully elucidated. Aim of the study: The present study aimed to explore the modulation effect of BBR on M2 macrophage polarization and elucidate the underlying mechanism. Materials and methods: Mice with colitis were induced by dextran sulfate sodium (DSS) and administrated with BBR. The distribution of M2-like phenotype of macrophage in colon tissues was determined by flow cytometry and immunofluorescence. Additionally, the Seahorse real-time cell metabolic analysis was applied to measure the oxygen consumption rate on RAW264.7 cells cultured under M2 macrophage polarization conditions. Protein levels were measured using western blotting and immunohistochemistry. Finally, the GW9662 was used for reverse validation experiments. Results: BBR notably alleviated colitis and resettled inflammatory macrophages toward M2 phenotype in a mouse model. Additionally, BBR significantly promoted peroxisome proliferator-activated receptor gamma (PPAR-gamma) expression in mice with colitis. In vitro findings demonstrated BBR significantly enhanced M2 macrophage polarization and increased the oxygen consumption and ATP production of RAW 264.7 cells cultured in M2 macrophage polarization condition. BBR also exerted a negative regulatory effect on the mTOR/HIF-1 alpha signaling pathway. Nevertheless, the modulation efficiency of BBR on M2 macrophage polarization and mTOR/HIF-1 alpha pathway were abrogated upon the application of GW9662 both in vivo and in vitro. Conclusion: BBR significantly contribute to drive M2 macrophage polarization via the PPAR-gamma/mTOR/HIF-1 alpha axis, and further confirmed the considerable approach of BBR for the clinical treatment of UC. C1 [He, Long] Guangzhou Univ Chinese Med, Affiliated Hosp 1, 16 Baiyun Rd, Guangzhou 510000, Peoples R China. [Zhong, Zhuotai] Beijing Univ Chinese Med, Dongfang Hosp, Dept Gastroenterol, 6 Dist 1,Fangxingyuan Fangzhuang, Beijing 100000, Peoples R China. [Liu, Fengbin] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Dept Gastroenterol, 16 Baiyun Rd, Guangzhou 510000, Peoples R China. [Wen, Shuting] Guangzhou Univ Chinese Med, Affiliated Hosp 2, Dept Gastroenterol, 55 Inner Ring West Rd, Guangzhou 510000, Peoples R China. C3 Guangzhou University of Chinese Medicine; Beijing University of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine RP Wen, ST (corresponding author), Guangzhou Univ Chinese Med, Affiliated Hosp 2, Dept Gastroenterol, 55 Inner Ring West Rd, Guangzhou 510000, Peoples R China. EM wst@gzucm.edu.cn FU Guangdong Basic and Applied Basic Research Foundation [2023A1515110209]; Science Project Foundation of Guangdong Province Hospital of Chinese Medicine [YN2023QN20] FX This work was supported by the Guangdong Basic and Applied Basic Research Foundation (No. 2023A1515110209) , and Science Project Foundation of Guangdong Province Hospital of Chinese Medicine (No. YN2023QN20) . 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Ethnopharmacol. PD MAY 10 PY 2026 VL 362 AR 121350 DI 10.1016/j.jep.2026.121350 EA MAY 2026 PG 11 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA DT3OQ UT WOS:001691591900001 PM 41679358 DA 2026-03-26 ER PT J AU Wu, SG Liu, P Wang, LL Zhang, KW Fei, J AF Wu, Shengguang Liu, Peng Wang, Lingli Zhang, Kaiwei Fei, Ji TI Study on the mechanism of traditional chinese medicine compound Shixiang Plaster improving diabetic wound healing through MAPK regulation of macrophage polarization SO BURNS LA English DT Article DE Diabetic foot ulcer; Diabetic wound healing; Shi Xiang Plaster; MAPK signaling pathway; Macrophage polarization ID DISEASE AB The healing impairment of diabetic foot ulcers (DFU) is closely related to chronic inflammation and the imbalance of M1/M2 polarization of macrophages. This study aims to elucidate the mechanism by which the traditional Chinese medicine compound Shixiang Plaster (SXP) promotes wound healing in diabetes by regulating the MAPK signaling pathway and modulating macrophage polarization. A full-thickness skin defect model in streptozotocin (STZ)-induced diabetic mice was established and divided into the control group, model group, SXP group, and basic fibroblast growth factor (BFGF) group. Histological, immunofluorescence, qRT-PCR, Western Blot, and metabolomics analyses were conducted. The results showed that SXP significantly accelerated wound healing (P < 0.05), promoted re-epithelialization and collagen deposition, and reduced inflammatory infiltration. The mechanism lies in its effective inhibition of M1-type macrophage (F4/80(+)CD86(+)) infiltration and promotion of M2-type (F4/80(+)CD206(+)) polarization, accompanied by a decrease in serum pro-inflammatory factors (IL-6, TNF-alpha) and an increase in anti-inflammatory factors (IL-10). At the molecular level, SXP significantly inhibited the expression of MAPK8 (JNK), p38, and p44/42 (ERK) at both transcriptional and protein levels, and reduced their phosphorylation activities (p-p38, p-p44/42). Metabolomics analysis suggested that the flavonoid components in SXP (kaempferol, daidzein) might indirectly affect the MAPK pathway by regulating the redox balance. This study reveals that SXP improves diabetic wound healing, which is associated with the inhibition of the MAPK signaling axis and a shift in macrophage polarization. Metabolomics analysis identified altered levels of flavonoids (e.g., kaempferol, daidzein) in wound tissue, suggesting their potential involvement in the observed effects via the "components-MAPK-macrophage" cascade. This multi-target mode of action provides a new therapeutic perspective for DFU. C1 [Wu, Shengguang; Liu, Peng; Wang, Lingli] Guizhou Univ Tradit Chinese Med, Coll Orthoped & Traumatol, Guiyang 550002, Guizhou, Peoples R China. [Zhang, Kaiwei; Fei, Ji] Guizhou Univ Tradit Chinese Med, Affiliated Hosp 1, Dept Orthoped & Traumatol, 71 Baoshan North Rd, Guiyang 550001, Guizhou, Peoples R China. C3 Guizhou University of Traditional Chinese Medicine; Guizhou University of Traditional Chinese Medicine RP Zhang, KW; Fei, J (corresponding author), Guizhou Univ Tradit Chinese Med, Affiliated Hosp 1, Dept Orthoped & Traumatol, 71 Baoshan North Rd, Guiyang 550001, Guizhou, Peoples R China. EM zkw1973@sina.com; FJ123e@163.com FU Guizhou Provincial Science and Technology Department (Guizhou Basic Research Project) [MS [2025] 131]; Guizhou Provincial Traditional Chinese Medicine Adminis-tration [QZYY-2023-013] FX This work was supported by (1) Guizhou Provincial Science and Technology Department (Guizhou Basic Research Project MS [2025] 131) , (2) Guizhou Provincial Traditional Chinese Medicine Adminis-tration (No. QZYY-2023-013) . 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However, the effectiveness of its ethanol extract in relieving UC and its mechanisms involved are not well comprehended. This study aimed to evaluate the therapeutic efficacy of AR ethanol extract on UC and explore the underlying mechanisms, focusing on its regulation of the intestinal microecology.MethodsA UC model in mice was induced with 2.5% dextran sulfate sodium and then treated with AR ethanol extract, L. reuteri, or microbial metabolites indole-3-carboxaldehyde (IAId) and formononetin (FMN). Changes in tissue damage and inflammation were evaluated. Adjustments in gut microbiota were identified using 16S rRNA sequencing analysis. Changes in the fecal metabonomics were analyzed. Levels of polarized M1 macrophages in colon tissues was detected using immunofluorescence staining. The mRNA levels of proinflammatory cytokines in RAW264.7 cells was quantified by RT-PCR. The binding affinity between FMN and PGK1 (IAId and AHR) was assessed using surface plasmon resonance analysis.ResultsAR ethanol extract relieved mucosal injury and decreased levels of proinflammatory cytokines in the colon. AR extract modulated the structure and composition of intestinal flora, specifically, it significantly increased the L. reuteri level, which facilitated the production of IAId and FMN. Moreover, Ononin was the key ingredient from AR to induce the L. reuteri growth. IAId and FMN could relieve UC symptoms, thereby improving the overall efficacy of AR extract on UC. Furthermore, IAId and FMN could inhibit M1 macrophages polarization, resulting in a reduction in TNF-alpha, IL-6, and IL-1 beta levels. IAId inhibited M1 macrophages polarization by AHR/NF-kappa B pathway, and FMN suppressed M1 macrophages via PGK1/NLRP3/NF-kappa B pathway, which exerts the synergistic effect on inflammatory responses.ConclusionAR ethanol extract can alleviate UC by inhibiting M1 macrophages activities via promoting L. reuteri-produced IAId and FMN. C1 [Zhang, Jia-Xuan; Dong, Shi-Qin; Ning, Hui-Jie; Su, Qi-Qi; Sun, Jia-Hui; Lin, Yan-Ni; Ke, Xue-Qi; Chen, Fei-Long; Wu, Zhi-Yong; Zhou, Feng-Hua; Liu, Chang-Shun] Southern Med Univ, Guangdong Prov Key Lab Chinese Med Pharmaceut, Guangdong Basic Res Ctr Excellence Integrated Trad, Sch Tradit Chinese Med, 1023 South Shatai Rd, Guangzhou 510515, Guangdong, Peoples R China. [Hu, Yin-Xia] PLA Gen Hosp Southern Theater Command, Dept Gastroenterol, Guangzhou 510010, Peoples R China. [Li, Yue] Southern Med Univ, Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Endoscopy Ctr, Guangzhou 510080, Peoples R China. [Zhang, Yu] Univ Toronto, Fac Art & Sci, Toronto, ON, Canada. C3 Southern Medical University - China; Southern Medical University - China; Guangdong Academy of Medical Sciences & Guangdong General Hospital; University of Toronto RP Wu, ZY; Zhou, FH; Liu, CS (corresponding author), Southern Med Univ, Guangdong Prov Key Lab Chinese Med Pharmaceut, Guangdong Basic Res Ctr Excellence Integrated Trad, Sch Tradit Chinese Med, 1023 South Shatai Rd, Guangzhou 510515, Guangdong, Peoples R China. EM 2544605841@qq.com; 1150869021@qq.com; 15017560826@163.com; 1961832165@qq.com; 2377177835@qq.com; sun17513306663@163.com; 3358563711@qq.com; 2727715513@qq.com; liyue_1989919@126.com; jos.zhang@mail.utoronto.ca; 11195719@163.com; 11100227@smu.edu.cn; wendyzhou515@126.com; lcshun1225@163.com FU the Scientific Research Project of Guangdong Provincial Administration of Traditional Chinese Medicine [20251245]; the Major Science and Technology Project of Traditional Chinese Medicine in Guangzhou Area [No. 2025QN005]; the Guangdong Medical Science and Technology Research Fund Project [B2025586] FX The Basic and Applied Basic Research Fund Project of Guangdong Province, 2026A1515012419, the Scientific Research Project of Guangdong Provincial Administration of Traditional Chinese Medicine, 20251245, the Guangdong Medical Science and Technology Research Fund Project, B2025586, and the Major Science and Technology Project of Traditional Chinese Medicine in Guangzhou Area, 2025QN005. 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Med. PD MAR 20 PY 2026 VL 21 IS 1 AR 99 DI 10.1186/s13020-026-01382-4 PG 16 WC Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine; Pharmacology & Pharmacy GA FH5VA UT WOS:001718927500002 PM 41857597 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Yang, F Hou, RS Liu, XG Du, Y Zhang, Q Pan, X Zhao, P Tian, YG Li, JS AF Yang, Fan Hou, Runsu Liu, Xinguang Du, Yan Zhang, Qin Pan, Xin Zhao, Peng Tian, Yange Li, Jiansheng TI Jinshui Chenfei formula alleviates SiO2-induced pulmonary fibrosis by inhibiting macrophage M2 polarization via Grb2/STAT6 in rats SO CHINESE MEDICINE LA English DT Article DE Jinshui Chenfei formula; Silicosis; Macrophages of M2 polarization; STAT6; Grb2 ID SILICOSIS; CELLS AB BackgroundJinshui Chenfei Formula (JCF), a proprietary Chinese medicinal prescription, has demonstrated remarkable therapeutic efficacy in treating pneumoconiosis patients. However, the precise mechanisms remain to be elucidated. This study aimed to investigate how JCF counteracts M2 macrophage polarization and thereby attenuates SiO2-triggered silicosis progression.MethodsThis study aimed to observe the effects of JCF on collagen deposition and macrophage M2 polarization in silicotic lungs induced by silica at 14 days, 28 days, and 42 days in rats. The active fraction of JCF was isolated and extracted using macroporous resin. Subsequently, RNA-seq was performed to predict the potential mechanism involved in the improvement of IL4-induced bone marrow-derived macrophages (BMDMs) by JCF. Finally, the targets of the active fraction of JCF were identified by the DARTS experiment. The underlying mechanisms were elucidated by combining siRNA and plasmid overexpression techniques.ResultsJCF significantly improved pulmonary function and pathological remodeling in silicosis rats across different time points, reduced collagen deposition in lung tissues, and downregulated the expression of M2 macrophage markers. JCF5, the active fraction of JCF, potently inhibited IL4-induced M2 polarization of bone marrow-derived macrophages (BMDMs). RNA-seq identified 96 differential expressed genes (DEGs) associated with M2 polarization and JCF5 treatment, which enriched signaling pathways such as JAK/STAT. In vitro experiment confirmed that JCF5 markedly reduced STAT6 phosphorylation. Drug affinity responsive target stability (DARTS) assays revealed that JCF5 suppress STAT6 activation by down-regulating Grb2, siRNA-mediated Grb2 knockdown potently reduced IL-4-induced M2 macrophages, whereas Grb2 overexpression significantly alleviated the inhibitory effects of JCF5 on STAT6 activation and M2 polarization. Further, Hesperidin is the main active ingredient verified by molecular docking and cell function assays.ConclusionJCF downregulate STAT6 activation by regulating Grb2, thereby inhibit M2 polarization of macrophage and improve pulmonary fibrosis in silicotic rats. C1 [Yang, Fan; Hou, Runsu; Liu, Xinguang; Du, Yan; Zhang, Qin; Pan, Xin; Zhao, Peng; Tian, Yange; Li, Jiansheng] Henan Univ Chinese Med, Henan Key Lab Chinese Med Resp Dis, 156 Jinshui Dong Rd, Zhengzhou 450046, Henan, Peoples R China. [Yang, Fan; Hou, Runsu; Liu, Xinguang; Du, Yan; Zhang, Qin; Pan, Xin; Zhao, Peng; Tian, Yange; Li, Jiansheng] Coconstructed Henan Prov & Educ Minist PR China, Collaborat Innovat Ctr Chinese Med & Resp Dis, Zhengzhou 450046, Henan, Peoples R China. [Hou, Runsu; Liu, Xinguang; Du, Yan; Zhang, Qin; Pan, Xin; Zhao, Peng; Tian, Yange] Henan Univ Chinese Med, Acad Chinese Med Sci, Zhengzhou 450046, Henan, Peoples R China. [Yang, Fan; Li, Jiansheng] Henan Univ Chinese Med, Affiliated Hosp 1, Dept Resp Dis, Zhengzhou 450000, Henan, Peoples R China. C3 Henan University of Traditional Chinese Medicine; Henan University of Traditional Chinese Medicine; Henan University of Traditional Chinese Medicine RP Li, JS (corresponding author), Henan Univ Chinese Med, Henan Key Lab Chinese Med Resp Dis, 156 Jinshui Dong Rd, Zhengzhou 450046, Henan, Peoples R China.; Li, JS (corresponding author), Coconstructed Henan Prov & Educ Minist PR China, Collaborat Innovat Ctr Chinese Med & Resp Dis, Zhengzhou 450046, Henan, Peoples R China.; Li, JS (corresponding author), Henan Univ Chinese Med, Affiliated Hosp 1, Dept Resp Dis, Zhengzhou 450000, Henan, Peoples R China. EM li_js8@163.com FU Henan Special Research Project of TCM on "Double First-Class" Construction [HSRP-DFCTCM-2023-5-05] FX The research was supported by Henan Special Research Project of TCM on "Double First-Class" Construction (HSRP-DFCTCM-2023-5-05). CR Adamcakova J, 2021, INT J MOL SCI, V22, DOI 10.3390/ijms22084162 ASHCROFT T, 1988, J CLIN PATHOL, V41, P467, DOI 10.1136/jcp.41.4.467 [邓欣祺 Deng Xinqi], 2025, [中国现代中药, Modern Chinese Medicine], V27, P1198 Du SL, 2025, TOXICOL MECH METHOD, V35, P89, DOI 10.1080/15376516.2024.2400323 Fan JM, 2025, MICROBIOL IMMUNOL, V69, P339, DOI 10.1111/1348-0421.13216 Fu CP, 2019, FRONT IMMUNOL, V10, DOI 10.3389/fimmu.2019.02638 Fu NF, 2013, EVID-BASED COMPL ALT, V2013, DOI 10.1155/2013/790792 Gao XH, 2024, INT J MOL MED, V53, DOI 10.3892/ijmm.2023.5327 Guo XH, 2017, J BIOL CHEM, V292, P14003, DOI 10.1074/jbc.M117.802066 Jiao BH, 2021, CELLS-BASEL, V10, DOI 10.3390/cells10113057 Ju W, 2020, MOL BIOL REP, V47, P2735, DOI 10.1007/s11033-020-05372-z Kim EM, 2017, PLOS NEGLECT TROP D, V11, DOI 10.1371/journal.pntd.0005614 Krefft S, 2020, CLIN CHEST MED, V41, P709, DOI 10.1016/j.ccm.2020.08.012 Krishnamurthy P, 2016, IMMUNE NETW, V16, P201, DOI 10.4110/in.2016.16.4.201 Li DQ, 2022, CANCER RES, V82, P3321, DOI 10.1158/0008-5472.CAN-22-0507 Li JS, 2022, FRONT MED-PRC, V16, P736, DOI 10.1007/s11684-021-0870-5 Li M, 2023, MEDCOMM, V4, DOI 10.1002/mco2.349 Liu X, 2023, BMC PUBLIC HEALTH, V23, DOI 10.1186/s12889-023-16295-2 Malagrinò F, 2024, BIOCHEM BIOPHYS REP, V39, DOI 10.1016/j.bbrep.2024.101803 Pang JL, 2021, THERANOSTICS, V11, P2381, DOI 10.7150/thno.47627 Parrish AB, 2013, CSH PERSPECT BIOL, V5, DOI 10.1101/cshperspect.a008672 Plataki M, 2005, CHEST, V127, P266, DOI 10.1378/chest.127.1.266 SZAPIEL SV, 1979, AM REV RESPIR DIS, V120, P893 Wei BK, 2024, HELIYON, V10, DOI 10.1016/j.heliyon.2024.e34592 Wu WH, 2023, FRONT MED-LAUSANNE, V10, DOI 10.3389/fmed.2023.1107967 Yang YJ, 2022, J NUTR BIOCHEM, V110, DOI 10.1016/j.jnutbio.2022.109148 Zhang ZQ, 2022, TOXICOL IND HEALTH, V38, P810, DOI 10.1177/07482337221136949 Zhao YL, 2020, ECOTOX ENVIRON SAFE, V193, DOI 10.1016/j.ecoenv.2020.110364 NR 28 TC 0 Z9 0 U1 0 U2 0 PU BMC PI LONDON PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1749-8546 J9 CHIN MED-UK JI Chin. Med. PD MAR 16 PY 2026 VL 21 IS 1 AR 85 DI 10.1186/s13020-026-01339-7 PG 15 WC Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine; Pharmacology & Pharmacy GA FE0YA UT WOS:001716552800002 PM 41840698 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Cui, LW Fan, XY Xiao, JL Qian, XY Sun, M Cui, YF Gao, K Liu, B Guo, SZ AF Cui, Lingwen Fan, Xinyi Xiao, Jin Ling Qian, Xiangyi Sun, Meng Cui, Yifang Gao, Kuo Liu, Bin Guo, Shuzhen TI Exosomes from macrophages intervened by Jiedu Yangxin decoction mediated endothelial-to-mesenchymal transition to improve myocardial fibrosis after myocardial infarction SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article; Early Access DE endothelial-to-mesenchymal transition; Jiedu Yangxin decoctions; macrophage-derived exosomes; myocardial fibrosis; myocardial infarction ID CONCISE GUIDE AB Background and Purpose Myocardial fibrosis, a critical pathological feature in myocardial infarction (MI) associated with adverse outcomes. Endothelial-to-mesenchymal transition (EndMT) emerges as a central driver of fibrosis, regulated by macrophage polarization and exosomal microRNAs (miRNAs). This study elucidates the anti-fibrotic mechanism of Jiedu Yangxin Decoction (JDYX), a Traditional Chinese Medicine, investigating regulation of macrophage-derived exosomes and suppression of EndMT in post-myocardial infarction (MI) cardiac remodelling.Experimental Approach In vivo, 8-week-old male C57BL/6J mice underwent left anterior descending (LAD) coronary artery ligation and received intragastric JDYX at different post-MI time windows. Cardiac function, fibrosis and EndMT were assessed by echocardiography, histology, Western blot and RT-qPCR. Co-staining was used to examine the association between M2 macrophages and EndMT. In vitro, endothelial cells were co-cultured with macrophage exosomes. Exosomes were characterized, and miRNA sequencing was performed to identify miR-23b-3p.HCAECs were exposed to exosomes from THP-1 with miR-23b-3p modulation, and Smad3 pathway was assessed by WB.Key Results In MI mice, early JDYX intervention (0-7 days) most effectively preserved cardiac function, while reducing fibrosis. JDYX attenuated EndMT, reversing mesenchymal marker upregulation and endothelial marker suppression. JDYX regulated macrophage phenotype, increasing Arg-1 and IL-10, thereby alleviating EndMT. Crucially, JDYX-reprogrammed macrophage-derived exosomes improved M1 macrophage-derived exosomes-induced EndMT in vitro. miRNA-seq revealed miR-23b-3p enrichment in JDYX-exosomes. The protective effect of JDYX against EndMT was compromised when using exosomes from miR-23b-3p-knockdown macrophages.Conclusion and Implications JDYX improves myocardial fibrosis by targeting macrophage-derived exosomal miRNAs, thereby attenuating EndMT. C1 [Cui, Lingwen; Sun, Meng; Cui, Yifang; Liu, Bin] Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing, Peoples R China. [Fan, Xinyi; Xiao, Jin Ling; Qian, Xiangyi; Gao, Kuo; Guo, Shuzhen] Beijing Univ Chinese Med, Sch Tradit Chinese Med, Beijing, Peoples R China. [Liu, Bin; Guo, Shuzhen] State Adm Tradit Chinese Med, Key Res Lab Exploring Effect Subst Class & Famous, Beijing, Peoples R China. C3 Beijing University of Chinese Medicine; Beijing University of Chinese Medicine RP Gao, K; Guo, SZ (corresponding author), Beijing Univ Chinese Med, Sch Tradit Chinese Med, Beijing, Peoples R China.; Liu, B; Guo, SZ (corresponding author), State Adm Tradit Chinese Med, Key Res Lab Exploring Effect Subst Class & Famous, Beijing, Peoples R China. EM gk@bucm.edu.cn; liubinyn67@163.com; guoshz@bucm.edu.cn FU National Natural Science Foundation of China [82474331] FX The authors thank the National Natural Science Foundation of China (No. 82474331) for financial support and thank Beijing University of Chinese Medicine for providing the necessary infrastructure to perform this research. 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J. Pharmacol. PD 2026 MAR 10 PY 2026 DI 10.1111/bph.70398 EA MAR 2026 PG 28 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA ET6KX UT WOS:001709453300001 PM 41804264 DA 2026-03-26 ER PT J AU Yu, JX Zhang, HW Wu, Y Di, ZZ Shi, Y Fan, X Dong, BQ Dai, JY Wang, ZM Chen, YR Liu, WN Zhang, WS AF Yu, Jiaxiang Zhang, Hanwen Wu, Yi Di, Zizhen Shi, Yan Fan, Xu Dong, Baoqiang Dai, Jianyu Wang, Zhimin Chen, Yiran Liu, Weinan Zhang, Wenshun TI Yitangkang decoction in the treatment of glomerular filtration barrier damage through AMPKα1/ZDHHC8/SLC7A11/GPX4 and TGF-β/Smad signaling pathways: A multi-omics analysis SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Yitangkang; Diabetic kidney disease; Multi-omics; Palmitoyl-proteomics; Glomerular filtration barrier damage; Ferroptosis ID DESIGN AB Ethnopharmacological relevance: Diabetic kidney disease (DKD) is a prevalent microvascular complication of diabetes mellitus (DM) that significantly impairs patients' quality of life. Its early stage is characterized by glomerular filtration barrier damage and the occurrence of proteinuria. Without timely intervention, this condition progresses to renal fibrosis, and therapeutic options remain limited despite recent advances. Yitangkang decoction (YTK) has shown potential in ameliorating this barrier damage, thereby inhibiting proteinuria and ultimately preventing renal fibrosis; however, its precise mechanisms remain unclear. Aim of the study: This study aimed to elucidate the therapeutic mechanism by which YTK ameliorates glomerular filtration barrier damage in DKD. Materials and methods: db/db mice were treated with high-, medium-, or low-dose YTK or with finerenone for 8 weeks. We employed a multi-omics approach-including data-independent acquisition (DIA) proteomics, transcriptomics, and palmitoyl-proteomics coupled with LC-MS/MS-to identify differentially expressed proteins, mRNAs, and palmitoylation sites related to YTK's renoprotective effects, as well as to characterize its absorbed serum components. In vitro validation was performed in D-glucose-injured MPC5 podocytes, mouse renal microvascular endothelial cells and mouse glomerular mesangial cells using YTK-medicated serum, finerenonemedicated serum, the active components puerarin and quercitrin, or pharmacological modulators of the AMPK and TGF-beta 1 pathways. YTK's efficacy was evaluated using biochemical, histopathological, and molecular biological indicators. Results: YTK treatment dose-dependently reduced urinary albumin-to-creatinine ratio (UACR), serum creatinine (Scr), urea, uric acid (UA), and lipid peroxide (LPO) levels, while restoring glutathione (GSH) levels and alleviating renal pathology in db/db mice. Multi-omics integration revealed enrichment in pathways involving extracellular matrix (ECM)-receptor interaction, AMPK signaling, and glutathione metabolism. YTK attenuated glomerular filtration barrier damage through several coordinated mechanisms: (1) Inhibition of the TGF-beta/Smad pathway, downregulating TMEM2, TGF-beta 1, Smad2/3/4, and MMP-9; (2) Enhancement of SLC7A11 palmitoylation via the AMPK alpha 1/ZDHHC8 axis, which stabilized SLC7A11 protein and inhibited ferroptosis-a role confirmed by site-directed mutagenesis of the critical Cys327 site; (3) Direct modulation of macrophage polarization, suppressing pro-inflammatory M1 markers and promoting anti-inflammatory M2 markers; and (4) Multi-target cytoprotection against renal cell injury. Surface plasmon resonance (SPR) analysis confirmed the direct, concentration-dependent binding of puerarin and quercitrin to GPX4 and TGF-beta 1. In vitro, YTK-medicated serum, puerarin, and quercitrin restored viability in injured MPC5 podocytes, renal microvascular endothelial cells and glomerular mesangial cells, induced consistent mRNA expression changes of key targets across both cell types, and inhibited apoptosis via modulation of the TGF-(3/Smad and AMPK/SLC7A11 pathways. Specificity validation of the palmitoylation detection method reinforced the reliability of the omics findings. Conclusions: This study comprehensively elucidates the multi-cellular protective mechanism of YTK on the glomerular filtration barrier. We demonstrate that YTK confers protection via a dual-pathway mechanism: (1) Suppression of the injury pathway by inhibiting TGF-(31/Smad overactivation via modulation of macrophage phenotype and ECM homeostasis, thereby mitigating inflammation and cellular damage; and (2) Activation of the protective pathway by enhancing SLC7A11 palmitoylation through the AMPK alpha 1/ZDHHC8 axis, which stabilizes SLC7A11, restores glutathione metabolism, and inhibits ferroptosis. These two axes functionally interact to rebalance injury and protective signaling. Furthermore, puerarin and quercitrin were identified as key serum-absorbed constituents that directly bind to targets including TGF-(31 and GPX4, mediating the described dual-pathway regulation. In summary, YTK represents a promising multi-target therapeutic strategy that coordinately regulates injury and protective signaling networks to prevent and alleviate proteinuria in DKD. C1 [Yu, Jiaxiang] Liaoning Univ Tradit Chinese Med, Key Lab Minist Educ TCM Viscera State Theory & App, Shenyang 110847, Peoples R China. [Yu, Jiaxiang; Fan, Xu] Liaoning Univ Tradit Chinese Med, Coll Hlth Preservat & Rehabil, Shenyang 110847, Peoples R China. [Zhang, Hanwen; Shi, Yan] Liaoning Univ Tradit Chinese Med, Coll Basic Med, Shenyang 110847, Peoples R China. [Dong, Baoqiang; Dai, Jianyu; Chen, Yiran] Liaoning Univ Tradit Chinese Med, Coll Acupuncture & Massage, Shenyang 110847, Peoples R China. [Wang, Zhimin] Liaoning Univ Tradit Chinese Med, Affiliated Hosp, Shenyang 110847, Peoples R China. [Wu, Yi; Di, Zizhen; Liu, Weinan; Zhang, Wenshun] Liaoning Univ Tradit Chinese Med, Affiliated Hosp 2, Liaoning Prov Tradit Chinese Med Res Inst, Shenyang 110847, Peoples R China. C3 Liaoning University of Traditional Chinese Medicine; Liaoning University of Traditional Chinese Medicine; Liaoning University of Traditional Chinese Medicine; Liaoning University of Traditional Chinese Medicine; Liaoning University of Traditional Chinese Medicine; Liaoning University of Traditional Chinese Medicine RP Zhang, WS (corresponding author), Liaoning Univ Tradit Chinese Med, Affiliated Hosp 2, Liaoning Prov Tradit Chinese Med Res Inst, Shenyang 110847, Peoples R China. EM wenshunzhang@163.com FU Open fund of Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine [zyzx 2402]; Joint Fund at the Department of Science and Technology in Liaoning [2023-MSLH-184, 2025JH2/101800272] FX This work was supported by the Open fund of Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine [grant number zyzx 2402] , and the Joint Fund at the Department of Science and Technology in Liaoning [grant number 2023-MSLH-184 and 2025JH2/101800272] . 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Ethnopharmacol. PD MAY 23 PY 2026 VL 363 AR 121410 DI 10.1016/j.jep.2026.121410 EA FEB 2026 PG 26 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA EM5ZI UT WOS:001704662500002 PM 41740333 DA 2026-03-26 ER PT J AU Han, X Pang, MJ Hu, CL Li, YT Xu, T Xu, HL Ye, HX Xie, LP Shen, AH Liu, B Zhang, GY Zhou, YC AF Han, Xin Pang, Mingjie Hu, Changlei Li, Yutong Xu, Tong Xu, Honglin Ye, Haixin Xie, Lingpeng Shen, Aihua Liu, Bin Zhang, Guoyong Zhou, Yingchun TI Taohong Siwu decoction and its components regulate the M1/M2 polarization of macrophages to alleviate inflammatory injury in sepsis via the RAGE SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE THSWD; Amygdalin; Sepsis; Inflammatory injury; M1/M2 polarization; RAGE ID ACUTE LUNG INJURY; MYOCARDIAL DYSFUNCTION; MORTALITY AB Ethnopharmacological relevance: Sepsis is a fatal disease induced by an abnormal anti-infection immune response. Macrophage M1/M2 polarization responses are essential for the systemic inflammatory response process in sepsis. Taohong Siwu Decoction (THSWD) is a traditional Chinese medicine (TCM) prescription that has been confirmed to regulate the macrophage M1/M2 polarization to improve inflammatory damage. However, the active components and the mechanisms by which it alleviates inflammatory injury in sepsis remain unclear. Amygdalin (AMY) is an active component found in Persicae Semen. Great attention has been paid to AMY, which is used in pharmacotherapy to manage inflammatory disorders. Further investigation is warranted to determine how AMY, as one of the active components of THSWD, contributes to its anti-sepsis effects and to clarify the underlying mechanism of action. Aim of the study: This work evaluated the protection of THSWD and AMY, one of its representative active components, against sepsis-related inflammatory injury and the mechanisms involved. Materials and methods: Using the cecal ligation and puncture (CLP) procedure, this study constructed a sepsis mouse model. Subsequently, histopathology, echocardiography, TUNEL staining and ELISA were conducted to assess the protection of THSWD against inflammatory injury in CLP mice. Network pharmacology, molecular docking, molecular dynamics simulations, cellular thermal shift assay and SPRi were performed for verifying the mechanism of THSWD and its active component Amygdalin (AMY) in improving inflammatory injury in sepsis. Moreover, the protection of AMY against inflammatory injury, as well as its role in regulating M1 macrophage polarization through the RAGE pathway, was investigated using qRT-PCR, Western blotting, immunofluorescence staining, and immunohistochemical staining. In vitro, M1-type polarization was induced in RAW 264.7 cells and BMDMs using LPS stimulation, thereby verifying the effects of AMY. The RAGE inhibitor FPS-ZM1 was also used for further investigation in vitro and in vivo. Results: In vivo, THSWD significantly protected against inflammation-induced heart and lung tissue injuries in CLP mice. Bioinformatics analysis and other studies revealed that AMY, an active component of THSWD, might directly regulate RAGE to inhibit inflammatory response damage. AMY protected against inflammatory injury through inhibiting M1 macrophage polarization in sepsis by directly suppressing RAGE/NF-kappa B/MAPK pathways in vivo. According to our in vitro study results, AMY blocked RAGE activity to mitigate the LPS-mediated M1-type polarization in RAW 264.7 cells and BMDMs. Notably, AMY's protection in vivo and in vitro was not markedly enhanced by combining FPS-ZM1, consistent with the pooled effect of AMY and FPS-ZM1 on a RAGE-related pathway under our experimental conditions. Conclusions: THSWD and AMY, one of its active components, inhibit M1 macrophage polarization and alleviate inflammatory injury in sepsis, at least partially by targeting RAGE and modulating the RAGE-mediated NF-kappa B/ MAPK signaling pathway. C1 [Han, Xin; Li, Yutong; Shen, Aihua] Yanbian Univ, Med Coll, Dept Tradit Chinese Med, Yanji 133002, Jilin, Peoples R China. [Han, Xin; Pang, Mingjie; Hu, Changlei; Xu, Tong; Ye, Haixin; Zhang, Guoyong; Zhou, Yingchun] Southern Med Univ, Sch Tradit Chinese Med, Guangzhou 510515, Peoples R China. [Zhang, Guoyong] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangzhou 510405, Peoples R China. [Liu, Bin] Guangzhou Med Univ, Affiliated Hosp 2, Dept Tradit Chinese Med, Guangzhou 510260, Peoples R China. [Xu, Honglin] Guangzhou Univ Chinese Med, Affiliated Hosp 3, Dept Cardiol, Guangzhou 510378, Peoples R China. [Xu, Honglin] Southern Med Univ, Affiliated Hosp 10, Dongguan Peoples Hosp, Dongguan 523000, Peoples R China. [Xie, Lingpeng] Guangzhou Med Univ, Affiliated Tradit Chinese Med Hosp, Guangzhou 510515, Peoples R China. C3 Yanbian University; Southern Medical University - China; Guangzhou University of Chinese Medicine; Guangzhou Medical University; Guangzhou University of Chinese Medicine; Southern Medical University - China; Guangzhou Medical University RP Zhang, GY; Zhou, YC (corresponding author), Southern Med Univ, Sch Tradit Chinese Med, Guangzhou 510515, Peoples R China.; Zhang, GY (corresponding author), Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangzhou 510405, Peoples R China.; Liu, B (corresponding author), Guangzhou Med Univ, Affiliated Hosp 2, Dept Tradit Chinese Med, Guangzhou 510260, Peoples R China. EM xmhoolv@163.com; 1092307280@qq.com; zhychun@126.com RI ; Ye, Haixin/NGR-2440-2025 OI LI, Yutong/0009-0002-3269-912X; FU National Natural Science Foundation of China [82505444, 82474399, 82274246, 82305110, 82305225]; Jilin Province Health Bureau [2025WS-KA019]; Guangdong Provincial Natural Science Foundation [2022A1515110870, 2025A1515011793]; Dongguan Science and Technology of So-cial Development Program [20231800932382] FX This work was funded by the National Natural Science Foundation of China (grant numbers 82505444, 82474399, 82274246, 82305110, 82305225) , Jilin Province Health Bureau (2025WS-KA019) , Guangdong Provincial Natural Science Foundation (2022A1515110870, 2025A1515011793) , and the Dongguan Science and Technology of So-cial Development Program (20231800932382) . 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Ethnopharmacol. PD MAY 10 PY 2026 VL 362 AR 121366 DI 10.1016/j.jep.2026.121366 EA FEB 2026 PG 18 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA DY5XF UT WOS:001695150800001 PM 41692111 DA 2026-03-26 ER PT J AU Chen, YJ Wei, HL Dai, AL Fu, Y Zhang, ZN Hong, R Liu, H Jiao, Y Wan, J Chen, WW AF Chen, Yajuan Wei, Huilin Dai, Anlin Fu, Yan Zhang, Zengni Hong, Ran Liu, Hui Jiao, Yu Wan, Jun Chen, Wenwen TI Huangtu Decoction regulates macrophage M1/M2 polarization to alleviate DSS- and rhubarb-induced Deficiency-Cold Pattern in Ulcerative Colitis by inhibiting the HIF-1α signaling pathway SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Inflammatory response; Macrophage polarization; HIF-1 alpha; Deficiency-Cold Pattern in Ulcerative Colitis; Huangtu Decoction ID INTESTINAL MACROPHAGES; DISEASE; M1 AB Ethnopharmacological relevance: Huangtu Decoction (HTD), a classic formula in TCM, was first documented in the Synopsis of the Golden Chamber and later included in numerous TCM texts. This formula is commonly used to treat various gastrointestinal disorders, including diarrhea, bloody stools, irritable bowel syndrome, and ulcerative colitis (UC). Aim of the study: This study aimed to explore the therapeutic efficacy and mechanism of HTD in treating Deficiency-Cold Pattern in Ulcerative Colitis (DCP-UC). The focus was on examining whether HTD alleviates colitis symptoms by regulating macrophage polarization via the HIF-1 alpha signaling pathway. Materials and methods: We established DSS-and rhubarb-induced DCP-UC models in mice, along with an LPSstimulated RAW264.7 macrophage inflammation model, to evaluate the effects of HTD on colonic injury, inflammatory responses, and macrophage polarization. To verify the central role of macrophages in HTD efficacy, we conducted macrophage depletion experiments in vivo. Additionally, we induced differentiation of M1 and M2-type bone marrow-derived macrophages (BMDMs) and explored the impact of HIF-1 alpha on HTD efficacy by activating and overexpressing HIF-1 alpha. Results: HTD therapy significantly alleviated colitis symptoms, reduced colonic histopathological damage, and effectively suppressed intestinal inflammation. Concurrently, it decreases M1 macrophage markers and increases M2 markers, suggesting that HTD modulates macrophage polarization. Macrophage depletion experiments indicate that HTD's therapeutic efficacy may depend on macrophages. In vitro BMDM experiments showed that HTD inhibited HIF-1 alpha expression in M1 macrophages, thereby reducing proinflammatory factors. However, overexpression and activation of HIF-1 alpha could reverse this effect, implying that HIF-1 alpha is a potentially crucial target for HTD in regulating intestinal inflammation. Conclusion: HTD may exert its therapeutic effects by suppressing the HIF-1 alpha signaling pathway, which in turn may promote a phenotypic switch of macrophages from the proinflammatory M1 state to the anti-inflammatory M2 state. These findings suggest that HTD represents a promising potential therapeutic approach for DCP-UC. C1 [Chen, Yajuan; Wei, Huilin; Dai, Anlin; Fu, Yan; Zhang, Zengni; Hong, Ran; Liu, Hui; Jiao, Yu; Wan, Jun] Southwest Jiaotong Univ, Sch Life Sci & Engn, Chengdu 610031, Peoples R China. [Chen, Wenwen] Univ Elect Sci & Technol China, Chengdu Womens & Childrens Cent Hosp, Sch Med, Chengdu 610091, Peoples R China. C3 Southwest Jiaotong University; University of Electronic Science & Technology of China RP Wan, J (corresponding author), Southwest Jiaotong Univ, Sch Life Sci & Engn, Chengdu 610031, Peoples R China.; Chen, WW (corresponding author), Univ Elect Sci & Technol China, Chengdu Womens & Childrens Cent Hosp, Sch Med, Chengdu 610091, Peoples R China. EM chenyajuan88@163.com; 2049892770@qq.com; 2064878122@qq.com; fuyan2722@126.com; zhang_zengni@163.com; hongran_0608@163.com; 15583410073@163.com; jiaoyu4272@163.com; wjun1013@swjtu.edu.cn; chenww@uestc.edu.cn FU National Natural Science Foundation of China [82204970]; Fundamental Research Funds for the Central University [2682025ZTPY049] FX This work was supported by the National Natural Science Foundation of China (No. 82204970) and the Fundamental Research Funds for the Central University (No. 2682025ZTPY049) . 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PD MAY 10 PY 2026 VL 362 AR 121353 DI 10.1016/j.jep.2026.121353 EA FEB 2026 PG 16 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA DY3WE UT WOS:001695010900003 PM 41687943 DA 2026-03-26 ER PT J AU Gang, W Xuan, Z Ye, W Chen, Y Jing, Y Zhang, TL Shao, MY Tao, YW Jiang, ZW AF Gang, Wang Xuan, Zhao Ye, Wang Chen, Yi Jing, Yu Zhang, Tianle Shao, Mingyue Tao, Yuewei Jiang, Zhiwei TI Yiqi Daozhi Formula Reduces the M1 Polarization of Macrophages in Mice With Postoperative Ileus Through Mediating Glycolysis Metabolism SO IMMUNITY INFLAMMATION AND DISEASE LA English DT Article DE M1 polarization; macrophage; postoperative ileus; Yiqi Daozhi Decoction ID ACTIVATION; ACID AB Background Postoperative ileus (POI) represents a disorder of gastrointestinal function following surgical procedures, characterized by a multifaceted etiology. There is an urgent clinical need to search for treatment regimens that improve the therapeutic effect for POI. Current research indicates that Traditional Chinese Medicine (TCM) demonstrates significant efficacy in treating POI. Our research was conducted to delve into the precise therapeutic action of Yiqi Daozhi Formula (YQDZF) in the treatment of POI.Methods In our study, H&E staining and carmine detection were employed to assess the gastrointestinal functionality in the POI mouse model. ELISA was used to detect levels of MPO, lactic acid, inflammatory factors, and glycolysis. Flow cytometry and qRT-PCR were employed to examine the levels and expression of macrophage phenotypic markers. Western blotting was used to detect the expression of glycolysis- and AKT/NF-kB/HIF-1 alpha signaling pathway-related proteins. Cycloheximide method and MG-132 method were used to detect the stability of AKT protein.Results After making the comparative analysis with the Control group, the POI group mice exhibited pronounced gastrointestinal dysfunction, which was mitigated by treatment with YQDZF. In vivo experiments confirmed that YQDZF treatment markedly decreased M1 macrophage polarization and inhibited the glycolytic pathway. Cellular experiments demonstrated that this therapeutic approach was related to the AKT/NF-kB/HIF-1 alpha signaling pathway in macrophages.Conclusions YQDZF inhibits the AKT/NF-kB/HIF-1 alpha pathway, thereby mediating the M1 polarization of macrophages and the glycolytic metabolism to effectively alleviate the progression of POI. C1 [Gang, Wang; Shao, Mingyue; Jiang, Zhiwei] Nanjing Univ Chinese Med, Affiliated Hosp, Nanjing, Jiangsu, Peoples R China. [Xuan, Zhao; Ye, Wang; Chen, Yi; Jing, Yu; Zhang, Tianle] Nanjing Univ Chinese Med, Clin Med Coll 1, Nanjing, Jiangsu, Peoples R China. [Tao, Yuewei] Univ Dundee, Ninewells Hosp, Sch Med, Dundee, Scotland. C3 Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine; University of Dundee RP Jiang, ZW (corresponding author), Nanjing Univ Chinese Med, Affiliated Hosp, Nanjing, Jiangsu, Peoples R China. EM surgery341@163.com OI Zhang, Tianle/0009-0004-6713-7498 FU Jiangsu Provincial Association of Chinese Medicine Revitalization and Development Project [ZXFZ2024001]; Jiangsu Provincial Key Discipline Project [ZDXK202251] FX This work was supported by Jiangsu Provincial Key Discipline Project (ZDXK202251) and Jiangsu Provincial Association of Chinese Medicine Revitalization and Development Project (ZXFZ2024001). 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INFLAMM. DIS. PD FEB 12 PY 2026 VL 14 IS 2 AR e70353 DI 10.1002/iid3.70353 PG 12 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA DU3MO UT WOS:001692267600001 PM 41684127 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Xing, SH Chen, HD Wang, L Lv, SY Zhu, JP Wang, ZT Han, J Zhang, HY Fang, RK Wu, JL Shao, FY Han, JC Sun, LP AF Xing, Sihui Chen, Huidan Wang, Ling Lv, Siye Zhu, Jinpu Wang, Zhongtian Han, Jing Zhang, Haiyang Fang, Ruikang Wu, Jiali Shao, Fengyan Han, Jicheng Sun, Liping TI Zhi-Chuan-Ling alleviates OVA-induced allergic asthma by suppressing M2 macrophage polarization via the PI3K/AKT/mTOR/STAT6 pathway SO PHYTOMEDICINE LA English DT Review DE Allergic asthma; Zhi-Chuan-Ling; Macrophage polarization; PI3K/AKT/mTOR/STAT6 pathway ID INHIBITION; MICE AB Background: Allergic asthma, predominantly driven by Th2 immune responses, is a chronic respiratory disease that poses a significant threat to human health. Zhi-Chuan-Ling (ZCL), a traditional Chinese medicine widely used for the treatment of asthma and wheezy bronchitis, has been shown to relieve airway constriction and suppress airway inflammation. However, its mechanisms in regulating macrophage polarization, a key Th2-driven inflammatory process, remain unclear. Purpose: This study aimed to assess the therapeutic effects of ZCL on allergic asthma and to investigate its molecular mechanisms in modulating macrophage polarization. Methods: The chemical profile of ZCL was characterized by high-performance liquid chromatography (HPLC). An ovalbumin (OVA)-induced mouse model of allergic asthma was established to assess the anti-asthmatic effects of ZCL. Mechanistic studies included hematoxylin-eosin (H&E) and Masson's trichrome (MT) staining, immunofluorescence (IF), ELISA, flow cytometry (FCM), transcriptomic profiling, Western blotting (WB), and in silico molecular docking to predict binding interactions of key ZCL compounds with target proteins involved in M2 macrophage polarization and airway inflammation. Results: ZCL treatment significantly alleviated asthma symptoms and reduced airway inflammation in vivo. Mechanistically, ZCL inhibited M2 macrophage polarization by modulating the PI3K/AKT/mTOR/STAT6 signaling pathway. Molecular docking analysis revealed favorable binding of major ZCL compounds to PI3K, AKT, mTOR, and STAT6, supporting their potential role in modulating these signaling molecules. Conclusion: ZCL protects against allergic asthma by suppressing M2 macrophage polarization through the PI3K/ AKT/mTOR/STAT6 axis and by directly interacting with key pathway proteins, thereby attenuating airway inflammation and remodeling. These findings provide both functional and molecular evidence for the therapeutic potential of ZCL in allergic asthma. C1 [Xing, Sihui; Chen, Huidan; Lv, Siye; Zhu, Jinpu; Wang, Zhongtian; Zhang, Haiyang; Sun, Liping] Changchun Univ Chinese Med, Coll Chinese Med, 1035 Boshuo Rd, Changchun 130117, Jilin, Peoples R China. [Han, Jing; Sun, Liping] Changchun Univ Chinese Med, Ctr Childrens Clin, Affiliated Hosp, Changchun 130022, Peoples R China. [Wang, Ling] Changchun Univ Chinese Med, Off Grad Studies, Affiliated Hosp, Changchun 130000, Peoples R China. [Fang, Ruikang; Wu, Jiali; Shao, Fengyan; Han, Jicheng] Changchun Univ Chinese Med, Coll Integrat Med, Key Lab Jilin Prov Tradit Chinese Med Prevent & Tr, Changchun 130117, Peoples R China. C3 Changchun University of Chinese Medicine; Changchun University of Chinese Medicine; Changchun University of Chinese Medicine; Changchun University of Chinese Medicine RP Sun, LP (corresponding author), Changchun Univ Chinese Med, Coll Chinese Med, 1035 Boshuo Rd, Changchun 130117, Jilin, Peoples R China.; Han, JC (corresponding author), Changchun Univ Chinese Med, Coll Integrat Med, 1035 Boshuo Rd, Changchun, Jilin, Peoples R China. EM 373108406@qq.com; slpcczyydx@sina.com FU Joint Research Project of the China Association of Chinese Medicine [2023DEPLHGG-07]; National Natural Science Foundation of China [82405318] FX This work was supported by the Joint Research Project of the China Association of Chinese Medicine (grant no. 2023DEPLHGG-07) , and the National Natural Science Foundation of China (grant no. 82405318) . 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Franco regulates M1/M2 polarization of macrophages and promotes hair regeneration SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Platycladus orientalis; Cedrol; Alopecia areata; Macrophage polarization; Immunosuppression ID ALOPECIA-AREATA; GROWTH; INFLAMMATION; ACTIVATION; ARTHRITIS; RESPONSES; EXTRACT; KINASE; MICE; P38 AB Ethnopharmacological relevance: Platycladus orientalis (L.) Franco is traditionally used to promote hair growth. Cedrol (CE) is the main active ingredient in Platycladus orientalis (PO), promoting hair growth. However, the anti-alopecia areata (AA) effect and mechanism of action of CE in the imiquimod-induced AA model have not been reported. Aim of the study: The macrophage polarization imbalance is a key pathological driving factor for AA. This study aims to elucidate the potential mechanism by which CE ameliorates AA by regulating macrophage polarization homeostasis. Materials and methods: The effect of CE (30 mg/kg) on the polarization of macrophages was studied using an AA model induced by imiquimod (62.5 mg/kg), and HaCaT and THP-1 macrophages induced with LPS/TNF-alpha/IFN-gamma (M3; 100 ng/mL+10 ng/mL+10 ng/mL). Results: CE exerted a good promoting effect on in vitro mouse hair follicle and AA mouse hair growth. Transcriptomics reveals that CE ameliorated alopecia by inhibiting inflammatory responses mediated by IFN-gamma and rebuilding the immune microenvironment. Mechanistic studies showed that CE inhibited the release of M1-type inflammatory factors, macrophage numbers, and related chemokines. When combined with IL-4, their expression was reversed, and they have an intervention effect on immune microenvironment disorders (CD4, CD8, etc). This indicates that CE has a good regulatory effect on M1/M2 polarization imbalance, possibly through the STATs and MAPK signaling pathways. The combination with the pathway inhibitor enhanced the inhibition of M1 polarization. Conclusion: The inhibition of macrophage-mediated inflammatory infiltration by CE showed a strong germinal effect, providing new insights into CE's effect on AA. C1 [Li, Tao; Lin, Lizhen; Zhou, Xinyang; Zhao, Wenjie; Zheng, Yifei; Zhao, Yuqing] Yanbian Univ, Sch Pharm, Key Lab Changbai Mt Nat Med Res, Minist Educ, Yanji, Peoples R China. [Wang, Peng] ORxes Therapeut Shanghai Co Ltd, Shanghai 200120, Peoples R China. C3 Yanbian University RP Zhao, YQ (corresponding author), Yanbian Univ, Sch Pharm, Key Lab Changbai Mt Nat Med Res, Minist Educ, Yanji, Peoples R China.; Wang, P (corresponding author), ORxes Therapeut Shanghai Co Ltd, Shanghai 200120, Peoples R China. EM 1464446763@qq.com; 1597831422@qq.com; 18340466758@163.com; lj11080615@163.com; zhengyifei9912@163.com; peng.wang@orxes.com; zyq2022@126.com FU Joint laboratory project of the original research medicine port and Changbai Mountain Natural Medicine [492023052]; Innovation Team Project of Yanbian University [012023051] FX This work was supported by the joint laboratory project of the original research medicine port and Changbai Mountain Natural Medicine (492023052) and the Innovation Team Project of Yanbian University (012023051) . 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PD APR 24 PY 2026 VL 361 AR 121268 DI 10.1016/j.jep.2026.121268 EA FEB 2026 PG 17 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA DH5GV UT WOS:001683558600001 PM 41611183 DA 2026-03-26 ER PT J AU Yu, ZM Zhao, BJ Song, W Liu, HQ Che, YF Qin, DS Liang, XC Yang, D AF Yu, Ziman Zhao, Bingjia Song, Wei Liu, Hangqi Che, Yanfei Qin, Dongshan Liang, Xiaochun Yang, Dan TI Elucidation of the mechanism of Jinmaitong against Diabetic peripheral neuropathy based on a combined strategy of network pharmacology and molecular biology SO CHINESE MEDICINE LA English DT Article DE Diabetic peripheral neuropathy; Jinmaitong; JAK2/STAT3 signaling; Macrophage polarization; Neuroinflammation ID IN-VITRO; INFLAMMATION; ACTIVATION; MODEL AB BackgroundDiabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM) with limited treatment options. The traditional Chinese medicine Jinmaitong (JMT) has demonstrated efficacy in treating DPN in both clinical and animal studies. It is worth noting that macrophage polarization appears to play a significant role in the onset and progression of DPN. However, whether the specific mechanism by which JMT exerts its neuroprotective effects is related to macrophage polarization still requires further in-depth investigation.MethodsT2DM model was established using Sprague-Dawley (SD) rats induced by a high-fat diet for six weeks combined with streptozotocin (STZ) injection. After modeling and drug administration, the DPN status was assessed using the von Frey test to test mechanical threshold, the hot plate test and tail flick test to evaluate thermal response latency, and the bioelectric amplifier to measure motor nerve conduction velocity.In the first batch of in-vivo experiments (Batch 1), after establishing the type 2 diabetes model, we conducted herbal formula JMT administered daily via oral gavage for another four weeks, eight weeks or twelve weeks, with each study comprising four groups: control group (CON), DPN group (DPN), low-dose JMT (7.6 mg/kg) treated group (DPN + JMT), and high-dose JMT (15.2 mg/kg) treated group (DPN + JMTH). The pharmacological effects of JMT on neurological function, neuropathology, and the levels of M1 and M2 macrophage cytokine markers were evaluated in serum and sciatic nerve, respectively. After chemical profiling of JMT by liquid chromatography coupled with high-resolution mass spectrometry, network pharmacology analysis was subsequently employed to predict the potential signaling pathways that JMT targeted in treating DPN. We further explored JMT's neuroprotective effect in a second batch of in-vivo experiments. To do this, we co-administered the JAK2/STAT3 inhibitor AG490 along with macrophage polarizing agents: LPS and interleukin-4 (IL-4). The changes of M1 and M2 macrophages in bone marrow was investigated by cytometry, while the macrophages in sciatic nerves were observed by immunofluorescence. Myelin morphology was observed with Luxel fast blue staining and transmission electron microscopy. Immunofluorescence was performed to evaluate nerve injury and regeneration, with S100 and neurofilament 160 (NF160) used to label Schwann cells and axons respectively in the sciatic nerve. The protein expressions of JAK2/STAT3 signaling in sciatic nerves were examined by Western blot.MethodsT2DM model was established using Sprague-Dawley (SD) rats induced by a high-fat diet for six weeks combined with streptozotocin (STZ) injection. After modeling and drug administration, the DPN status was assessed using the von Frey test to test mechanical threshold, the hot plate test and tail flick test to evaluate thermal response latency, and the bioelectric amplifier to measure motor nerve conduction velocity.In the first batch of in-vivo experiments (Batch 1), after establishing the type 2 diabetes model, we conducted herbal formula JMT administered daily via oral gavage for another four weeks, eight weeks or twelve weeks, with each study comprising four groups: control group (CON), DPN group (DPN), low-dose JMT (7.6 mg/kg) treated group (DPN + JMT), and high-dose JMT (15.2 mg/kg) treated group (DPN + JMTH). The pharmacological effects of JMT on neurological function, neuropathology, and the levels of M1 and M2 macrophage cytokine markers were evaluated in serum and sciatic nerve, respectively. After chemical profiling of JMT by liquid chromatography coupled with high-resolution mass spectrometry, network pharmacology analysis was subsequently employed to predict the potential signaling pathways that JMT targeted in treating DPN. We further explored JMT's neuroprotective effect in a second batch of in-vivo experiments. To do this, we co-administered the JAK2/STAT3 inhibitor AG490 along with macrophage polarizing agents: LPS and interleukin-4 (IL-4). The changes of M1 and M2 macrophages in bone marrow was investigated by cytometry, while the macrophages in sciatic nerves were observed by immunofluorescence. Myelin morphology was observed with Luxel fast blue staining and transmission electron microscopy. Immunofluorescence was performed to evaluate nerve injury and regeneration, with S100 and neurofilament 160 (NF160) used to label Schwann cells and axons respectively in the sciatic nerve. The protein expressions of JAK2/STAT3 signaling in sciatic nerves were examined by Western blot.ResultsJMT significantly improved neurological function and pathological damage in type 2 DPN rats. Eight weeks after diabetes induction, DPN rats showed a significant increase in pro-inflammatory cytokines and a concurrent decrease in anti-inflammatory cytokines. JMT administration effectively restored the imbalance. Furthermore, JMT reduced the proportion of M1 macrophages while increasing that of M2 macrophages. JMT promoted the polarization of macrophages from the M1 to the M2 phenotype in both bone marrow-derived macrophages and those infiltrating the sciatic nerve, which was mediated through the suppression of abnormal activation of the JAK2/STAT3 signaling pathway.ConclusionsJMT promotes the polarization of macrophages from the M1 to M2 phenotype and alleviates neuroinflammation in T2DM rats with DPN, which is associated with inhibition of the JAK2/STAT3 signaling pathway. These findings highlight the neuroprotective potential of JMT through immunomodulatory mechanisms. C1 [Yu, Ziman; Zhao, Bingjia; Che, Yanfei; Qin, Dongshan; Liang, Xiaochun; Yang, Dan] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Tradit Chinese Med, Beijing 100730, Peoples R China. [Song, Wei] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Inst Clin Med, Natl Infrastruct Translat Med, Beijing 100730, Peoples R China. [Liu, Hangqi] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Pathol, Beijing 100730, Peoples R China. C3 Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Peking Union Medical College Hospital; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College Hospital; Peking Union Medical College; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College Hospital; Peking Union Medical College RP Liang, XC; Yang, D (corresponding author), Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Tradit Chinese Med, Beijing 100730, Peoples R China. EM xiaochun_liang@yeah.net; jsj000jsj@163.com FU National Natural Science Foundation of China [NO.82004182] FX This work was supported by the National Natural Science Foundation of China (NO.82004182). 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Med. PD FEB 2 PY 2026 VL 21 IS 1 AR 60 DI 10.1186/s13020-025-01300-0 PG 28 WC Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine; Pharmacology & Pharmacy GA CZ6GA UT WOS:001678202300003 PM 41630054 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhao, QR Wang, JH Yan, ZW Liu, T Ma, L Qian, J Wang, Y Shao, R AF Zhao, Qianru Wang, Junhong Yan, Ziwei Liu, Tao Ma, Lin Qian, Jing Wang, Yu Shao, Rui TI NLRP3 Inflammasome Inhibition by Xuanfei Baidu Decoction Attenuates Pulmonary Inflammation and Collagen Deposition in Silicosis SO PHARMACEUTICALS LA English DT Article DE Xuanfei Baidu decoction; silicosis; macrophages; NLRP3 inflammasome; EMT ID FIBROSIS AB Background/Objectives: Silicosis is a chronic disease caused by long-term exposure to high levels of silica dust, which leads to extensive nodular fibrosis in the lungs. The disease is currently a serious occupational health hazard globally. Xuanfei Baidu decoction (XFBD) is a mature Chinese herbal medicine in China that has shown anti-inflammatory and anti-fibrotic effects in mouse experiments, making it a promising candidate for addressing the persistent inflammation and fibrosis in silicosis. Methods: Silicosis was induced in male C57BL/6J mice using crystalline silica (CS). XFBD's early anti-inflammatory role was verified in vitro in peritoneal macrophages (PMs) and in vivo in silicosis mice, while its late anti-collagen deposition and anti-fibrotic activities were further investigated. Results: In vitro, XFBD effectively inhibits the activation of the NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome in CS-induced lipopolysaccharide (LPS)-primed PMs, decreases the release of inflammatory cytokines, including interleukin (IL)-1 beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha), and modulates the phenotypic transition of macrophages from the M2 to the M1 phenotype. In vivo studies further validated that XFBD significantly downregulates the expression of NLRP3 and Cleaved-Caspase-1 proteins in the lung tissues of mice afflicted with silicosis. Additionally, XFBD enhanced pulmonary function, inhibited collagen deposition and pulmonary fibrosis in silicosis mice, and reversed epithelial-mesenchymal transition (EMT) by regulating key EMT-related proteins to slow fibrosis. Conclusions: The beneficial effects of XFBD on CS-induced pulmonary fibrosis can be attributed to the induction of macrophage polarization-mediated anti-inflammatory responses during the early stage of fibrotic development, as well as its anti-collagen deposition and anti-fibrotic activities during the intermediate stage of fibrotic development. This study provides preclinical evidence supporting XFBD as a promising candidate for prevention or adjunctive therapy, and its multi-target, time-phase mechanism offers a novel rationale and theoretical foundation for the development of new strategies against silicosis. C1 [Zhao, Qianru; Liu, Tao; Ma, Lin] Tianjin Univ Tradit Chinese Med, Inst Tradit Chinese Med, Tianjin 301617, Peoples R China. [Zhao, Qianru; Liu, Tao; Ma, Lin; Wang, Yu; Shao, Rui] Tianjin Univ Tradit Chinese Med, State Key Lab Chinese Med Modernizat, Tianjin 301617, Peoples R China. [Wang, Junhong] Tianjin Univ Tradit Chinese Med, Sch Med Technol, Tianjin 300193, Peoples R China. [Yan, Ziwei; Qian, Jing] Zhejiang Univ, Pharmaceut Informat Inst, Coll Pharmaceut Sci, Hangzhou 310058, Peoples R China. [Wang, Yu] Tianjin Univ Tradit Chinese Med, Sch Integrat Med, Tianjin 301617, Peoples R China. [Wang, Yu] Tianjin Univ Tradit Chinese Med, Haihe Lab Modern Chinese Med, Tianjin 301617, Peoples R China. C3 Tianjin University of Traditional Chinese Medicine; Tianjin University of Traditional Chinese Medicine; Tianjin University of Traditional Chinese Medicine; Zhejiang University; Tianjin University of Traditional Chinese Medicine; Tianjin University of Traditional Chinese Medicine RP Wang, Y; Shao, R (corresponding author), Tianjin Univ Tradit Chinese Med, State Key Lab Chinese Med Modernizat, Tianjin 301617, Peoples R China.; Wang, Y (corresponding author), Tianjin Univ Tradit Chinese Med, Sch Integrat Med, Tianjin 301617, Peoples R China.; Wang, Y (corresponding author), Tianjin Univ Tradit Chinese Med, Haihe Lab Modern Chinese Med, Tianjin 301617, Peoples R China. EM wangyu@tjutcm.edu.cn; rizycarrot@tjutcm.edu.cn RI WANG, Yu/PHO-7146-2026 FU Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine [25HHZYSS00004]; National Key R&D Program of China [2021YFE0200300]; National Administration of Traditional Chinese Medicine [ZYYCXTD-D-202406]; Special Research Project on Traditional Chinese Medicine Science and Technology of the National Administration of Traditional Chinese Medicine [GZY-KJS-2025-053]; National Natural Science Foundation of China [82204878, 82141201] FX This research was funded by the National Natural Science Foundation of China (No.82204878, No. 82141201), Special Research Project on Traditional Chinese Medicine Science and Technology of the National Administration of Traditional Chinese Medicine (GZY-KJS-2025-053), Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine (25HHZYSS00004), the National Key R&D Program of China (No. 2021YFE0200300) and the National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202406). 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Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA EF9LC UT WOS:001700150300001 PM 41754797 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Yang, RF Guo, JF Wang, N Qi, ZW Liu, CY Li, QS Wu, LL Qin, LL Liu, TH AF Yang, Ruifeng Guo, Jiangfan Wang, Ning Qi, Zhiwei Liu, Congyi Li, Qingsong Wu, Lili Qin, Lingling Liu, Tonghua TI Effects of Fanqi Tea and Swimming Exercise Intervention on Hepatic Glucolipid Metabolism and Inflammatory Response in db/db Mice SO NATURAL PRODUCT COMMUNICATIONS LA English DT Article DE Fanqi Tea; swimming exercise; type 2 diabetes mellitus; non-alcoholic fatty liver disease; db/db mice ID FATTY LIVER-DISEASE; MIGRATION-INHIBITORY FACTOR; INSULIN-RESISTANCE; MANAGEMENT; OBESITY AB Objective This study aimed to investigate the effect of the patented herbal formula Fanqi Tea (Guava leaf, Panax notoginseng flower, Momordica grosvenori, and Jasmine flower) and swimming exercise intervention on hepatic glucolipid metabolism and inflammatory response in db/db mice, to explore whether a combination intervention could bring in a synergistic effect on the treatment of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD).Method Network pharmacology and molecular docking were used to predict the mechanism of action of Fanqi Tea on T2DM and NAFLD. 36 db/db mice were divided randomly into six groups: the model control (Control) group, the metformin (MET) group, the Fanqi Tea low-dose (FT-L) group, the Fanqi Tea high-dose (FT-H) group, the swimming exercise (Exercise) group, and the Fanqi Tea high-dose combined with exercise (FT-H + Exercise) group. Six wt/wt mice were set as the (Normal) group.Results The screened main active ingredients and the key targets PIK3R1, AKT2, and GSK3 beta may have good binding activity. The hepatic Pik3r1 and Akt2 mRNA expression, as well as p-PI3K and p-AKT level tended to increase in the intervention groups, and the expression level of Gsk3 beta mRNA and p-GSK3 beta was significantly inhibited. Fanqi Tea and swimming exercise interventions differentially decreased CD86 fluorescence intensity and increased CD206 fluorescence intensity. The expression of pro-inflammatory cytokines, including interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), was significantly decreased. While the anti-inflammatory factor IL-10 was significantly increased.Conclusions Fanqi Tea and swimming exercise may regulate hepatic glucolipid metabolism by acting on the PI3K/AKT/GSK3 beta pathway. These interventions can decrease hepatic inflammatory responses, which may be attributed to the modulation of macrophage polarization. However, the effect of Fanqi Tea combined with exercise in improving glucolipid metabolism and alleviating inflammation was not significantly better than exercise alone or Fanqi Tea alone. C1 [Yang, Ruifeng; Guo, Jiangfan; Wang, Ning; Qi, Zhiwei; Liu, Congyi; Li, Qingsong; Wu, Lili; Qin, Lingling; Liu, Tonghua] Beijing Univ Chinese Med, Key Lab Hlth Cultivat, Minist Educ, Beijing, Peoples R China. [Guo, Jiangfan; Li, Qingsong] Shaanxi Univ Chinese Med, Sch Clin Med 1, Xianyang, Peoples R China. [Guo, Jiangfan] Xinjiang Second Med Coll, Sch Tradit Chinese Med, Karamay, Peoples R China. [Qin, Lingling] Beijing Univ Chinese Med, Sci & Technol Dept, Beijing, Peoples R China. C3 Beijing University of Chinese Medicine; Shaanxi University of Chinese Medicine; Xinjiang Second Medical College; Beijing University of Chinese Medicine RP Qin, LL; Liu, TH (corresponding author), Beijing Univ Chinese Med, Key Lab Hlth Cultivat, Minist Educ, Beijing, Peoples R China.; Qin, LL (corresponding author), Beijing Univ Chinese Med, Sci & Technol Dept, Beijing, Peoples R China. EM 700513@bucm.edu.cn; thliu@vip.163.com FU Traditional Chinese Medicine Intervention of Metabolic Diseases Research Project [90020165120003] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Traditional Chinese Medicine Intervention of Metabolic Diseases Research Project, (grant number 90020165120003), Creation and Talent Introduction Base of Prevention and Treatment of Diabetes and Its Complications with Traditional Chinese Medicine (grant number B20055), Key Laboratory of Health Cultivation of the Ministry of Education Preservation (grant number 2024-JYB-KYPT-002), (22) Beijing City "Double First-Class" to Support High-Level Key Disciplines of TCM Funding of 23 years - TCM Health Cultivation (grant number 90010963420018). 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Prod. Commun. PD FEB PY 2026 VL 21 IS 2 AR 1934578X261420563 DI 10.1177/1934578X261420563 PG 17 WC Chemistry, Medicinal; Food Science & Technology WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy; Food Science & Technology GA DY3YV UT WOS:001695017800001 OA gold DA 2026-03-26 ER PT J AU Ying, Y Guo, MM Ning, QY Wei, YY Qian, JJ Cai, R AF Ying, Yu Guo, Mengmeng Ning, Qingyun Wei, Yuyan Qian, Jiajia Cai, Ren TI SanHuang decoction may suppress breast cancer by regulating M1 macrophage polarization via NF-κB signaling pathway: in vitro and in vivo studies SO TRANSLATIONAL CANCER RESEARCH LA English DT Article DE Breast cancer (BC); SanHuang decoction (SHD); macrophage polarization; inflammation; nuclear factor kappa B (NF-kappa B) ID NEOADJUVANT CHEMOTHERAPY AB Background: Breast cancer (BC) is a major health concern among women. SanHuang decoction (SHD), a Chinese herbal formula, has exhibited the potential for clinical application in patients with BC. This study aimed to clarify the mechanism of SHD's action in the treatment of BC based on macrophage function and Methods: M1 polarized macrophages were cocultured with MDA-MB-231 BC cells, and treated with 10 mg/mL of SHD for 72 hours. Scratch and transwell assays were used to observe the inhibitory effect of SHD, and the levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), IL-1(3, cleaved caspase 3, B-cell lymphoma 2 (BCL-2), BCL-2-associated X (BAX), P65, phosphorylated P65 (p-P65), inhibitor of kappa B (I kappa B), and phosphorylated I kappa B (p-I kappa B) were detected via Western blotting. Forty patients with BC were randomly divided into a control group [neoadjuvant chemotherapy (NACT)] and observation group (NACT + SHD). After 9 weeks of treatment, magnetic resonance imaging scans were performed to evaluate the tumor size, and immunofluorescence staining was performed to investigate the effect of SHD on the regulation of M1 macrophages in tumor tissue. Results: SHD inhibited the migration ability of MDA-MB-231 cells, and the effect was significantly enhanced after coculture with M1/THP-1. Western blot results showed that SHD could significantly increase the expression of TNF-alpha, IL-1(3, IL-6, BAX, cleaved caspase 3, p-P65, and p-I kappa B while decreasing that of BCL-2. In vivo studies showed that SHD could reduce the tumor size and increase the expression of Conclusions: SHD could enhance the expression of M1/THP-1 cytokines, promote the inflammatory response in the tumor microenvironment, and thus inhibit the proliferation of BC and regulate its pathological process, likely through activating NF-kappa B signaling pathway. C1 [Ying, Yu; Wei, Yuyan; Qian, Jiajia; Cai, Ren] Nanjing Univ Chinese Med, Affiliated Hosp, Jiangsu Prov Hosp Chinese Med, Dept Breast Surg, Nanjing, Peoples R China. [Guo, Mengmeng] Nantong Univ, Affiliated Matern & Child Hlth Hosp, Dept Breast Surg, Nantong, Peoples R China. [Ning, Qingyun] Southeast Univ, Sch Med, Dept Rehabil Med, Nanjing, Peoples R China. C3 Nanjing University of Chinese Medicine; Nantong University; Southeast University - China RP Qian, JJ; Cai, R (corresponding author), Nanjing Univ Chinese Med, Affiliated Hosp, Jiangsu Prov Hosp Chinese Med, Dept Breast Surg, Nanjing, Peoples R China. EM 270724@njucm.edu.cn; 070007@njucm.edu.cn FU Nantong Municipal Health Commission General Project [MS2 024098]; Nanjing University of Chinese Medicine Natural Science Foundation [XZR2024230]; Jiangsu Provincial Hospital of Traditional Chinese Medicine Hospital-Level Research Project [Y2024033] FX Funding: This research was funded by the Nantong Municipal Health Commission General Project (MS2 024098) , Nanjing University of Chinese Medicine Natural Science Foundation (XZR2024230) , and Jiangsu Provincial Hospital of Traditional Chinese Medicine Hospital-Level Research Project (Y2024033) . 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Cancer Res. PD JAN 31 PY 2026 VL 15 IS 1 AR 33 DI 10.21037/tcr-2025-1975 PG 13 WC Oncology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology GA DO6QV UT WOS:001688408600040 PM 41674954 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Song, SQ Xu, HR Liu, MZ Xu, Q Wang, L Wang, FL Wan, XM Sun, XY Che, CY AF Song, Shiqi Xu, Huirong Liu, Mengzhu Xu, Qiang Wang, Ling Wang, Fenglei Wan, Xiaomei Sun, Xiaoyan Che, Chengye TI Isoimperatorin alleviates fungal keratitis by regulating NF-κB pathway and macrophage immune response SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE fungal keratitis; immune response; isoimperatorin; network pharmacology; TLR4/MyD88/IKK/NF-kappa B pathway ID INFLAMMATORY RESPONSES; APOPTOSIS AB Purpose The purpose of this research study was to investigate the impact of isoimperatorin on Aspergillus fumigatus (A. fumigatus) keratitis and elucidate its underlying mechanisms via the TLR4/MyD88/IKK/NF-kappa B signaling pathway.Materials and methods The targets of the active ingredient isoimperatorin were identified via network pharmacology. Key interactions between isoimperatorin and its predicted targets were validated using molecular docking. In vitro RAW264.7 macrophage cells of A. fumigatus keratitis, the effects of isoimperatorin on inflammatory signaling and cell apoptosis were assessed using western blotting, immunofluorescence, and flow cytometry. In vivo C57BL/6 mouse models of A. fumigatus keratitis, the effects of isoimperatorin on inflammatory signaling, neutrophil infiltration, macrophage polarization, and cell apoptosis were assessed using quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunofluorescence.Results Isoimperatorin inhibited TLR4/MyD88 complex formation and IKK/NF-kappa B phosphorylation, downregulated pro-inflammatory cytokines, reduced neutrophil infiltration, and promoted macrophage polarization from the M1 to the M2 phenotype. Additionally, it inhibited cell apoptosis and alleviated corneal epithelial damage.Conclusion This study demonstrates that isoimperatorin exerts a protective effect against A. fumigatus keratitis primarily by modulating the host immune response. The mechanism is mediated through the multi-target inhibition of the TLR4/MyD88/IKK/NF-kappa B pathway, leading to a coordinated reduction in inflammation and tissue damage. These findings highlight the therapeutic potential of isoimperatorin as a novel immunomodulatory strategy for managing fungal keratitis. C1 [Song, Shiqi; Liu, Mengzhu; Xu, Qiang; Wang, Ling; Wang, Fenglei; Wan, Xiaomei; Sun, Xiaoyan; Che, Chengye] Affiliated Hosp Qingdao Univ, Dept Ophthalmol, Qingdao, Peoples R China. [Xu, Huirong] Shandong Univ Tradit Chinese Med, Inst Pharm, Jinan, Peoples R China. C3 Qingdao University; Shandong University of Traditional Chinese Medicine RP Che, CY (corresponding author), Affiliated Hosp Qingdao Univ, Dept Ophthalmol, Qingdao, Peoples R China. EM chechengye@126.com FU Natural Science Foundation of Shandong Province; National Natural Science Foundation of China FX The author(s) declared that financial support was received for this work and/or its publication. This study was supported by grants from the National Natural Science Foundation of China (No. 82171019), the Science and Technology Project of Qingdao (2026), the Medical Science and Technology Key Project of Shandong (No. 202407021328) and the Natural Science Foundation of Qingdao (No. 25-1-1-248-zyyd-jch). 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PD JAN 27 PY 2026 VL 17 AR 1676397 DI 10.3389/fimmu.2026.1676397 PG 16 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA DJ0YU UT WOS:001684624000001 PM 41676152 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Li, HM Zhao, QT Yang, L Wang, L Ye, FL Yang, L Zhang, PJ Zhang, Y AF Li, Hongmin Zhao, Qitai Yang, Li Wang, Le Ye, Fanglei Yang, Lei Zhang, Peijun Zhang, Yi TI Single-cell sequencing and network pharmacology coupled with molecular docking and experimental validation reveal the effects of YPFS on macrophages in stage I non-small cell lung cancer SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Non-small cell lung cancer; Single-cell RNA sequencing; Macrophage polarization; AHSA1; Traditional Chinese medicine; Yu Ping Feng San (YPFS); Molecular docking; Immune microenvironment AB BackgroundNon-small cell lung cancer (NSCLC), the most common subtype of lung cancer, presents major clinical challenges owing to its highly complex tumor microenvironment and substantial cellular heterogeneity. A comprehensive understanding of the immune landscape-particularly the phenotypic diversity and functional roles of macrophage subpopulations-is critical for identifying novel therapeutic targets and developing more effective treatment strategies.MethodsWe constructed a comprehensive single-cell atlas of Stage I NSCLC using single-cell RNA sequencing (scRNA-seq) to characterize immune heterogeneity, with particular emphasis on macrophage subsets. Network pharmacology was employed to investigate the interactions between AHSA1 and bioactive compounds derived from the traditional Chinese medicine formulation Yu Ping Feng San (YPFS). To further evaluate these interactions, molecular docking simulations were performed to assess binding affinities and elucidate the potential regulatory effects on macrophage polarization.ResultsScRNA-seq analysis revealed heterogeneous macrophage subtypes, each exhibiting distinct roles in tumor progression. AHSA1 was identified as a key regulator of macrophage polarization, with higher expression levels associated with unfavorable prognosis. Through network pharmacology and molecular docking, strong binding affinities were observed between AHSA1 and Yu Ping Feng San (YPFS)-derived compounds, including wogonin, kaempferol, and quercetin. Notably, quercetin displayed the highest binding affinity and exerted the strongest inhibitory effect on M2 macrophage polarization.ConclusionThese findings identify AHSA1 as a pivotal regulator of macrophage polarization in NSCLC and position quercetin as a promising macrophage-targeted therapeutic candidate. Furthermore, the results highlight the potential of Yu Ping Feng San (YPFS) as a complementary therapeutic strategy for NSCLC, offering a bridge between traditional Chinese medicine and modern oncology. C1 [Li, Hongmin; Zhao, Qitai; Yang, Li; Yang, Lei; Zhang, Peijun; Zhang, Yi] Zhengzhou Univ, Biotherapy Ctr & Canc Ctr, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China. [Zhang, Yi] Henan Acad Innovat Med Sci, Zhongyuan Cell Therapy & Immunotherapy Lab, Zhengzhou, Peoples R China. [Zhang, Yi] Henan Univ, Sch Basic Med Sci, Kaifeng, Peoples R China. [Zhang, Yi] Zhengzhou Univ, Acad Med Sci, State Key Lab Metab Dysregulat & Prevent & Treatme, Tianjian Lab Adv Biomed Sci, Zhengzhou, Peoples R China. [Zhang, Yi] Zhengzhou Univ, Sch Life Sci, Zhengzhou, Henan, Peoples R China. [Zhang, Yi] Zhengzhou Univ, Sch Publ Hlth, Zhengzhou, Henan, Peoples R China. [Li, Hongmin; Wang, Le; Ye, Fanglei; Zhang, Peijun] Zhengzhou Univ, Dept Otolaryngol Head & Neck Surg, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China. C3 Zhengzhou University; Henan Academy of Innovations in Medical Science; Henan University; Zhengzhou University; Zhengzhou University; Zhengzhou University; Zhengzhou University RP Zhang, Y (corresponding author), Zhengzhou Univ, Biotherapy Ctr & Canc Ctr, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China.; Zhang, Y (corresponding author), Henan Acad Innovat Med Sci, Zhongyuan Cell Therapy & Immunotherapy Lab, Zhengzhou, Peoples R China.; Zhang, Y (corresponding author), Henan Univ, Sch Basic Med Sci, Kaifeng, Peoples R China.; Zhang, Y (corresponding author), Zhengzhou Univ, Acad Med Sci, State Key Lab Metab Dysregulat & Prevent & Treatme, Tianjian Lab Adv Biomed Sci, Zhengzhou, Peoples R China.; Zhang, Y (corresponding author), Zhengzhou Univ, Sch Life Sci, Zhengzhou, Henan, Peoples R China.; Zhang, Y (corresponding author), Zhengzhou Univ, Sch Publ Hlth, Zhengzhou, Henan, Peoples R China. EM yizhang@zzu.edu.cn RI zhao, qitai/NJR-9371-2025 FU China Postdoctoral Science Foundation [GZC20232435] FX Not applicable. 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Immunother. PD JAN 27 PY 2026 VL 75 IS 2 AR 58 DI 10.1007/s00262-026-04305-2 PG 14 WC Oncology; Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Immunology GA DC6DA UT WOS:001680230700011 PM 41591571 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Hu, M Huang, LB Deng, HZ Chen, ZF Cheng, GH Liu, XC AF Hu, Mi Huang, Liangbin Deng, Hongzhuan Chen, Zhifeng Cheng, Guanghui Liu, Xinchun TI Single-cell transcriptomics uncover RNF130-mediated TNF-α pathway activation and worenine synergy with paclitaxel in breast cancer SO CLINICAL EPIGENETICS LA English DT Article DE RNF130; Triple-negative breast cancer (TNBC); E3 ubiquitin ligase; Tumor microenvironment; Worenine ID MECHANISM AB BackgroundTriple-negative breast cancer (TNBC) is distinguished by high invasiveness and a tendency for recurrence. Recent studies have suggested that E3 ubiquitin ligases play a crucial role in the initiation and progression of various tumors. However, there is still an absence of systematic understanding regarding the specific function and molecular mechanisms of its member gene RNF130 in TNBC.MethodsThis study conducted a comprehensive analysis of large-scale transcriptomic data from databases such as TCGA and GEO. Additionally, single-cell RNA sequencing data from multiple breast cancer samples and their liver metastases were analyzed to evaluate the expression pattern, prognostic significance, and potential regulatory role of RNF130 in the tumor microenvironment. The effects of RNF130 on breast cancer cell proliferation, apoptosis, and chemotherapy sensitivity were explored through in vitro cell experiments and in vivo mouse models. Furthermore, the study screened and evaluated the targeted inhibitory effect of the Traditional Chinese Medicine active component Worenine on RNF130, as well as its combined therapeutic effect with paclitaxel.ResultsThe findings indicated that RNF130 was notably overexpressed in breast cancer tissues and associated with unfavorable patient survival outcomes. Single-cell transcriptomic analysis revealed that RNF130 was predominantly enriched in malignant epithelial cell populations and closely associated with tumor immune evasion phenotypes. RNF130 knockdown inhibited proliferation, induced apoptosis, reduced TNF-alpha pathway activation, and enhanced sensitivity to paclitaxel, whereas RNF130 overexpression exerted the opposite effects. Co-culture experiments further demonstrated that RNF130 depletion promoted M1 macrophage polarization while control cells induced M2-like phenotypes. Additionally, Worenine downregulated RNF130 expression and displayed a synergistic inhibitory effect with paclitaxel.ConclusionThis study identifies RNF130 as a critical mediator of TNBC progression that regulates tumor growth, apoptosis, immune evasion, and metabolic reprogramming, partly through activation of the TNF-alpha signaling pathway. Furthermore, Worenine was found to reduce RNF130 expression and enhance the antitumor effect of paclitaxel, suggesting its potential utility in combination therapy for TNBC. These findings provide mechanistic insights into RNF130-driven malignancy and offer a foundation for developing future therapeutic strategies. C1 [Hu, Mi; Huang, Liangbin; Deng, Hongzhuan; Chen, Zhifeng; Cheng, Guanghui; Liu, Xinchun] Univ South China, Affiliated Changsha Cent Hosp, HengyangMed Sch, Changsha, Peoples R China. C3 University of South China RP Liu, XC (corresponding author), Univ South China, Affiliated Changsha Cent Hosp, HengyangMed Sch, Changsha, Peoples R China. 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Epigenetics PD JAN 24 PY 2026 VL 18 IS 1 AR 32 DI 10.1186/s13148-026-02057-5 PG 22 WC Oncology; Genetics & Heredity WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Genetics & Heredity GA DW8UQ UT WOS:001693988000003 PM 41580768 OA Green Submitted, gold DA 2026-03-26 ER PT J AU He, XL Wang, C Zhang, RH Wang, YY Zhang, Y Yang, T Zhang, JZ Rao, S Tang, H Peng, X Wang, JG AF He, Xueling Wang, Chen Zhang, Ruihao Wang, Yuanyuan Zhang, Ying Yang, Tong Zhang, Junzhe Rao, Shuan Tang, Huan Peng, Xin Wang, Jigang TI Parthenolide ameliorates inflammation in sepsis via covalently targeting Trim33 and inhibiting NF-κB pathway SO PHYTOMEDICINE LA English DT Article DE Pharmacology; Inflammation; Traditional Chinese medicine; Target identification; Proteomics ID SEPTIC SHOCK; MECHANISMS; TIF1-GAMMA AB Background: Sepsis, a life-threatening condition, arises from an aberrant or uncontrolled immune response of the host to severe infection. Timely and precise control of this inflammatory response is of paramount importance in sepsis prevention and constitutes the core of sepsis prevention efforts. Parthenolide (PA), recognized as an NF-kappa B inhibitor, has previously demonstrated its capacity to mitigate the inflammatory response. This study aimed to investigate whether and how PA can inhibit inflammation, thereby alleviating sepsis, and to profile functional target proteins using chemoproteomics strategy. Methods: The cecal ligation and puncture (CLP) procedure was performed to induce a mouse model of sepsis, and lipopolysaccharide (LPS) was employed to establish a model of cellular inflammation in mouse mononuclear macrophage cells (RAW264.7) in vitro. Enzyme-linked immunosorbent assay (ELISA) and hematoxylin and eosin (H&E) staining were utilized to evaluate the therapeutic effects of PA on septic mice. In the in vitro experiments, streamlined cysteine activity-based protein profiling (SLC-ABPP) and proteomics techniques were employed to identify potential protein targets and molecular pathways responsible for the anti-inflammatory properties of PA. Results: We demonstrated that PA could enhance the survival rate, reduce inflammatory cytokines release, ameliorate histopathological changes, and balance macrophage polarization in a sepsis model. Similarly, PA could effectively alleviate the inflammatory response in LPS-stimulated RAW264.7 cells. Chemoproteomics profiling revealed that the Trim33 protein was a potential covalent target of PA via cysteine engagement, and the expression changes of global proteins indicated by proteomics analysis suggested that PA mitigated inflammation by inhibiting the NF-kappa B pathway. Finally, through a series of molecular biology experiments, we confirmed that PA suppresses the NF-kappa B pathway by functionally binding to Trim33 and subsequently reducing the ubiquitin dependent degradation of Smad4, thereby exhibiting anti-inflammatory activity. Conclusion: Our findings demonstrated that PA significantly mitigated inflammation in sepsis by targeting the Trim33 protein and consequently suppressing ubiquitination on Smad4 as well inhibiting the NF-kappa B pathway, thus providing new insights into the clinical use of PA in treatment of inflammation related diseases. C1 [He, Xueling; Peng, Xin] Zhejiang Chinese Med Univ, Ningbo Municipal Hosp, TCM Affiliated Hosp, Ningbo 315010, Peoples R China. [He, Xueling; Wang, Chen; Zhang, Ying; Yang, Tong; Zhang, Junzhe; Tang, Huan; Wang, Jigang] China Acad Chinese Med Sci, Artemisinin Res Ctr, State Key Lab Qual Ensurance & Sustainable Use Dao, Beijing 100700, Peoples R China. [He, Xueling; Wang, Chen; Zhang, Ying; Yang, Tong; Zhang, Junzhe; Tang, Huan; Wang, Jigang] China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China. [Zhang, Ruihao; Rao, Shuan] Southern Med Univ, Nanfang Hosp, Dept Thorac Surg, Guangzhou 510000, Guangdong, Peoples R China. [Wang, Yuanyuan] Southern Med Univ, Nanfang Hosp, Dept Hlth Management, Guangzhou 510000, Guangdong, Peoples R China. [Wang, Jigang] Jinan Univ, Clin Med Coll 2, Dept Urol, Shenzhen Peoples Hosp, Shenzhen 518020, Guangdong, Peoples R China. [He, Xueling] Guangdong Second Hosp Tradit Chinese Med, Guangdong Prov Key Lab Res & Dev TCM, Guangzhou 510000, Guangdong, Peoples R China. C3 Zhejiang Chinese Medical University; China Academy of Chinese Medical Sciences; China Academy of Chinese Medical Sciences; Institute of Chinese Materia Medica, CACMS; Southern Medical University - China; Southern Medical University - China; Jinan University RP Peng, X (corresponding author), Zhejiang Chinese Med Univ, Ningbo Municipal Hosp, TCM Affiliated Hosp, Ningbo 315010, Peoples R China.; Tang, H; Wang, JG (corresponding author), China Acad Chinese Med Sci, Artemisinin Res Ctr, State Key Lab Qual Ensurance & Sustainable Use Dao, Beijing 100700, Peoples R China.; Tang, H; Wang, JG (corresponding author), China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China.; Rao, S (corresponding author), Southern Med Univ, Nanfang Hosp, Dept Thorac Surg, Guangzhou 510000, Guangdong, Peoples R China.; Wang, JG (corresponding author), Jinan Univ, Clin Med Coll 2, Dept Urol, Shenzhen Peoples Hosp, Shenzhen 518020, Guangdong, Peoples R China. EM raoshuanl@smu.edu.cn; htang@icmm.ac.cn; pengx@nit.zju.edu.cn; jgwang@icmm.ac.cn FU National Natural Science Foundation of China [82522095, 82505127]; CACMS Innovation Fund [CI2025D002, CI2023E005TS01, CI2024E003]; Central Government Guidance Funds for Local Science and Technology Development Projects [2025ZY0072]; Fundamental Research Funds for the Central public welfare research institutes [ZZ14-YQ-061]; Guangdong Provincial Second Hospital of Traditional Chinese Medicine Scientific research innovation Foundation [SEZYY2025QB01] FX We gratefully acknowledge financial support from the National Natural Science Foundation of China (82522095, 82505127), the CACMS Innovation Fund (CI2025D002, CI2023E005TS01, and CI2024E003), Central Government Guidance Funds for Local Science and Technology Development Projects (2025ZY0072), the Fundamental Research Funds for the Central public welfare research institutes (ZZ14-YQ-061), and the Guangdong Provincial Second Hospital of Traditional Chinese Medicine Scientific research innovation Foundation (SEZYY2025QB01) . 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Total saponins from Rhizoma Panacis majoris (SRPM), bioactive compounds naturally extracted from the rhizome of Panax japonicus C.A.Mey. var. major (Burk.) C.Y.Wu and K.M.Feng, have demonstrated extensive anti-inflammatory and immunomodulatory properties. This study aims to elucidate the molecular mechanisms underlying the facilitative effects of SRPM on diabetic wound healing, with particular emphasis on its anti-inflammatory actions. A high-fat diet combined with streptozotocin (STZ) administration was used to induce type 2 diabetes in rats. After two weeks of oral treatment with SRPM suspension, a wound model was established. Subsequently, a two-week course of combined local and systemic therapy was administered using both SRPM suspension and SRPM gel. SRPM markedly reduces the levels of pro-inflammatory mediators, including IL-1 alpha, IL-1 beta, IL-6, MIP-1 alpha, TNF-alpha, and MCP-1, in both rat tissues and serum. Concurrently, it increases the expression of anti-inflammatory cytokines such as IL-10, TGF-beta 1, and PDGF-BB, while also enhancing the expression of the tissue remodelling marker bFGF. Additionally, SRPM significantly decreases the accumulation of apoptotic cells within tissues by downregulating the pro-apoptotic gene Caspase-3, upregulating the anti-apoptotic gene Bcl-2, and increasing the expression of the apoptotic cell clearance receptor MerTK. Moreover, SRPM inhibits neutrophil infiltration and the release of neutrophil extracellular traps (NETs) in tissues, promotes macrophage polarisation towards the M2 phenotype, and activates the Wnt/beta-catenin signalling pathway at the molecular level. SRPM promotes the healing of wounds in diabetic rats potentially due to its anti-inflammatory properties. C1 [Xu, Xiang; Wang, Mei-Xia; Zhu, Ya-Ning; Hu, Di; Li, Jing-Ping] Yunnan Univ Chinese Med, Fac Chinese Med, Kunming 650000, Peoples R China. [Zuo, Xiang-Duo] Kunming Med Univ, Fac Pharm, Kunming 650000, Peoples R China. C3 Yunnan University of Chinese Medicine; Kunming Medical University RP Li, JP (corresponding author), Yunnan Univ Chinese Med, Fac Chinese Med, Kunming 650000, Peoples R China. EM xxrrqqcn123@163.com; lijingping@ynucm.edu.cn FU Yunnan Provincial Key Joint Special Project for Basic Research in Traditional Chinese Medicine [202301AZ070001-001]; Yunnan Provincial Key Laboratory for Sustainable Utilisation of Southern Medicinal Plants [202105AG070012]; National Natural Science Foundation of China [82460795, 82260795]; Yunnan Provincial Reserve Talent Programme for Young and Middle-aged Academic and Technical Leaders [202405AC350030]; Yunnan Provincial Innovative Team for Traditional Chinese Medicine Prevention and Treatment of Metabolic Syndrome [202505AS350014] FX This work was supported by grants from the National Natural Science Foundation of China (82460795 and 82260795 to J.-P.L.), the Yunnan Provincial Key Joint Special Project for Basic Research in Traditional Chinese Medicine (202301AZ070001-001 to J.-P.L.), the Yunnan Provincial Reserve Talent Programme for Young and Middle-aged Academic and Technical Leaders (202405AC350030 to J.-P.L.), the Yunnan Provincial Innovative Team for Traditional Chinese Medicine Prevention and Treatment of Metabolic Syndrome (202505AS350014 to J.-P.L.), and the Yunnan Provincial Key Laboratory for Sustainable Utilisation of Southern Medicinal Plants (202105AG070012 to J.-P.L.). 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PD JAN 18 PY 2026 VL 27 IS 2 AR 955 DI 10.3390/ijms27020955 PG 25 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry GA CO4NN UT WOS:001670626500001 PM 41596601 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Huang, MY Yu, X Jiang, ZR Li, XF Yang, S Luo, SP Song, CG AF Huang, Mingyao Yu, Xin Jiang, Zirong Li, Xiaofen Yang, Shuo Luo, Shiping Song, Chuangui TI Genetically engineered macrophages delivering TRAIL targeting the Wnt/β-catenin pathway to induce cytotoxicity against TNBC SO CELL COMMUNICATION AND SIGNALING LA English DT Article DE TRAIL; Engineered macrophages; Pro-inflammatory; TNBC; Wnt/beta-catenin ID APOPTOSIS; CANCER AB Triple-negative breast cancer (TNBC) is a highly aggressive cancer subtype that lacks effective targeted therapies, posing significant challenges in its treatment. Engineered macrophages have emerged as promising tools for drug delivery and immunotherapy in cancer treatment. In this study, we developed a drug delivery strategy based on genetically modified macrophages. These macrophages were engineered in two ways to continuously secrete the apoptosis signal activator TRAIL, including monomeric TRAIL (Mono-TRAIL) and trimeric TRAIL (Tri-TRAIL). Engineered macrophages, particularly Tri-TRAIL-M, were found to promote M1 macrophage polarization within the tumor microenvironment (TME), thereby enhancing antitumor immune responses. Simultaneously, the engineered macrophages significantly inhibited the Wnt/beta-catenin signaling pathway in TNBC cells and induced G2/M phase cell cycle arrest. In an in vivo TNBC model, Tri-TRAIL-M effectively suppressed tumor growth, highlighting its therapeutic potential. These findings suggest that TRAIL-secreting engineered macrophages, especially Tri-TRAIL-M, provide a promising strategy for TNBC cytotoxicity. This approach opens new avenues for macrophage-based therapies in TNBC. C1 [Huang, Mingyao; Song, Chuangui] Fujian Med Univ, Union Hosp, Dept Breast Surg, Fuzhou 350001, Peoples R China. [Huang, Mingyao; Yu, Xin; Li, Xiaofen; Luo, Shiping; Song, Chuangui] Fujian Med Univ, Fujian Canc Hosp, Clin Oncol Sch, Dept Breast Surg, Fuzhou 350014, Peoples R China. [Jiang, Zirong] Fujian Med Univ, Ningde Clin Med Coll, Dept Thyroid & Breast Surg, Ningde 352100, Peoples R China. [Jiang, Zirong] Ningde Normal Univ, Ningde Municipal Hosp, Dept Thyroid & Breast Surg, Ningde 352100, Peoples R China. [Yang, Shuo] Med Univ, Affiliated Hosp 4, Dept Gen Surg, Shenyang 110000, Peoples R China. C3 Fujian Medical University; Fujian Medical University; Fujian Medical University; Ningde Normal University RP Song, CG (corresponding author), Fujian Med Univ, Union Hosp, Dept Breast Surg, Fuzhou 350001, Peoples R China.; Luo, SP; Song, CG (corresponding author), Fujian Med Univ, Fujian Canc Hosp, Clin Oncol Sch, Dept Breast Surg, Fuzhou 350014, Peoples R China.; Yang, S (corresponding author), Med Univ, Affiliated Hosp 4, Dept Gen Surg, Shenyang 110000, Peoples R China. EM yang024181818@163.com; shipingluo0627@gmail.com; Songcg1971@outlook.com RI Huang, Mingyao/OIU-3563-2025; Luo, Shiping/KBV-5123-2024; jiang, zirong/GLV-2077-2022 OI Huang, Mingyao/0000-0003-3446-2169; FU Joint Funds for the innovation of science and Technology, Fujian province [NO. 2021Y9084]; The High-level Talent Training Program of Fujian Cancer Hospital [NO. 2024YNG03]; The High-level Talent Introduction Project of Fujian Cancer Hospital [NO. F2328R-GC301-01] FX This study was funded by Joint Funds for the innovation of science and Technology, Fujian province (NO. 2021Y9084); The High-level Talent Introduction Project of Fujian Cancer Hospital (NO. F2328R-GC301-01); The High-level Talent Training Program of Fujian Cancer Hospital (NO. 2024YNG03). 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Signal. PD JAN 16 PY 2026 VL 24 IS 1 AR 30 DI 10.1186/s12964-025-02394-7 PG 12 WC Cell Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology GA CD5RT UT WOS:001663231300001 PM 41540435 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Liu, MH Wang, T Fu, JL Cui, TT Li, N Sun, TF Liu, J Su, CX Song, B AF Liu, Menghan Wang, Ti Fu, Jialei Cui, Tiantian Li, Na Sun, Tiefeng Liu, Jie Su, Chunxia Song, Bao TI Pinellia exosomal vesicles remodulate tumor-associated macrophage polarization via the serine synthesis/JAK/STAT signaling pathway to inhibit lung cancer growth SO PHYTOMEDICINE LA English DT Article DE Pinellia exosome vesicles; Serine synthesis pathway; Tumor-associated macrophage; JAK-STAT ID NANOVESICLES; RESISTANCE AB Plant-derived nanovesicles have emerged as promising vectors for cross-species signal transmission, enabling them to enter animal cells via endocytosis and offering new insights into the mechanisms underlying the bioactivity of medicinal herbs. Pinellia ternata, a traditional Chinese medicinal plant, shows diverse pharmacological properties, including immunomodulatory and anti-tumor effects, though its mechanism of action remains to be fully elucidated. In this study, nanoscale exosome-like vesicles (similar to 150 nm in diameter) were isolated and characterized from fresh Pinellia roots, referred to as Pinellia-derived exosome vesicles (PEVs). PEVs induced immune activation and promoted M1-like polarization of macrophages. Transcriptomic analysis of THP-1-derived macrophages revealed that PEV treatment significantly inhibited the expression of key serine synthesis genes, PHGDH, PSAT1, and PSPH, and activated the JAK-STAT signaling pathway. 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[Cui, Tiantian; Li, Na; Song, Bao] Shandong First Med Univ, Shandong Canc Hosp & Inst, Affiliated Tumor Hosp, Shandong Prov Key Lab Precis Med, Jinan, Peoples R China. [Liu, Jie] Shandong Univ, Canc Ctr, Shandong Publ Hlth Clin Ctr, Jinan, Peoples R China. C3 Tongji University; Wenzhou Medical University; Shandong First Medical University & Shandong Academy of Medical Sciences; Shandong University RP Su, CX (corresponding author), Tongji Univ, Sch Med, Shanghai Pulm Hosp, Dept Comprehens Oncol Ctr, Shanghai, Peoples R China.; Song, B (corresponding author), Shandong First Med Univ, Shandong Canc Hosp & Inst, Affiliated Tumor Hosp, Shandong Prov Key Lab Precis Med, Jinan, Peoples R China. EM susu_mail@126.com; songbaojn@126.com FU National Key R&D Program of China [2023YFC2508604, 2023YFC2508605]; Tongji University Medicine-X Interdisciplinary Research Initiative [2025-0554-ZD-08]; Shandong Province Natural Science Foundation [ZR2021MH233]; Taishan Scholars Program [Tstp 20231239] FX This work was supported by the National Key R&D Program of China (Grant numbers: 2023YFC2508604, 2023YFC2508605) , the Tongji University Medicine-X Interdisciplinary Research Initiative (Grant number: 2025-0554-ZD-08) , the Shandong Province Natural Science Foundation (ZR2021MH233) , and the Taishan Scholars Program (NO. Tstp 20231239). 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Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA CQ2FB UT WOS:001671823900001 PM 41539095 DA 2026-03-26 ER PT J AU Ye, ZL Wang, B Wan, ZD Guo, JW AF Ye, Zilv Wang, Bo Wan, Zhengdong Guo, Jiawei TI Macrophage polarization in acute myocardial infarction: multidimensional regulation and emerging therapeutic opportunities SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE acute myocardial infarction; immune modulation; inflammatory microenvironment; intervention strategies; macrophage polarization ID SIGNALING PATHWAY; M2 POLARIZATION; T-CELLS; ACTIVATION; MONOCYTE; INFLAMMATION; PLASTICITY; EXOSOMES; HEART; DIFFERENTIATION AB Macrophage polarization is a central determinant of the inflammatory response and tissue repair following acute myocardial infarction (AMI). The dynamic transition from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype is critical for limiting myocardial injury and promoting functional recovery. Recent advances have uncovered complex regulatory mechanisms governing macrophage polarization, including metabolic reprogramming, immune signaling pathways, and alterations within the cardiac microenvironment. Elucidating these processes provides important insights for the development of innovative therapeutic strategies aimed at enhancing cardiac repair. This review summarizes current knowledge on macrophage polarization in AMI, with a particular focus on the multifaceted regulatory networks that modulate the balance between M1 and M2 macrophages. Emerging therapeutic approaches targeting these pathways-such as molecular interventions, gene editing technologies, nanomedicine-based delivery systems, and modulation through traditional Chinese medicine-hold significant promise for improving cardiac repair and preventing adverse remodeling. The integration of these strategies may offer novel opportunities for the clinical management of AMI, ultimately advancing efforts to optimize heart recovery after infarction. C1 [Ye, Zilv; Wan, Zhengdong; Guo, Jiawei] Yangtze Univ, Affiliated Hosp 1, Dept Vasc & Endovasc Surg, Jingzhou, Peoples R China. [Wang, Bo] Yangtze Univ, Jingzhou Hosp, Thyroid & Vasc Surg Dept, Jingzhou, Peoples R China. [Guo, Jiawei] Yangtze Univ, Sch Med, Dept Pharmacol, Jingzhou, Peoples R China. C3 Yangtze University; Yangtze University; Yangtze University RP Guo, JW (corresponding author), Yangtze Univ, Affiliated Hosp 1, Dept Vasc & Endovasc Surg, Jingzhou, Peoples R China.; Guo, JW (corresponding author), Yangtze Univ, Sch Med, Dept Pharmacol, Jingzhou, Peoples R China. EM guojw9@alumni.sysu.edu.cn RI Guo, Jiawei/AAI-5403-2020 FU National Natural Science Foundation of China [82300526]; Health commission of Hubei Province Scientific Research Project [WJ2025M003] FX The author(s) declared that financial support was received for this work and/or its publication. This study was supported by National Natural Science Foundation of China (grant nos. 82300526); Health commission of Hubei Province Scientific Research Project (grant nos. WJ2025M003). 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Immunol. PD JAN 9 PY 2026 VL 16 AR 1710249 DI 10.3389/fimmu.2025.1710249 PG 25 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA CJ4WY UT WOS:001667255800001 PM 41583440 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Ren, JY Jiang, XX Yu, GJ Wu, WT Chen, MY Zhao, Y Yang, MJ Zou, ZQ He, CX AF Ren, Jingyi Jiang, Xiaoxin Yu, Gejun Wu, Wentao Chen, Mengyuan Zhao, Yun Yang, Mengjie Zou, Zuquan He, Canxia TI Sulforaphane ameliorates DSS-induced colitis and secondary liver injury in mice: Proposed mechanism in the SCFAs-FFAR2/3-macrophage polarization axis SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE Sulforaphane; Ulcerative colitis; Short-chain fatty acids; Macrophage polarization; Liver; Phytochemicals ID CHAIN FATTY-ACIDS; INFLAMMATORY-BOWEL-DISEASE; MANIFESTATIONS; GPR43 AB Sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables, has shown therapeutic potential in inflammatory diseases. Our previous studies demonstrated that SFN ameliorates ulcerative colitis (UC) and restores gut microbiota composition in dextran sulfate sodium (DSS)-induced mice. In the present study, we further investigate the protective effects and underlying mechanisms of SFN against secondary liver injury associated with UC. The results revealed that SFN significantly alleviated pathological damage in both the colon and liver, improved liver function parameters, upregulated intestinal tight junction proteins and Muc2 expression, and inhibited inflammation in DSS-induced colitis mice. Additionally, SFN significantly elevated short-chain fatty acid (SCFA) concentrations, enhanced the expression of SCFA receptors (free fatty acid receptors 2 and 3, FFAR2/3), and modulated macrophage polarization by inhibiting M1 and promoting M2 phenotypes in the colon and liver. Collectively, these findings suggest that SFN may alleviate colitis and secondary liver injury by enhancing intestinal barrier function and reducing inflammatory responses, potentially via the SCFAs-FFAR2/3-macrophage polarization signaling cascade. Thus, SFN may serve as a promising adjunctive therapeutic agent for the prevention and treatment of UC. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies. C1 [Ren, Jingyi; Jiang, Xiaoxin; Yu, Gejun; Wu, Wentao; Chen, Mengyuan; Yang, Mengjie; He, Canxia] Ningbo Univ, Hlth Sci Ctr, Sch Publ Hlth, 818 Fenghua Rd, Ningbo 315211, Zhejiang, Peoples R China. [Zhao, Yun] Ningbo Univ, Hlth Sci Ctr, Ningbo, Zhejiang, Peoples R China. [Zou, Zuquan] Beilun Dist Ctr Dis Control & Prevent, Ningbo, Zhejiang, Peoples R China. C3 Ningbo University; Ningbo University RP He, CX (corresponding author), Ningbo Univ, Hlth Sci Ctr, Sch Publ Hlth, 818 Fenghua Rd, Ningbo 315211, Zhejiang, Peoples R China. EM hecanxia@nbu.edu.cn FU National Natural Science Foundation of China [82103819]; Natural Science Foundation of Zhejiang Province [LMS25H260001]; Natural Science Foundation of Ningbo City [2024J316, 2022J019]; Ningbo Public Welfare Science and Technology Plan Project [2023S137] FX This work was supported by grants from the National Natural Science Foundation of China (No.82103819). Natural Science Foundation of Zhejiang Province (No. LMS25H260001), Natural Science Foundation of Ningbo City (No. 2024J316 , No. 2022J019 ), Ningbo Public Welfare Science and Technology Plan Project (No. 2023S137). The authors thank the Laboratory Animal Center of Ningbo University for the technical support. 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Interestingly, its aerial parts, which are also rich in bioactive compounds, remain underutilized. This study aims to optimize the extraction and purification processes to obtain the aerial part extract of Echinacea purpurea (APE-EP) to enhance the content of active constituents and improve its anti-inflammatory and immunomodulatory effects. Methods: We analyzed the chemical composition of APE-EP using HPLC-MS. The intestinal absorption characteristics of APE-EP were evaluated using an ex vivo everted gut sac assay. Furthermore, the anti-inflammatory and immunomodulatory effects of APE-EP were validated using a DSS-induced colitis mouse model. Results: Several phenolic acids were identified, including chicoric acid and caffeic acid, which have significant antioxidant and anti-inflammatory activities. The everted gut sac assay revealed concentration-dependent absorption of chicoric acid in the gut. Results from the mouse model showed that APE-EP promoted macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 macrophages at the lesion sites, effectively suppressing inflammation and alleviating colitis-related pathological damage. Conclusions: This study enhances the medicinal value of the E. purpurea, provides new insights for the efficient utilization of plant resources, and offers a potential natural drug candidate for inflammatory bowel disease treatment. C1 [Jia, Huanhuan; Xing, Huanling; Wu, Hong] South China Agr Univ, Guangdong Technol Res Ctr Tradit Chinese Vet Med &, Guangzhou 510006, Peoples R China. [Jia, Huanhuan] South China Univ Technol, Med Devices Res & Testing Ctr, Guangzhou 510006, Peoples R China. [Lu, Geng; Huang, Sa; Yang, Chuangzan; Peng, Zhixuan; Ban, Junfeng] Guangdong Pharmaceut Univ, Innovat Team Integrating Pharm Entrepreneurship, Guangzhou 510006, Peoples R China. [Lu, Geng] Luohu Hosp Tradit Chinese Med, Dept Pharm, Shenzhen 518001, Peoples R China. [Huang, Sa; Ban, Junfeng] Guangdong Pharmaceut Univ, Guangdong Prov Key Lab Adv Drug Delivery Syst, Guangzhou 510006, Peoples R China. C3 South China Agricultural University; South China University of Technology; Guangdong Pharmaceutical University; Guangdong Pharmaceutical University RP Wu, H (corresponding author), South China Agr Univ, Guangdong Technol Res Ctr Tradit Chinese Vet Med &, Guangzhou 510006, Peoples R China. EM wh@scau.edu.cn RI ban, junfeng/GZL-3106-2022; Yang, Chuangzan/ODI-6498-2025 OI Peng, Zhixuan/0009-0006-1800-1134 FU Open Competition Program of Ten Major Directions of Agricultural Science and Technology Innovation for the 14th Five-Year Plan of Guangdong Province [2022SDZG07] FX This work was supported by the Open Competition Program of Ten Major Directions of Agricultural Science and Technology Innovation for the 14th Five-Year Plan of Guangdong Province (2022SDZG07). 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However, the specific effective components of CL remain unclear. This study investigated the phytochemical composition and diabetic wound healing activities of a novel ethanol extract-derived fractions from CL (CLP2). UHPLC-TOF-MS/MS phytochemical analysis revealed 14 active components in CLP2. HPLC analysis showed that ergosterol was the most prevalent component in CLP2, with a content of 837.3 mu g/mg. CLP2 significantly accelerated wound healing in db/db diabetic mice, facilitated re-epithelialization and inhibited the polarization of M1 macrophages, downregulated the transcription levels of the inflammatory cytokines, and promoted the expression of anti-inflammatory factors. In vitro tests indicated that CLP2 can promote the proliferation and migration of mouse skin fibroblasts, suppress the expression of M1 macrophage-associated proinflammatory cytokines, and enhance M2 polarization. Additionally, in vivo and in vitro experiments confirmed that CLP2 accelerated diabetic wound healing by suppressing M1 macrophages and promoting the polarization of macrophages towards the M2 phenotype, facilitating a faster transition from the inflammatory stage to the proliferative stage. These results highlight CLP2 as a potential therapeutic intervention for diabetic wound healing. C1 [Li, Yan; Dong, Tiantian; He, Tangtang; Yang, Chenxi; Mo, Ruiwen; Chen, Jun; Dong, Jie] Nanjing Univ Chinese Med, Jiangsu Prov Engn Res Ctr TCM External Medicat Dev, 138 Xianlin Rd, Nanjing 210023, Peoples R China. [Li, Yan; Dong, Tiantian; He, Tangtang; Mo, Ruiwen; Chen, Jun; Dong, Jie] Nanjing Univ Chinese Med, Sch Pharm, 138 Xianlin Rd, Nanjing 210023, Peoples R China. [Yang, Chenxi] Nanjing Univ Chinese Med, Sch Med, Dept Immunol, 138 Xianlin Rd, Nanjing 210023, Peoples R China. [Chen, Jun] Nanjing Univ Chinese Med, Jiangsu Collaborat Innovat Ctr Chinese Med Resourc, 138 Xianlin Rd, Nanjing 210023, Peoples R China. [Zhao, Yurong] Jiangsu Food & Pharmaceut Sci Coll, Sch Hlth Sci, 4 Meicheng Rd, Huaian 223003, Jiangsu, Peoples R China. [Xiao, Hanlu] Jinhua Guangfu Oncol Hosp, Clin Pharm Dept, 1296 Huancheng North Rd, Jinhua 321000, Peoples R China. C3 Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine; Jiangsu Food & Pharmaceutical Science College RP Chen, J; Dong, J (corresponding author), Nanjing Univ Chinese Med, Jiangsu Prov Engn Res Ctr TCM External Medicat Dev, 138 Xianlin Rd, Nanjing 210023, Peoples R China. EM chenjun75@njucm.edu.cn; dongjie@njucm.edu.cn FU National Natural Science Foundation of China [82474200]; Jiangsu Province Traditional Chinese Medicine Development Project [MS2022006]; Key Science and Technology Program Projects of Jinhua Science and Technology Bureau [2022-3-147]; Jiangsu Graduate Student Research and Innovation Program Project [KYCX24_2291]; Jiangsu Graduate Student Practice and Innovation Program Project [SJCX24_0905] FX This work was supported by National Natural Science Foundation of China (No. 82474200) , Jiangsu Province Traditional Chinese Medicine Development Project (MS2022006) , Key Science and Technology Program Projects of Jinhua Science and Technology Bureau (2022-3-147) , Jiangsu Graduate Student Research and Innovation Program Project (KYCX24_2291) , Jiangsu Graduate Student Practice and Innovation Program Project (SJCX24_0905) . 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The traditional Chinese medicine (TCM) formula Pudilan (PDL) has demonstrated clinical efficacy against inflammatory diseases including ALI. However, its multi-component complexity has obscured the precise molecular targets and mechanisms underlying its antiinflammatory action. Purpose: This study aimed to systematically identify the direct protein targets of PDL and elucidate the mechanistic basis for its anti-inflammatory effects in ALI. Methods: We employed a cysteine-reactive activity-based protein profiling (ABPP) chemoproteomic strategy to map covalent targets of PDL in macrophages. Target engagement and functional impact were validated through competitive ABPP, cellular thermal shift assay (CETSA), enzymatic activity assays, bio-layer interferometry (BLI), and molecular docking. Functional consequences were assessed using metabolic flux analysis (Seahorse), cytokine profiling, and models of LPS-induced inflammation both in vitro and in vivo. Results: ABPP identified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as the primary covalent target of PDL, specifically modified at its catalytic cysteine residue (Cys150). Baicalein (BC) was pinpointed as the principal bioactive component responsible for GAPDH engagement. Both PDL and BC covalently bound to GAPDH Cys150, inhibiting its enzymatic activity. Functionally, this inhibition suppressed glycolytic flux (the Warburg effect), promoted a metabolic shift toward oxidative phosphorylation (OXPHOS) in macrophages, and reversed pro-inflammatory M1 polarization. This metabolic reprogramming was functionally linked to the suppression of NF-kappa B p65 nuclear translocation and inflammatory mediator production. Critically, both PDL and BC alleviated LPS-induced lung injury in a murine ALI model, with direct evidence of GAPDH engagement and inhibition confirmed in lung tissues. Conclusion: Our study establishes GAPDH as a direct covalent target of PDL and its active component BC, defining a novel "metabolism-immunity" axis through which PDL ameliorates ALI. The ABPP-driven target deconvolution strategy overcomes traditional limitations in TCM mechanism research. These findings provide a mechanistic foundation for the anti-inflammatory efficacy of PDL and offer a targeted therapeutic strategy for inflammatory lung injury. C1 [Jiang, Mengyao; Zhang, Ying; Zhou, Jie] China Acad Chinese Med Sci, Guanganmen Hosp, Beijing 100053, Peoples R China. [Yang, Yang; Zhang, Qianyu; Yang, Tong; Zhang, Guoxin; Chu, Zheng; Li, Shuyu; Wang, Yaxu; Zhang, Junzhe; Shen, Shengnan; Wang, Jigang; Tang, Huan] China Acad Chinese Med Sci, Artemisinin Res Ctr, State Key Lab Qual Ensurance & Sustainable Use Dao, Beijing 100700, Peoples R China. [Yang, Yang; Zhang, Qianyu; Yang, Tong; Zhang, Guoxin; Chu, Zheng; Li, Shuyu; Wang, Yaxu; Zhang, Junzhe; Shen, Shengnan; Wang, Jigang; Tang, Huan] China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China. [Song, Ping] China Acad Chinese Med Sci, Xiyuan Hosp, Beijing 100091, Peoples R China. [Zhang, Panpan] Jinan Stomatol Hosp, Ctr Esthet Dent, Jinan Key Lab Oral Dis & Tissue Regenerat, Shandong Prov Key Med & Hlth Lab Oral Dis & Tissue, Jinan 250001, Peoples R China. [Wang, Jigang] Southern Univ Sci, Shenzhen Peoples Hosp,Dept Pulm & Crit Care Med, Affiliated Hosp 1,Guangdong Prov Clin Res Ctr Geri, Shenzhen Inst Resp Dis,Shenzhen Clin Res Ctr Geria, Shenzhen, Peoples R China. [Wang, Jigang] Shandong Univ Tradit Chinese Med, Inst Acupuncture & Moxibust, 4655 Univ Rd, Jinan 250355, Peoples R China. C3 Guang'anmen Hospital, CACMS; China Academy of Chinese Medical Sciences; China Academy of Chinese Medical Sciences; China Academy of Chinese Medical Sciences; Institute of Chinese Materia Medica, CACMS; Xiyuan Hospital, CACMS; China Academy of Chinese Medical Sciences; Jinan University; Shandong University of Traditional Chinese Medicine RP Wang, JG; Tang, H (corresponding author), China Acad Chinese Med Sci, Artemisinin Res Ctr, State Key Lab Qual Ensurance & Sustainable Use Dao, Beijing 100700, Peoples R China.; Wang, JG; Tang, H (corresponding author), China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China.; Song, P (corresponding author), China Acad Chinese Med Sci, Xiyuan Hosp, Beijing 100091, Peoples R China.; Wang, JG (corresponding author), Southern Univ Sci, Shenzhen Peoples Hosp,Dept Pulm & Crit Care Med, Affiliated Hosp 1,Guangdong Prov Clin Res Ctr Geri, Shenzhen Inst Resp Dis,Shenzhen Clin Res Ctr Geria, Shenzhen, Peoples R China.; Wang, JG (corresponding author), Shandong Univ Tradit Chinese Med, Inst Acupuncture & Moxibust, 4655 Univ Rd, Jinan 250355, Peoples R China. EM songping_cacms@163.com; jgwang@icmm.ac.cn; htang@icmm.ac.cn FU National Natural Science Foundation of China [82522095]; CACMS Innovation Fund [CI2025D002, CI2023E005TS01, CI2024E003]; Central Government Guidance Funds for Local Science and Technology Development Projects [2025ZY0072]; Fundamental Research Funds for the Central public welfare research institutes [ZZ14-YQ-061] FX We gratefully acknowledge financial support from National Natural Science Foundation of China (82522095), the CACMS Innovation Fund (CI2025D002, CI2023E005TS01, and CI2024E003), Central Government Guidance Funds for Local Science and Technology Development Projects (2025ZY0072), the Fundamental Research Funds for the Central public welfare research institutes (ZZ14-YQ-061). 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Persistent pain substantially diminishes patients' quality of life. Glycyrrhiza, a component of traditional Chinese medicine, has shown effectiveness in the treatment of KOA. Liquiritin (LQ), a principal active compound in licorice, demonstrates therapeutic potential; however, its mechanisms of action have yet to be comprehensively understood. This study aims to investigate the underlying pharmacological mechanisms by which LQ alleviates KOA nociceptive sensitization by establishing in vivo and in vitro KOA models and integrating transcriptomic analyses. In vivo, a KOA mice model was established via destabilization of the medial meniscus (DMM) surgery. The ameliorative effects of LQ on mechanical allodynia were assessed. We established an in vitro coculture model of bone marrow-derived macrophages (BMDM) and dorsal root ganglion (DRG) to investigate the effects of various treatments on TRP channels in mouse DRG neurons and further elucidated the mechanism of LQ action on BMDM through transcriptomic analysis. In vivo findings demonstrated that inflammatory conditions reduced M2 macrophage infiltration in DRG tissues while concurrently elevating transcriptional and protein expression levels of TRPA1, TRPV1, TRPM8, NGF, and Substance P. LQ intervention significantly increased M2 macrophage infiltration in DRG tissues and simultaneously suppressed transcriptional and protein expression of TRPA1, TRPV1, TRPM8, NGF, and Substance P. This result is consistent with the findings from mice behavioral assessments, indicating that LQ effectively alleviates KOA-induced nociceptive sensitization. In vitro experiments revealed that LQ alleviates KOA nociceptive sensitization by promoting M2 macrophage activation. Integrated transcriptomic analysis further demonstrated that LQ likely facilitates M2 macrophage polarization by suppressing the Rap1/PI3K/Akt signaling pathway in BMDMs. LQ alleviates nociceptive sensitization in KOA mice by modulating the Rap1/PI3K/Akt signaling pathway to promote M2 macrophage polarization in DRG tissues. C1 [Fu, Hou-Yu; Jie, Li-Shi; Gong, Zi-Jian; Liu, Jiang-Yu; Liu, De-Ren; Wang, Pei-Min; Li, Xiao-Chen] Nanjing Univ Chinese Med, Dept Orthoped, Affiliated Hosp, Nanjing, Peoples R China. [Fu, Hou-Yu; Jie, Li-Shi; Gong, Zi-Jian; Liu, Jiang-Yu; Liu, De-Ren; Wang, Pei-Min; Li, Xiao-Chen] Nanjing Univ Chinese Med, Coll Clin Med 1, Nanjing, Peoples R China. [Huang, Ze-Ling] Fujian Univ Tradit Chinese Med, Fuzhou, Fujiang, Peoples R China. [Zhu, Zai-Shi] Nanjing Univ Chinese Med, Suzhou TCM Hosp, Suzhou, Jiangsu, Peoples R China. [Wang, Pei-Min; Li, Xiao-Chen] Jiangsu Prov Engn Res Ctr TCM External Medicat Dev, Nanjing, Peoples R China. [Wang, Pei-Min; Li, Xiao-Chen] Nanjing Univ Chinese Med Clin Res Inst Knee Osteoa, Nanjing, Peoples R China. C3 Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine; Fujian University of Traditional Chinese Medicine; Nanjing University of Chinese Medicine RP Wang, PM; Li, XC (corresponding author), Nanjing Univ Chinese Med, Dept Orthoped, Affiliated Hosp, Nanjing, Peoples R China.; Wang, PM; Li, XC (corresponding author), Nanjing Univ Chinese Med, Coll Clin Med 1, Nanjing, Peoples R China.; Wang, PM; Li, XC (corresponding author), Jiangsu Prov Engn Res Ctr TCM External Medicat Dev, Nanjing, Peoples R China.; Wang, PM; Li, XC (corresponding author), Nanjing Univ Chinese Med Clin Res Inst Knee Osteoa, Nanjing, Peoples R China. EM drwpm@163.com; drlixiaochen@njucm.edu.cn RI ; HUANG, ZELING/JVN-2020-2024 OI 黄, 泽灵/0000-0002-2014-9844; FU Jiangsu Provincial Hospital of Traditional Chinese Medicine [Y2023zx05]; Clinical Specialty Institute for Knee Osteoarthritis; Excellent Young Doctoral Program of Jiangsu Province Hospital of Chinese Medicine [2023QB0118]; National Natural Science Foundation of China [82305276]; Clinical Medical Innovation Center Project for Knee Osteoarthritis of Traditional Chinese Medicine; Nanjing University of Chinese Medicine [LCZBYJYZZ2024-003]; Jiangsu Province Science and Technology Development Project of Traditional Chinese Medicine [QN202105]; Natural Science Research Project of Jiangsu Higher Education Institutions [22KJB360008]; Key Medical Discipline/Laboratory Construction Project of Jiangsu Province [JSDW202252] FX This research was supported by National Natural Science Foundation of China (No. 82305276); Jiangsu Province Science and Technology Development Project of Traditional Chinese Medicine (No. QN202105); Natural Science Research Project of Jiangsu Higher Education Institutions (No. 22KJB360008); Excellent Young Doctoral Program of Jiangsu Province Hospital of Chinese Medicine (2023QB0118); Clinical Medical Innovation Center Project for Knee Osteoarthritis of Traditional Chinese Medicine, Jiangsu Provincial Hospital of Traditional Chinese Medicine (No. Y2023zx05); Key Medical Discipline/Laboratory Construction Project of Jiangsu Province (No. JSDW202252); Clinical Specialty Institute for Knee Osteoarthritis, Nanjing University of Chinese Medicine (No. LCZBYJYZZ2024-003). 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PD FEB PY 2026 VL 40 IS 2 BP 701 EP 720 DI 10.1002/ptr.70174 EA JAN 2026 PG 20 WC Chemistry, Medicinal; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA DH8TD UT WOS:001654786100001 PM 41494619 DA 2026-03-26 ER PT J AU Ma, CQ Liu, Y Zeng, TQ Li, X Tan, XY Ma, XQ Lu, X Wang, YR Wu, XY AF Ma, Chengqi Liu, Yun Zeng, Tangqing Li, Xiang Tan, Xinyue Ma, Xiaoqiang Lu, Xu Wang, Yirui Wu, Xiaoyu TI Zexie-Baizhu herb pair attenuates MASH via the gut-liver Axis by suppressing NLRP3 Inflammasome activation and M1-macrophage polarization SO BIOORGANIC CHEMISTRY LA English DT Article DE ZB; MASH; NLRP3; Macrophages; FXR; BAs; Gut-liver axis ID NONALCOHOLIC STEATOHEPATITIS; FXR; CHOLESTASIS; ACID AB Metabolic dysfunction-associated steatohepatitis (MASH), a severe form of MASLD lacking effective treatments, may be therapeutically targeted by the Traditional Chinese Medicine herb pair Zexie-Baizhu (ZB), known for its lipid-modulating and anti-inflammatory properties. This study investigated ZB's effects and mechanisms in diet-induced MASH mouse models. We began by identifying potential active ingredients in ZB using UPLC-MS/MS. When administered preventively over an 8-week period, ZB significantly improved serum lipids, reduced hepatic inflammation, and alleviated liver lipid accumulation. Mechanistic studies revealed that ZB restores beneficial gut microbiota, enhances intestinal barrier integrity, modulate the hepatic bile acid receptor FXR signaling pathway to regulate bile acid metabolism, and crucially suppresses NLRP3 inflammasome activation and M1 macrophage polarization. Fecal microbiota transplantation confirmed the role of gut microbiota modulation. Collectively, these results demonstrate that ZB alleviates MASH progression primarily via the gut-liver axis by inhibiting NLRP3 inflammasome and M1 macrophage polarization, highlighting this axis as a promising therapeutic target. C1 [Lu, Xu; Wang, Yirui; Wu, Xiaoyu] Nanjing Univ Chinese Med, Affiliated Hosp, Nanjing 210029, Peoples R China. Nanjing Univ Chinese Med, Nanjing 210023, Peoples R China. C3 Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine RP Lu, X; Wang, YR; Wu, XY (corresponding author), Nanjing Univ Chinese Med, Affiliated Hosp, Nanjing 210029, Peoples R China. EM docluxu@139.com; 956689734@qq.com; yfy154@njucm.edu.cn FU National Natural Science Foundation of China [82174466]; Program for Leading Talents of Traditional Chinese Medicine of Jiangsu Province [SLJ0314]; Jiangsu Provincial Natural Science Foundation-Youth Foundation Project [BK20241147]; Jiangsu Provincial Natural Science Foundation-Youth Foundation Project [BK20251145] FX This research received Funding from National Natural Science Foundation of China (82174466) ; Program for Leading Talents of Traditional Chinese Medicine of Jiangsu Province (SLJ0314) ; Jiangsu Provincial Natural Science Foundation-Youth Foundation Project (BK20241147) and Jiangsu Provincial Natural Science Foundation-Youth Foundation Project (BK20251145) . 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PD FEB PY 2026 VL 169 AR 109451 DI 10.1016/j.bioorg.2025.109451 EA JAN 2026 PG 16 WC Biochemistry & Molecular Biology; Chemistry, Organic WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry GA AY6CV UT WOS:001659855700001 PM 41485442 DA 2026-03-26 ER PT J AU Fu, Y Zhang, JF Fang, XZ An, YN Huang, SN Feng, XM Jiang, XM Chen, ZH Quan, XG Jin, D Zhao, YQ Li, FF AF Fu, Yuan Zhang, Jinfang Fang, Xizhu An, Yining Huang, Shengnan Feng, Xianmin Jiang, Xiaoming Chen, Zhihua Quan, Xingguo Jin, Dan Zhao, Yuqing Li, Fangfang TI Ginsenoside derivative AD-1 suppresses colitis-associated colorectal cancer progression by reprogramming tumor-associated macrophage polarization via the AMPK/mTOR-glycolysis pathway SO BIOORGANIC CHEMISTRY LA English DT Article DE Ginsenoside derivative AD-1; Colitis-associated colorectal cancer; Tumor-associated macrophage polarization; Glycolysis; AMPK/mTOR signaling pathway ID IMMUNOMETABOLISM; METABOLISM; INFLAMMATION; MECHANISMS; IMMUNITY; SIGNAL; CELLS AB Persistent inflammation plays a pivotal role in the development of colorectal cancer (CRC), and the incidence of colitis-associated colorectal cancer (CAC) continues to rise. Thus, exploring treatment strategies for CAC is critical for the prevention and management of CRC. Natural products derived from traditional Chinese medicine have recently gained attention for their therapeutic potential in cancer prevention. Here, we demonstrate that the ginsenoside derivative AD-1 significantly inhibits tumor progression in both AOM/DSS-induced CAC mice and CRC xenograft models. Moreover, AD-1 modulates tumor-associated macrophage (TAM) polarization both in vivo and in vitro. Specifically, AD-1 increases M1-like TAM polarization while suppressing M2-like TAM in the spleens and colonic tissues of CAC mice, as well as in tumor tissues of CRC xenograft models. In vitro, AD-1 similarly promotes M1-like polarization and inhibits M2-like polarization in a TAM model established by co-culturing RAW264.7 cells with CT26 supernatant. Mechanistically, AD-1 activates AMPK signaling and inhibits mTOR activation, leading to enhanced glycolysis, which contributes to TAM metabolic reprogramming and polarization. Collectively, our study suggests that AD-1 represents a promising natural agent for modulating the tumor immune microenvironment and preventing the progression of inflammation-associated CRC. C1 [Fu, Yuan; Zhang, Jinfang; Fang, Xizhu; An, Yining; Huang, Shengnan; Jiang, Xiaoming; Chen, Zhihua; Quan, Xingguo; Jin, Dan; Li, Fangfang] Yanbian Univ, Immunol Biol Key Lab, Yanji 133002, Peoples R China. [Fu, Yuan; Zhang, Jinfang; An, Yining; Huang, Shengnan; Chen, Zhihua; Jin, Dan; Zhao, Yuqing] Yanbian Univ, Key Lab Nat Med Changbai Mt, Minist Educ, Yanji 133002, Peoples R China. [Fu, Yuan; Zhang, Jinfang; Fang, Xizhu; An, Yining; Huang, Shengnan; Quan, Xingguo; Jin, Dan; Li, Fangfang] Yanbian Univ, Coll Med, Dept Immunol & Pathogen Biol, Yanji 133002, Peoples R China. [Chen, Zhihua] Yanbian Univ, Coll Nursing, Dept Nursing Sci, Yanji 133002, Peoples R China. [Feng, Xianmin; Jiang, Xiaoming] Jilin Prov Key Lab Changbai Mt Authent Med Materia, Jilin 132013, Peoples R China. C3 Yanbian University; Yanbian University; Yanbian University; Yanbian University RP Jin, D; Li, FF (corresponding author), Yanbian Univ, Immunol Biol Key Lab, Yanji 133002, Peoples R China.; Jin, D; Zhao, YQ (corresponding author), Yanbian Univ, Key Lab Nat Med Changbai Mt, Minist Educ, Yanji 133002, Peoples R China.; Jin, D; Li, FF (corresponding author), Yanbian Univ, Coll Med, Dept Immunol & Pathogen Biol, Yanji 133002, Peoples R China. EM 0000002048@ybu.edu.cn; zyq2022@126.com; ffli@ybu.edu.cn RI Li, Fangfang/D-9908-2013 FU Jilin Provincial Scientific and Techno-logical Development Program [YDZJ202401044ZYTS] FX This research was funded by Jilin Provincial Scientific and Techno-logical Development Program, grant number YDZJ202401044ZYTS. 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PD FEB PY 2026 VL 169 AR 109458 DI 10.1016/j.bioorg.2025.109458 EA JAN 2026 PG 15 WC Biochemistry & Molecular Biology; Chemistry, Organic WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry GA AX9FA UT WOS:001659385300001 PM 41483706 DA 2026-03-26 ER PT J AU Li, HL Wang, GR Fan, YC Li, ZX Wei, HX Mao, SN Miao, C Liu, L Chen, JS Li, CJ Ding, ZF Cao, YB AF Li, Honglin Wang, Guanru Fan, Yuchen Li, Zhixuan Wei, Hongxuan Mao, Suning Miao, Cheng Liu, Liu Chen, Junsheng Li, Chunjie Ding, Zhangfan Cao, Yubin TI Shengmai San attenuates irradiation-induced salivary gland injury and fibrosis by inhibiting the SPHK1-S1P-S1PR1 axis SO PHYTOMEDICINE LA English DT Article DE Shengmai San; Radiation; Salivary gland injury; Ophiopogonanone E AB Background: Radiation-induced salivary gland injury is a common complication of radiotherapy for head and neck tumors. The traditional Chinese herbal compound Shengmai San (SMS) can regulate Qi-Yin deficiency, promote fluid secretion, and alleviate thirst. However, its therapeutic effects on radiation-induced salivary gland damage remain unexplored. Purpose: This study aimed to investigate the therapeutic efficacy of Shengmai San in irradiation-induced salivary gland injury, identify its active pharmaceutical components, and elucidate the underlying molecular mechanisms of radioprotection. Material and methods: The natural drug components of Shengmai San were analyzed, and a murine model of irradiation-induced salivary gland injury was established. SMS extract was administered to irradiated mice, and the functional restoration of salivary glands was evaluated. Network pharmacology was employed to identify the active constituents of SMS, while molecular docking and protein-protein interaction analysis were used to screen key signaling pathways associated with glandular functional preservation. In vitro and in vivo experiments were conducted to validate these findings. Results: Shengmai San significantly alleviated irradiation-induced salivary gland injury by promoting M2 macrophage polarization and reducing the levels of Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-alpha) in serum and salivary gland tissues. It also ameliorated glandular fibrosis and inflammation. Network pharmacology analysis revealed that ophiopogonanone E was one of the primary active components, and molecular docking demonstrated its strong interaction with sphingosine kinase 1 (SPHK1) protein. In vivo experiments showed that SMS suppressed SPHK1 activity and sphingosine-1-phosphate (S1P) production in irradiated salivary glands. Additionally, SMS effectively inhibited the downstream receptor S1PR1. In vitro studies confirmed that SMS attenuated mitochondrial damage in acinar cells by inhibiting the SPHK1-S1P-S1PR1 axis and reduced glandular inflammation and oxidative stress by suppressing Nucleotide-binding Oligomerization Domain-like Receptor Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation, thereby preserving salivary gland function. Conclusion: Shengmai San effectively attenuates irradiation-induced salivary gland hypofunction and fibrosis, mainly through inhibition of the SPHK1-S1P-S1PR1 signaling pathway. C1 [Li, Honglin; Wang, Guanru; Fan, Yuchen; Li, Zhixuan; Wei, Hongxuan; Mao, Suning; Miao, Cheng; Liu, Liu; Li, Chunjie; Ding, Zhangfan; Cao, Yubin] Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610041, Peoples R China. [Li, Honglin; Wang, Guanru; Fan, Yuchen; Li, Zhixuan; Wei, Hongxuan; Mao, Suning; Miao, Cheng; Liu, Liu; Li, Chunjie; Ding, Zhangfan; Cao, Yubin] Sichuan Univ, West China Hosp Stomatol, Natl Ctr Stomatol, Chengdu 610041, Peoples R China. [Li, Honglin; Wang, Guanru; Fan, Yuchen; Li, Zhixuan; Wei, Hongxuan; Mao, Suning; Miao, Cheng; Liu, Liu; Li, Chunjie; Ding, Zhangfan; Cao, Yubin] Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, Chengdu 610041, Peoples R China. [Li, Honglin; Wang, Guanru; Li, Zhixuan; Wei, Hongxuan; Miao, Cheng; Li, Chunjie; Ding, Zhangfan] Sichuan Univ, West China Hosp Stomatol, Dept Head & Neck Oncol, Chengdu 610041, Peoples R China. [Liu, Liu] Sichuan Univ, West China Hosp Stomatol, Dept Conservat Dent & Endodont, Chengdu 610041, Peoples R China. [Chen, Junsheng] Hosp Sick Children, Dev Stem Cell & Canc Biol Program, Toronto, ON, Canada. [Chen, Junsheng] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON, Canada. [Cao, Yubin] Sichuan Univ, West China Hosp Stomatol, Dept Oral & Maxillofacial Surg, Chengdu 610041, Peoples R China. C3 Sichuan University; Sichuan University; Sichuan University; Sichuan University; Sichuan University; University of Toronto; Hospital for Sick Children (SickKids); University of Toronto; Hospital for Sick Children (SickKids); Sichuan University RP Ding, ZF; Cao, YB (corresponding author), Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610041, Peoples R China. EM dingzf16@163.com; yubin.cao@scu.edu.cn RI Chen, Junsheng/HNJ-2233-2023; Mao, Suning/PMF-3653-2026 FU National Natural Science Foundation of China [82470997, 82270994, 82301106]; Sichuan Medical Association Youth Innovation Project [Q2024072]; Natural Science Foundation of Sichuan Province [2024NSFSC1585] FX This study was supported by the National Natural Science Foundation of China (Grant number: 82470997, 82270994, 82301106) , Sichuan Medical Association Youth Innovation Project (Grant number: Q2024072) , and Natural Science Foundation of Sichuan Province (Grant number: 2024NSFSC1585) . 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While the Yi-Qi-Dao-Zhi Formula (YQDZ) has proven its worth in treating premature ovarian insufficiency in clinical settings, the exact therapeutic mechanisms that make it tick continue to fly under the radar. Methods: This investigation employed ultra-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) to pinpoint the key bioactive compounds in YQDZ. For in vivo experiments, a POI mouse model was created through surgical intervention, and gastrointestinal transport function was assessed via charcoal ink experiments. Intestinal histopathology was examined using HE staining. The therapeutic impact of YQDZ on POI was thoroughly assessed using a battery of advanced laboratory techniques, including immunofluorescence staining, immunohistochemical analysis, Western blot procedures, real-time quantitative PCR assays, and ELISA testing. In vitro experiments involved the establishment of an M1-type inflammatory model by inducing mouse mononuclear macrophage RAW264.7 cells with LPS. Additional evaluations encompassed CCK-8 assays, flow cytometry, transcriptomic profiling, real-time PCR, and protein level examinations, all aimed at delving into the mode of action of YQDZ. Results: YQDZ steers M1 macrophage differentiation through the TLR4/NF-xB/MAPK signaling pathway. This action effectively curtails the levels of key inflammatory mediators including TNF-alpha, IL-1 beta, and IL-6. Consequently, it acts as a therapeutic agent for inflamed bowels in postoperative ileus mice, helping to restore their gastrointestinal functionality. Conclusion: The therapeutic approach of YQDZ for POI might be connected to the adjustment of the TLR4/NF-xB/MAPK signaling pathway, alongside the inhibition of macrophage polarization. C1 [Yu, Jing; Zhao, Xuan; Zhang, Liuchuang; Chen, Yanlin; Zhang, Tianle; Wang, Ye; Yi, Chen] Nanjing Univ Chinese Med, Affiliated Hosp, Nanjing, Jiangsu, Peoples R China. [Pan, Huafeng; Wang, Haifeng; Ge, Miaomiao; Jiang, Zhiwei; Wang, Gang] Nanjing Univ Chinese Med, Jiangsu Prov Hosp Chinese Med, Affiliated Hosp, Dept Gen Surg, Nanjing, Jiangsu, Peoples R China. C3 Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine RP Jiang, ZW; Wang, G (corresponding author), Nanjing Univ Chinese Med, Jiangsu Prov Hosp Chinese Med, Affiliated Hosp, Dept Gen Surg, Nanjing, Jiangsu, Peoples R China. EM surgery34@163.com; gwang82@163.com FU Jiangsu Provincial Key Discipline Project [ZDXK202251]; Jiangsu Provincial Association of Chinese Medicine Revitalization and Development Project [ZXFZ2024001]; Jiangsu Postgraduate Research Innovation Program [KYCX25_2279] FX This work was supported by the Jiangsu Provincial Key Discipline Project (ZDXK202251) , Jiangsu Provincial Association of Chinese Medicine Revitalization and Development Project (ZXFZ2024001) , and Jiangsu Postgraduate Research Innovation Program (KYCX25_2279) . 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Inflamm. Res. PY 2026 VL 19 AR 589449 DI 10.2147/JIR.S589449 PG 19 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA EM9ZD UT WOS:001704934100001 PM 41789416 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Xia, BY Li, X Gao, JY Zhang, Z Lan, QT Tao, JY Tang, AC AF Xia, Bing-Yu Li, Xin Gao, Jia-Yi Zhang, Zheng Lan, Qing-Tong Tao, Jun-Yu Tang, Ai-Cun TI Mechanism of Shenqi Qiangjing Granules in Treating Cyclophosphamide-Induced Oligozoospermia Based on Network Pharmacology and Experimental Validation SO ANDROLOGIA LA English DT Article DE network pharmacology; NF-kappa B pathway; oligospermia; Shenqi Qiangjing granules; testicular macrophage polarization ID NF-KAPPA-B; OXIDATIVE STRESS; IDENTIFICATION; ACTIVATION AB BackgroundResearch indicates that cyclophosphamide (CY), a cancer treatment, can cause oligozoospermia in men. Traditional Chinese medicine, particularly Shenqi Qiangjing (SQ) granules, may help improve this issue, but the exact way it works against CY-induced oligozoospermia is not completely clear.AimThis study aimed to verify that SQ can improve oligozoospermia caused by CY and explore its potential mechanism.MethodsThis research uses network pharmacology to identify common genes linked to SQ and oligozoospermia, as well as testicular macrophage polarization (TMP). Using databases such as TCMSP and GeneCard, relevant genes were identified, and a protein interaction network was created with STRING and Cytoscape. GO and KEGG analyses was used to identify pathways related to SQ. To induce oligozoospermia, male mice were given a 60 mg/kg dose of CY for 5 days. The plants were then treated with two doses of SQ (200 and 800 mg/kg) for 21 days to assess its protective effects on reproductive organs. Measurements included testicular and epididymal indices, sperm quality, hormone levels, oxidative stress markers, inflammatory cytokines, tissue changes, and proteins related to the nuclear factor kappa B (NF-kappa B) pathway.ResultsResearchers identified 883 genes linked to SQ, with 16 key genes that help improve oligozoospermia by affecting TMP. Analysis suggests that SQ may promote oligozoospermia by regulating TMP through NF-kappa B. Studies have shown that SQ improves sperm quality, reduces oxidative damage, balances sex hormones, shifts macrophages from the M1 phenotype to the M2 phenotype, and decreases NF-kappa B protein levels.ConclusionSQ alleviates oligozoospermia by reversing M1 macrophage polarization via NF-kappa B, supporting its potential in treating male infertility and aligning with national fertility strategies. C1 [Xia, Bing-Yu; Li, Xin; Gao, Jia-Yi; Zhang, Zheng; Lan, Qing-Tong; Tao, Jun-Yu; Tang, Ai-Cun] Guangxi Univ Chinese Med, Nanning, Guangxi, Peoples R China. [Xia, Bing-Yu; Li, Xin; Gao, Jia-Yi; Zhang, Zheng; Tao, Jun-Yu] Guangxi Key Lab Translat Med Treating High Inciden, Nanning, Guangxi, Peoples R China. [Xia, Bing-Yu; Li, Xin; Gao, Jia-Yi; Zhang, Zheng; Tao, Jun-Yu] Guangxi Univ Chinese Med, Sch Publ Hlth & Management, Lab Prevent Med, Nanning, Guangxi, Peoples R China. C3 Guangxi University of Chinese Medicine; Guangxi University of Chinese Medicine RP Lan, QT; Tao, JY; Tang, AC (corresponding author), Guangxi Univ Chinese Med, Nanning, Guangxi, Peoples R China.; Tao, JY (corresponding author), Guangxi Key Lab Translat Med Treating High Inciden, Nanning, Guangxi, Peoples R China.; Tao, JY (corresponding author), Guangxi Univ Chinese Med, Sch Publ Hlth & Management, Lab Prevent Med, Nanning, Guangxi, Peoples R China. EM 155190131@qq.com; 149058404@qq.com; tangaicun321@126.com FU Guangxi Graduate Education Innovation Program Project [YCSY2025025]; Guangxi Key Research and Development Program [AB22035073] FX The authors sincerely thank the Guangxi Key Laboratory of Translational Medicine Treating High-Incidence Diseases Integrative Medicine and Preventive Medicine Laboratory for the assistance and site support provided during this period. CR Abu-Risha SE, 2022, LIFE SCI, V289, DOI 10.1016/j.lfs.2021.120218 Bhushan S, 2015, J IMMUNOL, V194, P5455, DOI 10.4049/jimmunol.1401132 Biniwale S, 2022, J REPROD IMMUNOL, V151, DOI 10.1016/j.jri.2022.103618 Cao Y, 2024, PHYTOMEDICINE, V132, DOI 10.1016/j.phymed.2024.155820 Deng XiangLiang Deng XiangLiang, 2015, Drugs and Clinic, V30, P253 DiDonato JA, 2012, IMMUNOL REV, V246, P379, DOI 10.1111/j.1600-065X.2012.01099.x Fani F, 2024, J BIOCHEM MOL TOXIC, V38, DOI 10.1002/jbt.23696 Furlanut M, 2003, ONCOLOGY-BASEL, V65, P2, DOI 10.1159/000073350 Gan D. 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H., 2023, CHINESE J EUGENICS G, V31, P1383 NR 47 TC 0 Z9 0 U1 2 U2 2 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-4569 EI 1439-0272 J9 ANDROLOGIA JI Andrologia PY 2026 VL 2026 IS 1 AR 7034264 DI 10.1155/and/7034264 PG 15 WC Andrology WE Science Citation Index Expanded (SCI-EXPANDED) SC Endocrinology & Metabolism GA EA5BI UT WOS:001696451600001 OA hybrid DA 2026-03-26 ER PT J AU He, WW Ma, S Lin, WL Hu, JR Su, YP Yang, JS AF He, Weiwei Ma, Sai Lin, Weilong Hu, Jiarui Su, Yingpeng Yang, Jiashuo TI Curcumin Mediates Macrophage Polarization by Regulating the AXIN2/β-catenin Pathway, Inhibits Inflammatory Responses and Hinders the Progression of Oral Squamous Cell Carcinoma SO DISCOVERY MEDICINE LA English DT Article DE curcumin; macrophage; AXIN2/beta-catenin; oral squamous cell carcinoma AB Background: Macrophage polarization to M2 type plays a key role in promoting the progression of oral squamous cell carcinoma (OSCC). Curcumin, as a natural active ingredient, has been proven to have anti-tumor activity, but its regulatory mechanism on macrophage polarization in OSCC remains unclear. This study aims to explore whether curcumin affects the M2 polarization of macrophages by regulating the axis inhibition protein 2 (AXIN2)/beta-catenin pathway, and to clarify its effects and molecular mechanisms on the growth and invasion of OSCC cells. Methods: RAW264.7 cells were selected to be treated with different concentrations (0, 5, 10, 20 mu M) of curcumin, and the expression of M2 markers was detected by Real-time fluorescence quantitative PCR (qRT-PCR) and flow cytometry. The expression of AXIN2/beta-catenin pathway molecules and downstream genes was detected using Western blotting. The localization and expression intensity of arginase-1 (ARG1) and beta-catenin were observed using immunofluorescence staining. The secretion levels of cytokines were detected by enzyme-linked immunosorbent assay (ELISA). The conditioned medium of curcumin-pre-treated macrophages was collected and used to treat OSCC cell lines (HSC3, CAL33). Cell viability, proliferation, apoptosis and invasion ability were evaluated. The role of AXIN2 in curcumin-regulated macrophage polarization and OSCC cell behavior was verified by knockdown of AXIN2 in macrophages. Results: Curcumin inhibited the polarization of M2 type macrophages in a concentration-dependent manner (p < 0.01). Mechanistically, curcumin upregulated AXIN2 expression in macrophages and inhibited the nuclear translocation of beta-catenin and the expression of its downstream target genes (p < 0.01). The conditioned medium from curcumin-pre-treated macrophages significantly inhibited the viability, colony formation ability, and invasion ability of OSCC cells, and promoted cell apoptosis (p < 0.01). Knockdown of AXIN2 partially reversed the inhibitory effect of curcumin on M2 polarization of macrophages and weakened the inhibitory effect of the conditioned medium on the growth and invasion of OSCC cells (p < 0.01). Conclusions: Curcumin inhibits the activation of the beta-catenin pathway by up-regulating AXIN2 expression, thereby blocking the polarization of macrophages to the M2 type, reducing the secretion of pro-cancer cytokines, and ultimately suppressing the growth and invasion of OSCC cells. This study reveals a new mechanism by which curcumin regulates the polarization of macrophages in the tumor microenvironment, providing experimental evidence for targeted therapy of OSCC. C1 [He, Weiwei; Ma, Sai; Lin, Weilong; Yang, Jiashuo] Hebei North Univ, Affiliated Hosp 1, Dept Stomatol, Zhangjiakou 075000, Hebei, Peoples R China. [Hu, Jiarui] Hebei North Univ, Affiliated Hosp 1, Tradit Chinese Med Dept, Zhangjiakou 075000, Hebei, Peoples R China. [Su, Yingpeng] Hebei North Univ, Affiliated Hosp 1, Cent Lab, Zhangjiakou 075000, Hebei, Peoples R China. C3 Hebei North University; Hebei North University; Hebei North University RP He, WW (corresponding author), Hebei North Univ, Affiliated Hosp 1, Dept Stomatol, Zhangjiakou 075000, Hebei, Peoples R China. EM gege13993@126.com FU Program of Research Projects in Traditional Chinese Medicine Sciences [2025385] FX This research was supported by 2025 Program of Research Projects in Traditional Chinese Medicine Sciences, Grant No.2025385. 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Med. PD JAN PY 2026 VL 38 IS 204 BP 143 EP 154 DI 10.24976/Discov.Med.202638204.12 PG 12 WC Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine GA CY5IJ UT WOS:001677463000012 DA 2026-03-26 ER PT J AU Ge, FL Wang, XM Li, Z Su, GY Li, LL Yu, J Miao, WL Ma, YR Liang, HX Ren, ZG AF Ge, Feilin Wang, Xuemei Li, Zhe Su, Guanyue Li, Lili Yu, Jia Miao, Wenlong Ma, Yarong Liang, Hongxia Ren, Zhigang TI Study on the anti-liver cirrhosis of Fuzheng Huayu tablet : Targeting macrophage PPARα axis-fatty acid metabolic SO PHYTOMEDICINE LA English DT Article DE Liver cirrhosis; Macrophage; PPAR alpha/PGC-1 alpha/CPT1A axis; Fatty acid metabolism; TCM ID GUIDELINES AB Background: Currently, no first-line conventional drugs are recommended worldwide by clinical guidelines for liver cirrhosis treatment. Some clinical studies have shown that the Fuzheng Huayu Tablet (FZHY) has an anticirrhotic effect, but further validation of the anticirrhotic effect and its mechanism is needed. Purpose: In this study, the anticirrhotic effect of FZHY was evaluated for the first time at the basic research level, and both its mechanism and active compounds were analysed. Study design: Firstly, the efficacy of FZHY was evaluated using the liver cirrhosis model. Further, the mechanism of FZHY was analyzed through multi-omics and molecular biology experiments, and was verified through the target inhibitor model. Finally, the effective components of FZHY were analyzed through bioinformatics analysis and experimental verification. Methods: Liver cirrhosis mouse models were used to evaluate the efficacy of FZHY. Single-cell transcriptomics, metabolomics, and 16S RNA microbiota were used to explore the mechanism underlying the effects of FZHY against liver cirrhosis. Flow cytometry, immunohistochemistry, immunoconfocal microscopy, WB, PCR, Oil red O staining and other techniques were used to investigate the mechanism underlying the effects of FZHY on liver cirrhosis. A macrophage clearance model and an in vivo PPAR alpha inhibitor model, as well as an in vitro PPAR alpha inhibitor model, were used to verify the mechanism through which FZHY affects liver cirrhosis. LC-MS, molecular docking, and molecular biology experiments were used to analyse the active components of FZHY associated with its effect against liver cirrhosis. Results: In the CCL4-mediated liver cirrhosis mouse model, FZHY significantly reversed the formation of liver pseudolobules and inhibited liver and serum inflammation. Single-cell transcriptomics revealed that M2 macrophages were more abundant in the FZHY group. The metabolomics and 16S RNA microbiota pathways were enriched in fatty acid oxidation (FAO)-and PPAR-related pathways. The Flow results revealed that FZHY promoted the M2 polarization of Kupffer cells in the liver and THP1 cells but had no effect on the polarization of total macrophages in the liver or spleen. Immunoconfocal microscopy/Immunofluorescence and pathological tests revealed that FZHY significantly decreased the levels of fatty acids in liver and THP1 cells. A variety of molecular biology experiments revealed that FZHY regulated the expression level of the PPAR alpha pathway, regulated FAO and macrophage polarization and promoted the entry of PPAR alpha into the nucleus. On the basis of in vivo macrophage scavenger and in vitro PPAR alpha inhibitor models, the anticirrhotic effect of the PPAR alpha pathway and the M2 polarization effect of FZHY were significantly reduced. Integrated LC-MS, molecular docking and experimental verification revealed that quercetin and luteolin could induce M2 polarization, promote the entry of PPAR alpha into the nucleus, and significantly decrease the levels of fatty acids. Conclusion: FZHY has an anticirrhotic effect, which may promote FAO by targeting the PPAR alpha axis in macrophages and inducing changes in M2 polarization. The above results are expected to provide reliable basic research evidence for the clinical application of FZHY against liver cirrhosis, and offer a potential solution for liver cirrhosis, which currently has no first-line medication recommended by clinical guidelines. C1 [Ge, Feilin] Zhengzhou Univ, Affiliated Hosp 1, Dept Chinese Med, State Key Lab Antiviral Drugs, Zhengzhou 450052, Peoples R China. [Ge, Feilin; Wang, Xuemei; Li, Zhe; Su, Guanyue; Li, Lili; Yu, Jia; Miao, Wenlong; Ma, Yarong; Liang, Hongxia; Ren, Zhigang] Zhengzhou Univ, Affiliated Hosp 1, Dept Infect Dis, State Key Lab Antiviral Drugs, Zhengzhou 450052, Peoples R China. C3 Zhengzhou University; Zhengzhou University RP Liang, HX; Ren, ZG (corresponding author), Zhengzhou Univ, Affiliated Hosp 1, Dept Infect Dis, 1 Jianshe East Rd, Zhengzhou 450052, Peoples R China. EM hxliang@zzu.edu.cn; fccrenzg@zzu.edu.cn RI ; Ma, Yarong/ABC-9319-2021; ren, zhigang/AAO-8576-2020 OI , xuemeiwang/0000-0003-4191-4450; ren, zhigang/0000-0003-0798-3444 FU National Natural Science Foundation of China [82404975, 82470654]; Postdoctoral Science Foundation of China [2024M763015]; National Funded Postdoctoral Researcher Program of China [GZC20232406]; Henan Province Traditional Chinese Medicine Science Research Project [2023ZY3040]; Henan Province Medical Science and Technology Research Plan Joint Construction Project [LHGJ20230233, LHGJ20240263]; Natural Science Foundation Key Project Henan Province [232300421124] FX This work was financially supported by the National Natural Science Foundation of China (grant numbers 82404975 and 82470654) , the Postdoctoral Science Foundation of China (2024M763015) , the National Funded Postdoctoral Researcher Program of China (No. GZC20232406) , the Henan Province Traditional Chinese Medicine Science Research Project (No. 2023ZY3040) , the Henan Province Medical Science and Technology Research Plan Joint Construction Project (LHGJ20230233 and LHGJ20240263) , and the Natural Science Foundation Key Project Henan Province, No. 232300421124. 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People's Health, V37, P126, DOI [10.3969/j.issn.1672-0369.2025.01.039, DOI 10.3969/J.ISSN.1672-0369.2025.01.039] Lyu Wenliang, 2023, Journal of Clinical Hepatology, V39, P2543, DOI 10.3969/j.issn.1001-5256.2023.11.005 Schulz MS, 2025, LIVER INT, V45, DOI 10.1111/liv.15861 Sharma S., 2025, Chronic Liver Disease Su GY, 2023, BONE RES, V11, DOI 10.1038/s41413-023-00290-9 Taddeo JR, 2024, GUT MICROBES, V16, DOI 10.1080/19490976.2024.2419567 Yang Y, 2024, INT IMMUNOPHARMACOL, V143, DOI 10.1016/j.intimp.2024.113304 Yang Y, 2024, J INFLAMM RES, V17, P6547, DOI 10.2147/JIR.S477202 Yoshiji H, 2021, J GASTROENTEROL, V56, P593, DOI 10.1007/s00535-021-01788-x NR 19 TC 0 Z9 0 U1 4 U2 4 PU ELSEVIER GMBH PI MUNICH PA HACKERBRUCKE 6, 80335 MUNICH, GERMANY SN 0944-7113 EI 1618-095X J9 PHYTOMEDICINE JI Phytomedicine PD JAN PY 2026 VL 150 AR 157586 DI 10.1016/j.phymed.2025.157586 PG 18 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA W5112 UT WOS:001639676400001 PM 41380414 DA 2026-03-26 ER PT J AU Ding, RT Miao, QF Ma, XD Zhou, L Liu, JR Cui, JR Ding, SS Song, ZW Mou, FF Wang, CC Ma, YM Wang, Q Su, SW Chen, XY AF Ding, Ruoting Miao, Qingfeng Ma, Xindi Zhou, Lin Liu, Jiarui Cui, Junru Ding, Shanshan Song, Ziwei Mou, Feifei Wang, Chuchu Ma, Yumei Wang, Qiao Su, Suwen Chen, Xueyan TI M1 macrophage activation via TLR4/NF-κB/mincle is essential for triptolide-induced hepatotoxicity SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Triptolide; Hepatotoxicity; Macrophage polarization; TLR4; Mincle ID TRIPTERYGIUM-WILFORDII; MINCLE; RECEPTOR; PHARMACOLOGY; MECHANISM; DISEASE AB Ethnopharmacology relevance: Triptolide (TP), extracted from the traditional Chinese herb Tripterygium wilfordii (T. wilfordii) Hook f., is a major bioactive ingredient with potent antitumor, immunosuppressive biological activities. However, its narrow therapeutic window and high toxicity greatly limit its clinical use. Therefore, uncovering the molecular mechanisms responsible for hepatotoxicity is critical for safe clinical application. Aim of the study: This research was designed to investigate the role of macrophage M1 polarization in TP-induced hepatotoxicity and to explore the mechanisms. Materials and method: Mincle expression was examined in TP-induced mouse model of liver injury, the activation of TLR4/NF-kappa B/Mincle pathway and macrophage polarization were examined using Western Blot, q-PCR, ELISA, immunohistochemistry and molecular docking in a mouse model of knockout Mincle and a model of macrophage inflammation. In addition, AML12 cells were stimulated with RAW264.7 cell supernatant after TP stimulation to observe the changes of the cell numbers and damage. Results: Numerous inflammatory factors released from M1 polarization of macrophages in TP-induced liver injury, the activation of TLR4/NF-kappa B/Mincle pathway played a key role in M1 polarization of macrophages. Knockout of Mincle in overall experiments reversed TP-induced liver injury. The results of in vitro experiments showed that substances released from TP-stimulated polarization of RAW264.7 cells had a killing effect on hepatic parenchymal cells, as evidenced by increased SAP130 release and cellular autophagy impairment, and that inhibitors of TLR4 effectively reduced Mincle expression and cellular M1 polarization in RAW264.7 cells. Conclusions: These results demonstrate that M1 macrophage activation, mediated by the TLR4/NF-kappa B/Mincle pathway, is essential for TP-induced hepatotoxicity, and Mincle was a promising therapeutic target for mitigating TP's hepatotoxicity. C1 [Ding, Ruoting; Miao, Qingfeng; Zhou, Lin; Liu, Jiarui; Cui, Junru; Ding, Shanshan; Song, Ziwei; Wang, Chuchu; Su, Suwen; Chen, Xueyan] Hebei Med Univ, Dept Pharmacol, Key Lab Pharmacol & Toxicol New Drugs, Key Lab Neural & Vasc Biol,Minist Educ, Shijiazhuang, Peoples R China. [Ding, Ruoting] Third Hosp Shijiazhuang, Dept Pharm, Shijiazhuang, Hebei, Peoples R China. [Ma, Xindi] Hebei Med Univ, Hosp 1, Dept Gastrointestinal Dis Diag, Shijiazhuang 050000, Peoples R China. [Ma, Xindi] Hebei Med Univ, Hosp 1, Treatment Ctr, Shijiazhuang 050000, Peoples R China. [Mou, Feifei] Shijiazhuang Med Coll, Nursing Dept, Shijiazhuang, Hebei, Peoples R China. [Ma, Yumei] Hebei Prov Hosp Chinese Med, Res Ctr, Shijiazhuang, Peoples R China. [Wang, Qiao] Hebei Med Univ, Sch Pharmaceut Sci, Shijiazhuang, Peoples R China. [Liu, Jiarui] Hebei Med Univ, Undergraduate Coll Basic Med, Shijiazhuang 050017, Peoples R China. C3 Hebei Medical University; Hebei Medical University; Hebei Medical University; Hebei University of Chinese Medicine; Hebei Medical University; Hebei Medical University RP Su, SW; Chen, XY (corresponding author), Hebei Med Univ, Dept Pharmacol, Key Lab Pharmacol & Toxicol New Drugs, Key Lab Neural & Vasc Biol,Minist Educ, Shijiazhuang, Peoples R China. EM suswmk@hebmu.edu.cn; 17800677@hebmu.edu.cn RI Liu, Jiarui/JEP-7826-2023; Ziwei, Song/HKE-4120-2023 FU Key Project of Hebei Province Precision Medicine Innovation and Development Joint Fund [H2025206402]; Hengrui Hebei Innovative Development Medical Cooperation Program [HR202502070]; Natural Science Foundation of China (NSFC) [81773828]; Natural Science Foundation of Hebei Province [H2022206295, H2018206297, H2021206300]; Key Projects Planned by Hebei Administration of Traditional Chinese Medicine [Z2022013] FX This work was supported by Key Project of Hebei Province Precision Medicine Innovation and Development Joint Fund (H2025206402) , Hengrui Hebei Innovative Development Medical Cooperation Program (HR202502070) , the Natural Science Foundation of China (NSFC, No. 81773828) , the Natural Science Foundation of Hebei Province (H2022206295, H2018206297, H2021206300) , and the Key Projects Planned by Hebei Administration of Traditional Chinese Medicine (Z2022013) . 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PD MAR 25 PY 2026 VL 359 AR 121127 DI 10.1016/j.jep.2025.121127 EA DEC 2025 PG 15 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA AW5CR UT WOS:001658428200001 PM 41475624 DA 2026-03-26 ER PT J AU Chen, Y Zhu, QY Yin, AK Wang, W Wang, J AF Chen, Yi Zhu, Qiuyu Yin, Ankang Wang, Wei Wang, Juan TI Triptolide-mediated immunomodulation of macrophages: from pathophysiology to therapy SO ANNALS OF MEDICINE LA English DT Review DE Triptolide; macrophage; immunomodulation; molecular target ID WILFORDII HOOK-F; OXIDE-RELEASING DERIVATIVES; PARTICLE-INDUCED OSTEOLYSIS; COLONY-STIMULATING FACTOR; ANTI-NEOVASCULAR THERAPY; REGULATORY T-CELLS; RHEUMATOID-ARTHRITIS; (5R)-5-HYDROXYTRIPTOLIDE LLDT-8; BIOLOGICAL EVALUATION; IMMUNE-RESPONSES AB BackgroundTriptolide (TP), a potent bioactive compound from the Chinese herb Tripterygium wilfordii, demonstrates strong anti-inflammatory and immunosuppressive effects. Evidence indicates that TP modulates macrophage polarization and regulates inflammatory responses through multiple signaling pathways, exerting significant immunomodulatory effects in various diseases.ObjectiveThis review summarizes the immunomodulatory mechanisms of TP on macrophage function, with a focus on its therapeutic potential in diverse diseases. We also explore strategies to mitigate TP's toxicity, including formulation enhancements, targeted delivery, ligand conjugation, and structural modifications. Finally, we highlight the therapeutic utility and clinical progress of TP derivatives, offering insights into their broad clinical applications.ResultsTP modulates macrophage migration, polarization, phagocytosis, and the production of cytokines and chemokines, thereby alleviating various macrophage-centric diseases. Strategies to reduce TP's toxicity not only mitigate systemic adverse effects but also enhance therapeutic efficacy through macrophage-targeted delivery. The clinical progress of TP derivatives demonstrates their broad therapeutic potential.ConclusionTP's macrophage-targeted immunomodulation shows promising therapeutic potential for macrophage-centric diseases. However, its limited clinical use due to poor water solubility and significant toxicity highlights the need for further research to develop effective toxicity-reduction strategies. C1 [Chen, Yi; Zhu, Qiuyu] Zhejiang Chinese Med Univ, Sch Med Technol & Informat Engn, Hangzhou, Zhejiang, Peoples R China. [Yin, Ankang] Zhejiang Prov Blood Ctr, Inst Transfus Med, Hangzhou, Zhejiang, Peoples R China. [Wang, Wei; Wang, Juan] Zhejiang Chinese Med Univ, Tongde Hosp, Tongde Hosp Zhejiang Prov, Dept Clin Lab, Hangzhou, Zhejiang, Peoples R China. C3 Zhejiang Chinese Medical University; Tongde Hospital of Zhejiang Province; Zhejiang Chinese Medical University RP Wang, W; Wang, J (corresponding author), Zhejiang Chinese Med Univ, Tongde Hosp, Tongde Hosp Zhejiang Prov, Dept Clin Lab, Hangzhou, Zhejiang, Peoples R China. EM wangweihz8@163.com; wangjuanzju@163.com OI Chen, Yi/0009-0009-0714-9274 FU National Natural Science Foundation of China [82004007]; Zhejiang Provincial Science and Technology Program of Traditional Chinese Medicine [2025ZL234]; Zhejiang Provincial Medical and Health Science and Technology Program [2024ZF043] FX This work was supported by the National Natural Science Foundation of China under Grant number 82004007; the Zhejiang Provincial Science and Technology Program of Traditional Chinese Medicine under Grant number 2025ZL234; and the Zhejiang Provincial Medical and Health Science and Technology Program under Grant number 2024ZF043. 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PD DEC 31 PY 2025 VL 57 IS 1 AR 2575302 DI 10.1080/07853890.2025.2575302 PG 24 WC Medicine, General & Internal WE Science Citation Index Expanded (SCI-EXPANDED) SC General & Internal Medicine GA 8ZY2N UT WOS:001601340100001 PM 41144250 OA Green Submitted, Green Accepted, gold DA 2026-03-26 ER PT J AU Zhou, L Huang, LY He, GF Li, HX Liu, MC Xu, JW AF Zhou, Lei Huang, Leyuan He, Guanfeng Li, Haixin Liu, Manchun Xu, Jingwen TI Xiao-Qing-Long-Tang alleviates allergic rhinitis by inhibiting M1 macrophage polarization and modulating the TRPV1 channel SO PHYTOMEDICINE LA English DT Article DE Allergic rhinitis; Xiao-Qing-Long-Tang; TRPV1; Inflammation; Macrophage ID OLFACTORY DYSFUNCTION; ANTAGONISTS; EXPRESSION; SB-705498 AB Background: Allergic rhinitis (AR) is a common IgE-mediated inflammatory disease of the nasal mucosa, involving immune-neural interactions such as mast cell activation, cytokine release, and transient receptor potential vanilloid 1 (TRPV1)-mediated neuronal sensitization. Xiao-Qing-Long-Tang (XQLT) is a classical traditional Chinese medicine used clinically for AR. However, its mechanisms, particularly in macrophage regulation and TRPV1 activity, remain not fully understood. Objective: This study aimed to evaluate the therapeutic effects of XQLT in an ovalbumin (OVA)-induced AR mouse model and to investigate its molecular mechanisms focusing on immune regulation, macrophage-mediated inflammation, and TRPV1 channel activity. Methods: The chemical composition of XQLT was analyzed by UPLC-Q Exactive Orbitrap-HRMS system. The therapeutic effectiveness of XQLT was assessed in an OVA-induced AR mouse model. Clinical symptoms, serum biomarkers (OVA-sIgE, interleukin-4 (IL-4), histamine), and histopathological changes were assessed. Transcriptomic analysis of nasal mucosa was performed to explore molecular pathways. The anti-inflammatory effects of XQLT were evaluated in LPS-stimulated RAW264.7 and bone marrow-derived macrophages by measuring NO, cytokine expression, and NF-kappa B activation. TRPV1 involvement was examined using immunohistochemistry in AR mice model, calcium imaging in HEK293 cells overexpressing TRPV1, as well as molecular docking. Results: XQLT treatment significantly reduced nasal rubbing and sneezing frequencies in AR mice, decreased serum OVA-sIgE, IL-4, and histamine levels, and ameliorated nasal and lung histopathological remodeling without observable toxicity. Transcriptomic profiling revealed that XQLT modulated DEGs associated with immune response, inflammatory signaling, olfactory transduction, and sensory perception of pain. In macrophages, XQLT suppressed LPS-induced NO production, downregulated IL-6, IL-1(1, CCL2, iNOS, and COX-2 expression, and inhibited NF-kappa B nuclear translocation. Importantly, XQLT reduced TRPV1 expression in AR nasal mucosa and inhibited TRPV1-mediated calcium influx in HEK293 TRPV1-overexpressing cells. Zingiberis Rhizoma (Ganjiang) was identified as a key herb contributing to TRPV1 inhibition in XQLT, supported by molecular docking analysis. C1 [Zhou, Lei; Huang, Leyuan; He, Guanfeng; Li, Haixin; Liu, Manchun; Xu, Jingwen] Guangdong Pharmaceut Univ, Sch Pharm, Guangzhou 510006, Peoples R China. C3 Guangdong Pharmaceutical University RP Zhou, L; Xu, JW (corresponding author), Guangdong Pharmaceut Univ, Sch Pharm, Guangzhou 510006, Peoples R China. EM leizhou@gdpu.edu.cn; Jingwen_xu@gdpu.edu.cn FU National Natural Science Foundation of China [82204968] FX This work was financially supported by the National Natural Science Foundation of China (No. 82204968) . 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The alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) is a key regulator of the cholinergic anti-inflammatory pathway. Despite its therapeutic potential, how alpha 7nAChR coordinates macrophage metabolic reprogramming to resolve synovitis remains underexplored. This study aims to elucidate the therapeutic effects of Notopterol, a bioactive constituent derived from the rhizome of Notopterygium incisum Ting ex H.T. Chang, a traditional Chinese medicine known for its potent anti-inflammatory and antioxidant properties, in treating inflammatory arthritis and the molecular mechanisms by which alpha 7nAChR modulates macrophage reprogramming in synovitis. An in vivo mouse model of IA was established through complete Freund's adjuvant (CFA)-induced, Notopterol administration significantly attenuated synovitis progression, reduced joint swelling, and enhanced mechanical pain thresholds as well as suppressed the production of pro-inflammatory cytokines (IL-1 beta, TNF-alpha, and IFN-gamma) while promoting antiinflammatory IL-4 secretion. Complementary in vitro models employing lipopolysaccharide (LPS)-stimulated macrophages demonstrated that Notopterol exerts anti-inflammatory effects, restores mitochondrial function while shifting energy metabolism towards oxidative phosphorylation, a transition mechanistically linked to M1/ M2 polarisation. Mechanistically, Notopterol promotes a shift from glycolysis to oxidative phosphorylation in macrophages, restoring mitochondrial function and enhancing their polarizing capacity through alpha 7nAChR activation, thus revealing this receptor's pivotal role in macrophage metabolic regulation. Furthermore, biophysical validation confirms the high-affinity binding of Notopterol to alpha 7nAChR, supporting its therapeutic potential in anti-inflammatory treatment. These findings highlight the innovative prospect of targeting macrophage metabolic pathways as a novel strategy for treating inflammatory arthritis. C1 [Chen, Xiaomei; Zhang, Cheng; Ye, Yonghua; Zhuang, Yixue; Huang, Meixia; Yu, Hongmin; Qin, Zitong; Chen, Ying; Hong, Zhiyuan; Tu, Hongyang; Wang, Yingzheng; Wang, Yinghao] Fujian Univ Tradit Chinese Med, Coll Pharm, Fuzhou 350122, Peoples R China. [Chen, Xiaomei] Fudan Univ, Inst Brain Sci, Shanghai 200032, Peoples R China. [Wang, Zhifu] Fujian Univ Tradit Chinese Med, Coll Acupuncture & Tuina, Fuzhou 350122, Peoples R China. [Wang, Zhifu] Fujian Univ Tradit Chinese Med, Affiliated Peoples Hosp, Fuzhou 350122, Peoples R China. C3 Fujian University of Traditional Chinese Medicine; Fudan University; Fujian University of Traditional Chinese Medicine; Fujian University of Traditional Chinese Medicine RP Wang, YZ; Wang, YH (corresponding author), Fujian Univ Tradit Chinese Med, Coll Pharm, Fuzhou 350122, Peoples R China.; Wang, ZF (corresponding author), Fujian Univ Tradit Chinese Med, Coll Acupuncture & Tuina, Fuzhou 350122, Peoples R China.; Wang, ZF (corresponding author), Fujian Univ Tradit Chinese Med, Affiliated Peoples Hosp, Fuzhou 350122, Peoples R China. EM wangyingzheng@live.com; 2007015@fjtcm.edu.cn; wyhtcm@163.com RI Qin, Zitong/OLQ-9013-2025; HUANG, Meixia/HKM-6526-2023 FU Joint Research Project of Basic and Clinical Studies of Fujian University of Traditional Chinese Medicine [X2023030]; Natural Science Foundation of China [82,505,046] FX This work was supported by the Joint Research Project of Basic and Clinical Studies of Fujian University of Traditional Chinese Medicine [X2023030] and Natural Science Foundation of China [82,505,046] . 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And it has been demonstrated to alleviate colonic mucosal inflammation in ulcerative colitis. However, the mechanism through which its main active ingredient, baicalin, alleviates ulcerative colitis remains unclear. Aim of the study: This study investigated whether baicalin regulates macrophages to ameliorate ulcerative colitis through the JAK1/STAT1/SOCS1 pathway. Materials and methods: LPS-induced RAW264.7 cells were used to investigate the anti-inflammatory and regulatory effects of baicalin on macrophage polarization. The NO content was assessed by a Griess assay, and label-free optical diffraction tomography for live-cell imaging and confocal imaging were conducted to observe macrophage polarization and analyze the expression of CD86 and CD206. The protective effect of baicalin on DSS-induced colitis mice was evaluated through the Disease Activity Index (DAI) system, endoscopy, enzyme-linked immunosorbent assay (ELISA), hematoxylin and eosin (HE) staining, Alcian Blue periodic acid Schiff (AB-PAS) staining, and immunofluorescence. Macrophages in the lamina propria of the colon were analyzed by tiling light sheet microscopy imaging and flow cytometry. Western blotting (WB) was used to evaluate the expression of JAK1/STAT1/SOCS1 pathway members, and the expression of the downstream transcription factors were quantified through qPCR. Key results: Baicalin markedly inhibited NO levels induced by LPS and delayed the timing and quantity of macrophage polarization toward the M1 phenotype. Furthermore, baicalin ameliorated the symptoms of colitis in mice, such as diarrhea, hematochezia, weight loss, colon shortening, decreased spleen weight, pathological changes, intestinal mucosal barrier dysfunction, and decreased DAI and inflammatory factor levels. Moreover, baicalin promoted macrophage polarization toward the M2 phenotype and inhibited the polarization of M1 macrophages in the intestinal lamina propria. Mechanistically, baicalin inhibited the phosphorylation of JAK1 and STAT1 and restored the negative feedback inhibition of JAK1/STAT1 by upregulating SOCS1. In addition, baicalin reduced the mRNA levels of downstream genes. Conclusions and implications: Baicalin can alleviate intestinal inflammation, ameliorate intestinal barrier damage, and regulate macrophage polarization by inhibiting M1 macrophage polarization in an ulcerative colitis model. This protective effect was achieved through the JAK1/STAT1/SOCS1 pathway. C1 [Liu, Si-yu; Wang, Chang-qing; Luo, Tong-tong; Cui, Gui-juan; Zhang, Zi-jian; Liu, Wen-xiu; Sun, Chen; Peng, Cheng] Chengdu Univ Tradit Chinese Med, Dept Pharmacol, State Key Lab Southwestern Chinese Med Resources, Chengdu 611137, Peoples R China. [Zhang, Yuan; Zou, Xing-ju] Chengdu Univ Tradit Chinese Med, Dept Basic Med, State Key Lab Southwestern Chinese Med Resources, Chengdu 611137, Peoples R China. C3 Chengdu University of Traditional Chinese Medicine; Chengdu University of Traditional Chinese Medicine RP Sun, C; Peng, C (corresponding author), 1166 Liutai Ave, Chengdu 611137, Sichuan, Peoples R China. EM 1317295721@qq.com; 361356120@qq.com; 3290973365@qq.com; 2245732601@qq.com; 1529143705@qq.com; 491048436@qq.com; zzj1393752513@163.com; liuwenxiu@stu.cdutcm.edu.cn; sunchencd@126.com; pengchengchengdu@126.com OI Liu, Siyu/0009-0003-4285-8996 FU Sichuan Traditional Chinese Medicine Science and Technology Industry Innovation Team: Multi-dimensional evaluation and Product Development innovation team of characteristic Traditional Chinese medicine resources [D-202209]; [2022C001] FX This work was supported by grants from The Key project of National Natural Science Foundation of China (U24A20790) , National Interdisciplinary Innovation Team of Traditional Chinese Medicine (ZYYCXTD-D-202209) , and Sichuan Traditional Chinese Medicine Science and Technology Industry Innovation Team: Multi-dimensional evaluation and Product Development innovation team of characteristic Traditional Chinese medicine resources (2022C001) . 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PD MAR 25 PY 2026 VL 359 AR 121057 DI 10.1016/j.jep.2025.121057 EA DEC 2025 PG 14 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA AK7AW UT WOS:001650413800003 PM 41423154 DA 2026-03-26 ER PT J AU Wong, PI Li, RY Li, D Fang, B Lan, Y Qi, YH Zheng, JQ Mo, H AF Wong, Puiian Li, Ruoyu Li, Ding Fang, Bin Lan, Yun Qi, Yuhang Zheng, Jiaqian Mo, Hui TI Machine learning-assisted network pharmacology reveals that the Chaihu-Longgu-Muli decoction modulates the inflammatory microenvironment to treat perimenopausal syndrome SO FRONTIERS IN MOLECULAR BIOSCIENCES LA English DT Article DE perimenopausal syndrome; Chaihu-Longgu-Muli decoction; network pharmacology; machine learning; molecular docking; molecular dynamics simulation; inflammation aging ID DEPRESSION; CANCER; MECHANISMS; RISK AB Background: Chaihu-Longgu-Muli decoction (CLMD) is a traditional Chinese medicine formula that shows promise in alleviating symptoms related to premenstrual syndrome (PMS). However, the underlying mechanism remains unclear. This study uses a machine learning-assisted framework integrated with network pharmacology and experimental validation to elucidate the key targets and signaling pathways involved in the therapeutic effects of CLMD on PMS. Methods: We developed an integrative research framework that incorporates network pharmacology, machine learning, molecular dynamics, and in vitro validation. First, we built an overlap network by intersecting disease-related gene sets with data from the TCMSP, BATMAN-TCM, and other relevant databases. We subsequently performed GO and KEGG enrichment analyses. Second, we generated a protein-protein interaction (PPI) network and screened key targets via machine learning algorithms. Third, we evaluated key active components and targets for ligand-receptor binding stability via molecular docking and 200 ns MD simulations. Finally, we validated the proposed mechanism by assessing the ability of CLMD to modulate the inflammatory microenvironment using Raw264.7 cells as the experimental model. Results: By constructing an intersecting network of CLMD-active ingredient-disease targets, we identified 204 representative active components and nearly 300 potential targets. Intersecting these genes with PMS-related genes yielded 46 key targets. The PPI network built in Cytoscape/STRING, together with multiple machine learning algorithms (LASSO, SVM-RFE, and random forest), was used to select key targets, including IL6, TNF, and IL1B. At the molecular level, the key active components (quercetin, kaempferol, and wogonin) showed strong docking affinities to these targets (binding energies <-5.0 kcal/mol) and exhibited stable MD conformations. CLMD intervention significantly downregulated IL6, TNF, and IL1B, reduced reactive oxygen species (ROS) accumulation, and promoted macrophage polarization from the proinflammatory M1 phenotype to the reparative M2 phenotype. Consequently, the experimental findings corroborate the network pharmacology predictions. Conclusion: CLMD exerts its therapeutic effects through multicomponent-multitarget-multipathway synergy that modulates the inflammatory microenvironment, which provides mechanistic insight into relieving the multidimensional symptoms of PMS. C1 [Wong, Puiian; Mo, Hui] Macau Univ Sci & Technol, Fac Chinese Med, Taipa, Macau, Peoples R China. [Li, Ruoyu; Li, Ding; Fang, Bin; Lan, Yun; Zheng, Jiaqian] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China. [Qi, Yuhang] Guangzhou Univ Chinese Med, Clin Med Coll 1, Guangzhou, Guangdong, Peoples R China. C3 Macau University of Science & Technology; Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine RP Mo, H (corresponding author), Macau Univ Sci & Technol, Fac Chinese Med, Taipa, Macau, Peoples R China.; Zheng, JQ (corresponding author), Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China. EM provin0925@outlook.com; mohui@ssm.gov.mo RI Li, Ruoyu/MVY-4460-2025; Qi, Yuhang/JCF-2163-2023; Zheng, Jiaqian/AAA-3090-2020 FU Guangdong Province Department of Education FX The authors declare that financial support was received for the research and/or publication of this article. Financial support was received from the Guangdong Province Department of Education. 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Mol. Biosci. PD DEC 18 PY 2025 VL 12 AR 1719463 DI 10.3389/fmolb.2025.1719463 PG 20 WC Biochemistry & Molecular Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology GA AM9NU UT WOS:001651934600001 PM 41488049 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Chen, K Xu, BW Xue, Q Ma, X Tong, JB Zhu, J Yang, QJ Li, ZG AF Chen, Ke Xu, Bowen Xue, Qian Ma, Xiao Tong, Jiabing Zhu, Jie Yang, Qinjun Li, Zegeng TI Shenqi Tiaoshen formula attenuates COPD through METTL16-dependent m6A regulation of MALT1-NF-κB SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE COPD; SQTSF; METTL16; MALT1; Traditional Chinese medicine; Epitranscriptomic modulation ID PULMONARY; TRANSLATION AB Ethnopharmacological relevance: Chronic obstructive pulmonary disease (COPD) is a leading cause of global mortality. Shenqi Tiaoshen Formula (SQTSF), a classical prescription refined from Xin'an medicine, has been clinically used for over 30 years and demonstrated efficacy in improving lung function and reducing exacerbations in multicenter trials. However, its molecular basis-particularly epitranscriptomic regulation-remains largely unknown. Aim of the study: This study aimed to elucidate the molecular basis of SQTSF's anti-inflammatory and immunomodulatory effects in COPD, with particular focus on epitranscriptomic regulation of macrophage polarization. Materials and methods: UPLC-MS/MS was used to characterize SQTSF constituents. COPD was modeled by cigarette smoke/LPS exposure in rats and by cigarette smoke extract stimulation in THP-1-derived macrophages. Integrated MeRIP-seq and RNA-seq analyses were performed to identify m6A-regulated targets, followed by validation using RIP-qPCR (METTL16-RIP and IGF2BP2-RIP), functional assays, and MALT1 rescue experiments. Results: A total of 131 compounds were identified in SQTSF. SQTSF dose-dependently improved lung function, reduced airway injury, and restored the M1/M2 balance in COPD. MeRIP-seq identified MALT1 as the most hypermethylated NF-kappa B-related transcript. Screening of m6A regulators showed that METTL16 and its reader IGF2BP2 were the only factors strongly altered by CSE and SQTSF. SQTSF reduced METTL16 expression, decreased MALT1 m6A modification, shortened its mRNA half-life, and suppressed NF-kappa B activation. RIP-qPCR confirmed direct binding of METTL16 and IGF2BP2 to MALT1 transcripts, supporting IGF2BP2-mediated recognition as the mechanism linking m6A modification to mRNA stability. In vitro, SQTSF restored macrophage immune homeostasis via the METTL16-m6A-MALT1 axis, while MALT1 overexpression reversed these effects. Conclusion: SQTSF alleviates COPD-associated inflammation by inhibiting METTL16-mediated m6A modification of MALT1 and subsequent NF-kappa B activation. These findings bridge traditional Chinese medicine principles with modern epitranscriptomic insights and provide quantitative and mechanistic evidence supporting the ethnopharmacological rationale of SQTSF in COPD management. C1 [Chen, Ke; Xu, Bowen; Li, Zegeng] Anhui Univ Chinese Med, Affiliated Hosp 1, Hefei 230031, Peoples R China. [Xue, Qian; Tong, Jiabing; Zhu, Jie; Yang, Qinjun; Li, Zegeng] Anhui Univ Chinese Med, Hefei 230012, Peoples R China. [Ma, Xiao] Wuhu Hosp Tradit Chinese Med, Dept Anesthesiol, Wuhu 241100, Peoples R China. [Tong, Jiabing; Li, Zegeng] Anhui Prov Chinese Med Hosp, Hefei 230031, Peoples R China. [Tong, Jiabing; Zhu, Jie; Yang, Qinjun; Li, Zegeng] Anhui Prov Key Lab Translat Med Prevent & Treatmen, Hefei 2300316, Peoples R China. C3 Anhui University of Chinese Medicine; Anhui University of Chinese Medicine RP Li, ZG (corresponding author), Anhui Univ Chinese Med, Affiliated Hosp 1, Hefei 230031, Peoples R China.; Yang, QJ; Li, ZG (corresponding author), Anhui Univ Chinese Med, Hefei 230012, Peoples R China. EM yangqjahtcm@163.com; li6609@126.com RI Xu, Bowen/ABC-6303-2021; Ma, Xiao/D-9568-2015 OI chen, ke/0000-0003-2196-2025; FU National Natural Science Foundation of China [82374399]; The 2024 Higher Education Research Program [2024AH051047] FX This study was partially supported by the National Natural Science Foundation of China (Grant No. 82374399) and the 2024 Higher Education Research Program (Project No. 2024AH051047). All funding sources were government agencies. The research team has no affiliation with the funding bodies. The funders had no role in the design or implementation of the study; the collection, management, analysis, or interpretation of the data; or the writing, review, or approval of the manuscript. No pharmaceutical companies were involved in this study. The experimental compounds were provided by our institution, a state owned public hospital. All other reagents were purchased from vendors that meet the institutional procurement standards; these vendors supplied materials only and were not involved in any aspect of the research, with no conflicts of interest. CR Agusti A, 2018, EUR RESPIR J, V52, DOI 10.1183/13993003.01219-2018 Barnes PJ, 2013, J ALLERGY CLIN IMMUN, V131, P636, DOI 10.1016/j.jaci.2012.12.1564 Cazzola M, 2023, INT J CHRONIC OBSTR, V18, P1333, DOI 10.2147/COPD.S419056 Chen FX, 2025, EUR J PHARMACOL, V988, DOI 10.1016/j.ejphar.2024.177214 Chen YJ, 2023, J ALLERGY CLIN IMMUN, V152, P1683, DOI 10.1016/j.jaci.2023.08.022 Dandan Y., 2023, China Pharmacy, V34, P666, DOI DOI 10.6039/j.issn.1001-0405.2023.06.05 Doxtader KA, 2018, MOL CELL, V71, P1001, DOI 10.1016/j.molcel.2018.07.025 Hailfinger S, 2011, P NATL ACAD SCI USA, V108, P14596, DOI 10.1073/pnas.1105020108 Han YQ, 2024, EMBO J, V43, P1990, DOI 10.1038/s44318-024-00082-9 Hu TT, 2023, FRONT IMMUNOL, V14, DOI 10.3389/fimmu.2023.1137195 Kim B, 2024, J GINSENG RES, V48, P384, DOI 10.1016/j.jgr.2024.01.006 Lan CC, 2025, INT J MOL SCI, V26, DOI 10.3390/ijms26073365 Lortet-Tieulent J, 2019, EUR RESPIR J, V54, DOI 10.1183/13993003.01791-2019 Mermoud JE, 2022, GENES-BASEL, V13, DOI 10.3390/genes13122312 Mkorombindo T, 2020, CLIN CHEST MED, V41, P475, DOI 10.1016/j.ccm.2020.05.006 Moud BN, 2024, FRONT IMMUNOL, V15, DOI 10.3389/fimmu.2024.1412347 O'Neill TJ, 2023, FRONT IMMUNOL, V14, DOI 10.3389/fimmu.2023.1111398 Oeckinghaus A, 2007, EMBO J, V26, P4634, DOI 10.1038/sj.emboj.7601897 Oerum S, 2021, NUCLEIC ACIDS RES, V49, P7239, DOI 10.1093/nar/gkab378 Pendleton KE, 2017, CELL, V169, P824, DOI 10.1016/j.cell.2017.05.003 Pinello N, 2024, CELL MOL LIFE SCI, V81, DOI 10.1007/s00018-024-05261-9 Qinjun Yang, 2024, J Tradit Chin Med, V44, P770, DOI 10.19852/j.cnki.jtcm.20240610.002 Reagan-Shaw S, 2008, FASEB J, V22, P659, DOI 10.1096/fj.07-9574LSF Rong XW, 2024, J PHARMACEUT BIOMED, V241, DOI 10.1016/j.jpba.2024.115981 Srivastava D, 2025, CYTOKINE, V194, DOI 10.1016/j.cyto.2025.157011 Su R, 2022, NAT CELL BIOL, V24, P205, DOI 10.1038/s41556-021-00835-2 Subramanian, 2015, J CLIN DIAGN RES, V9, pOC10, DOI 10.7860/JCDR/2015/10803.5527 Teng Y, 2023, J INNATE IMMUN, V15, P804, DOI 10.1159/000534162 Wang CY, 2017, CELL PHYSIOL BIOCHEM, V43, P743, DOI 10.1159/000481558 Wang CY, 2015, J TRADIT CHIN MED, V35, P54, DOI 10.1016/S0254-6272(15)30009-1 Wang HL, 2025, FRONT IMMUNOL, V16, DOI 10.3389/fimmu.2025.1521196 [叶红 Ye Hong], 2022, [中华中医药杂志, China Journal of Traditional Chinese Medicine and Pharmacy], V37, P7094 Zhang H, 2023, OPEN MED-WARSAW, V18, DOI 10.1515/med-2023-0856 Zhang J, 2015, DRUG METAB DISPOS, V43, P1181, DOI 10.1124/dmd.115.063800 Zhang L., 2025, Nan Fang Yi Ke Da Xue Xue Bao, V45, P969, DOI [10.12122/j.issn.1673-4254.2025.05.09., DOI 10.12122/J.ISSN.1673-4254.2025.05.09] NR 35 TC 0 Z9 0 U1 15 U2 15 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-8741 EI 1872-7573 J9 J ETHNOPHARMACOL JI J. Ethnopharmacol. PD MAR 1 PY 2026 VL 358 AR 121036 DI 10.1016/j.jep.2025.121036 EA DEC 2025 PG 16 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA AH0WT UT WOS:001647969500001 PM 41389888 DA 2026-03-26 ER PT J AU Yi, JM Na, SW Jeong, MK AF Yi, Jin-Mu Na, Se Won Jeong, Mi-Kyung TI Bojungikki-tang enhances M1-like macrophage activation and promotes antitumor responses through IFN-γ co-stimulation SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Bojungikki-tang; M1-like macrophages; IFN-gamma Co-Stimulation; TLR4 signaling; Tumor-associated macrophages; Macrophage polarization ID TUMOR-ASSOCIATED MACROPHAGES; INTERFERON-GAMMA; POLARIZATION; EXPRESSION; CANCER; PLASTICITY; MECHANISMS AB Ethnopharmacological relevance: Bojungikki-tang (BJIKT), a traditional East-Asian multi-herbal prescription known for enhancing immune function, treating chronic fatigue, and improving general vitality, is often prescribed for conditions related to immune deficiency or cancer-related fatigue. However, its cellular mechanisms remain poorly defined. Aim of the study: To determine whether BJIKT promotes M1-like macrophage activation and exerts antitumor effects, particularly with interferon-gamma (IFN-gamma), and elucidate the underlying signaling mechanisms. Materials and methods: THP-1 monocytes were differentiated into M0 macrophages using PMA and treated with BJIKT alone or with IFN-gamma. Expression of M1/M2 markers and pro-inflammatory cytokines was assessed using RT-qPCR and ELISA. TLR4 signaling involvement was evaluated using the selective inhibitor TAK-242. Conditioned media (CM) from treated macrophages were applied to A549 lung cancer cells, followed by MTT, LDH, and Annexin V/7-AAD assays to assess antitumor activity. Individual herbs and BJIKT phytochemicals were also tested for cytokine-inducing potential. Results: BJIKT alone increased the secretion of pro-inflammatory cytokines (IL-6 and TNF-alpha) but did not induce full M1 polarization-co-treatment with IFN-gamma markedly upregulated M1 genes, including CD80 and TNF-alpha. TAK242 inhibited IFN-gamma/LPS-induced cytokine and suppressed IFN-gamma/BJIKT-induced effects, suggesting partial TLR4 dependence. CM from BJIKT/IFN-gamma-treated macrophages reduced A549 cell viability, increased cytotoxicity, and induced apoptosis. Notably, Ginseng Radix and Glycyrrhizae Radix et Rhizoma partially mimicked BJIKT, while major phytochemicals showed no comparable activity. Conclusions: BJIKT synergistically promotes M1-like macrophage activation through partial TLR4 dependence and elicits antitumor effects via macrophage-derived cytokines. These findings provide insight into how a traditional multi-herbal formula can influence macrophage activation and cytokine-mediated antitumor responses. C1 [Yi, Jin-Mu; Na, Se Won; Jeong, Mi-Kyung] Korea Inst Oriental Med, KM Convergence Res Div, Daejeon 34054, South Korea. C3 Korea Institute of Oriental Medicine (KIOM) RP Jeong, MK (corresponding author), Korea Inst Oriental Med, KM Convergence Res Div, Daejeon 34054, South Korea. EM oiny2000@kiom.re.kr FU Korea Institute of Oriental Medicine [KSN2026240] FX This research was supported by the Korea Institute of Oriental Medicine (KSN2026240) . 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Ethnopharmacol. PD MAR 1 PY 2026 VL 358 AR 121059 DI 10.1016/j.jep.2025.121059 EA DEC 2025 PG 14 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA AC9JA UT WOS:001645161400001 PM 41412233 DA 2026-03-26 ER PT J AU Daryabor, G Kheshtchin, N Hashemi, SZ Kahmini, FR Gholijani, N AF Daryabor, Gholamreza Kheshtchin, Nasim Hashemi, Seyede Zahra Kahmini, Fatemeh Rezaei Gholijani, Nasser TI Priming of rat bone marrow-derived mesenchymal stem cells with curcumin induces an anti-inflammatory M2 phenotype in J774A.1 macrophage cell line SO BMC COMPLEMENTARY MEDICINE AND THERAPIES LA English DT Article DE Curcumin; Cur-primed MSCs-CM, immunomodulation; J774.1.1 macrophage cell line; Mesenchymal stem cells ID POLARIZATION; PROLIFERATION; ENHANCE; MSCS AB Context In recent years, several strategies have been used to enhance mesenchymal stem cells' (MSCs) immunomodulatory and therapeutic potential. Curcumin (Cur), the main active component of turmeric from the Curcuma longa plant, might improve the effectiveness of MSCs. Materials and methods Lipopolysaccharide (LPS)-stimulated J774.1 macrophages were treated with either Cur (10, 20, and 40 mu M) or Rat bone marrow-derived MSCs-conditioned media (MSCs-CM) cultured in the presence or absence of Cur. Macrophage polarization was evaluated by qRT-PCR for M1/M2 markers, while ELISA and the Griess assay quantified TNF-alpha/TGF-beta and NO levels, respectively. Results Treatment with Cur-primed MSCs-CM potently induced an anti-inflammatory M2 phenotype in LPS-stimulated macrophages. It demonstrated superior efficacy over free Cur by significantly upregulating TGF-beta at 40 mu M and producing a broader, more consistent suppression of key M1 markers, including IL-1 beta, IL-12, and TNF-alpha. While 10 mu M Cur was the strongest inducer of IL-10 and Cur alone was more potent at suppressing IL-6 and nitric oxide production, the primed MSCs-CM provided a more balanced and robust immunomodulatory profile, effectively countering the pro-inflammatory effects of low-dose Cur. Conclusions In conclusion, priming MSCs with Cur generates a synergistic therapy that capitalizes on the strengths of both components. This strategy yields a potent, multifaceted anti-inflammatory agent capable of effectively reprogramming macrophages toward a therapeutic M2 phenotype, presenting a promising cell-free approach for treating inflammatory diseases. C1 [Daryabor, Gholamreza; Kahmini, Fatemeh Rezaei; Gholijani, Nasser] Shiraz Univ Med Sci, Autoimmune Dis Res Ctr, Sch Med, POB 71345-1583, Shiraz, Iran. [Kheshtchin, Nasim] Shiraz Univ Med Sci, Sch Med, Dept Immunol, Shiraz, Iran. [Hashemi, Seyede Zahra] Ahvaz Jondishapur Univ Med Sci, Dept Med Virol, Ahvaz, Iran. C3 Shiraz University of Medical Science; Shiraz University of Medical Science; Ahvaz Jundishapur University of Medical Sciences (AJUMS) RP Daryabor, G; Gholijani, N (corresponding author), Shiraz Univ Med Sci, Autoimmune Dis Res Ctr, Sch Med, POB 71345-1583, Shiraz, Iran. EM Daryabor_gh@sums.ac.ir; gholijani@yahoo.com RI Kheshtchin, Nasim/AAQ-5988-2020; Daryabor, Gholamreza/AAA-1502-2019; Kahmini, Fatemeh/F-3225-2018; Gholijani, Nasser/I-1110-2016 FU Shiraz University of Medical Sciences [23115 and 22487] FX This research was funded by the Shiraz University of Medical Science (Grant Numbers: 23115 and 22487). 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Med. Ther. PD DEC 11 PY 2025 VL 26 IS 1 AR 17 DI 10.1186/s12906-025-05207-z PG 9 WC Integrative & Complementary Medicine WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine GA CD3KZ UT WOS:001663077700002 PM 41382111 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Li, SQ Chen, TZ Shen, XJ Su, WY Li, XS AF Li, Shuoqi Chen, Tiezhu Shen, Xiongjie Su, Wanying Li, Xiaosheng TI Gentisic acid ameliorates lumbar disc herniation by regulating M1/M2 Polarization via the MAPK14/S100A9/Rac1/2 pathway SO CELL BIOLOGY AND TOXICOLOGY LA English DT Article DE Lumbar disc herniation; Gentisic acid; MAPK14; Rac1/2; M1/M2 polarization ID EXPRESSION AB Traditional Chinese medicine is gaining prominence in lumbar disc herniation (LDH) management, but the mechanisms of its active compounds and their molecular targets remain largely unclear. Herein, we aim to elucidate the therapeutic mechanism of Gentisic acid by investigating its role in regulating S100A9 in LDH. Clinical analysis reveals that S100A9 expression and inflammatory levels correlat positively with LDH severity. S100A9 is found to promote M1 macrophage polarization and impair dorsal root ganglion (DRG) neuronal activity. Mechanistically, Gentisic acid binds to MAPK14, downregulates S100A9 via MAPK14, and then suppresses M1 polarization, enhances neuronal autophagic flux, and improves neuronal viability through the S100A9/Rac1/2 pathway. In vivo experiments demonstrate that Gentisic acid ameliorates disc injury, improves neurological function, and alleviates pain in a rat LDH model, with efficacy comparable to celecoxib. These results suggest that Gentisic acid could alleviate LDH symptoms by modulating macrophage polarization and autophagy through the MAPK14/S100A9/Rac1/2 axis, offering a promising therapeutic strategy for LDH. C1 [Li, Shuoqi] Hunan Prov Peoples Hosp, Dept Sci Res, Changsha, Peoples R China. [Chen, Tiezhu; Su, Wanying] Hunan Prov Peoples Hosp, Dept Orthoped, Changsha, Peoples R China. [Shen, Xiongjie] Hunan Prov Peoples Hosp, Dept Spine Surg, Changsha, Peoples R China. [Li, Xiaosheng] Hunan Prov Peoples Hosp, Changsha, Peoples R China. RP Li, XS (corresponding author), Hunan Prov Peoples Hosp, Changsha, Peoples R China. EM lxsld2009@163.com FU Research and Development Program of Hunan Province of China [2022SK2024] FX The work was supported by [Research and Development Program of Hunan Province of China] (Grant number [2022SK2024]). 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Toxicol. PD DEC 11 PY 2025 VL 41 IS 1 AR 161 DI 10.1007/s10565-025-10117-4 PG 24 WC Cell Biology; Toxicology WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology; Toxicology GA R4005 UT WOS:001635554500001 PM 41372605 OA Green Submitted, hybrid DA 2026-03-26 ER PT J AU Liu, YL Liu, XK Zhu, XX Zhou, MM Chu, C Zhang, YH Li, W Song, WW Qin, LP Shi, FF Niu, LZ Kikete, S Zhang, Z Zhang, M Li, X AF Liu, Yonglin Liu, Xinkui Zhu, Xiaoxiao Zhou, Miaomiao Chu, Chu Zhang, Yunhong Li, Wei Song, Weiwei Qin, Liping Shi, Feifei Niu, Liangzhong Kikete, Siambi Zhang, Zhen Zhang, Min Li, Xia TI Bushen Guchong decoction facilitates M2 polarization through JAK2/STAT3 for URSA treatment SO PHYTOMEDICINE LA English DT Article DE Unexplained recurrent spontaneous abortion; Macrophages; Bushen Guchong decoction; JAK2/STAT3 signaling pathway ID REGULATORY T-CELLS; MACROPHAGE POLARIZATION; RECURRENT MISCARRIAGE AB Background: Unexplained recurrent spontaneous abortion (URSA) poses a significant threat to women's reproductive health. While macrophage polarization imbalance has been implicated in URSA pathogenesis, the therapeutic potential of traditional Chinese medicine (TCM) formulations targeting this process remains underexplored. Bushen Guchong Decoction (BSGCD) has been extensively utilized in the treatment of URSA; however, the bioactive constituents and the underlying mechanisms remain insufficiently characterized. Purpose: This study aims to conduct comprehensive investigation of molecular mechanisms underlying the therapeutic effects of BSGCD in the management of URSA to bridge TCM and reproductive immunology. Methods: RNA sequencing (RNA-seq) was conducted to investigate transcriptomic aberrations in decidua tissues of URSA. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was employed to analyze the natural ingredients as well as the bioactive compounds derived from both aqueous extract and blood samples of BSGCD. Subsequently, network pharmacology was applied to delineate the potential mechanism through which BSGCD exerts its therapeutic effects on URSA. Furthermore, a murine model of URSA was established to assess the impact of BSGCD on pregnancy outcomes in mice. Flow cytometry, qRT-PCR, Western blot, ELISA, molecular docking, CETSA and SPR were utilized to validate the therapeutic mechanisms of BSGCD. Results: RNA-seq analysis elucidated that the aberrant polarization of macrophage significantly contributed to the pathogenesis of URSA. A total of thirty-four bioactive compounds from BSGCD were identified as being absorbed in vivo. Network pharmacology analysis revealed that BSGCD may exert therapeutic effects on URSA by modulating macrophage polarization through targeted regulation of the JAK2/STAT3 signaling pathway. In addition, in vivo assays confirmed that BSGCD markedly reduced embryonic resorption in the murine model of URSA and upregulated the expression of M2 macrophage marker genes, the corresponding proteins, and the regulatory cytokines. Moreover, BSGCD was found to enhance the phosphorylation of STAT3 and JAK2 in the decidual cells of URSA mice. Our findings indicate that the principal bioactive constituents of BSGCD, including baicalin, salicylic acid, wogonin, oroxylin A, calycosin, glycyrrhizin, daidzein, and hyperin, may underlie its therapeutic effects. Conclusion: Our work represents a comprehensive demonstration that BSGCD functions as a novel TCM formula capable of restoring maternal-fetal tolerance through immuno-regulation of JAK2/STAT3-mediated macrophage polarization, thereby establishing a new paradigm for TCM modernization. C1 [Liu, Yonglin; Li, Xia] Shandong Univ Tradit Chinese Med, Coll Tradit Chinese Med, Jinan 250355, Peoples R China. [Liu, Yonglin; Liu, Xinkui; Zhu, Xiaoxiao; Zhou, Miaomiao; Chu, Chu; Zhang, Yunhong; Li, Wei; Qin, Liping; Shi, Feifei; Niu, Liangzhong; Zhang, Zhen; Li, Xia] Shandong Univ Tradit Chinese Med, Innovat Inst Chinese Med & Pharm, Jinan 250355, Peoples R China. [Liu, Yonglin; Liu, Xinkui; Zhu, Xiaoxiao; Zhou, Miaomiao; Chu, Chu; Zhang, Yunhong; Li, Wei; Qin, Liping; Shi, Feifei; Niu, Liangzhong; Zhang, Zhen; Li, Xia] Shandong Univ Tradit Chinese Med, Tradit Chinese Med Immunoregulat Engn Res Ctr Shan, Jinan Key Lab Tradit Chinese Med Immunoregulat,Min, Key Lab Interdisciplinary Innovat Tradit Chinese M, Jinan 250355, Peoples R China. [Song, Weiwei] Shandong Univ Tradit Chinese Med, Affiliated Hosp 2, Jinan 250001, Peoples R China. [Kikete, Siambi] Kenyatta Univ, Sch Hlth Sci, Dept Pharmacognosy & Pharmaceut Chem, Nairobi 00609, Kenya. [Zhang, Min] Shandong First Med Univ, Shandong Prov Hosp, Dept Hlth Comprehens 2, Jinan 250021, Peoples R China. C3 Shandong University of Traditional Chinese Medicine; Shandong University of Traditional Chinese Medicine; Shandong University of Traditional Chinese Medicine; Shandong University of Traditional Chinese Medicine; Kenyatta University; Shandong First Medical University & Shandong Academy of Medical Sciences RP Li, X (corresponding author), Shandong Univ Tradit Chinese Med, Coll Tradit Chinese Med, Jinan 250355, Peoples R China.; Zhang, Z; Li, X (corresponding author), Shandong Univ Tradit Chinese Med, Innovat Inst Chinese Med & Pharm, Jinan 250355, Peoples R China.; Zhang, Z; Li, X (corresponding author), Shandong Univ Tradit Chinese Med, Tradit Chinese Med Immunoregulat Engn Res Ctr Shan, Jinan Key Lab Tradit Chinese Med Immunoregulat,Min, Key Lab Interdisciplinary Innovat Tradit Chinese M, Jinan 250355, Peoples R China.; Zhang, M (corresponding author), Shandong First Med Univ, Shandong Prov Hosp, Dept Hlth Comprehens 2, Jinan 250021, Peoples R China. EM 60230133@sdutcm.edu.cn; 946641669@qq.com; 60230033@sdutcm.edu.cn RI Zhu, Xiaoxiao/AAD-1561-2019; Zhou, Miaomiao/OVY-5985-2025 OI li, wei/0009-0003-6683-9933; FU National Natural Science Foundation of China [82274575, 82474564, 82471704, 82405614]; Major Basic Research Project of Shandong Natural Science Foundation [ZR2023ZD56]; Natural Science Foundation of Shandong Province [ZR2021MH175, ZR2022LZY011]; Co-construction project of State Administration of TCM [GZY-KJS-SD-2023-034, GZY-KJS-SD-2023-046]; Taishan Scholars Program [tstp20240513]; Central Government Guides Local Science and Technology Development Fund Projects of Shandong Province [YDZX20203700001407]; Undergraduate Education Reform Project of Shandong Province Key Laboratory of TCM Classical Theory, Ministry of Education, Open Research Project [Z2024231]; National Youth Qihuang Scholar Training Program and Shandong Province TCM High Level Talent Cultivation Project FX This research received support from the National Natural Science Foundation of China (82274575, 82474564, 82471704, 82405614), Major Basic Research Project of Shandong Natural Science Foundation (ZR2023ZD56), the Natural Science Foundation of Shandong Province (ZR2021MH175, ZR2022LZY011), Co-construction project of State Administration of TCM (GZY-KJS-SD-2023-034, GZY-KJS-SD-2023-046), Taishan Scholars Program (tstp20240513), Central Government Guides Local Science and Technology Development Fund Projects of Shandong Province (YDZX20203700001407). 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It has been widely used in clinical practice for the treatment of respiratory diseases such as cough, acute and chronic bronchitis, and pneumonia. Severe bronchitis and pneumonia can precipitate acute lung injury (ALI) through the propagation of inflammation or worsening infection. As a common and severe critical condition, ALI is characterized by high morbidity and mortality. However, the active constituents and underlying mechanism of G. veitchiorum in the treatment of ALI remain unclear. In this study, a lipopolysaccharide (LPS)-induced ALI mouse model was established to evaluate the therapeutic effects of G. veitchiorum extract on ALI. Network pharmacology and molecular docking were employed to identify potential active compounds and elucidate the molecular mechanisms involved. Both in vivo and in vitro experiments were then performed to validate the pharmacological efficacy and mechanisms of the extracts and principal active compounds. Preliminary pharmacodynamic experiments showed that G. veitchiorum effectively ameliorated LPSinduced ALI in mice, likely by alleviating pulmonary edema, mitigating inflammatory infiltration and diffuse hemorrhage in the lung tissue, and regulating oxidative stress. Network pharmacology and molecular docking further identified swertiamarin (SWE) as the key active compound responsible for the therapeutic effects against ALI. In vivo experiments showed that SWE significantly reduced lung edema, suppressed the expression of inflammatory factors, restored oxidative stress-related enzyme activity, regulated macrophage polarization, and downregulated both the expression and phosphorylation of key proteins, thereby inhibiting activation of the TLR4/NF-kappa B/PI3K signaling pathway. In vitro experiments further confirmed that SWE significantly inhibited reactive oxygen species (ROS) generation as well as the secretion and mRNA expression of inflammatory cytokines. Inhibition of TLR4 and MyD88 protein expression, along with phosphorylation of p65, AKT and PI3K, as well as suppression of the nuclear translocation of p65 and p-AKT, collectively contributed to the blockade of NF kappa B activation. These results suggest that G. veitchiorum and its active ingredients exert anti-ALI effects primarily through the inhibition of inflammatory responses, attenuation of oxidative stress, and modulation of the TLR4/ NF-kappa B/PI3K signaling pathway. C1 [Li, Yuan; He, Shi-qi; Yang, Si-yan; Zhong, Li-wen] Chengdu Univ Tradit Chinese Med, Sch Pharm, Chengdu 611137, Peoples R China. [Zhang, Jie-lin; Gu, Rui] Chengdu Univ Tradit Chinese Med, Sch Ethn Med, 1166 Liutai Ave, Chengdu 611137, Peoples R China. [Deng, Wei] Chengdu Univ Tradit Chinese Med, Grad Sch, 1166 Liutai Ave, Chengdu 611137, Peoples R China. C3 Chengdu University of Traditional Chinese Medicine; Chengdu University of Traditional Chinese Medicine; Chengdu University of Traditional Chinese Medicine RP Gu, R (corresponding author), Chengdu Univ Tradit Chinese Med, Sch Ethn Med, 1166 Liutai Ave, Chengdu 611137, Peoples R China.; Deng, W (corresponding author), Chengdu Univ Tradit Chinese Med, Grad Sch, 1166 Liutai Ave, Chengdu 611137, Peoples R China. EM dengweicd@qq.com; gurui@cdutcm.edu.cn FU Ministry of Science and Technology of the People's Republic of China [2019YFC1712305]; National Natural Science Foundation of China [82073964]; Sichuan Provincial Administration of Traditional Chinese Medicine Project [2023MS616] FX Funding This work was supported by the Ministry of Science and Technology of the People's Republic of China (No. 2019YFC1712305) , the National Natural Science Foundation of China (No. 82073964) , and Sichuan Provincial Administration of Traditional Chinese Medicine Project (No. 2023MS616) . 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Immunopharmacol. PD JAN 1 PY 2026 VL 168 AR 115922 DI 10.1016/j.intimp.2025.115922 EA NOV 2025 PN 2 PG 19 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA N5494 UT WOS:001631685000001 PM 41314044 DA 2026-03-26 ER PT J AU Zheng, XY Long, YJ Li, L Li, JW Wang, YQ Meng, H Qiu, Q Chen, J Yang, H Xia, Q Han, CX Du, D AF Zheng, Xiaoyin Long, Yijing Li, Lu Li, Jiawang Wang, Yiqin Meng, Hui Qiu, Qi Chen, Jing Yang, Hao Xia, Qing Han, Chenxia Du, Dan TI Chaihu shugan powder ameliorated chronic pancreatitis by reprogramming SMS2-mediated sphingolipid metabolism in M1 macrophages SO PHYTOMEDICINE LA English DT Article DE Chronic pancreatitis; Sphingolipid metabolism; Sphingomyelin synthase 2; Macrophages; Chaihu shugan powder ID NF-KAPPA-B; BIOSYNTHESIS AB Background: Chronic pancreatitis (CP) lacks targeted therapies. Its pathogenesis involves macrophage polarization-activated pancreatic stellate cells (PSCs), with sphingolipid metabolism playing an emerging role. The traditional formula Chaihu shugan powder (CSP) shows clinical potential for CP treatment. Purpose: This study aimed to elucidate the role of CSP in CP and to identify the key components and underlying mechanisms involved in macrophage polarization-PSC activation crosstalk. Study design: We investigated the effects of CSP in vivo and in vitro, identified differentially altered sphingolipids and metabolic enzymes, and assessed their impact on macrophage polarization and PSC activation, followed by screening for the active components of CSP. Methods: CP was induced in mice by cerulein injections for four weeks, with CSP treatment given in the final two weeks. Bone marrow-derived macrophages and primary PSCs were isolated for in vitro studies. Underlying targets and mechanisms were explored using targeted sphingolipid analysis, scRNA-seq, flow cytometry and genetic knockdown, while molecular docking and molecular interaction helped identify active CSP components. Results: CSP significantly attenuated pancreatic fibrosis and M1 macrophage polarization, and restored sphingolipid metabolism in both serum and pancreas. Elevated sphingomyelin (18:1) and sphingomyelin synthase 2 (SMS2) in macrophages were identified as promoting PSC activation. Hesperetin in CSP bound to SMS2, inhibiting M1 macrophage polarization and PSC activation. Conclusion: CSP ameliorates CP partially through hesperetin-targeted SMS2, reprograms sphingolipid metabolism, and suppresses M1 macrophage-induced PSC activation. C1 [Zheng, Xiaoyin; Li, Lu; Wang, Yiqin; Qiu, Qi; Xia, Qing; Han, Chenxia; Du, Dan] Sichuan Univ, West China Hosp, Inst Integrated Tradit Chinese & Western Med, West China Ctr Excellence Pancreatitis, 37 Guoxue Alley, Chengdu 610041, Peoples R China. [Zheng, Xiaoyin; Long, Yijing; Li, Jiawang; Meng, Hui; Chen, Jing; Du, Dan] Sichuan Univ, West China Hosp, Adv Mass Spectrometry Ctr & Res Core Facil, Frontiers Sci Ctr Dis Related Mol Network, Chengdu 610213, Peoples R China. [Yang, Hao] Sichuan Univ, West China Hosp, Div Liver Surg, Chengdu 610041, Peoples R China. [Yang, Hao] Sichuan Univ, West China Hosp, NHC Key Lab Transplant Engn & Immunol, Chengdu 610041, Peoples R China. C3 Sichuan University; Sichuan University; Sichuan University; Sichuan University RP Han, CX; Du, D (corresponding author), Sichuan Univ, West China Hosp, Inst Integrated Tradit Chinese & Western Med, West China Ctr Excellence Pancreatitis, 37 Guoxue Alley, Chengdu 610041, Peoples R China.; Du, D (corresponding author), Sichuan Univ, West China Hosp, Frontiers Sci Ctr Dis Related Mol Network, 2222 Xinchuan Rd, Chengdu 610213, Peoples R China. EM hanchenxia@scu.edu.cn; dudan1520@163.com FU National Natural Science Foundation of China [82374256]; National Key Research and Development Program of China [2021YFF0702003-02]; Key Research and Development Project of Sichuan Province [2024YFFK0153] FX We thank Rui Wang, Manjiangcuo Wang, Qianlun Pu and Fei Fu for helping with metabolomic sample preparation and analysis; Xiaojiao Wang for helping with flow cytometry experiments; Yi Zhang and Li Li for the technical assistance with the immunohistochemistry and H & E staining; Sisi Wu, Yanjing Zhang, Yinchan Wang, Li Chai and Haihui Chen for helping with biomolecular experiments. All of these people are from West China Hospital of Sichuan University. The study was supported by the National Natural Science Foundation of China (No. 82374256 to Dan Du) , National Key Research and Development Pro-gram of China (2021YFF0702003-02 to Hao Yang) and Key Research and Development Project of Sichuan Province (No. 2024YFFK0153 to Chenxia Han) . We thank BioRender ( www.biorender.com ) for the assistance in creating the graphic abstract, Figs. 3A, 6B, and 8. 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Chlorogenic acid (CGA), a principal active component of Lonicera japonica (honeysuckle), has been shown to have therapeutic effects on various liver diseases. However, the specific mechanism by which CGA confers hepatoprotective effects through the modulation of macrophage polarization and inflammatory responses remains unclear. In this study, rats were subjected to 6 h of daily restraint stress for 21 consecutive days, with the experimental group receiving concurrent administration of CGA (100 mg/kg, via gavage). The results demonstrated that CGA intervention effectively mitigated chronic stress-induced impairments in growth performance and hepatic structural and functional integrity. CGA significantly inhibited M1 macrophage polarization and the expression of pro-inflammatory cytokines (IL-6, IL-1 beta, and TNF-alpha), while simultaneously promoting M2 polarization and the expression of the anti-inflammatory cytokine IL-10. Furthermore, the administration of CGA was found to inhibit the activation of the JAK2/STAT3 signaling pathway. Additionally, the use of the JAK2/STAT3 signaling pathway inhibitor, S3I-201, demonstrated effects similar to those observed with CGA treatment. In summary, CGA modulates macrophage polarization and the inflammatory response through the regulation of the JAK2/STAT3 signaling pathway, thereby mitigating the liver injury induced by chronic stress. C1 [Ji, Yaxin; Tan, Haoyang; Cheng, Xin; Yu, Xiaoqing; Hu, Jiahuan; Wang, Jiaxing; Yang, Haotian; Feng, Guofeng; Jiao, Wenjing; Fan, Honggang; Zhao, Yuan] Northeast Agr Univ, Coll Vet Med, Heilongjiang Key Lab Lab Anim & Comparat Med, Harbin 150030, Peoples R China. [Yang, Haotian] Heilongjiang Acad Agr Sci, Branch Anim Husb & Vet Branch, Qiqihar 161000, Peoples R China. C3 Northeast Agricultural University - China; Heilongjiang Academy of Agricultural Sciences RP Fan, HG; Zhao, Y (corresponding author), Northeast Agr Univ, Coll Vet Med, Heilongjiang Key Lab Lab Anim & Comparat Med, Harbin 150030, Peoples R China. EM fanhonggang2002@163.com; zhaoyuanneau2020@163.com RI Yu, Xiaoqing/LJK-8152-2024; Tan, Haoyang/MGT-5839-2025 OI Fan, Honggang/0000-0002-7671-6908 FU Young Talents' Project of Northeast Agricultural University [23YJQA02]; China Postdoctoral Science Foundation [2024M750390]; Natural Science Foundation of Heilongjiang Province [LH2022C041] FX This work was supported by the Natural Science Foundation of Heilongjiang Province (Grant No. LH2022C041), China Postdoctoral Science Foundation (Grant No. 2024M750390), and the Young Talents' Project of Northeast Agricultural University (Grant No. 23YJQA02). 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However, its underlying therapeutic mechanisms remain poorly understood. Aim of the study: We aimed to assess the therapeutic efficacy of YMKJD against UC and to unravel its underlying mechanisms through both in vivo and in vitro investigations. Materials and methods: Dextran sulfate sodium (DSS)-induced murine UC model mice, TNF-alpha-treated Caco-2 cells, LPS-stimulated RAW264.7 macrophages, and colon organoids were utilized to investigate YMKJD's therapeutic effects. Macrophage polarization (M1/M2 subsets) was assessed via flow cytometry and immunofluorescence. Immunofluorescence staining and Western blot were performed to evaluate the intestinal epithelial barrier (IEB). Untargeted metabolomics, transcriptomic sequencing, and network pharmacology were integrated to elucidate key pathways. Candidate targets were further verified using qRT-PCR and Western blot. Results: YMKJD administration markedly improved clinical symptoms and mitigated colonic tissue damage in UC mice. YMKJD attenuated IEB disruption in vivo and in vitro. Mechanistically, combined bioinformatics and experimental analyses revealed that YMKJD downregulated the expression of the key enzymes (COX-2, 5-LOX, PTGES) in the arachidonic acid (AA) metabolism, thereby suppressing proinflammatory mediators (Leukotriene B4, Prostaglandin E2, ROS) and inhibiting PI3K/AKT signaling in inflamed epithelial cells. Interestingly, YMKJD also blocked COX-2-driven M1 polarization in macrophages, diminishing ROS levels in cocultured colon organoids. Rescue studies confirmed that AA metabolism activation counteracted YMKJD's protective effects in both animal and cellular UC models. Conclusions: Our findings demonstrate YMKJD's therapeutic potential and its mechanism in UC, suggesting its utility as a novel treatment strategy. C1 [Liu, Yunze; Zhu, Wanhong; Zheng, Haocheng; Ding, Xia] Beijing Univ Chinese Med, Dongzhimen Hosp, Beijing 100700, Peoples R China. [Liu, Yunze] Xuzhou Med Univ, Clin Med Coll 1, Xuzhou 221000, Peoples R China. [Gu, Yixiao; Li, Chengze; Liu, Dianchun; Ding, Xia] Beijing Univ Chinese Med, Sch Tradit Chinese Med, Beijing 100029, Peoples R China. [Wang, Tieshan] Beijing Univ Chinese Med, Beijing Res Inst Chinese Med, Beijing 100029, Peoples R China. [Li, Yuan] Beijing Univ Chinese Med, Natl Inst TCM Constitut & Prevent Med, Beijing 100029, Peoples R China. C3 Beijing University of Chinese Medicine; Xuzhou Medical University; Beijing University of Chinese Medicine; Beijing University of Chinese Medicine; Beijing University of Chinese Medicine RP Ding, X (corresponding author), Beijing Univ Chinese Med, Dongzhimen Hosp, Beijing 100700, Peoples R China.; Li, Y (corresponding author), Beijing Univ Chinese Med, Natl Inst TCM Constitut & Prevent Med, Beijing 100029, Peoples R China. EM liyuan@bucm.edu.cn; dingx@bucm.edu.cn OI , Yixiao Gu/0009-0003-6317-2782 FU Basic Scientific Research Fund Project of Beijing University of Chinese Medicine [2024-JYB-JBZD-004]; National Natural Science Foundation of China [82374292]; Vertical Development Fund of Beijing University of Chinese Medicine [2023-ZXFZJJ-005]; National Administration of Traditional Chinese Medicine High- level Key Discipline construction Project [zyyzdxk-2023262] FX This work is supported by Basic Scientific Research Fund Project of Beijing University of Chinese Medicine (2024-JYB-JBZD-004) , the National Natural Science Foundation of China (No. 82374292) , and Vertical Development Fund of Beijing University of Chinese Medicine (2023-ZXFZJJ-005) , and National Administration of Traditional Chinese Medicine High- level Key Discipline construction Project (zyyzdxk-2023262) . 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PD FEB 28 PY 2026 VL 357 AR 120892 DI 10.1016/j.jep.2025.120892 EA NOV 2025 PG 19 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA L5382 UT WOS:001629663700005 PM 41241212 DA 2026-03-26 ER PT J AU Ni, JC Lu, YC Tan, JY Jiang, JQ Wang, YY Gan, D Cui, C Wu, J Yang, HJ Wang, ZY AF Ni, Jiachun Lu, Yuchang Tan, Jiaying Jiang, Jiaqi Wang, Yunyun Gan, Dan Cui, Can Wu, Jiong Yang, Haojie Wang, Zhenyi TI QuYuShengXin formula reshapes bile-acid-mediated macrophage polarization in the treatment of ulcerative colitis SO BMC COMPLEMENTARY MEDICINE AND THERAPIES LA English DT Article DE Ulcerative colitis; Traditional chinese medicine; Bile acid metabolism; Macrophage polarization; Inflammation ID INFLAMMATORY-BOWEL-DISEASE; STIMULATORY FACTOR-II; INTESTINAL MACROPHAGES; TGR5; DIFFERENTIATION; EPIDEMIOLOGY; INFLIXIMAB; IL-1-BETA; DYSBIOSIS; MONOCYTES AB BackgroundQuYuShengXin Formula (QYSX), a multi-herbal preparation, has previously demonstrated robust clinical efficacy against ulcerative colitis (UC), with preliminary evidence suggesting that QYSX could reconfigure the fecal bile acid BA landscape and restore the M2/M1 macrophage balance, but their interaction remains unknown. We therefore dissected the therapeutic footprint of QYSX in a dextran sulfate sodium (DSS)-induced mice model of UC, focusing on its specific mechanism of regulating BA metabolism and macrophage polarization.MethodsDSS-induced mice received QYSX or mesalazine for comparative efficacy. Disease activity index (DAI), body-weight trajectory and stool consistency were monitored daily. Colonic histopathology was graded after H&E staining. Liquid chromatography-mass spectrometry, enzyme-linked immunosorbent assay, flow cytometry, western blot and real-time quantitative PCR were conducted to evaluate the possible mechanism of QYSX.ResultsQYSX markedly attenuated he symptoms and colonic pathology of UC. It simultaneously downregulated IL-1 beta, IL-6, TNF-alpha, LPS and NF-kappa B p65, while elevating TGR5 expression. DSS-elicited disruption of the fecal BAs structure and concentration were largely reversed by QYSX. Flow-cytometric profiling revealed a decreased expression of M1 macrophages without alteration of M2 macrophages, yielding a rise in the M2/M1 ratio.ConclusionBy re-instating the physiologic fecal BA landscape, QYSX engages TGR5 to inhibit NF-kappa B signaling, thereby suppressing LPS- and TNF-alpha-driven M1 hyper-activation. This restoration of M2/M1 homeostasis curbs mucosal inflammation and maintains intestinal immune equilibrium, providing a mechanistic rationale for the clinical efficacy of QYSX in UC. C1 [Ni, Jiachun; Lu, Yuchang; Tan, Jiaying; Jiang, Jiaqi; Gan, Dan; Cui, Can; Wu, Jiong; Yang, Haojie; Wang, Zhenyi] Shanghai Univ Tradit Chinese Med, Yueyang Hosp Integrated Tradit Chinese & Western M, Dept Coloproctol, Shanghai, Peoples R China. [Wang, Yunyun] Hunan Normal Univ, Hunan Aerosp Hosp, Dept Coloproctol, Changsha, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine; Hunan Normal University RP Yang, HJ; Wang, ZY (corresponding author), Shanghai Univ Tradit Chinese Med, Yueyang Hosp Integrated Tradit Chinese & Western M, Dept Coloproctol, Shanghai, Peoples R China. EM yanghaojie@shyueyanghospital.com; drxinhuo@163.com FU Yueyang Hospital's "Revealing the Leader" Translational Medicine Research Fund in 2024 [2024YJJB09]; National Natural Science Foundation of China [82274531] FX This work is supported financially by National Natural Science Foundation of China (NO. 82274531), Yueyang Hospital's "Revealing the Leader" Translational Medicine Research Fund in 2024(NO.2024YJJB09). 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Med. Ther. PD NOV 22 PY 2025 VL 26 IS 1 AR 1 DI 10.1186/s12906-025-05177-2 PG 15 WC Integrative & Complementary Medicine WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine GA AO9AK UT WOS:001653255800001 PM 41275228 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Yan, SF Xie, YZ Xv, J Wang, K Wang, J Cao, Y Han, XT Chen, F Zhou, L Jiang, Y Liu, YJ AF Yan, Shifan Xie, Yuanzhu Xv, Jing Wang, Ke Wang, Jia Cao, Yan Han, Xiaotong Chen, Fang Zhou, Lin Jiang, Yu Liu, Yanjuan TI Shengjiang San attenuates sepsis-induced acute intestinal injury via Lactobacillus murinus derived IAAld-mediated macrophage polarization through NF-κB and TGF-β signaling SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Sepsis; Intestinal injury; Shengjiang San; Lactobacillus murinus; Macrophage polarization; Indoleacetaldehyde ID GUT; INFLAMMATION; MICE AB Ethnopharmacology associated: Sepsis is a life-threatening condition triggered by a dysregulated host response to infection, characterized by uncontrolled systemic inflammation and often culminating in multiple organ damage. Shengjiang San (SJS), a classic traditional Chinese medicinal (TCM) formula, has been historically utilized for its efficacy in removing heat, resolving toxicity, and reducing inflammation. Nevertheless, the precise role and mechanisms through which SJS modulates inflammatory responses and protects against sepsis-induced multi-organ injury are not yet fully understood. Objective: To investigate the protective mechanisms of SJS that improve sepsis-induced acute intestinal injury (SAII) by modulating the abundance and metabolism of the gut microbiota. Methods: A sepsis animal model was established using cecal ligation and puncture. The protective effects of SJS in SAII were evaluated through behavioral assessments, enzyme-linked immunosorbent assay, histological examination, and immunofluorescence analysis. Fecal samples were subjected to 16S rRNA sequencing and non-targeted metabolomics to identify probiotic taxa and metabolites associated with SJS administration. Proteomic analysis integrated with network pharmacology was performed to explore the underlying mechanisms. Fecal microbiota transplantation (FMT) and microbial metabolite analysis were utilized to elucidate the potential mechanism. Results: SJS was observed to significantly improve clinical scores, reduce pro-inflammatory cytokines, including IL-6, TNF-alpha and IL-1 beta. SJS also restored integrity of the intestinal barrier by upregulating the expression of ZO-1 and Claudin-1. 16S rRNA sequencing analysis demonstrated that SJS induced significant restructuring of the gut microbiota, including a marked increase in Lactobacillus murinus (L.M.) abundance. Proteomic and network pharmacological analyses revealed that SJS was protected against SAII by inhibiting NF-kappa B-mediated M1 polarization while promoting TGF-beta-mediated M2 polarization. In particular, this protective effect was found to depend on the abundance of L.M., which regulated intestinal inflammation through its specific metabolites, indoleacetaldehyde (IAAld). Conclusion: SJS improves SAII by orchestrating L.M. derived IAAld-mediated macrophage polarization through modulation of NF-kappa B and TGF-beta signaling pathways. C1 [Yan, Shifan] Nanchang Univ, Dept Rehabil Med, Affiliated Hosp 2, Nanchang, Jiangxi, Peoples R China. [Yan, Shifan; Xie, Yuanzhu; Xv, Jing; Wang, Jia; Cao, Yan; Han, Xiaotong; Chen, Fang; Jiang, Yu; Liu, Yanjuan] Hunan Normal Univ, Hunan Prov Peoples Hosp, Affiliated Hosp 1, Dept Emergency Med, Changsha, Peoples R China. [Wang, Ke] Cent South Univ, Xiangya Hosp 2, Changsha, Peoples R China. [Zhou, Lin] Changsha Med Univ, Coll Clin Lab, Changsha, Hunan, Peoples R China. C3 Nanchang University; Hunan Normal University; Central South University; Changsha Medical University RP Jiang, Y; Liu, YJ (corresponding author), 61 Jiefang West Rd, Changsha 410000, Hunan, Peoples R China. EM jiangyu@hunnu.edu.cn; liuyanjuan@hunnu.edu.cn RI wang, ke/PFJ-7535-2025 OI xie, yuanzhu/0000-0003-3485-7902; Shaw, Catherine/0009-0002-3950-4583 FU National Natural Science Foundation of China [82372178, 82102278, 82505524]; Natural Science Foundation of Hunan Province [2024JJ8203, 2024JJ6275, 2024JJ9296]; Scientific research project of Hunan Provincial Health Commission [W20243096]; Natural Science Foundation of Changsha City [kq2403138]; Research Project of Hunan Provincial Department of Education [24B0090]; Hunan Provincial Natural Science Foundation-Enterprise Joint Project [2025JJ90189]; Key cultivation project of Hunan Provincial People's Hospital [RS2022A08, RS2022A11]; Hunan Provincial Health High-Level Talent Scientific Research Project [R2023018] FX This project was financially supported by the National Natural Science Foundation of China (82372178, 82102278, 82505524) , the Natural Science Foundation of Hunan Province (2024JJ8203, 2024JJ6275, 2024JJ9296) , the Scientific research project of Hunan Provincial Health Commission (W20243096) , the Natural Science Foundation of Changsha City (kq2403138) , Research Project of Hunan Provincial Department of Education (24B0090) , Hunan Provincial Natural Science Foundation-Enterprise Joint Project (2025JJ90189) , the key cultivation project of Hunan Provincial People's Hospital (RS2022A08, RS2022A11) and Hunan Provincial Health High-Level Talent Scientific Research Project (R2023018) . 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PD FEB 28 PY 2026 VL 357 AR 120910 DI 10.1016/j.jep.2025.120910 EA NOV 2025 PG 14 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA J6784 UT WOS:001627790900001 PM 41265501 OA hybrid DA 2026-03-26 ER PT J AU Shi, CR Li, R Deng, LC Pan, D Fu, ZN He, GS Qu, YL Liu, R Wang, X Chen, XM Hong, Q AF Shi, Chunru Li, Run Deng, Lingchen Pan, Dan Fu, Zhangning He, Guosen Qu, Yilun Liu, Ran Wang, Xu Chen, Xiangmei Hong, Quan TI Paeoniflorin Attenuates the Progression of Diabetic Kidney Disease by Regulating Macrophage Differentiation SO PHYTOTHERAPY RESEARCH LA English DT Article DE diabetic kidney disease; HIF-1 alpha; macrophage polarization; paeoniflorin ID APOPTOSIS; PROTECTS AB Paeoniflorin (PF), a bioactive compound from Paeonia lactiflora, exhibits anti-inflammatory and immunomodulatory effects. Macrophage-driven inflammation is a key contributor to diabetic kidney disease (DKD). This study aimed to determine whether PF mitigates DKD by regulating macrophage polarization. The db/db mice were treated orally with PF (50 or 100 mg/kg/day) for 10 weeks. Renal function, histopathology, and macrophage infiltration were assessed. In vitro, RAW264.7 macrophages were exposed to high glucose. Network pharmacology, molecular docking, cellular thermal shift assays (CETSA), and HIF-1 alpha siRNA knockdown were used to investigate mechanistic targets. PF improved renal function, reduced albuminuria, and attenuated glomerular injury. It decreased CD68+ macrophage infiltration and inhibited M1 polarization, lowering TNF-alpha and iNOS expression. PF directly bound and stabilized HIF-1 alpha, while HIF-1 alpha knockdown abolished PF's anti-inflammatory effects. PF reduced HIF-1 alpha protein expression without affecting mRNA expression, indicating post-transcriptional regulation. PF protects against DKD by inhibiting HIF-1 alpha-mediated M1 macrophage polarization, revealing a novel mechanism to modulate macrophage-driven renal inflammation and supporting PF as a potential therapeutic agent for DKD. C1 [Shi, Chunru; Li, Run; Deng, Lingchen; Pan, Dan; Fu, Zhangning; He, Guosen; Qu, Yilun; Liu, Ran; Wang, Xu; Chen, Xiangmei; Hong, Quan] Chinese Peoples Liberat Army Gen Hosp, Beijing Key Lab Med Devices & Integrated Tradit Ch, State Key Lab Kidney Dis, Sr Dept Nephrol,Natl Clin Res Ctr Kidney Dis, Beijing, Peoples R China. [Shi, Chunru; Pan, Dan; He, Guosen; Chen, Xiangmei] Guangdong Pharmaceut Univ, Coll Tradit Chinese Med, Guangzhou, Peoples R China. [Li, Run; Deng, Lingchen; Chen, Xiangmei] Chengdu Univ Tradit Chinese Med, Coll Basic Med, Chengdu, Peoples R China. C3 Chinese People's Liberation Army General Hospital; Guangdong Pharmaceutical University; Chengdu University of Traditional Chinese Medicine RP Chen, XM; Hong, Q (corresponding author), Chinese Peoples Liberat Army Gen Hosp, Beijing Key Lab Med Devices & Integrated Tradit Ch, State Key Lab Kidney Dis, Sr Dept Nephrol,Natl Clin Res Ctr Kidney Dis, Beijing, Peoples R China.; Chen, XM (corresponding author), Guangdong Pharmaceut Univ, Coll Tradit Chinese Med, Guangzhou, Peoples R China.; Chen, XM (corresponding author), Chengdu Univ Tradit Chinese Med, Coll Basic Med, Chengdu, Peoples R China. EM xmchen301@126.com; hongquan@301hospital.com.cn RI He, Guosen/NUP-9226-2025 FU National Natural Science Foundation of China [32141005, 82070741, 82570862]; the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation [GZB20240415] FX This work was supported by the National Natural Science Foundation of China (32141005, 82070741, and 82570862) and the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation (No. GZB20240415). 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Res. PD JAN PY 2026 VL 40 IS 1 BP 213 EP 226 DI 10.1002/ptr.70118 EA NOV 2025 PG 14 WC Chemistry, Medicinal; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA CE0DC UT WOS:001616600400001 PM 41253730 DA 2026-03-26 ER PT J AU Wuniqiemu, T Wei, Y Sun, J Teng, FZ Zhou, YL Qin, JJ Tang, WF Xie, C Gao, Z Huang, X Lv, YB Nabijan, M Zhu, XY Liu, BJ Dong, JC AF Wuniqiemu, Tulake Wei, Ying Sun, Jing Teng, Fangzhou Zhou, Yaolong Qin, Jingjing Tang, Weifeng Xie, Cong Gao, Zhen Huang, Xi Lv, Yubao Nabijan, Mohammadtursun Zhu, Xueyi Liu, Baojun Dong, Jingcheng TI scRNA-sequencing Reveals Bu-Shen-Yi-Qi formula (BSYQF) ameliorates airway remodeling via regulating imbalanced M1/M2 macrophage subtypes in chronic asthmatic mice SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Single-cell RNA sequencing; M1/M2 macrophages; Chronic asthma; Airway remodeling; Traditional Chinese medicine ID ALLERGIC-ASTHMA; POLARIZATION; PATHOGENESIS; INFLAMMATION; CATALPOL; CELLS AB Ethnopharmalogical relevence: Airway remodeling is an end result of excessive tissue repair in chronic asthma, a heterogeneous disease with complex pathogenic features. Traditional Chinese Medicine (TCM) is known for its substantial history for asthma treatment and Bu-Shen-Yi-Qi Formula (BSYQF) has strong clinically and laboratory proven evidences as effective asthma controller. However, its underlying therapeutic mechanism remains unknown. Aim of the study: In present study, we aim to investigate how BSYQF exerts its therapeutic function in chronic asthmatic mice using single-cell RNA-sequencing. Materials and methods: We established a chronic asthma mouse model to evaluate the therapeutic effects of BSYQF, assessing airway inflammation, hyperresponsiveness, and remodeling through functional, histological, and molecular analyses. Single-cell RNA sequencing (scRNA-seq) and bulk transcriptomics were employed to investigate immune cell dynamics, significant modulation of macrophage polarization and key inflammatory pathways. Immunohistochemistry was applied to assess the transforming growth factor-beta 1 (TGF-beta 1) expression in lung tissues. Immunofluorescence analyses were conducted to assess airway remodeling, particularly myofibroblast expansion and the expression of key fibrosis-related markers, including Col1a1(+)alpha-SMA(+) co-expression and osteopontin (OPN) protein. Results: Our result showed that BSYQF treatment, particularly 2.6 g/kg group, significantly improve airway hyperresponsiveness (AHR), mirrored by significantly reduced lung resistance and increased dynamic lung compliance in asthmatic mice (P < 0.05). Histopathological assessment reveals that BSYQF mitigated the airway inflammation and airway remodeling, reflected by markedly reduced goblet cell metaplasia and collagen deposition on subepithelial layer of the airway(P < 0.05). By single cell RNA sequencing technique on eight samples, we profiled over 60 000 mouse lung tissue cells, 21 distinct cell clusters and discovered a unique pattern of BSYQF-targeted M1 and M2 macrophage subtypes in chronic asthmatic mice. Significantly disturbed M1/M2 macrophage ratio was restored by BSYQF treatment and highly resemble to healthy mice status, compared to asthmatic condition (P < 0.05). Our qRT-PCR analysis validated the total of 23 asthmatic genes significantly regulated by BSYQF treatment in M1 and M2 macrophages (P < 0.05), which were highly associated with M2 Mediated airway remodeling. Immunofluorescence analyses showed BSYQF treatment markedly reduced the OPN protein expression on the airway and significantly suppressed the Col1a1(+)alpha-SMA(+) co-expressed myofibroblast expansion on subepithelial airway layer, compared to asthmatic group (P < 0.05). Conclusions: BSYQF significantly improved airway hyperresponsiveness, reduced airway inflammation and remodeling, and restored the disturbed M1/M2 macrophage balance in asthmatic mice. Mechanistically, BSYQF treatment regulated 23 asthma-related genes, suppressed OPN expression, and inhibited Col1a1(+)alpha-SMA(+) myofibroblast expansion, highlighting its potential as a therapeutic intervention for chronic asthma. C1 [Wuniqiemu, Tulake; Wei, Ying; Sun, Jing; Teng, Fangzhou; Zhou, Yaolong; Qin, Jingjing; Tang, Weifeng; Xie, Cong; Gao, Zhen; Huang, Xi; Lv, Yubao; Nabijan, Mohammadtursun; Zhu, Xueyi; Liu, Baojun; Dong, Jingcheng] Fudan Univ, Huashan Hosp, Dept Integrat Med, 12 Middle Urumqi Rd, Shanghai 200040, Peoples R China. [Wuniqiemu, Tulake; Wei, Ying; Sun, Jing; Teng, Fangzhou; Zhou, Yaolong; Qin, Jingjing; Tang, Weifeng; Xie, Cong; Gao, Zhen; Huang, Xi; Nabijan, Mohammadtursun; Zhu, Xueyi; Liu, Baojun; Dong, Jingcheng] Fudan Univ, Inst Integrat Med, Shanghai, Peoples R China. C3 Fudan University; Fudan University RP Liu, BJ; Dong, JC (corresponding author), Fudan Univ, Huashan Hosp, Dept Integrat Med, 12 Middle Urumqi Rd, Shanghai 200040, Peoples R China. EM wuniqiemu_t@163.com; weiying_acup@126.com; sjing0610@163.com; tengfangzhou@outlook.com; 20211220084@fudan.edu.cn; shane9607@163.com; 19211220067@fudan.edu.cn; xiecong21@163.com; gaozhen@fudan.edu.cn; Hx1220091@163.com; lvyubao80313@163.com; nabijanm@126.com; 19211220066@fudan.edu.cn; lbj825@163.com; jcdong2004@126.com RI zhu, xueyi/HKM-4511-2023; Xie, Cong/GRS-6136-2022 OI Xie, Cong/0000-0001-7269-0678 FU National Natural Science Foundation of China [82174170, 82205044]; Shanghai science and technology commission [21902500]; Shanghai Municipal Commission of Health [2022QD056]; Clinical cross sectional study from Yunnan province [YDZX00003008] FX This work was supported by grants the National Natural Science Foundation of China (Grant No. 82174170 and 82205044) , the Shanghai science and technology commission (grant No. 21902500) . Shanghai Municipal Commission of Health (grant No. 2022QD056) . Clinical cross sectional study from Yunnan province (grant No. YDZX00003008) .This work has also been supported by an innovative research team of high-level local universities in Shanghai, which are involved in clinical and basic research on the prevention and treatment of the inflammatory diseases COPD and Asthma by integrative medicine. 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Ethnopharmacol. PD FEB 28 PY 2026 VL 357 AR 120883 DI 10.1016/j.jep.2025.120883 EA NOV 2025 PG 15 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA D6372 UT WOS:001621732500010 PM 41237867 DA 2026-03-26 ER PT J AU Zhong, YY Cai, SS Fang, CY Dai, W AF Zhong, Yuanyuan Cai, Shanshan Fang, Chunyue Dai, Wei TI Exploring the mechanism of Stephania tetrandra S. Moore in the treatment of cisplatin resistance against ovarian cancer through integration of network pharmacology and molecular docking SO MEDICINE LA English DT Article DE cisplatin resistance; machine learning; molecular dynamics simulation; network pharmacology; ovarian cancer; Stephania tetrandra S. Moore AB Cisplatin resistance is a major contributor to treatment failure in ovarian cancer (OC). This study investigates the mechanisms of action and therapeutic targets of Stephania tetrandra S. Moorefor cisplatin-resistant OC. OC datasets were obtained from the gene expression omnibus database, and differentially expressed genes were identified through weighted gene co-expression network analysis. Cisplatin resistance-related targets were screened using the GeneCards, OMIM, and MsigDB databases, while active components of S tetrandra were retrieved from the TCMSP, ETCM, and BATMAN databases. Commonly shared genes between these 2 sets were selected for further analysis. A protein-protein interaction network was constructed using the STRING database, and 4 machine learning algorithms were integrated to identify core targets. Binding affinities were evaluated by molecular docking with AutoDock Vina. Molecular dynamics simulations were then conducted to assess the stability of the ligand-target complexes. We performed ADMET analysis to assess the pharmacokinetic properties and drug-likeness of S tetrandra. Machine learning algorithms further identified 8 core targets including threonine tyrosine kinase (TTK), AURKA, B-cell lymphoma 2, vitamin D receptor, NFKB1, cyclin dependent kinase 1, DNMT1, and SMAD7. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that these targets were significantly enriched in pathways such as the PI3K-AKT, cell cycle regulation, p53 signaling pathway, and platinum resistance pathway. Receiver operating characteristic curve analysis demonstrated diagnostic potential for all genes except SMAD7 (AUC = 0.603 < 0.7). Immune infiltration analysis indicated a positive correlation between AURKA/TTK expression and M0/M1 macrophage infiltration (P <.05). Molecular dynamics simulations demonstrated that hesperidin, cissamine and tetrandrine exhibited strong binding affinities toward AURKA, vitamin D receptor, and TTK. Future studies are encouraged to focus on the experimental validation of these compounds and delve deeper into the possible mechanisms of drug resistance, aiming to improve their therapeutic effectiveness and real-world applicability. C1 [Zhong, Yuanyuan; Fang, Chunyue; Dai, Wei] Third Peoples Hosp Yunnan Prov, Dept Pharm, Kunming 650011, Yunnan, Peoples R China. [Zhong, Yuanyuan] Peking Univ, Kunming Med Univ, Yunnan Canc Hosp, Affiliated Hosp 3, Kunming, Yunnan, Peoples R China. [Cai, Shanshan] Univ Lancaster, Fac Hlth & Med, Div Biomed & Life Sci, Lancaster, England. [Fang, Chunyue] Dali Univ, Coll Pharm, Dali, Yunnan, Peoples R China. C3 Peking University; Kunming Medical University; Lancaster University; Dali University RP Dai, W (corresponding author), Third Peoples Hosp Yunnan Prov, Dept Pharm, Kunming 650011, Yunnan, Peoples R China. EM zhongy02@126.com; s.cai6@lancaster.ac.uk; 18213709795@163.com; 24190285@qq.com OI Zhong, Yuanyuan/0000-0003-2601-7030; Cai, Shanshan/0000-0002-0594-0953 FU the Scientific Research Fund of Education Department of Yunnan Province [2025J0784] FX This work was supported by the Scientific Research Fund of Education Department of Yunnan Province (2025J0784). 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Emerging evidence suggests that traditional Chinese medicine (TCM) formulations may offer therapeutic benefits in managing inflammatory respiratory diseases. Jinbei decoction (JBD), a 12-herb TCM preparation currently used for pulmonary fibrosis, has shown preliminary therapeutic potential in ALI; however, mechanistic studies remain limited. This study systematically evaluated JBD's therapeutic efficacy and elucidated its molecular mechanisms in LPS-induced ALI. Survival analysis demonstrated that JBD significantly improved survival rates in a concentration-dependent manner, while histopathological evaluation revealed a marked reduction in pulmonary tissue damage. These effects were further supported by significant decreases in circulating levels of major pro-inflammatory cytokines, such as TNF-alpha, IL-6 and IL-1 beta. Network pharmacology analysis identified 111 molecular targets associated with ALI pathogenesis influenced by JBD components, highlighting the regulatory effect on inflammatory signalling pathways in macrophages as the key intervening mechanism. Specifically, JBD suppressed LPS-induced inflammatory responses by inhibiting ERK phosphorylation and blocking IKK alpha/beta activation, thereby preventing NF-kappa B-dependent cytokine production in macrophages. Notably, astrapterocarpan was identified as the primary bioactive constituent of JBD through integrated network pharmacology and biochemical analyses. It was found to directly destabilise TRAF6 protein and to exhibit therapeutic efficacy comparable to that of dexamethasone in promoting histological recovery. In vivo experiments further confirmed that JBD significantly reduced TRAF6 expression in murine models, reinforcing the conclusion that its therapeutic effects are predominantly mediated by astrapterocarpan. Collectively, these findings suggest that JBD functions as an agent capable of regulating macrophage polarisation and mitigating cytokine storm through TRAF6-dependent signalling pathways, thereby providing a mechanistic basis for its potential clinical application in inflammatory lung diseases. C1 [Li, Wei; Cai, Yongqing; Sun, Haoyu; Teng, Yao; Zhou, Weiwei; Zhang, Zhen; Li, Xia] Shandong Univ Tradit Chinese Med, Innovat Inst Chinese Med & Pharm, Jinan, Peoples R China. [Li, Wei; Cai, Yongqing; Sun, Haoyu; Teng, Yao; Zhou, Weiwei; Zhang, Zhen; Li, Xia] Shandong Univ Tradit Chinese Med, Minist Educ, Tradit Chinese Med Immunoregulat Engn Res Ctr Shan, Key Lab Tradit Chinese Med Class Theory,Key Lab Tr, Jinan, Peoples R China. [Zhang, Aijun; Meng, Zhaoqing; Tian, Jingzhen] Shandong Hongji Tang Pharmaceut Grp Co Ltd, Jinan, Peoples R China. [Liu, Ruixin] Henan Univ Chinese Med, Sch Pharm, Zhengzhou, Peoples R China. [Li, Xia] Shandong Univ Tradit Chinese Med, Coll Tradit Chinese Med, Jinan, Peoples R China. C3 Shandong University of Traditional Chinese Medicine; Shandong University of Traditional Chinese Medicine; Henan University of Traditional Chinese Medicine; Shandong University of Traditional Chinese Medicine RP Zhang, Z; Li, X (corresponding author), Shandong Univ Tradit Chinese Med, Innovat Inst Chinese Med & Pharm, Jinan, Peoples R China.; Zhang, Z; Li, X (corresponding author), Shandong Univ Tradit Chinese Med, Minist Educ, Tradit Chinese Med Immunoregulat Engn Res Ctr Shan, Key Lab Tradit Chinese Med Class Theory,Key Lab Tr, Jinan, Peoples R China.; Tian, JZ (corresponding author), Shandong Hongji Tang Pharmaceut Grp Co Ltd, Jinan, Peoples R China.; Li, X (corresponding author), Shandong Univ Tradit Chinese Med, Coll Tradit Chinese Med, Jinan, Peoples R China. EM 60230133@sdutcm.edu.cn; tianjingzhen@163.com; 60230033@sdutcm.edu.cn FU National Natural Science Foundation of China [82274575, 82474564, 82471704, 82405614]; Major Basic Research Project of Shandong Natural Science Foundation [ZR2023ZD56]; Science and Technology Cooperation Program of Shandong [2025KJHZ035]; Co-construction project of State Administration of TCM [GZY-KJS-SD-2023-034, GZY-KJS-SD-2023-046]; Taishan Scholars Program [tstp20240513]; Central Government Guides Local Science and Technology Development Fund Projects of Shandong Province [YDZX20203700001407]; Key Laboratory of TCM Classical Theory, Ministry of Education, Open Research Project; National Youth Qihuang Scholar Training Program; Shandong Province TCM High Level Talent Cultivation Project; Research and Development of New Traditional Chinese Medicines for Treating Respiratory Viral Diseases and Study on Common Key Technologies [2020CXGC010505] FX This research received support from the National Natural Science Foundation of China (82274575, 82474564, 82471704 and 82405614), Major Basic Research Project of Shandong Natural Science Foundation (ZR2023ZD56), Science and Technology Cooperation Program of Shandong (2025KJHZ035) Co-construction project of State Administration of TCM (GZY-KJS-SD-2023-034, GZY-KJS-SD-2023-046), Taishan Scholars Program (tstp20240513), Central Government Guides Local Science and Technology Development Fund Projects of Shandong Province (YDZX20203700001407), Key Laboratory of TCM Classical Theory, Ministry of Education, Open Research Project, National Youth Qihuang Scholar Training Program and Shandong Province TCM High Level Talent Cultivation Project, and Research and Development of New Traditional Chinese Medicines for Treating Respiratory Viral Diseases and Study on Common Key Technologies (2020CXGC010505). 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Cell. Mol. Med. PD NOV 13 PY 2025 VL 29 IS 21 AR e70944 DI 10.1111/jcmm.70944 PG 20 WC Cell Biology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology; Research & Experimental Medicine GA 9SC4K UT WOS:001613704100001 PM 41230791 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhou, T Zhao, S Meng, CX Zhang, Q Zhang, J Sun, FP Wang, X Guo, B AF Zhou, Tian Zhao, Shuai Meng, Chunxue Zhang, Qian Zhang, Jing Sun, Fengping Wang, Xing Guo, Bin TI Rehmannin attenuates bleomycin-induced pulmonary fibrosis via THBS4-dependent modulation of fibroblast-dendritic cell interplay and matrix dynamics SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Rehmannin; Rehmannia glutinosa; Pulmonary fibrosis; THBS4; Fibroblast ID MARROW-DERIVED CELLS AB Objective: Rehmannia glutinosa, a renowned yin-enriching herb in traditional Chinese medicine (TCM), has been used to manage chronic pulmonary conditions marked by qi-yin deficiency and progressive fibrotic changes. Rehmannin, a representative iridoid glycoside derived from this herb, is regarded as one of its primary active components. However, the molecular basis underlying its antifibrotic activity remains insufficiently understood. This work aimed to assess the protective effects of Rehmannin against bleomycin-induced pulmonary fibrosis and to explore its mechanistic involvement in THBS4-associated stromal-immune regulation. Methods: C57BL/6 mice were challenged with bleomycin via intratracheal instillation to establish a fibrosis model. Rehmannin was administered orally at doses of 20 and 40 mg/kg. Lung function parameters, tissue pathology, oxidative stress markers, apoptotic rates, and fibrosis-related proteins were comprehensively analyzed. Integrated transcriptomic and metabolomic profiling was employed to uncover key molecular targets. The role of THBS4 was investigated through surface plasmon resonance (SPR), immunofluorescence, quantitative PCR, and in vitro functional assays in NIH-3 T3 fibroblasts and bone marrow-derived dendritic cells (BMDCs), with additional gain- and loss-of-function approaches. Results: Rehmannin treatment markedly reduced lung injury, improved pulmonary function, suppressed oxidative damage, and alleviated extracellular matrix deposition. Multi-omics analysis highlighted THBS4 as a central molecule responsive to Rehmannin intervention. Binding affinity between Rehmannin and THBS4 was confirmed by SPR assays. In vitro studies showed that Rehmannin diminished fibroblast migration and ECM-related protein expression, inhibited PI3K/AKT pathway activity, and facilitated M2 macrophage polarization in BMDCs. These regulatory effects were weakened upon THBS4 overexpression and strengthened following its knockdown. Conclusion: Our findings indicate that Rehmannin may exert its antifibrotic activity by modulating THBS4mediated signaling between stromal and immune cells, thereby influencing matrix remodeling in pulmonary fibrosis. These mechanistic insights provide scientific support for the traditional application of Rehmannia glutinosa in respiratory disorders and suggest Rehmannin as a promising molecular candidate for further pharmacological exploration. C1 [Zhou, Tian; Zhao, Shuai; Sun, Fengping] Zhengzhou Univ, Affiliated Childrens Hosp, Zhengzhou, Peoples R China. [Meng, Chunxue; Zhang, Qian; Zhang, Jing; Guo, Bin] Ningxia Med Univ, Key Lab Dryness Syndrome Chinese Med, Ningxia Reg Key Lab Integrated Tradit Chinese & We, Minist Educ, Yinchuan, Peoples R China. [Zhao, Shuai] Henan Acad Innovat Med Sci, Zhengzhou 451162, Peoples R China. [Wang, Xing] North Sichuan Med Coll, Sch Pharm, Dept Pharmacol, Nanchong 637100, Peoples R China. C3 Zhengzhou University; Ningxia Medical University; Henan Academy of Innovations in Medical Science; North Sichuan Medical University RP Guo, B (corresponding author), Ningxia Med Univ, Key Lab Dryness Syndrome Chinese Med, Ningxia Reg Key Lab Integrated Tradit Chinese & We, Minist Educ, Yinchuan, Peoples R China.; Wang, X (corresponding author), North Sichuan Med Coll, Sch Pharm, Dept Pharmacol, Nanchong 637100, Peoples R China. EM wangxing@nsmc.edu.cn; guo12200055@163.com FU Key R & D Program of Ningxia Hui Autonomous Region [2022BEG02040]; Zhengzhou City's Famous Teachers, Doctors, and Scholars Project [34]; Scientific Cultivation Project of Outstanding Young People in North Sichuan Medical College [CBY23-JQ03]; Scientific research development plan project of the affiliated hospital of clinical medical college of North Sichuan Medical College [2023PTZK022] FX This study was supported by Key R & D Program of Ningxia Hui Autonomous Region (2022BEG02040) Key R & D Plan of Yanchi County in 2023 (2023YCYDCT003Zhengzhou City's Famous Teachers, Doctors, and Scholars Project (Zheng Wei Ren [2022] No. 34) , the Scientific Cultivation Project of Outstanding Young People in North Sichuan Medical College (No. CBY23-JQ03) , and the Scientific research development plan project of the affiliated hospital of clinical medical college of North Sichuan Medical College (No. 2023PTZK022) . 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In response to microenvironmental cues, macrophages differentiate into pro-inflammatory M1 or anti-inflammatory M2 phenotypes, which respectively exacerbate or mitigate inflammatory responses and influence plaque progression. Emerging evidence highlights the therapeutic potential of targeting macrophage polarization through signaling pathways such as Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-kappa B), peroxisome proliferator-activated receptor gamma (PPAR-gamma), Janus kinase (JAK)-signal transducer and activator of transcription (STAT), phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, and mitogen-activated protein kinase (MAPK) pathway. Bioactive metabolites derived from traditional Chinese medicine (TCM)-including ginsenosides (e.g., Rb1, Rg3), berberine (BBR), curcumin (CUR), and tanshinone IIA (Tan IIA)-as well as herbal formulas like Bu Yang Huan Wu Decoction (BYHW) and Zhuyu Pill (ZYP), have demonstrated efficacy in promoting M2 polarization and suppressing M1 phenotypes, thereby attenuating AS. This review critically synthesizes the current body of evidence, with a primary focus on preclinical studies (in vitro and in vivo), which comprehensively synthesizes evidence on the targeted modulation of AS-associated macrophage polarization by bioactive metabolites and herbal formulas, with a unique emphasis on the role of TCM as a multi-target regulator of macrophage plasticity. This approach provides novel perspectives for the prevention and treatment of AS. C1 [Liu, Shixin; Jing, Jinpeng] Tianjin Univ Tradit Chinese Med, Grad Sch, Tianjin, Peoples R China. [Zhang, Yunsha] Tianjin Univ Tradit Chinese Med, Tianjin, Peoples R China. [Zhang, Yunsha; Sun, Junchao; Zhu, Chaojun] Tianjin Univ Tradit Chinese Med, TCM Inst Sore & Ulcer, Tianjin, Peoples R China. [Sun, Junchao; Zhu, Chaojun] Tianjin Inst Tradit Chinese Med Surg, Tianjin, Peoples R China. [Sun, Junchao; Zhu, Chaojun] Tianjin Univ Tradit Chinese Med, Affiliated Hosp 2, Tianjin, Peoples R China. C3 Tianjin University of Traditional Chinese Medicine; Tianjin University of Traditional Chinese Medicine; Tianjin University of Traditional Chinese Medicine; Tianjin University of Traditional Chinese Medicine RP Zhu, CJ (corresponding author), Tianjin Univ Tradit Chinese Med, TCM Inst Sore & Ulcer, Tianjin, Peoples R China.; Zhu, CJ (corresponding author), Tianjin Inst Tradit Chinese Med Surg, Tianjin, Peoples R China.; Zhu, CJ (corresponding author), Tianjin Univ Tradit Chinese Med, Affiliated Hosp 2, Tianjin, Peoples R China. EM zcj0706@126.com FU Research Project of the Education Commission of Tianjin Municipality [2021ZD020] FX The author(s) declare that financial support was received for the research and/or publication of this article. This work was financially supported by the Research Project of the Education Commission of Tianjin Municipality (2021ZD020). 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U2 6 PU FRONTIERS MEDIA SA PI LAUSANNE PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND EI 1663-9812 J9 FRONT PHARMACOL JI Front. Pharmacol. PD NOV 6 PY 2025 VL 16 AR 1631274 DI 10.3389/fphar.2025.1631274 PG 23 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 9ZH2W UT WOS:001618591200001 PM 41282621 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Chen, HD Xing, SH Wu, JQ Li, Y Yang, X Wang, ZT Lv, SY Zhu, JP Xu, SG Zhu, YL Sun, LP AF Chen, Huidan Xing, Sihui Wu, Jiaqi Li, Yue Yang, Xia Wang, Zhongtian Lv, Siye Zhu, Jinpu Xu, Shangge Zhu, Yilong Sun, Liping TI Zhichuanling oral liquid attenuates airway inflammation in asthma by targeting the STIM1/CHOP/JNK axis SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Asthma; Airway inflammation; Proteomics; Zhichuanling oral liquid; STIM1/CHOP/JNK axis ID ENDOPLASMIC-RETICULUM STRESS; HYPERRESPONSIVENESS; EPIDEMIOLOGY AB Ethnopharmacological relevance: Zhichuanling oral liquid (ZCLOL) is a multi-component traditional Chinese medicine formulation that has been widely used in the clinical management of asthma. However, the molecular mechanisms underlying its clinical efficacy remain largely undefined, particularly regarding calcium homeostasis and endoplasmic reticulum stress (ERS) regulation. Aim of the study: This study aimed to elucidate the mechanisms by which ZCLOL mitigates asthma-related airway inflammation through the integration of in vivo and in vitro models with proteomic profiling. Methods: In this study, an OVA-induced asthma model was established to evaluate the therapeutic effects of ZCLOL by assessing pulmonary function, serum Th2 cytokine levels, and macrophage polarization. To further elucidate the underlying mechanisms of ZCLOL in asthma treatment, we conducted proteomic analysis, measured calcium levels in lung tissue, and performed Western blotting. Additionally, an inflammatory BEAS-2B cell model induced by LPS and IL-13, combined with BAPTA-AM treatment, was used to explore the molecular pathways involved. Results: ZCLOL effectively alleviated airway hyperresponsiveness, reduced lung tissue injury, inhibited M1 macrophage polarization and Th2 cytokine secretion, decreased intracellular calcium ion levels, mitigated endoplasmic reticulum stress, and downregulated the expression of STIM1, Bip, Ero1-L alpha, PDI, CHOP, and phosphorylated JNK (p-JNK). Conclusion: ZCLOL alleviates airway inflammation and hyperresponsiveness in asthma by restoring Ca2+ homeostasis and suppressing ERS through inhibition of the STIM1/CHOP/JNK axis. These findings provide mechanistic evidence supporting ZCLOL as a potential multi-target therapeutic strategy for asthma. C1 [Chen, Huidan; Xing, Sihui; Wang, Zhongtian; Lv, Siye; Zhu, Jinpu; Zhu, Yilong; Sun, Liping] Changchun Univ Chinese Med, Coll Chinese Med, Changchun, Peoples R China. [Sun, Liping] Changchun Univ Chinese Med, Affliated Hosp, Ctr Tradit Chinese Med, Changchun, Peoples R China. [Zhu, Yilong] Changchun Univ Chinese Med, Key Lab Jilin Prov Tradit Chinese Med Prevent & Tr, Coll Integrat Med, Changchun 130117, Peoples R China. [Wu, Jiaqi] Foshan Women & Childrens Hosp, Foshan, Peoples R China. [Li, Yue] Chinese Acad Agr Sci, Changchun Vet Res Inst, Changchun, Peoples R China. [Yang, Xia] Yanbian Univ, Coll Med, Dept Pathol & Pathophysiol, Yanji, Peoples R China. [Xu, Shangge] Guangzhou Univ Chinese Med, Affiliated Hosp 2, Dept Pediat, Guangzhou, Peoples R China. C3 Changchun University of Chinese Medicine; Changchun University of Chinese Medicine; Changchun University of Chinese Medicine; Chinese Academy of Agricultural Sciences; Yanbian University; Guangzhou University of Chinese Medicine RP Zhu, YL (corresponding author), Changchun Univ Chinese Med, Key Lab Jilin Prov Tradit Chinese Med Prevent & Tr, Coll Integrat Med, Changchun 130117, Peoples R China.; Sun, LP (corresponding author), Changchun Univ Chinese Med, Affliated Hosp, Coll Chinese Med, Ctr Tradit Chinese Med, Changchun 130117, Peoples R China. EM HD13578889182@163.com; 17808071164@163.com; 836193949@qq.com; 1594391973@qq.com; 1669554669@qq.com; wztccucm@163.com; 576616756@qq.com; joanna_1000@163.com; zhuyilong66@163.com; slpwzt7063@163.com FU Joint research project of the China Association of Chinese Medicine [2023DEPLHGG-07]; Natural Science Foundation of Jilin Province [YDZJ202401687ZYTS] FX Funding This study was supported by the Joint research project of the China Association of Chinese Medicine (Grant no. 2023DEPLHGG-07) . Natural Science Foundation of Jilin Province (No. YDZJ202401687ZYTS) . 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Ethnopharmacol. PD FEB 10 PY 2026 VL 356 AR 120859 DI 10.1016/j.jep.2025.120859 EA NOV 2025 PG 14 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 9TX5T UT WOS:001614934800004 PM 41197928 OA hybrid DA 2026-03-26 ER PT J AU Du, L Wang, ML Zhou, SS Fu, XY Shi, WJ Tao, YD Zhou, HX AF Du, Lin Wang, Mei-Ling Zhou, Shuang-Shuang Fu, Xian-Yun Shi, Wen-Jie Tao, Yi-Dan Zhou, Hao-Xin TI Glycolytic Hyperactivity in Endometriotic Diseases: From Molecular Mechanisms to Precise Interventions SO PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS LA Chinese DT Article DE endometriosis; adenomyosis; glycolysis; metabolism-immune interaction; infertility ID PROMOTES; PHOSPHORYLATES; CELLS; PKM2 AB Endometriosis (EM) and adenomyosis (AM) are chronic, estrogen-dependent gynecological disorders that significantly impair the quality of life and reproductive health of millions of women worldwide. Clinically, both conditions are characterized by dysmenorrhea, abnormal uterine bleeding, infertility, and high recurrence rates. Despite decades of research, their pathogenesis remains incompletely understood, and current therapeutic options are limited in both efficacy and long-term safety. Emerging studies have identified glycolytic metabolic reprogramming (GMR)-a shift from mitochondrial oxidative phosphorylation (OXPHOS) to aerobic glycolysis -as a unifying and critical feature in the development and progression of EM and AM. In ectopic lesions, enhanced glycolysis supports cellular proliferation, survival, and adaptation to hypoxic microenvironments. Key glycolytic enzymes, including hexokinase 2 (HK2), phosphofructokinase-1 (PFK1), pyruvate dehydrogenase kinase (PDK), and lactate dehydrogenase A (LDHA), are markedly upregulated, whereas oxidative metabolism is suppressed, reflecting a Warburg-like metabolic phenotype. Notably, single-cell and spatial transcriptomic analyses reveal significant heterogeneity between EM and AM lesions. EM lesions often contain cell clusters co-expressing glycolytic and OXPHOS-related genes, suggesting metabolic flexibility. In contrast, AM tissues exhibit a more uniform, glycolysis-dominant profile, with preferential HK2 expression over HK1-potentially linked to defective repair of the endometrial basal layer. Multiple regulatory layers contribute to this glycolytic shift. Hypoxia-inducible factors (HIFs) act as upstream transcriptional activators in response to oxygen deprivation. Kinase cascades, such as those involving PIM2 and AURKA, enhance glycolytic enzyme activity via phosphorylation. Epigenetic mechanisms-including N6-methyladenosine (m6A) RNA modification and histone H3K18 lactylation-further stabilize glycolytic gene expression and reinforce metabolic reprogramming. These alterations form an integrated regulatory network that sustains high glycolytic flux in ectopic cells. Importantly, GMR profoundly affects the immune microenvironment. Lactate produced by glycolytic stromal cells promotes M2 macrophage polarization and impairs the function of cytotoxic T cells and dendritic cells, leading to immune evasion and chronic inflammation. Meanwhile, immune cells themselves undergo metabolic reprogramming, exhibiting increased dependence on glycolysis and diminished oxidative capacity. This bidirectional metabolic-immune feedback loop facilitates lesion persistence and disease progression. GMR is also closely linked to infertility in EM and AM. In the ovarian microenvironment, glycolytic imbalance leads to lactate accumulation in follicular fluid, negatively affecting oocyte quality and embryo development. In the endometrium, excessive glycolysis disrupts decidualization, angiogenesis, and immune tolerance-processes essential for implantation and pregnancy. Targeting glycolysis offers promising therapeutic potential. Small-molecule inhibitors such as dichloroacetate and meclozine target PDK and HK2, respectively. Natural compounds like cinnamic acid and protoberberine derivatives exhibit both anti-glycolytic and anti-inflammatory effects. Traditional Chinese medicine formulations, including Guizhi Fuling Wan, have shown efficacy in modulating metabolism, vascular remodeling, and fibrosis. Combination therapies, such as atorvastatin with resveratrol, may provide synergistic benefits by inhibiting both glucose uptake and lactate export. In conclusion, glycolytic metabolic reprogramming is a central mechanism linking inflammation, immune dysfunction, lesion progression, and reproductive failure in endometriotic diseases. Future research should focus on identifying metabolic subtypes, developing combined metabolic-immune therapies, and evaluating the safety of these treatments in reproductive-age women. These insights may pave the way toward personalized, mechanism-driven interventions for EM and AM. C1 [Du, Lin; Wang, Mei-Ling; Fu, Xian-Yun; Shi, Wen-Jie; Tao, Yi-Dan; Zhou, Hao-Xin] China Three Gorges Univ, Coll Med & Hlth Sci, Third Grade Pharmacol Lab Chinese Med, Natl Adm Tradit Chinese Med, Yichang 443002, Peoples R China. [Zhou, Shuang-Shuang] Sanxia Vocat & Tech Coll Hubei, Yichang 443000, Peoples R China. C3 China Three Gorges University RP Fu, XY (corresponding author), China Three Gorges Univ, Coll Med & Hlth Sci, Third Grade Pharmacol Lab Chinese Med, Natl Adm Tradit Chinese Med, Yichang 443002, Peoples R China.; Zhou, SS (corresponding author), Sanxia Vocat & Tech Coll Hubei, Yichang 443000, Peoples R China. EM 845960065@qq.com; dinnar1@16.com RI shi, wenjie/KUD-7050-2024; Zhou, haoxin/PMS-0181-2026 FU Natural Science Foundation of Hubei Province [2024AFB808] FX This work was supported by a grant from Natural Science Foundation of Hubei Province (2024AFB808) . 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Biochem. Biophys. PD NOV PY 2025 VL 52 IS 11 BP 2717 EP 2728 DI 10.3724/j.pibb.2025.0192 PG 12 WC Biochemistry & Molecular Biology; Biophysics WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Biophysics GA N3670 UT WOS:001631502600003 DA 2026-03-26 ER PT J AU Shang, Z Zhou, L Liu, Y Yang, X Yao, DK Zhai, FX Liu, BY Chen, YL Zhu, XJ Liu, D Yi, B AF Shang, Zhao Zhou, Li Liu, Yue Yang, Xiao Yao, Dengke Zhai, Feixiang Liu, Biyu Chen, Yanglin Zhu, Xiaojian Liu, Dan Yi, Bo TI Tongxie Yaofang attenuates ulcerative colitis by modulating gut microbiota and IL-10RA/NF-κB-mediated macrophage polarization SO PHYTOMEDICINE LA English DT Article DE Tongxie Yaofang; Ulcerative colitis; Gut microbiota; IL-10RA; NF-kappa B signaling; Macrophage polarization AB Background: Tongxie Yaofang (TXYF), a traditional Chinese herbal formula, has shown therapeutic potential in gastrointestinal disorders. However, its mechanism in ulcerative colitis (UC) remains unclear. This study provides new insights into immune-microbiota crosstalk as a key mechanism driving the protective effects of TXYF. Methods: A DSS-induced colitis mouse model was used to evaluate TXYF's efficacy. Gut microbiota was profiled by 16S rRNA sequencing, while transcriptomics and network pharmacology identified core pathways. In vivo and in vitro assays examined immune regulation and epithelial barrier function. A THP-1/Caco-2 co-culture system explored IL-10RA-dependent immune-epithelial crosstalk, and fecal microbiota transplantation (FMT) tested the functional role of microbial remodeling. Results: TXYF alleviated colitis symptoms, improved colon histology, and reduced pro-inflammatory cytokines. It reshaped gut microbiota by enriching SCFA-producing beneficial taxa and suppressing pathogenic bacteria. Transcriptomic analyses identified IL-10RA/NF-kappa B as a novel regulatory axis, and TXYF enhanced IL-10RA expression, inhibited NF-kappa B activation, and promoted M2 macrophage polarization. The co-culture model revealed IL-10RA-dependent macrophage-epithelial signaling that strengthened tight junction integrity. Importantly, FMT from TXYF-treated donors yielded these therapeutic benefits, reinforcing the evidence for microbiota-driven causality. Conclusion: This study is the first to identify IL-10RA/NF-kappa B as a key immunoregulatory pathway of TXYF, uncover IL-10RA-dependent immune-epithelial communication, and validate gut microbiota as a functional mediator through FMT. Collectively, these findings demonstrate the innovative potential of TXYF as a multi-target herbal therapy for UC. C1 [Shang, Zhao; Yao, Dengke; Chen, Yanglin; Zhu, Xiaojian; Yi, Bo] Nanchang Med Coll, Jiangxi Canc Hosp, Abdominal Surg Dept 2, Affiliated Hosp 2, Nanchang 330029, Jiangxi, Peoples R China. [Shang, Zhao; Zhou, Li; Liu, Yue; Zhai, Feixiang; Liu, Biyu; Liu, Dan] Nanchang Univ, Sch Pharm, Jiangxi Med Coll, Jiangxi Prov Key Lab Drug Target Discovery & Vali, Nanchang 330006, Peoples R China. [Zhou, Li; Yao, Dengke; Zhu, Xiaojian; Yi, Bo] Nanchang Med Coll, Jiangxi Canc Hosp, Jiangxi Prov Colorectal Tumor Ctr, Affiliated Hosp 2, Nanchang 330029, Jiangxi, Peoples R China. [Shang, Zhao] Peoples Hosp Jiaxiang, Dept Pharm, Jining City 272400, Shandong, Peoples R China. [Yang, Xiao] Nanchang Univ, Jiangxi Med Coll, Clin Med Coll 2, Nanchang 330006, Peoples R China. C3 Nanchang Medical College; Nanchang University; Nanchang Medical College; Nanchang University RP Zhu, XJ; Yi, B (corresponding author), Nanchang Med Coll, Jiangxi Canc Hosp, Abdominal Surg Dept 2, Affiliated Hosp 2, Nanchang 330029, Jiangxi, Peoples R China.; Liu, D (corresponding author), Nanchang Univ, Sch Pharm, Jiangxi Med Coll, Jiangxi Prov Key Lab Drug Target Discovery & Vali, Nanchang 330006, Peoples R China. EM zhuxj8@mail2.sysu.edu.cn; liudan1201jx@ncu.edu.cn; yibo@ncmc.edu.cn OI Chen, Yanglin/0009-0000-4787-0378 FU Key Project of Jiangxi Provincial Administration of Traditional Chinese Medicine Science and Technology Plan [2022Z019]; National Natural Science Foundation of China [82404050]; Jiangxi Provincial Key Clinical Specialty Construction Project-Gastrointestinal Tumor Surgery; Scientific and Technological Research Project of the Jiangxi Provincial Department of Education [GJJ2403619]; Jiangxi Province Health Commission [202310886]; Gastrointestinal Tumors Diagnosis, Treatment, and Drug Resistance Research Team of Nanchang Medical College [NYTD202209] FX This study was supported by grants from the Key Project of Jiangxi Provincial Administration of Traditional Chinese Medicine Science and Technology Plan (2022Z019), National Natural Science Foundation of China (No. 82404050), Jiangxi Provincial Key Clinical Specialty Construction Project-Gastrointestinal Tumor Surgery, the Scientific and Technological Research Project of the Jiangxi Provincial Department of Education (GJJ2403619), the Jiangxi Province Health Commission (202310886), and Gastrointestinal Tumors Diagnosis, Treatment, and Drug Resistance Research Team of Nanchang Medical College (NYTD202209). 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Sci. Food, V9 Zhao H, 2025, MOL NUTR FOOD RES, V69, DOI 10.1002/mnfr.202400785 Zhou L, 2025, J FUNCT FOODS, V130, DOI 10.1016/j.jff.2025.106937 NR 25 TC 0 Z9 0 U1 13 U2 13 PU ELSEVIER GMBH PI MUNICH PA HACKERBRUCKE 6, 80335 MUNICH, GERMANY SN 0944-7113 EI 1618-095X J9 PHYTOMEDICINE JI Phytomedicine PD NOV 25 PY 2025 VL 148 AR 157459 DI 10.1016/j.phymed.2025.157459 EA OCT 2025 PG 17 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA AN2DD UT WOS:001652109900005 PM 41175586 DA 2026-03-26 ER PT J AU Wang, ZQ Zhou, XR Guo, YL Zhang, JM Liu, YU Zeng, J Zhao, JN AF Wang, Zhiqiao Zhou, Xuerong Guo, Yanlei Zhang, Jinmei Liu, Yaou Zeng, Jin Zhao, Junning TI Integrating network pharmacology and metabolomics to explore the mechanism of Xihuang Pill in exerting anti-tumor immune effects against pancreatic ductal adenocarcinoma SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Xihuang Pill; Pancreatic ductal adenocarcinoma; Network pharmacology; L-kynurenine; Macrophage polarization ID PROGRESSION; INHIBITOR; RECEPTOR AB Ethnopharmacological relevance: Xihuang Pill (XHP), a traditional Chinese medicine formula, has demonstrated anti-pancreatic ductal adenocarcinoma (PDAC) efficacy in prior studies. However, its effects on tumor-associated macrophages (TAMs) and underlying mechanisms remain unclear. Aim of the study: This study aimed to elucidate the mechanism of XHP in exerting anti-tumor immune effects against PDAC through network pharmacology, widely targeted metabolomics, and in vitro and in vivo experiments. Materials and methods: UPLC-QTOF-MS and network pharmacology were employed to analyze the components and potential mechanisms of XHP, and molecular docking and molecular dynamics were used to analyze targetcomponent interactions. Survival analysis and immune infiltration assessment of target were performed through public databases. The effects of XHP were evaluated in vitro and in vivo experiments. Widely targeted metabolomics was performed to identify key metabolites, and the effect of L-kynurenine (Kyn) was verified. WB and RT-qPCR were conducted to verify the molecular mechanism. Results: A total of 238 chemical components of XHP were identified. Network pharmacology analysis revealed that XHP might regulate multi-target and influence the PI3K/AKT pathway for PDAC treatment. Molecular docking and dynamics simulations indicated stable interactions between active components and targets. The target was linked to poor prognosis in PAAD and was correlated with macrophages. In vitro and in vivo experimental results showed that XHP inhibited tumor growth, reduced the serum CA19-9 level, and suppressed the proliferation and migration of PDAC cells. In addition, XHP increased M1 phenotype and inhibited the polarization to M2 phenotype. Metabolomics analysis revealed that XHP decreased Kyn levels and confirmed that Kyn inhibited Cd86 mRNA expression and upregulated the mRNA expression of Akt1 and Mtor. Furthermore, XHP also downregulated the expression of proteins related to the AKT/mTOR pathway, and it was revealed that beta-boswellic acid affected the Kyn levels and macrophage polarization. Conclusion: XHP may exert an anti-PDAC effect by influencing the Kyn level to regulate the tumor immune microenvironment and downregulating the AKT/mTOR signaling pathway. Kyn is a key metabolite of XHP for the treatment of PDAC. C1 [Wang, Zhiqiao; Zhao, Junning] Chengdu Univ Tradit Chinese Med, Sch Pharm, Chengdu 611137, Peoples R China. [Wang, Zhiqiao; Zeng, Jin; Zhao, Junning] Sichuan Inst Translat Chinese Med, Sichuan Chongqing Joint Key Lab Innovat New Drugs, Translat Chinese Med Key Lab Sichuan, Chengdu 610041, Peoples R China. [Wang, Zhiqiao; Zhou, Xuerong; Zhang, Jinmei; Liu, Yaou; Zeng, Jin] Sichuan Acad Chinese Med Sci, Chengdu 610041, Peoples R China. [Guo, Yanlei] Chongqing Acad Chinese Mat Med, Chongqing 400065, Peoples R China. [Zhao, Junning] Natl Ctr Nanosci & Technol, Beijing 100190, Peoples R China. C3 Chengdu University of Traditional Chinese Medicine; Chinese Academy of Sciences; National Center for Nanoscience & Technology, CAS RP Zeng, J; Zhao, JN (corresponding author), Sichuan Inst Translat Chinese Med, Sichuan Chongqing Joint Key Lab Innovat New Drugs, Translat Chinese Med Key Lab Sichuan, Chengdu 610041, Peoples R China.; Zhao, JN (corresponding author), Natl Ctr Nanosci & Technol, Beijing 100190, Peoples R China. EM 18628322650@163.com; zarmy@189.cn FU Sichuan Central-Guided Local Sci-Tech Development Special Fund of China [2024ZYD0047] FX This study was supported by the Sichuan Central-Guided Local Sci-Tech Development Special Fund of China (2024ZYD0047) . 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Ethnopharmacol. PD FEB 10 PY 2026 VL 356 AR 120788 DI 10.1016/j.jep.2025.120788 EA OCT 2025 PG 20 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 9MU6X UT WOS:001610097900001 PM 41161625 DA 2026-03-26 ER PT J AU Zheng, SH Li, SZ Wang, QY Zao, X Li, XK Qi, WY Cheng, FN Geng, YX Zhang, P Shi, XY Ye, YG AF Zheng, Shihao Li, Size Wang, Qiuyue Zao, Xiaobin Li, Xiaoke Qi, Wenying Cheng, Fane Geng, Yuexiao Zhang, Peng Shi, Xinyue Ye, Yongan TI New perspectives in the treatment of liver cirrhosis: targeting macrophage regulatory mechanisms SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Review DE Liver cirrhosis; Macrophage; Mechanism; Immune regulation ID FIBROSIS; POLARIZATION; ACTIVATION; EXPRESSION; CCL2-CCR2; INJURY; CELLS AB Liver cirrhosis is a major manifestation of end-stage liver disease, and its pathogenesis and therapeutic strategies are key areas of research in hepatology. The limitations of traditional treatments have prompted researchers to turn their attention to immune regulatory mechanisms, among which macrophage polarization regulation has become the most promising therapeutic target. In this paper, the central role of macrophages in the development of cirrhosis and their regulatory network are described, with a focus on the critical role of M1/M2 polarization balance in the process of liver fibrosis. The dynamic polarization process of macrophages in the hepatic microenvironment is finely regulated: the M1 type activates hepatic stellate cells through proinflammatory factors, such as TNF-alpha and IL-1 beta, and promotes ECM deposition, whereas the M2 type participates in tissue repair and fibrosis reversal through the secretion of anti-inflammatory factors, such as IL-10 and TGF-beta, and MMPs. On the basis of this mechanism, three main classes of intervention strategies have been developed: first, immunomodulatory therapies, including CCR2/CCR5 antagonists and cytokine modulation; second, small molecule-targeted drugs, such as JNK inhibitors and natural active ingredients; and third, cutting-edge biotherapeutic technologies, including genetically engineered macrophage and stem cell combination therapies. Importantly, the modulation of macrophage polarization through the targeted delivery of siRNA via nanocarriers or the induction of M2-type polarization using mesenchymal stem cells can significantly reduce the degree of fibrosis. However, these strategies still face challenges in translational applications, such as dynamic changes in the polarization state and insufficient target specificity. In the future, we need to analyse the heterogeneity of macrophages with the help of new technologies such as single-cell sequencing, develop spatiotemporal specific regulation schemes, and explore multitarget synergistic therapeutic strategies. The breakthroughs in this field will not only revolutionize the treatment mode of liver cirrhosis but also provide important reference information for the treatment of fibrotic diseases in other organs, marking the shift in liver disease treatment from traditional symptomatic treatment to a new era of precise immunomodulation. In conclusion, the targeted regulation of macrophage polarization has demonstrated significant therapeutic potential for liver cirrhosis, with its clinical application poised to revolutionize the treatment paradigm for liver diseases. Future studies should focus on leveraging single-cell technologies to elucidate macrophage heterogeneity and develop precision delivery strategies targeting macrophages, thereby advancing the clinical translation of personalized combination therapies based on macrophage modulation. C1 [Zheng, Shihao; Li, Size; Wang, Qiuyue; Zao, Xiaobin; Li, Xiaoke; Qi, Wenying; Cheng, Fane; Geng, Yuexiao; Shi, Xinyue; Ye, Yongan] Beijing Univ Chinese Med, Dongzhimen Hosp, Beijing 100007, Peoples R China. [Zheng, Shihao; Li, Size; Wang, Qiuyue; Zao, Xiaobin; Qi, Wenying; Shi, Xinyue] Beijing Univ Chinese Med, Beijing 100102, Peoples R China. [Li, Xiaoke; Ye, Yongan] Beijing Univ Chinese Med, Liver Dis Acad Tradit Chinese Med, Beijing 100029, Peoples R China. [Cheng, Fane] Beijing Univ Chinese Med, Key Lab Chinese Internal Med, Minist Educ, Beijing 100007, Peoples R China. [Cheng, Fane; Zhang, Peng] Beijing Univ Chinese Med, Dongzhimen Hosp, Beijing 100007, Peoples R China. C3 Beijing University of Chinese Medicine; Beijing University of Chinese Medicine; Beijing University of Chinese Medicine; Beijing University of Chinese Medicine; Beijing University of Chinese Medicine RP Zheng, SH; Shi, XY; Ye, YG (corresponding author), Beijing Univ Chinese Med, Dongzhimen Hosp, Beijing 100007, Peoples R China.; Zheng, SH; Shi, XY (corresponding author), Beijing Univ Chinese Med, Beijing 100102, Peoples R China.; Ye, YG (corresponding author), Beijing Univ Chinese Med, Liver Dis Acad Tradit Chinese Med, Beijing 100029, Peoples R China. EM zz94080266@163.com; sxy199656@163.com; yeyongan@vip.163.com RI Shi, Xinyue/OXC-8769-2025; Qi, Wenying/MCI-9586-2025; Zao, Xiaobin/GQH-6052-2022 OI Zao, Xiaobin/0000-0002-7533-1301 FU Pilot Program for Enhancing Clinical Research and Achievement Transformation Capabilities [No. DZMG-ZJXY-23012]; 2025 Beijing University of Chinese Medicine Graduate Student Independent Research Projects [No. DZMYJS2025010] FX This work was supported by Pilot Program for Enhancing Clinical Research and Achievement Transformation Capabilities (No. DZMG-ZJXY-23012) and 2025 Beijing University of Chinese Medicine Graduate Student Independent Research Projects (No. DZMYJS2025010). 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PHARMACOTHER, V106, P868, DOI 10.1016/j.biopha.2018.07.028 Zheng KX, 2023, WORLD J GASTROENTERO, V29, P3103, DOI 10.3748/wjg.v29.i20.3103 Zhou LY, 2022, J DRUG TARGET, V30, P577, DOI 10.1080/1061186X.2022.2044485 NR 85 TC 1 Z9 1 U1 5 U2 5 PU BMC PI LONDON PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND EI 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD OCT 31 PY 2025 VL 23 IS 1 AR 1201 DI 10.1186/s12967-025-07239-y PG 13 WC Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine GA 9ID2X UT WOS:001606914600002 PM 41174741 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Cui, ZH Shang, QX AF Cui, Zhenhua Shang, Qingxin TI Mechanistic insights into the antitumor effects of astragaloside IV and astragalus polysaccharide in digestive system cancers SO FRONTIERS IN PHARMACOLOGY LA English DT Review DE astragaloside IV; Astragalus polysaccharide; digestive system cancers; natural compounds; antitumor mechanisms ID INHIBITS PATHOLOGICAL FUNCTIONS; HEPATOCELLULAR-CARCINOMA CELLS; GASTRIC-CANCER; COLORECTAL-CANCER; RISK-FACTORS; MEDICINE; PROLIFERATION; EPIDEMIOLOGY; ANGIOGENESIS; MEMBRANACEUS AB Malignant tumors of the digestive system are among the leading causes of cancer-related mortality worldwide. Characterized by complex pathogenesis and insidious early symptoms, these cancers remain major challenges in clinical management. With the growing interest in natural medicines, Astragalus membranaceus and its active components, Astragaloside IV (AS-IV) and Astragalus polysaccharide (APS), have attracted considerable attention for their therapeutic potential against digestive system malignancies. Based on more than 41 peer-reviewed studies published in recent years, this review summarizes the key antitumor mechanisms of AS-IV and APS in hepatocellular carcinoma, colorectal cancer, gastric cancer, and other digestive system malignancies. AS-IV exerts anticancer effects through the regulation of PI3K/AKT, MAPK, NF-kappa B, and TGF-beta/Smad pathways, leading to apoptosis induction, inhibition of epithelial-mesenchymal transition, modulation of the tumor immune microenvironment, reversal of multidrug resistance, and enhancement of chemosensitivity. APS, a bioactive macromolecule with immunostimulatory and multitarget regulatory properties, enhances antitumor immunity by activating dendritic cells, promoting macrophage polarization, and suppressing immune evasion, while also improving the efficacy of chemotherapy and targeted therapies. This comprehensive review highlights molecular targets, signaling networks, and novel delivery strategies of AS-IV and APS, providing mechanistic insights and translational perspectives for their potential application in digestive system cancers. C1 [Cui, Zhenhua; Shang, Qingxin] Shandong Univ Tradit Chinese Med, Coll Tradit Chinese Med, Jinan, Shangdong, Peoples R China. C3 Shandong University of Traditional Chinese Medicine RP Shang, QX (corresponding author), Shandong Univ Tradit Chinese Med, Coll Tradit Chinese Med, Jinan, Shangdong, Peoples R China. 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10.1016/j.heliyon.2024.e31450 Zhou LX, 2023, ONCOL REP, V49, DOI 10.3892/or.2022.8442 Zhu JH, 2018, PHYTOTHER RES, V32, P1289, DOI 10.1002/ptr.6057 Zhu YZ, 2024, BMC CANCER, V24, DOI 10.1186/s12885-024-12438-9 NR 115 TC 2 Z9 2 U1 11 U2 11 PU FRONTIERS MEDIA SA PI LAUSANNE PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND EI 1663-9812 J9 FRONT PHARMACOL JI Front. Pharmacol. PD OCT 29 PY 2025 VL 16 AR 1691011 DI 10.3389/fphar.2025.1691011 PG 12 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 9PY1D UT WOS:001612232900001 PM 41235109 OA Green Submitted, Green Accepted, gold DA 2026-03-26 ER PT J AU Wang, B Lu, BW Lv, JQ Dong, CX Bai, CC AF Wang, Bo Lu, Bowen Lv, Junqiang Dong, Caixia Bai, Changcai TI A galactoarabinan-containing glycoprotein isolated from the fruits of Lycium barbarum reverses the tumor-associated macrophage phenotype SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE Lycium barbarum; polysaccharide; tumor-associated macrophage; immunomodulatory activity; colorectal cancer ID STRUCTURAL-CHARACTERIZATION; BIOLOGICAL-ACTIVITIES; HYPOGLYCEMIC ACTIVITY; POLYSACCHARIDE; CANCER; PURIFICATION; ELUCIDATION; L. AB Lycium barbarum fruits possess a well-established history of use in traditional Chinese medicine due to their potent immunomodulatory properties, extending to cancer immunity. In this study, a purified galactoarabinan-containing glycoprotein, designated LBNP-1, with an apparent molecular weight of 56.2 kDa, was isolated from the aqueous extract of L. barbarum fruits. Our findings revealed that LBNP-1 possesses a branched arabinan structure as its saccharide moiety. Bioactivity assays demonstrated that LBNP-1 polarized M2 macrophages towards the M1 phenotype. Furthermore, the LBNP-1-induced macrophage phenotypic shift was inhibited by a TLR4 antagonist. Western blot analysis indicated that LBNP-1 activated the NF-kappa B signaling pathway, thereby promoting polarization of tumor-associated macrophages (TAMs) towards the M1 phenotype. Moreover, conditioned medium derived from RAW264.7 cells pretreated with LBNP-1 exhibited anticancer effects against colorectal cancer (CRC) cells. Our research highlights the antitumor effect of LBNP-1 against CRC, mediated by reversing the TAM phenotype. LBNP-1 may represent a potential immunomodulator for the treatment of malignancies. C1 [Wang, Bo] Ningxia Med Univ, Peoples Hosp Ningxia Hui Autonomous Reg, Dept Pharm, Yinchuan, Peoples R China. [Wang, Bo; Bai, Changcai] Ningxia Med Univ, Coll Pharm, Yinchuan, Peoples R China. [Wang, Bo; Bai, Changcai] Ningxia Med Univ, Key Lab Ningxia Ethnomedicine Modernizat, Minist Educ, Yinchuan, Peoples R China. [Lu, Bowen] Jiamusi Univ, Coll Pharm, Dept Pharmacognosy, Jiamusi, Peoples R China. [Lv, Junqiang] Tianjin Med Univ, Sch Basic Med Sci, Tianjin Key Lab Cellular & Mol Immunol, Key Lab,Educ Minist China, Tianjin, Peoples R China. [Dong, Caixia] Tianjin Med Univ, Sch Pharm, Tianjin Key Lab Technol Enabling Dev Clin Therapeu, Tianjin, Peoples R China. C3 Ningxia Medical University; Ningxia Medical University; Ningxia Medical University; Jiamusi University; Tianjin Medical University; Tianjin Medical University RP Bai, CC (corresponding author), Ningxia Med Univ, Coll Pharm, Yinchuan, Peoples R China.; Bai, CC (corresponding author), Ningxia Med Univ, Key Lab Ningxia Ethnomedicine Modernizat, Minist Educ, Yinchuan, Peoples R China.; Lv, JQ (corresponding author), Tianjin Med Univ, Sch Basic Med Sci, Tianjin Key Lab Cellular & Mol Immunol, Key Lab,Educ Minist China, Tianjin, Peoples R China.; Dong, CX (corresponding author), Tianjin Med Univ, Sch Pharm, Tianjin Key Lab Technol Enabling Dev Clin Therapeu, Tianjin, Peoples R China. EM lvjunqiang@tmu.edu.cn; dongcaixia@tmu.edu.cn; changcaibai@163.com RI Lu, BoWen/LRD-0596-2024 FU Keynote Development Program of the Ningxia Hui Autonomous Region [2018BFH03023] FX The author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by the Keynote Development Program of the Ningxia Hui Autonomous Region (General Project), project number: 2018BFH03023. 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Pharmacol. PD OCT 29 PY 2025 VL 16 AR 1593407 DI 10.3389/fphar.2025.1593407 PG 13 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 9PY0Y UT WOS:001612232400001 PM 41235105 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Liu, XY Pan, YJ Deng, CX Zhu, ML Guo, DM Wu, JQ Feng, F Pan, LH Wang, CL Xu, K AF Liu, Xinyue Pan, Yijing Deng, Chenxi Zhu, Meiliang Guo, Dongmei Wu, Jiaqin Feng, Fan Pan, Lianhong Wang, Chunli Xu, Kang TI Parishin E from ginger-processed Gastrodia elata Bl. alleviates rheumatoid arthritis by regulating histone 3 lactylation at H3K18la and H3K27la sites SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE rheumatoid arthritis; ginger-processedtreated Gastrodia elata Bl.; Gastrodia elata Bl.; non-targeted metabolomics; glycolysis; H3 histone lactylation ID CAPSULE; RATS AB Background This study investigated the natural small molecule drug Parishin E (PE) derived from the orchid plant Gastrodia elata Bl. (GEB). We evaluated the therapeutic effects of ginger-processed Gastrodia elata Bl. (G-GEB) on rheumatoid arthritis (RA) and focused on paracine E to elucidate its potential regulatory mechanisms.Methods An Sprague-Dawley rat model of rheumatoid arthritis was constructed to evaluate the pharmacological effects of G-GEB. Plant non-targeted metabolomics, serum non-targeted metabolomics, and RAW264.7 inflammation models elucidate Parishin E as the core anti-inflammatory component of G-GEB. Subsequently, transcriptomic and metabolomic analyses were performed to elucidate the molecular signaling mechanism of Parishin E in the treatment of RA.Results G-GEB significantly improves RA, with 363 active compounds identified by untargeted metabolomics. PE, its main active component, affects cell glycolysis by downregulating HK2 and LDHA to inhibit macrophage polarization. PE also shows anti-inflammatory properties by suppressing H3 lactylation at H3K18la and H3K27la.Conclusion PE in G-GEB exerts an RA ameliostatic effect by inhibiting macrophage polarization by regulating cellular glycolysis and by inhibiting the emulsylation modification of histone H3 sites, specifically H3K18la and H3K27la. Therefore, PE is a promising drug candidate for the development of RA treatments. C1 [Liu, Xinyue; Pan, Yijing; Deng, Chenxi; Zhu, Meiliang; Guo, Dongmei; Feng, Fan; Xu, Kang] Hubei Univ Chinese Med, Hubei Prov Engn Technol Res Ctr Chinese Med Proc, Sch Pharm, Wuhan, Peoples R China. [Liu, Xinyue; Pan, Yijing; Deng, Chenxi; Zhu, Meiliang; Guo, Dongmei; Wu, Jiaqin; Feng, Fan; Wang, Chunli; Xu, Kang] Hubei Univ Chinese Med, Wuhan, Peoples R China. [Wu, Jiaqin; Wang, Chunli] Hubei Univ Chinese Med, Sch Lab Med, Wuhan, Peoples R China. [Pan, Lianhong] Chongqing Three Gorges Med Coll, Chongqing Engn Res Ctr Antitumor Nat Drugs, Chongqing Key Lab Dev & Utilizat Genuine Med Mat, Chongqing, Peoples R China. C3 Hubei University of Chinese Medicine; Hubei University of Chinese Medicine; Hubei University of Chinese Medicine RP Xu, K (corresponding author), Hubei Univ Chinese Med, Hubei Prov Engn Technol Res Ctr Chinese Med Proc, Sch Pharm, Wuhan, Peoples R China.; Wang, CL; Xu, K (corresponding author), Hubei Univ Chinese Med, Wuhan, Peoples R China.; Wang, CL (corresponding author), Hubei Univ Chinese Med, Sch Lab Med, Wuhan, Peoples R China.; Pan, LH (corresponding author), Chongqing Three Gorges Med Coll, Chongqing Engn Res Ctr Antitumor Nat Drugs, Chongqing Key Lab Dev & Utilizat Genuine Med Mat, Chongqing, Peoples R China. EM 20220445@cqtgmc.edu.cn; lilywang@cqu.edu.cn; kangxu05@hbucm.edu.cn RI Feng, Fan/KOC-1183-2024 FU Natural Science Foundation of Hubei Province FX The author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by the Science and Technology Special Project of National Administration of Traditional Chinese Medicine (GZY-KJS-2025-010), Natural Science Foundation of Hubei Province, China (2025AFD483), the Young Elite Scientists Sponsorship Program by the China Association of Chinese Medicine (CACM-2023-QNRC2-B06), the Science and Technology Research Program of Chongqing Municipal Education Commission (Nos., KJZD-K202202705, KJQN202302710), The High-level Talent Research start-up fund Program of Chongqing Three Gorges Medical College (Nos., XJ2022000103), The Science and Technology Research Program of Chongqing Wanzhou district (Nos., wzstc20230416). Project of Hubei Province Traditional Chinese Medicine Innovation Team (ZY2025J002). 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Pharmacol. PD OCT 28 PY 2025 VL 16 AR 1682504 DI 10.3389/fphar.2025.1682504 PG 19 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 9OL1I UT WOS:001611207800001 PM 41230092 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Qin, WB Tang, WZ Wang, M Lin, L Zhang, QW Yu, LY Yang, FF He, GX AF Qin, Weibin Tang, Weizhi Wang, Meng Lin, Lin Zhang, Qingwei Yu, Liyan Yang, Feifei He, Guixin TI Qishen Yiqi Dropping Pills Combined with Exosomes Alleviate Myocardial I/R Injury by Regulating Macrophage Polarization via miRNA-155-5P SO CURRENT STEM CELL RESEARCH & THERAPY LA English DT Article; Early Access DE Qishen yiqi dropping pills; ginsenosides; exosome-based therapy; myocardial ischemia-reperfusion injury; macrophage polarization; miRNA-155-5P ID ISCHEMIA-REPERFUSION INJURY; CONTRIBUTES; ACTIVATION; INFARCTION; CANCER; NADH; ROS AB Introduction To investigate the protective mechanism of Qishen Yiqi Dropping Pills (Qishen) and its key active ingredients in combination with exosomes from bone marrow mesenchymal stem cells (BMSCs) against myocardial ischemia/reperfusion (I/R) injury.Methods Infarct area was assessed by Evan's Blue/TTC double staining, myocardial apoptosis was analyzed by TUNEL staining, ATP content and NAD+/NADH ratio were detected biochemically, macrophage phenotype of myocardial tissues was detected by flow cytometry, activation of the mTOR/PI3K/Akt pathway was detected by Western blotting, and miR-155-5p expression was detected by qRT-PCR. 155-5p expression. Exo were given to identify the M1/M2 phenotypic transition by immunofluorescence, and the molecular mechanism was verified as in the in vivo experiments.Results Compared with the model group, the Qishen, ginsenoside, and Exo group significantly reduced the infarcted area of the heart and promoted M2 and M2 phenotypic conversion, promoted M2-type macrophage infiltration, up-regulated the p-Akt/Akt ratio, and inhibited the expression of miR-155-5p, but the combination therapy group did not show a synergistic effect, but the above protective effects were significantly weakened by the removal of macrophages. Ginsenoside and Exo synergistically promoted M2 polarization, activated the mTOR/PI3K/Akt pathway and upregulated miR-155-5p expression.Discussion Qishen, particularly its active component ginsenoside, synergizes with BMSC-Exo to alleviate myocardial I/R injury by modulating macrophage polarization via the miR-155-5p/mTOR/PI3K/Akt signaling axis.Conclusion Qishen synergistically regulates the miR-155-5p/mTOR/PI3K/Akt signaling axis through ginsenoside components in BMSCs exosomes, promoting macrophage polarization toward M2-type, improving myocardial energy metabolism and attenuating I/R injury, and this protective effect is macrophage-dependent. C1 [Qin, Weibin; Wang, Meng; Lin, Lin; Zhang, Qingwei; Yu, Liyan] Guangxi Univ Chinese Med, Affiliated Hosp 1, Cardiovasc Med 2, Nanning 530000, Guangxi, Peoples R China. [Tang, Weizhi; Yang, Feifei] Guangxi Univ Chinese Med, Clin Med Coll 1, Nanning 530000, Guangxi, Peoples R China. [He, Guixin] Guangxi Univ Chinese Med, Int Zhuang Med Hosp, Cardiovasc Med, Nanning 530000, Guangxi, Peoples R China. C3 Guangxi University of Chinese Medicine; Guangxi University of Chinese Medicine; Guangxi University of Chinese Medicine RP Yang, FF (corresponding author), Guangxi Univ Chinese Med, Clin Med Coll 1, Nanning 530000, Guangxi, Peoples R China.; He, GX (corresponding author), Guangxi Univ Chinese Med, Int Zhuang Med Hosp, Cardiovasc Med, Nanning 530000, Guangxi, Peoples R China. EM he_guixin@163.com; ffy0510@126.com RI qin, weibin/MDS-6613-2025; Zhang, Yu-Qin/AEH-7339-2022 FU National Natural Science Foundation of China [81960861]; National Traditional Chinese Medicine Inheritance and Innovation Center Project [2023019-11]; Guangxi Natural Science Foundation Project [2020JJD140038]; Yao Chun Gui School of Chinese Medicine Master Inheritance Workshop [GZY2024002]; Innovation Project of Guangxi Graduate Education [YCBZ2024157] FX The work is supported by National Natural Science Foundation of China (81960861), National Traditional Chinese Medicine Inheritance and Innovation Center Project (2023019-11), Guangxi Natural Science Foundation Project (2020JJD140038), Yao Chun Gui School of Chinese Medicine Master Inheritance Workshop (GZY2024002), Innovation Project of Guangxi Graduate Education (YCBZ2024157). 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Stem Cell Res. Ther. PD 2025 OCT 27 PY 2025 DI 10.2174/011574888X408846251007045430 EA OCT 2025 PG 16 WC Cell & Tissue Engineering; Cell Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology GA L9848 UT WOS:001630113400001 PM 41147270 DA 2026-03-26 ER PT J AU Qin, RZ Peng, SY Huang, ZX Zhang, BF Tang, RN Zhao, YC Jiang, FS Xu, XH Pan, JL Li, MY AF Qin, Run-ze Peng, Su-yu Huang, Zi-xin Zhang, Bo-fei Tang, Ruo-nan Zhao, Yu-cong Jiang, Fu-sheng Xu, Xiao-hua Pan, Jie-li Li, Mei-ya TI Coelonin, an active component extract from Bletilla striata (Thunb.) Reichb. f., alleviates lipopolysaccharide-induced acute lung injury by increasing the expression of non-coding RNA Gm27505 and inhibiting the M1 polarization of macrophages caused by inflammatory responses SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE Acute lung injury; Coelonin; ncRNA; Gm27505; macrophages polarization; Inflammation ID ALZHEIMERS-DISEASE; PATHOPHYSIOLOGY; OUTCOMES; PATHWAY AB Coelonin is a dihydrophenanthrene compound derived from the traditional Chinese medicine Bletilla striata (Thunb.) Reichb.f., which exhibits significant anti-inflammatory activity and effectively inhibits lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 cells. Although previous studies have demonstrated the protective effect of Bletilla striata against LPS-induced acute lung injury (ALI), the potential protective role and underlying molecular mechanisms of its major active component, Coelonin, in ALI remain unclear. In this study, an LPS-induced mouse ALI model was established to systematically evaluate the protective effects of Coelonin on ALI. Furthermore, transcriptomic analysis was utilized to investigate the anti-inflammatory mechanisms mediated by Coelonin through the regulation of non-coding RNA (ncRNA)-associated inflammatory pathways. The results indicated that Coelonin significantly ameliorated LPS-induced pathological damage in lung tissues and markedly reduced the levels of inflammatory markers in bronchoalveolar lavage fluid (BALF). In vitro experiments using the murine alveolar macrophages (MH-S) cell line further confirmed the anti-inflammatory activity of Coelonin. Transcriptome analysis revealed that Coelonin markedly upregulates the expression of the ncRNA Gm27505, which was previously found to be downregulated in a mouse model of Alzheimer's disease. To date, there have been no reports on the biological functions of Gm27505. Bioinformatics analysis and realtime quantitative fluorescence PCR (qPCR) confirmed that this ncRNA is primarily localized within the nucleus. Overexpression of Gm27505 in MH-S cells significantly downregulated the expression of inflammation-related genes such as Il6, Tnf alpha, Il27, and Ccl3 induced by LPS stimulation. Moreover, overexpression of Gm27505 promoted macrophage polarization toward the M2 phenotype while suppressing M1 polarization. These findings suggest that the ncRNA Gm27505 plays an important biological role and is critically involved in the regulation of inflammatory responses. Coelonin may alleviate LPS-induced ALI in mice by up-regulating Gm27505 expression and modulating macrophage polarization. Therefore, Gm27505 may represent a potential target for the prevention and treatment of ALI, providing new research directions for future therapeutic strategies against related diseases. C1 [Qin, Run-ze; Peng, Su-yu; Huang, Zi-xin; Zhao, Yu-cong; Jiang, Fu-sheng; Li, Mei-ya] Zhejiang Chinese Med Univ, Coll Pharmaceut Sci, Hangzhou 310053, Zhejiang, Peoples R China. [Pan, Jie-li; Li, Mei-ya] Zhejiang Chinese Med Univ, Acad Chinese Med Sci, Hangzhou 310053, Peoples R China. [Zhang, Bo-fei; Tang, Ruo-nan] Zhejiang Chinese Med Univ, Coll Life Sci, Hangzhou 310053, Zhejiang, Peoples R China. [Xu, Xiao-hua] Peoples Hosp Quzhou, Quzhou 324002, Peoples R China. C3 Zhejiang Chinese Medical University; Zhejiang Chinese Medical University; Zhejiang Chinese Medical University RP Li, MY (corresponding author), Zhejiang Chinese Med Univ, Coll Pharmaceut Sci, Hangzhou 310053, Zhejiang, Peoples R China.; Pan, JL; Li, MY (corresponding author), Zhejiang Chinese Med Univ, Acad Chinese Med Sci, Hangzhou 310053, Peoples R China.; Xu, XH (corresponding author), Peoples Hosp Quzhou, Quzhou 324002, Peoples R China. EM 406302383@qq.com; panjieli_zj@163.com; lmeiya@126.com FU Zhejiang Provincial Natural Science Foundation of China [LY23H280002]; Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project [2024ZF181]; Xinmiao Talent Project of Zhejiang Province [2025R435007]; Academy of Chinese Medical Sciences Research Competition Project at Zhejiang Chinese Medicine University [2024J03] FX The present research was carried out with the financial support of Zhejiang Provincial Natural Science Foundation of China (No. LY23H280002) , a grant from the Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project (No. 2024ZF181) , a grant from Xinmiao Talent Project of Zhejiang Province (No. 2025R435007) and a grant from the Academy of Chinese Medical Sciences Research Competition Project at Zhejiang Chinese Medicine University (No. 2024J03) . 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J. Biochem. Cell Biol. PD DEC PY 2025 VL 189 AR 106871 DI 10.1016/j.biocel.2025.106871 EA OCT 2025 PG 16 WC Biochemistry & Molecular Biology; Cell Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Cell Biology GA 9GA4W UT WOS:001605476400001 PM 41110688 DA 2026-03-26 ER PT J AU Zhao, WJ Wang, H Peng, SJ Wei, Q Zhang, L Li, YL Yang, WQ AF Zhao, Wenjie Wang, Hui Peng, Shijing Wei, Qing Zhang, Lei Li, Yunlun Yang, Wenqing TI Ershen Dan attenuates atherosclerosis by modulating the NOTCH1/NF-κB/NLRP3 signaling pathway to suppress M1 macrophage polarization SO CHINESE MEDICINE LA English DT Article AB BackgroundAtherosclerosis is a chronic inflammatory disease. Inhibition of macrophage inflammatory secretion is the key to the prevention and treatment of atherosclerosis. Ershen Dan (ESD) has been shown to be effective in treating atherosclerosis; however, its pharmacological mechanisms remain unclear. This study elucidated the mechanism of action of ESD by investigating its relationship with macrophages.Materials and methodsThe chemical composition of ESD was analyzed using ultra performance liquid chromatography (UPLC)-Q-Exactive-tandem mass spectrometry (MS/MS). In the in vivo experiments, serum levels of low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (TC) in ApoE-/- mice were measured using a biochemical analyzer. The serum levels of key inflammatory factors were quantified using an enzyme-linked immunosorbent assay (ELISA). The aortic lipid plaque area was assessed using Oil Red O staining, while plaque characteristics were evaluated using hematoxylin and eosin (H&E), Masson trichrome, and Sirius Red staining techniques. Network pharmacology analyses in conjunction with molecular dynamics simulations was used to screen the active components of ESD and their target proteins. By integrating database resources, the key target genes related to inflammatory responses in atherosclerosis were identified. The expression levels of neurogenic locus notch homolog protein 1 (NOTCH1), hairy and enhancer of split-1 (HES1), NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), and nuclear factor (NF)-kappa B in mouse aortic tissue were detected using western blot analyses. CD86 levels in mouse aortas were quantitatively analyzed by immunohistochemistry. In the in vitro experiments, RAW264.7 cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. Macrophage phenotypic changes were evaluated using immunofluorescence analyses. Intracellular levels of reactive oxygen species (ROS) were measured using dichloro-dihydro-fluorescein diacetate (DCFH-DA) probes. The expression levels of key proteins and genes were validated by western blotting and quantitative real-time polymerase chain reaction (qRT-PCR).ResultsTwenty bioactive chemical components were identified in ESD. In vivo studies demonstrated that ESD inhibits macrophage secretion of inflammatory factors through the NOTCH1/NF-kappa B/NLRP3 signaling pathway, indicating its therapeutic potential for atherosclerosis. In vitro studies further revealed that ginsenoside Rg1 and tanshinone IIA, which are active constituents of ESD, exert anti-inflammatory effects by suppressing the NOTCH1/NF-kappa B/NLRP3 pathway and reducing intracellular ROS levels in macrophages, supporting their role in atherosclerosis treatment. C1 [Zhao, Wenjie; Wang, Hui; Peng, Shijing; Wei, Qing; Li, Yunlun; Yang, Wenqing] Shandong Univ Tradit Chinese Med, Innovat Res Inst Tradit Chinese Med, Jinan 250300, Peoples R China. [Zhang, Lei; Yang, Wenqing] Shandong Univ Tradit Chinese Med, Key Lab Tradit Chinese Med Class Theory, Minist Educ, Jinan, Peoples R China. [Zhang, Lei] Shandong Univ Tradit Chinese Med, Affiliated Hosp, Dept Cardiovasc, Jinan 250014, Peoples R China. [Li, Yunlun] Shandong Prov Engn Res Ctr Precis Diag & Treatment, Jinan 250300, Peoples R China. C3 Shandong University of Traditional Chinese Medicine; Shandong University of Traditional Chinese Medicine; Shandong University of Traditional Chinese Medicine RP Li, YL; Yang, WQ (corresponding author), Shandong Univ Tradit Chinese Med, Innovat Res Inst Tradit Chinese Med, Jinan 250300, Peoples R China.; Yang, WQ (corresponding author), Shandong Univ Tradit Chinese Med, Key Lab Tradit Chinese Med Class Theory, Minist Educ, Jinan, Peoples R China.; Li, YL (corresponding author), Shandong Prov Engn Res Ctr Precis Diag & Treatment, Jinan 250300, Peoples R China. EM yunlun.lee@hotmail.com; wenqing-yang@hotmail.com RI Yang, Wenqing/F-7026-2011 FU National Science Foundation of China; Open Project of the Key Laboratory of Classical Theory of Traditional Chinese Medicine, Ministry of Education, China FX This research was supported by the Open Project of the Key Laboratory of Classical Theory of Traditional Chinese Medicine, Ministry of Education, China. CR Aday AW, 2021, CIRC RES, V128, P1818, DOI 10.1161/CIRCRESAHA.121.318535 Akoumianakis I, 2022, NAT REV CARDIOL, V19, P783, DOI 10.1038/s41569-022-00718-5 [Anonymous], 2020, Pharmacopoeia of the People's Republic of China Buldak L, 2022, INT J MOL SCI, V23, DOI 10.3390/ijms23094695 Chen WJ, 2023, CHIN MED-UK, V18, DOI 10.1186/s13020-023-00784-y Chen XX, 2022, LANCET, V400, P1967, DOI 10.1016/S0140-6736(22)01546-X Fan JL, 2022, PATHOL INT, V72, P151, DOI 10.1111/pin.13202 Geng JA, 2020, FRONT PHARMACOL, V11, DOI 10.3389/fphar.2020.00500 Hu SS, 2023, J GERIATR CARDIOL, V20, P399, DOI 10.26599/1671-5411.2023.06.001 Hu XR, 2023, MOLECULES, V28, DOI 10.3390/molecules28052140 Jiang S, 2024, NUCLEIC ACIDS RES, V53, pD1670, DOI 10.1093/nar/gkae973 Kong P, 2022, SIGNAL TRANSDUCT TAR, V7, DOI 10.1038/s41392-022-00955-7 Lei Q, 2021, CIRC RES, V129, P1141, DOI 10.1161/CIRCRESAHA.121.318908 Li L, 2022, PATHOL RES PRACT, V234, DOI 10.1016/j.prp.2022.153894 Li XD, 2020, INT IMMUNOPHARMACOL, V88, DOI 10.1016/j.intimp.2020.106911 Libby P, 2021, CARDIOVASC RES, V117, P2525, DOI 10.1093/cvr/cvab303 Libby P, 2021, NATURE, V592, P524, DOI 10.1038/s41586-021-03392-8 Miao JY, 2020, ADV EXP MED BIOL, V1207, P237, DOI 10.1007/978-981-15-4272-5_18 Noreng S, 2022, NAT COMMUN, V13, DOI 10.1038/s41467-022-33711-0 Park JH, 2023, J ETHNOPHARMACOL, V309, DOI 10.1016/j.jep.2023.116362 Poznyak AV, 2021, INT J MOL SCI, V22, DOI 10.3390/ijms22137061 Schroeter MR, 2009, ATHEROSCLEROSIS, V205, P63, DOI 10.1016/j.atherosclerosis.2008.11.013 Sha Y., 2020, J Shandong Univ Tradit Chin Med, V44, P356 Song LX, 2022, FRONT IMMUNOL, V13, DOI 10.3389/fimmu.2022.910444 Su JS, 2023, J ETHNOPHARMACOL, V310, DOI 10.1016/j.jep.2023.116402 Sul OJ, 2021, MOLECULES, V26, DOI 10.3390/molecules26226949 Sun JX, 2022, J ETHNOPHARMACOL, V294, DOI 10.1016/j.jep.2022.115368 Wang JZ, 2024, J CHEM INF MODEL, V64, P9009, DOI 10.1021/acs.jcim.4c01558 Wang N, 2020, LANCET DIABETES ENDO, V8, P36, DOI 10.1016/S2213-8587(19)30388-2 Wang ST, 2022, FRONT PHARMACOL, V12, DOI 10.3389/fphar.2021.764130 Wang WT, 2024, PHYTOMEDICINE, V129, DOI 10.1016/j.phymed.2024.155591 Wang Y, 2022, PHARMACOL RES, V179, DOI 10.1016/j.phrs.2022.106236 Wei BY, 2023, J ETHNOPHARMACOL, V317, DOI 10.1016/j.jep.2023.116697 Wei EH, 2021, CELL TRANSPLANT, V30, DOI 10.1177/09636897211002787 Wu Ruoyu, 2023, Cardiovasc Hematol Agents Med Chem, V21, P232, DOI [10.2174/1871525721666230206112134, 10.2174/1871525721666230206112134] Xie FB., 1987, J Sichuan Tradit Chin Med, V2, P26 Xu RN, 2024, TRENDS ENDOCRIN MET, V35, P981, DOI 10.1016/j.tem.2024.04.009 Xu Z, 2024, J ETHNOPHARMACOL, V319, DOI 10.1016/j.jep.2023.117356 Yang H, 2022, CURR PHARM DESIGN, V28, P671, DOI 10.2174/1381612828666220128104636 You L, 2022, J GINSENG RES, V46, P711, DOI 10.1016/j.jgr.2021.12.007 Zhang XY, 2021, FRONT PHARMACOL, V12, DOI 10.3389/fphar.2021.753881 Zhang ZQ, 2023, BBA-MOL BASIS DIS, V1870, DOI 10.1016/j.bbamcr.2023.119521 Zhao YX, 2021, PHYTOMEDICINE, V84, DOI 10.1016/j.phymed.2021.153519 Zheng Y, 2022, CELL MOL LIFE SCI, V79, DOI 10.1007/s00018-022-04331-0 Zhou ZK, 2024, NUTRIENTS, V16, DOI 10.3390/nu16010099 NR 45 TC 1 Z9 1 U1 7 U2 7 PU BMC PI LONDON PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1749-8546 J9 CHIN MED-UK JI Chin. Med. PD OCT 23 PY 2025 VL 20 IS 1 AR 178 DI 10.1186/s13020-025-01232-9 PG 20 WC Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine; Pharmacology & Pharmacy GA 8WS4B UT WOS:001599151400003 PM 41131540 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhai, Q Liang, FY Yang, GL Liu, ZM Dong, X Bu, R Xue, PF Na, SS Zhang, X Zhao, PW Wang, XN Wei, Q Lu, JK Wang, YW AF Zhai, Qiong Liang, Fangyuan Yang, Guanlin Liu, Zhimin Dong, Xin Bu, Ren Xue, Peifeng Na, Shengsang Zhang, Xuan Zhao, Pengwei Wang, Xiaoning Wei, Qiang Lu, Jingkun Wang, Yuewu TI Zhuriheng pills improve adipose tissue dysfunction and inflammation by modulating PPARγ to stabilize atherosclerotic plaques SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE Zhuriheng Pills; Atherosclerotic plaques; the adipose tissue dysfunction and inflammation; PPAR gamma signaling pathway; the adipose tissue dysfunction; the adipose tissue inflammation ID TARGETS AB Background Adipose tissue dysfunction and chronic inflammation contribute to atherosclerosis plaque development. Zhuriheng pills (ZRH) are an effective Mongolian herbal formula used in treating coronary heart disease in China, but their mechanisms of action have not been fully elucidated.Purpose To assess whether ZRH alleviates atherosclerosis (AS) and stabilizes plaque, this study investigates the modulatory effects of ZRH on AS and adipose tissue profiles in atherosclerotic model mice with vulnerable plaque to reveal the potential mechanisms and representative quality markers (Q-markers) of ZRH.Methods In vivo, the vulnerable atherosclerotic plaque model was induced in ApoE-/- mice treated with intense co-stimulation. The anti-AS effect of ZRH was assessed by serum lipid profile, hematoxylin-eosin (HE), Oil O Red, Masson staining, immunohistochemistry (IHC), immunofluorescence, and plasma lipidomics. In vitro, a co-culture model was established with 3T3-L1 adipocytes treated with palmitic acid (PA) and RAW264.7 macrophages treated with lipopolysaccharide (LPS). The potential mechanism and Q-markers of ZRH were identified by lipid content test, inflammatory factors and adipocytokine analysis, flow cytometry for macrophage polarization, and Western blotting for PPAR gamma and UCP-1 proteins.Results In vivo, ZRH stabilizes plaques by improving serum lipid profiles, lowering macrophage infiltration, and boosting collagen content in plaques. ZRH can counteract HFD-induced adipocyte hypertrophy, increase UCP-1 and PPAR gamma expression, enhance the "browning" of adipose tissue, and inhibit macrophage M1 polarization. Lipidomics results showed that ZRH treatment increased the abundance of lipid species with multiple unsaturated bonds and decreased harmful TAG, DAG, and HexCer. In addition, ZRH regulates inflammatory factors and adipokines in co-culture to inhibit macrophage M1 polarization and adipocyte abnormal lipid metabolism. In contrast, RDK and its monomers have a stronger anti-inflammatory effect, whereas GZ and its monomers regulate lipid metabolism better. ZRH was shown to be a PPAR gamma agonist for improving adipose tissue dysfunction and inflammation for anti-AS effects of ZRH. MIX, which comprises ellagic acid (G3), quercetin (G8), 3,3 '-Di-O-methylellagic acid (G9), elemicin (R5), and safrole (R8) in equal proportions, is only one of ZRH's Q-markers. More research is needed on the roles of different ZRH metabolites.Conclusion Our results demonstrated that ZRH stabilizes atherosclerotic plaques by ameliorating adipose tissue dysfunction and inflammation by regulating the PPAR gamma pathway. C1 [Zhai, Qiong; Zhang, Xuan; Zhao, Pengwei; Wang, Xiaoning; Wei, Qiang; Lu, Jingkun] Inner Mongolia Med Univ, Sch Basic Med, Hohhot, Peoples R China. [Liang, Fangyuan] Nantong Vocat Univ, Sch Pharmaceut & Environm Engn, Nantong, Peoples R China. [Yang, Guanlin] Zaozhuang Thorac Hosp, Zaozhuang Canc Hosp, Pharmaceut Dept, Zaozhuang, Peoples R China. [Liu, Zhimin] Chifeng Coll, Affiliated Hosp, Pharmaceut Dept, Chifeng, Peoples R China. [Dong, Xin; Bu, Ren; Xue, Peifeng; Wang, Yuewu] Inner Mongolia Med Univ, Sch Pharm, Hohhot, Peoples R China. [Na, Shengsang] Inner Mongolia Med Univ, Med Innovat Ctr Nationalities, Hohhot, Peoples R China. C3 Inner Mongolia Medical University; Chifeng University; Inner Mongolia Medical University; Inner Mongolia Medical University RP Lu, JK (corresponding author), Inner Mongolia Med Univ, Sch Basic Med, Hohhot, Peoples R China.; Wang, YW (corresponding author), Inner Mongolia Med Univ, Sch Pharm, Hohhot, Peoples R China. EM 20070123@immu.edu.cn; wywimmu@163.com RI Dong, Xin/IUO-2907-2023 FU National Natural Science Foundation of China [81960757 82260813] FX The author(s) declare that financial support was received for the research and/or publication of this article. This research was funded by the National Natural Science Foundation of China (grant no. 81960757, 82260813), the Scientific and Technological Transformative Project of the Inner Mongolia Autonomous Region of China (grant no. 2019CG042, 2023YFDZ0059), the Key Programs at the Inner Mongolia Medical University of China (grant no. YKD2023ZD005), and the Natural Science Research Project of the Nantong Vocational University of China (grant no. 24ZK07). 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PD OCT 20 PY 2025 VL 16 AR 1576521 DI 10.3389/fphar.2025.1576521 PG 20 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 9GD2E UT WOS:001605547400001 PM 41190023 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Han, YC Li, MT Chen, T Wang, C Zhou, H Zhou, TA Jia, RQ Chen, Y Hu, Q AF Han, Yuncong Li, Mengting Chen, Tian Wang, Chen Zhou, Hong Zhou, Tunan Jia, Runqing Chen, Ying Hu, Qin TI Berberine Alleviates Intestinal Inflammation by Disrupting Pathological Macrophage-Epithelial Crosstalk in Macrophage-Organoid Co-Culture Model SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE berberine; intestinal organoid; co-culture model; anti-inflammation ID MUCOSAL BARRIER; INDUCED COLITIS; ACTIVATION; RESPONSES; CELLS; PATHWAY; PROTEIN AB Berberine (BBR), a benzylisoquinoline alkaloid isolated from Chinese herb Coptis chinensis, has been widely used clinically to treat intestinal infectious diseases. Recently, it has been found to have multiple pharmacological effects, including anti-inflammatory activity and immune effects in inflammatory bowel disease (IBD). However, its exact targets remain to be elucidated. In this study, we used a mouse intestinal organoid-macrophage co-culture model to investigate the anti-inflammatory effects and immune effects of BBR. Our findings demonstrated that lipopolysaccharide (LPS) induced more robust inflammatory responses and epithelium damage in the co-culture system compared to the organoid alone. BBR effectively attenuated inflammation and restored epithelial barrier integrity by suppressing M1 macrophage polarisation and infiltration, alongside upregulating the expression and organisation of tight junction protein zonula occludens-1 (ZO-1). RNA sequencing and proteomic analysis revealed that BBR disrupted organoid-macrophage interaction by inhibiting chemokine (e.g., C-X-C motif chemokine ligand 1 (CXCL1) and macrophage migration inhibitory factor (MIF)) release from epithelial cells, thereby reducing macrophage recruitment. Collectively, our study establishes the organoid-macrophage co-culture system as a more physiologically relevant model for studying epithelial-immune interactions and elucidates the multi-target mechanism of BBR, which concurrently modulates epithelial cells, macrophages, and their crosstalk. These findings lay the foundation for further exploration of the therapeutic potential of BBR in inflammatory bowel disease and the development of targeted therapies that regulate cell interactions. C1 [Han, Yuncong; Chen, Tian; Wang, Chen; Zhou, Hong; Zhou, Tunan; Jia, Runqing; Hu, Qin] Beijing Univ Technol, Coll Chem & Life Sci, Beijing 100124, Peoples R China. [Li, Mengting; Chen, Ying] China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China. C3 Beijing University of Technology; China Academy of Chinese Medical Sciences; Institute of Chinese Materia Medica, CACMS RP Jia, RQ; Hu, Q (corresponding author), Beijing Univ Technol, Coll Chem & Life Sci, Beijing 100124, Peoples R China. EM hanyuncong@emails.bjut.edu.cn; lmthahaha@outlook.com; chentian@emails.bjut.edu.cn; wangchen202484048@emails.bjut.edu.cn; zhouhong@emails.bjut.edu.cn; z969081067@emails.bjut.edu.cn; runqingjia@bjut.edu.cn; ychen@icmm.ac.cn; hq07616@bjut.edu.cn OI HU, QIN/0000-0003-1196-879X FU National Natural Science Foundation of China [82074103]; Fundamental Research Funds [ZXKT25004]; National Key Research and Development Program of China [2023YFF0724803]; Major Science and Technology Project in the Autonomous Region [2023A02010-3]; Space Medical Experiment Project of CMSP [HYZHXMX2003] FX This research was funded by the National Key Research and Development Program of China (No. 2023YFF0724803), Major Science and Technology Project in the Autonomous Region (2023A02010-3), the National Natural Science Foundation of China (No. 82074103), the Fundamental Research Funds for the Central public welfare research institutes (ZXKT25004), and Space Medical Experiment Project of CMSP (HYZHXMX2003). 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J. Mol. Sci. PD OCT 19 PY 2025 VL 26 IS 20 AR 10161 DI 10.3390/ijms262010161 PG 19 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry GA 9AL4O UT WOS:001601684300001 PM 41155453 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Yang, YY Wang, XY Kong, YQ Pan, Y Yang, XD Zhang, ZY Li, ZG AF Yang, Yuanyuan Wang, Xiaoyu Kong, Youqian Pan, Yang Yang, Xiadong Zhang, Ziyi Li, Zeguang TI Modulating M1/M2 macrophage polarization with plant metabolites: a therapeutic strategy for rheumatoid arthritis SO FRONTIERS IN PHARMACOLOGY LA English DT Review DE plant metabolite; macrophage polarization; rheumatoid arthritis; mechanism; traditional Chinese medicine ID NF-KAPPA-B; TRIPTOLIDE; ACTIVATION; INJURY AB Rheumatoid arthritis (RA) is a systemic autoimmune disorder marked by persistent synovitis and the degradation of joint cartilage and surrounding bone due to inflammation. A variety of immune cells, particularly macrophages, are involved in the initiation and maintenance of inflammation in RA, along with leukocyte adhesion and migration, matrix breakdown, and neovascularization. Environmental and internal stimuli drive macrophages to polarize into two major phenotypes: M1, which exerts strong bactericidal effects and contributes to chronic inflammation and tissue injury, and M2, which inhibits inflammation and facilitates tissue repair. The dysregulation of M1/M2 macrophage polarization is a key contributor to the pathogenesis and disease progression of RA. Plant metabolites are typically characterized by multi-component, multi-target, and multi-pathway actions, and their underlying mechanisms may include regulation of immune function, especially the balance of macrophage polarization. Current evidence indicates that such metabolites may provide certain therapeutic benefits and a relatively manageable safety profile in the management of RA and related disorders. In this review, we summarize the potential mechanisms by which various plant metabolites modulate macrophage function and polarization under inflammatory conditions, providing evidence for their clinical application in RA treatment and offering new insights into precision therapy for RA. C1 [Yang, Yuanyuan; Wang, Xiaoyu; Pan, Yang; Yang, Xiadong; Zhang, Ziyi] Heilongjiang Univ Chinese Med, Grad Sch, Harbin, Peoples R China. [Kong, Youqian] Lanzhou Univ, Hosp 1, Dept Tradit Chinese Med, Lanzhou, Peoples R China. [Li, Zeguang] Heilongjiang Univ Chinese Med, Affiliated Hosp 1, Harbin, Peoples R China. C3 Heilongjiang University of Chinese Medicine; Lanzhou University; Heilongjiang University of Chinese Medicine RP Li, ZG (corresponding author), Heilongjiang Univ Chinese Med, Affiliated Hosp 1, Harbin, Peoples R China. 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Pharmacol. PD OCT 17 PY 2025 VL 16 AR 1651763 DI 10.3389/fphar.2025.1651763 PG 14 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 9FN4N UT WOS:001605136500001 PM 41181606 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Song, QY Cui, YJ Lu, WP AF Song, Qing-Ya Cui, Yong-Jia Lu, Wen-Ping TI Isolation of exosome-like nanovesicles from Yiqi Huoxue Jiedu decoction and their anti-ovarian cancer activity SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE Chinese medicine compound; exosome-like nanovesicles (ELNVs); decoction conditions; isolate; ovarian cancer ID CELLS; SAFETY AB Background: Ovarian cancer, the deadliest gynecologic malignancy, is marked by high recurrence and poor prognosis. Exosome-like nanovesicles (ELNVs) derived from decocted traditional Chinese medicine (TCM) formulas encapsulate key bioactive components, and show promising therapeutic efficacy with good biocompatibility and targeting ability. However, research on ELNV extraction methodologies remains limited. Yiqi Huoxue Jiedu Decoction (YQHXJDD), an empirically validated TCM formula for ovarian cancer, lacks systematic investigation into its ELNV isolation protocols and therapeutic mechanisms. This study took YQHXJDD as the research subject, with a focus on extracting ELNVs from this TCM formula and validating their anti-ovarian cancer activity. Methods: YQHXJDD was extracted using varied decoction protocols. ELNVs were enriched by gradient and ultracentrifugation, resuspended in phosphate-buffered saline, and were characterized by size and concentration using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The number of ELNVs enriched per dose of YQHXJDD was calculated to screen the decoction method that maximized ELNV yield and aligned with clinical medication practices. The colloidal stability of YQHXJDD ELNVs was evaluated via zeta potential measurement, and the bioactive components of YQHXJDD ELNVs were identified using untargeted metabolomics and RNA sequencing. An ID8-Luc peritoneal tumor-bearing mouse model was established and randomized into three groups: model, YQHXJDD, and YQHXJDD ELNVs. Mice received oral gavage for 3 consecutive weeks. Tumor burden was monitored via in vivo small animal imaging. Immunofluorescence was used to quantify CD86, CD206, CD4, and CD8 fluorescence in omental tumors. Luminex xMAP (R) Multiplex Assay was used to detect 36 cytokines/chemokines in serum, and flow cytometry was used to analyze splenic immune cell proportions and activity. Results: The creation efficiency of ELNVs formed during decoction is the highest with the optimal protocol, which is identified for maximizing YQHXJDD ELNV yield and involves 40 min of high-heat treatment followed by an additional 30 min of low-heat treatment. Zetaview-based zeta potential analysis demonstrated that YQHXJDD ELNVs by this protocol had an average zeta potential of -35.52 mV, indicating favorable colloidal stability. Untargeted metabolomics analysis revealed "Lipids and lipid-like molecules" as the most abundant metabolite superclass (34.98% of total metabolites), while "Carboxylic acids and derivatives" represented the dominant subclass (11.66%). Regarding small RNAs, those enriched in YQHXJDD ELNVs were confirmed to be typical, functionally active small RNAs. Notably, miR8783 and other miRNAs exhibited significantly high expression, along with high conservation and abundance across samples, suggesting they might act as core regulators of YQHXJDD ELNV biological functions. In in vivo assessments, compared with the model group, YQHXJDD ELNVs significantly inhibited ovarian cancer growth and metastasis, increased tumor necrosis factor-alpha (TNF-alpha) levels in mouse peripheral blood, and positively regulated the M1/M2 macrophage ratio and CD4(+)/CD8(+) T cell ratio in omental tissues (all P < 0.05). However, YQHXJDD ELNVs had no significant effect on the proportions of splenic effector T cells, natural killer (NK) cells, activated CD8(+) T cells, and activated NK cells (all P >= 0.05). Conclusion: The decoction ELNVs isolated from YQHXJDD can inhibit the growth and dissemination of ovarian cancer. The miRNAs and lipid components encapsulated in these ELNVs are presumed to be the critical mediators of these anti-ovarian cancer effects. C1 [Song, Qing-Ya; Cui, Yong-Jia; Lu, Wen-Ping] China Acad Chinese Med Sci, Guanganmen Hosp, Dept Oncol, Beijing, Peoples R China. C3 China Academy of Chinese Medical Sciences; Guang'anmen Hospital, CACMS RP Lu, WP (corresponding author), China Acad Chinese Med Sci, Guanganmen Hosp, Dept Oncol, Beijing, Peoples R China. EM lu_wenping@sina.com FU National Natural Science Foundation of China FX The author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by grants from National Natural Science Foundation of China (Grant Number 82474354). 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PD OCT 15 PY 2025 VL 16 AR 1680551 DI 10.3389/fphar.2025.1680551 PG 16 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 9ES1O UT WOS:001604576700001 PM 41170390 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Huang, YJ Chen, HW Jiang, YH Meng, ZW She, C Miao, ZY Fan, YL AF Huang, Yongjun Chen, Haowei Jiang, Yuhan Meng, Ziwei She, Chun Miao, Zhiying Fan, Youlong TI Ailanthone: A multi-targeting Quassinoid from Ailanthus altissima for broad-spectrum cancer therapy-a comprehensive review of mechanisms, pharmacokinetics, and clinical prospects SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Ailanthone; Anticancer; Pharmacological activities; Mechanisms of action; Pharmacokinetics; Toxicology ID CELL-CYCLE ARREST; CHINESE MEDICINE; DOWN-REGULATION; RESISTANCE; APOPTOSIS; PROLIFERATION; CISPLATIN; GROWTH; NRF2; YAP AB Ethnopharmacological relevance: Ailanthus altissima (Mill.) Swingle (A. altissima) has been used in traditional Chinese medicine for centuries. In recent years, its active compound, ailanthone, has received increasing attention due to its significant anti-tumor activity. Ailanthone exhibits several advantageous properties, including multi-target synergy in anti-tumor effects, broad-spectrum anticancer activity, the ability to overcome drug resistance, and good bioavailability. This positions it as a promising candidate for tumour treatment. Aim of the review: This review aims to explore the anti-tumour activities and pharmacological mechanisms of ailanthone, providing a foundation for further investigation of its therapeutic potential. Methods: We have systematically summarized the current knowledge of ailanthone's pharmacological activities, mechanisms of action, pharmacokinetic characteristics, toxicology and toxicokinetics in tumor therapy (up to 2025). Furthermore, we analyzed, discussed and prospected the current research deficiencies of ailanthone and its limitations in clinical applications. Results: Ailanthone exhibits anti-cancer activity against variety of cancers, including lung cancer, tongue squamous cell carcinoma, glioblastoma, colorectal cancer, melanoma, breast cancer, gastric cancer, osteosarcoma, renal cell carcinoma, bladder cancer, hepatic cancer, prostate cancer, leukemia and ovarian cancer. The broadspectrum anti-cancer effects of ailanthone are mediated by triggering ferroptosis/apoptosis/autophagy, inducing mitochondrial/DNA damage while blocking DNA repair, arresting cell cycle and suppressing proliferation/ migration/invasion/EMT and remodeling tumor microenvironment via inhibiting macrophage polarization and osteoclast differentiation. The corresponding targets and molecular mechanisms of ailanthone in different types of tumors, including YAP, RPA1, STAT3, OTUB1, P23, lncRNAs, miRNAs, NF-kappa B, JAK/STAT3, AMPK/mTOR/ p70S6K, UPF1/GAS5/ULK1, PI3K/AKT/mTOR, PINK1-PRKN, HIF-1 alpha/LINC01956/FUS/beta-catenin, c-Jun-PD-L1, ATM/ATR-Chk1/Chk2 and KMT2A-MEN1. In addition, ailanthone exhibits rapid absorption and extensive tissue distribution following oral administration. However, its short half-life, low bioavailability and toxic effects significantly limit its clinical potential. Conclusion: Ailanthone exhibits significant, effective, broad-spectrum anti-tumor effects with multiple targets and mechanisms in both in vitro and in vivo models. However, challenges remain for its clinical application of ailanthone due to its short half-life, low bioavailability and off-target effects. Chemical proteomic strategies, structure-activity relationship (SAR) optimization, delivery systems and combination strategies are urgently needed to overcome these challenges. C1 [Huang, Yongjun; Chen, Haowei; Jiang, Yuhan; Meng, Ziwei] Guangxi Univ, Sch Med, Guangxi Key Lab Special Biomed, Nanning 530004, Peoples R China. [Fan, Youlong] Guangzhou Natl Lab, Guangzhou Int Bio Isl, Guangzhou, Peoples R China. [Miao, Zhiying] Gannan Med Univ, Coll Pharm, Ganzhou 341000, Peoples R China. [She, Chun] Sun Yat Sen Univ, Canc Ctr, State Key Lab Oncol South China, Guangzhou 510000, Peoples R China. C3 Guangxi University; Guangzhou Laboratory; Gannan Medical University; State Key Lab Oncology South China; Sun Yat Sen University RP Huang, YJ (corresponding author), Guangxi Univ, Sch Med, Guangxi Key Lab Special Biomed, Nanning 530004, Peoples R China.; Fan, YL (corresponding author), Guangzhou Natl Lab, Guangzhou Int Bio Isl, Guangzhou, Peoples R China.; Miao, ZY (corresponding author), Gannan Med Univ, Coll Pharm, Ganzhou 341000, Peoples R China. EM huangyj@gxu.edu.cn; miaozhiying_gmu@163.com; FAN_YOULONG@gzlab.ac.cn RI MENG, ZIWEI/KLD-7922-2024 FU Guangxi Natural Science Foundation [2025GXNSFBA069414]; Guangxi University High-level Talent Fund Project [ZX01080033724004] FX The work was supported by the Guangxi Natural Science Foundation (No. 2025GXNSFBA069414) and Guangxi University High-level Talent Fund Project (ZX01080033724004) . 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ETHNOPHARMACOL JI J. Ethnopharmacol. PD JAN 30 PY 2026 VL 355 AR 120716 DI 10.1016/j.jep.2025.120716 EA OCT 2025 PN B PG 20 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 8WJ9J UT WOS:001598930600001 PM 41083063 DA 2026-03-26 ER PT J AU Ji, XX Fang, WH Zhu, XD Zhang, YJ Zhu, WN Long, HY AF Ji, Xixi Fang, Wenhui Zhu, Xudong Zhang, Yajie Zhu, Weina Long, Hongyan TI HuangLong oral liquid alleviates cough variant asthma in mice via inhibiting M2 macrophage chemotaxis and polarization by regulating the PI3K/AKT/ERK pathway SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Cough variant asthma; HLOL; Macrophage M2 polarization; PI3K/AKT/ERK signalling pathway; Chemokine signalling pathway ID ACTIVATION AB Ethnopharmacological relevance: Huanglong Oral Liquid (HLOL), a traditional Chinese medicine formulation, has been clinically employed for decades in paediatric cough variant asthma (CVA) management, demonstrating efficacy in symptom relief. Nevertheless, the molecular mechanisms governing the therapeutic effects of HLOL remain incompletely characterised. Aim of the study: This study seeks to decipher how HLOL alleviates Ovalbumin-induced airway inflammation and hyperresponsiveness in murine CVA models. Materials and methods: The main chemical components of HLOL were identified using liquid chromatography tandem mass spectrometry (HPLC-MS). OVA was used to establish a CVA mouse model, and the antiinflammatory and anti-airway hyperresponsiveness therapeutic effects of HLOL were evaluated using pathological staining, capsaicin inhalation experiment, and lung function tests. Through RNA-sequencing (RNA-seq) revealed the potential mechanism of HLOL in regulating M2 recruitment and polarization in the lung tissues of CVA mice, which was further verified via in vivo and in vitro experiments using quantitative polymerase chain reaction, enzyme linked immunosorbent assay, western blot, immunofluorescence staining, immunohistochemistry for paraffin-embedded sections, and cell migration assays. Results: HPLC-MS analysis identified 40 potential active ingredients. HLOL improved lung function in CVA mice, attenuated airway hyperresponsiveness, and reduced both inflammatory cell infiltration and mucus production in the lung tissue. The intervention additionally decreased macrophage aggregation near the airway and inhibited M2 macrophage polarization, thus maintaining a dynamic balance of M1/M2 macrophages in CVA mice. RNA-seq implicated the PI3K/AKT/ERK and chemokine signalling axes as key mediators for the effect of HLOL on macrophage recruitment and polarization, which was subsequently validated through comprehensive in vivo and in vitro experiments. Conclusions: HLOL reduces macrophage chemotaxis and M2 polarization near the airway of CVA mice by regulating the PI3K/AKT/ERK and chemokine signalling pathways, thereby inhibiting airway inflammation and hyperresponsiveness in CVA mice. C1 [Ji, Xixi; Fang, Wenhui; Long, Hongyan] Nanjing Univ Chinese Med, Nanjing Hosp Chinese Med, Dept Pediat, Nanjing 210022, Peoples R China. [Ji, Xixi; Fang, Wenhui] Nanjing Univ Chinese Med, Nanjing 210023, Peoples R China. [Zhu, Xudong] China Acad Chinese Med Sci, Guanganmen Hosp, Beijing 100000, Peoples R China. [Zhang, Yajie; Zhu, Weina] Nanjing Univ Chinese Med, Cent Lab, Nanjing Hosp Chinese Med, Nanjing 210022, Peoples R China. [Long, Hongyan] Nanjing Hosp Chinese Med, Sci & Technol Dept, Nanjing 210022, Peoples R China. C3 Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine; Guang'anmen Hospital, CACMS; China Academy of Chinese Medical Sciences; Nanjing University of Chinese Medicine RP Long, HY (corresponding author), Nanjing Univ Chinese Med, Nanjing Hosp Chinese Med, Dept Pediat, Nanjing 210022, Peoples R China. EM longhongyan@njucm.edu.cn RI Zhu, Xudong/GPX-4495-2022; Zhang, Yajie/J-6726-2017; Fang, Wenhui/OJS-8471-2025 FU Jiangsu Provincial Administration of Traditional Chinese Medicine [ZT202210]; Jiangsu Provincial Department of Science and Technology [BK20241733] FX This work was supported by the Jiangsu Provincial Administration of Traditional Chinese Medicine (ZT202210) and the Jiangsu Provincial Department of Science and Technology (BK20241733) . 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Ethnopharmacol. PD JAN 30 PY 2026 VL 355 AR 120726 DI 10.1016/j.jep.2025.120726 EA OCT 2025 PN B PG 19 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 8VD5K UT WOS:001598083100007 PM 41077315 DA 2026-03-26 ER PT J AU Liu, M Duan, XZ Lou, CJ AF Liu, Ming Duan, Xiaozong Lou, Chaoju TI Quercetin alleviates intervertebral disc degeneration by disrupting CEBPB-HMGA1 interaction to suppress TNFA production and reduce ECM degradation SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE intervertebral disc degeneration; extracellular matrix degradation; macrophage polarization; quercetin; CEBPB; HMGA1 AB Background: Intervertebral disc degeneration (IVDD) is a highly prevalent degenerative disease related to macrophage M1 polarization and nucleus pulposus cells (NPCs) dysfunction. Quercetin is a common flavonoid found in various plants, and its therapeutic roles have been proved in several diseases. However, its protective role and mechanism in IVDD remain inadequately explored. Methods: Bioinformatics analyses were employed to identify differentially expressed genes in IVDD and to annotate their functions and pathways. Quercetin was prioritized for further investigation based on bioinformatic drug enrichment analysis, which identified it as a top candidate targeting IVDD-associated pathways, alongside its well-documented anti-inflammatory and ECM-modulating properties in prior literature. A rat IVDD model was established by punctured in vivo to evaluate the protective effects of quercetin. Mice macrophage RAW 264.7 cells were stimulated with lipopolysaccharide (LPS) to mimic IVDD to assess M1 polarization and its downstream effects in response to quercetin. Dual-luciferase reporter assay was conducted to confirm the regulation of transcriptional activity. CoIP-MS and ChIP-PCR were utilized to examine protein-protein interactions and DNA-protein interactions, respectively. Results: Bioinformatics analysis of GEO datasets (GSE56081, GSE15227) identified 51 differentially expressed genes (DEGs) in IVDD, with functional enrichment revealing their significant association with extracellular matrix (ECM) organization and cell adhesion pathways. Drug enrichment analysis identified quercetin as the most significant phytochemical candidate after calcium, with established roles in ECM and inflammation pathways. In vivo experiments demonstrated that quercetin significantly mitigated puncture-induced disc degeneration by modulating ECM and adhesion-related pathways. Additionally, quercetin effectively attenuated LPS-induced macrophage M1 polarization in vitro, leading to reduced apoptosis of nucleus pulposus cells (NPCs) and decreased ECM degradation. Mechanistic analyses revealed that quercetin suppressed the expression and transcriptional activity of CEBPB by disrupting its interaction with HMGA1, which subsequently led to reduced transcription of the pro-inflammatory gene TNFA. Conclusion: Quercetin suppressed CEBPB expression and transcriptional activity by disrupting the interaction between CEBPB and HMGA1, which in turn reduced the transcription of TNFA. This research established a foundation for further exploration of quercetin's molecular mechanisms and its therapeutic potential in degenerative disc diseases. C1 [Liu, Ming; Duan, Xiaozong; Lou, Chaoju] Zhengzhou Univ, Affiliated Hosp 1, Dept Orthoped, 1 Jianshe East Rd, Zhengzhou 450052, Peoples R China. C3 Zhengzhou University RP Liu, M (corresponding author), Zhengzhou Univ, Affiliated Hosp 1, Dept Orthoped, 1 Jianshe East Rd, Zhengzhou 450052, Peoples R China. EM L2025403liumingliu@126.com FU Medical Science and Technology Project of Henan Province (Joint construction) [LHGJ20190178] FX This research was supported by Medical Science and Technology Project of Henan Province (Joint construction) (LHGJ20190178) . 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Immunopharmacol. PD DEC 22 PY 2025 VL 167 AR 115654 DI 10.1016/j.intimp.2025.115654 EA OCT 2025 PG 15 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA 8VZ9D UT WOS:001598669000001 PM 41092768 DA 2026-03-26 ER PT J AU Tang, X Tan, YW Gao, FQ Wang, ZC Ye, XY Qiu, X Lou, ZJ Yang, XY Chen, J Xu, H Chen, J Xu, X Wang, K AF Tang, Xiao Tan, Yawen Gao, Fengqiang Wang, Zhoucheng Ye, Xinyu Qiu, Xun Lou, Zijian Yang, Xinyu Chen, Jun Xu, Hao Chen, Jian Xu, Xiao Wang, Kai TI Paeoniflorin attenuates hepatic ischemia-reperfusion injury by modulating Tmem176b+macrophages polarization SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Hepatic ischemia-reperfusion injury; Paeoniflorin; Single cell RNA-sequencing; Cell crosstalk; Tmem176b; Macrophages polarization ID LIVER-TRANSPLANTATION; TMEM176B; IMMUNE AB Background: Hepatic ischemia-reperfusion (I/R) injury, a major complication in liver transplantation and extensive resection, involves complex mechanisms with limited therapeutic options. The M1 polarization of macrophages has been confirmed as one of the contributing factors to hepatic I/R injury. Paeoniflorin (PF), a bioactive compound from traditional Chinese medicine, exhibits hepatoprotective and immunomodulatory properties, its precise mechanism in regulating macrophage polarization during hepatic I/R remains unclear. Methods: Single-cell RNA sequencing was performed on 45,673 cells isolated from the PF-treated hepatic I/R mouse model liver. Bioinformatics analysis was employed to assess the functional characteristics, phenotypic switching, and cell-cell interaction of different macrophage subpopulations. TMEM176B inhibitor and mice hepatic I/R model were utilized to validate Tmem176b+ macrophages as PF' s therapeutic target. Results: PF administration markedly improved hepatic function, evidenced by reduced serum ALT/AST levels, diminished necrotic area and suppressed apoptosis. Single-cell RNA sequencing revealed PF' s preferential modulation of macrophage subpopulations, inducing a significant shift from M1-like to M2-like phenotypes. Pseudotime trajectory analysis demonstrated PF-facilitated conversion of inflammatory macrophages toward this reparative subset. Functional studies demonstrated that Tmem176b+ macrophages are essential, as their depletion could abolish the protective effect of PF. Mechanistically, PF mediates its effects through Tmem176b+ macrophage by upregulating the THBS1-CD47 immunosuppressive axis while suppressing the SPP1-CD44 pro-inflammatory signaling pathway. C1 [Tang, Xiao; Tan, Yawen; Gao, Fengqiang; Wang, Zhoucheng; Ye, Xinyu; Qiu, Xun; Lou, Zijian] Zhejiang Univ, Sch Med, Hangzhou 310058, Peoples R China. [Yang, Xinyu] Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Gen Surg, Hangzhou 310016, Peoples R China. [Chen, Jun; Chen, Jian] Nanjing Med Univ, Affiliated Hosp 1, Hepatobil Ctr, Nanjing 210000, Peoples R China. [Xu, Hao] Zhejiang Chinese Med Univ, Zhejiang Prov Hosp Chinese Med, Affiliated Hosp 1, Dept Orthoped Surg, Hangzhou 310006, Zhejiang, Peoples R China. [Xu, Hao] Zhejiang Chinese Med Univ, Sch Clin Med 1, Hangzhou 310006, Zhejiang, Peoples R China. [Xu, Xiao; Wang, Kai] Zhejiang Univ, Inst Organ Transplantat, Sch Med, Hangzhou 310003, Peoples R China. [Xu, Xiao; Wang, Kai] Hangzhou Med Coll, Sch Clin Med, Hangzhou 310059, Peoples R China. C3 Zhejiang University; Zhejiang University; Nanjing Medical University; Zhejiang Chinese Medical University; Zhejiang Chinese Medical University; Zhejiang University; Hangzhou Medical College RP Chen, J (corresponding author), Nanjing Med Univ, Affiliated Hosp 1, Hepatobil Ctr, Nanjing 210000, Peoples R China.; Xu, X; Wang, K (corresponding author), Zhejiang Univ, Inst Organ Transplantat, Sch Med, Hangzhou 310003, Peoples R China.; Xu, X; Wang, K (corresponding author), Hangzhou Med Coll, Sch Clin Med, Hangzhou 310059, Peoples R China. EM 11818377@zju.edu.cn; zjxu@zju.edu.cn; kaiw3@zju.edu.cn FU National Key Research and Development Program of China [2021YFA1100500]; National Natural Science Foundation of China [82470683]; Joint TCM Science & Technology Projects of National Demonstration Zones for Comprehensive TCM Reform [GZY-KJS-ZJ-2025-002]; Key Research & Development Program of Zhejiang Province [2022C03108]; Medical Expert Studio Fund of the First Affiliated Hospital of Zhejiang Chinese Medical University FX National Key Research and Development Program of China (No. 2021YFA1100500 to X.X.) ; National Natural Science Foundation of China (No. 82470683 to K.W.) ; Joint TCM Science & Technology Projects of National Demonstration Zones for Comprehensive TCM Reform (GZY-KJS-ZJ-2025-002) ; Key Research & Development Program of Zhejiang Province (NO. 2022C03108 to J.C) ; Medical Expert Studio Fund of the First Affiliated Hospital of Zhejiang Chinese Medical University (X.X.) . 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PD DEC 22 PY 2025 VL 167 AR 115657 DI 10.1016/j.intimp.2025.115657 EA OCT 2025 PG 15 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA 8TW4W UT WOS:001597217600001 PM 41092769 DA 2026-03-26 ER PT J AU Lin, GX Li, MY Duan, TT Xia, T Li, MQ Meng, LQ Lin, ZY Li, MH Lai, Y Liang, BE Du, Y Yang, JZ Tang, D AF Lin, Gui-Xuan Li, Min-Yi Duan, Ting-Ting Xia, Tao Li, Meng-Qiu Meng, Lan-Qing Lin, Zi-Yang Li, Min-Hua Lai, Ying Liang, Bai-En Du, Ying Yang, Jun-Zheng Tang, Dan TI Schaftoside ameliorates MCD diet-induced nonalcoholic steatohepatitis via modulating immune microenvironment SO PHYTOMEDICINE LA English DT Article DE Non-alcoholic steatohepatitis; Schaftoside; Macrophages; Dendritic cells ID LIVER-INJURY; ACTIVATION; NASH; MACROPHAGES; REGRESSION; DISEASE AB Background: Schaftoside (SS), a bioactive natural flavonoid di-C-glycoside derived from some famous Chinese herbs including Scutellaria baicalensis, Glycyrrhiza uralensis and Abrus mollis, has been reported to mitigate hepatic lipid accumulation and enhance liver health. Purpose: This study aimed to assess the effects of SS on non-alcoholic steatohepatitis (NASH) and to investigate the potential mechanisms. Methods: A methionine-choline deficiency (MCD)-induced model of NASH was established. The efficacy of SS in intervening NASH was evaluated through assessments of blood lipids, liver function, and pathological conditions. Transcriptomic analysis was conducted to predict potential pathways of SS intervention in NASH, and the prediction results were validated by testing biochemical parameters, real-time quantitative PCR (qPCR), ELISA assays, and immunohistochemistry. Results: Our results revealed that SS markedly ameliorated liver dysfunction and lipid metabolism disorders, as indicated by decreased serum concentrations of ALT and AST, along with lower liver levels of TG and TC. Based on RNA-sequencing results, we found that the expression of genes associated with inflammatory processes and fibrotic responses, including Ccl2, Cxcl2, Col1a1, Col3a1, Mmp13, Itgax, Itgam, and Acta2, were reduced following intervention with SS. In conjunction with the immune cell infiltration analysis and qPCR, we determined that SS significantly restored the disrupted immune microenvironment via regulating the functional properties of various immunocyte, particularly the modulation of genes expression related to macrophages (Cd80, Cd86, Cd204, MCP-1, Cd206, Il10, Arg1 and Tgfb1) and dendritic cells (Itgax/Cd11c, Itgam/Cd11b, MMP8, MMP9, MMP13, and TNF-alpha). Conclusion: In summary, our study provides the first evidence that SS exerts anti-NASH effects by orchestrating immune cell functions, particularly through macrophage polarization and dendritic cell modulation, thereby rectifying the dysregulated immune microenvironment. These findings position SS as a promising candidate for novel NASH therapies. C1 [Lin, Gui-Xuan; Tang, Dan] Guangdong Pharmaceut Univ, Key Lab Digital Qual Evaluat Chinese Mat Med, State Adm TCM & Engn, Guangzhou 510006, Peoples R China. [Lin, Gui-Xuan; Tang, Dan] Guangdong Pharmaceut Univ, Technol Res Ctr Chinese Mat Med Qual Guangdong Pro, Guangzhou 510006, Peoples R China. [Lin, Gui-Xuan; Li, Min-Yi; Duan, Ting-Ting; Xia, Tao; Li, Meng-Qiu; Meng, Lan-Qing; Lin, Zi-Yang; Li, Min-Hua; Lai, Ying; Liang, Bai-En; Du, Ying; Yang, Jun-Zheng] Guangdong Consun Pharmaceut Grp, Inst Consun Co Chinese Med Kidney Dis, Guangzhou 510530, Peoples R China. C3 Guangdong Pharmaceutical University; Guangdong Pharmaceutical University RP Tang, D (corresponding author), Guangdong Pharmaceut Univ, Key Lab Digital Qual Evaluat Chinese Mat Med, State Adm TCM & Engn, Guangzhou 510006, Peoples R China.; Tang, D (corresponding author), Guangdong Pharmaceut Univ, Technol Res Ctr Chinese Mat Med Qual Guangdong Pro, Guangzhou 510006, Peoples R China.; Yang, JZ (corresponding author), Guangdong Consun Pharmaceut Grp, Inst Consun Co Chinese Med Kidney Dis, Guangzhou 510530, Peoples R China. EM yangjunzheng606403@163.com; tdpharm@126.com RI Yang, Junzheng/AFC-7121-2022; Lin, Ziyang/GXM-4635-2022 OI Yang, Junzheng/0000-0001-9992-3179; Liang, Baien/0009-0001-4722-471X; Lin, Ziyang/0000-0001-7228-6851 FU National Natural Sci-ence Foundation of China [82374177, 82074137]; Guangdong Basic and Applied Basic Research Foundation [2022A1515220068]; Key Project of Department of Education of Guangdong Province [2022ZDZX2032] FX This research was received funding from the National Natural Sci-ence Foundation of China (No. 82374177, 82074137) , Guangdong Basic and Applied Basic Research Foundation (No. 2022A1515220068) , Key Project of Department of Education of Guangdong Province (No. 2022ZDZX2032) . CR Alukal JJ, 2019, HEPATOL INT, V13, P534, DOI 10.1007/s12072-019-09970-3 Campana L, 2017, SEMIN LIVER DIS, V37, P1, DOI 10.1055/s-0036-1597816 Cao Li, 2024, Food Med. Homol, DOI [10.26599/FMH.2024.9420002, DOI 10.26599/FMH.2024.9420002] Chen L., 2024, Acta Mater. Med, V3 Clément S, 2008, HEPATOLOGY, V48, P799, DOI 10.1002/hep.22404 Connolly MK, 2009, J CLIN INVEST, V119, P3213, DOI 10.1172/JCI37581 Duffield JS, 2005, J CLIN INVEST, V115, P56, DOI 10.1172/JCI200522675 Friedman SL, 2018, NAT MED, V24, P908, DOI 10.1038/s41591-018-0104-9 Jiao JJ, 2012, HEPATOLOGY, V55, P243, DOI 10.1002/hep.24621 Karim Gres, 2023, touchREV Endocrinol, V19, P60, DOI [10.17925/ee.2023.19.1.60, 10.17925/EE.2023.19.1.60] Kingwell K, 2024, NAT REV DRUG DISCOV, V23, P235, DOI 10.1038/d41573-024-00051-1 Konerman MA, 2018, J HEPATOL, V68, P362, DOI 10.1016/j.jhep.2017.10.015 Krenkel O, 2017, SEMIN LIVER DIS, V37, P189, DOI 10.1055/s-0037-1604480 Li X, 2022, FRONT PHARMACOL, V13, DOI 10.3389/fphar.2022.1073535 Li YW, 2023, CHIN J NAT MEDICINES, V21, P643, DOI 10.1016/S1875-5364(23)60443-1 Li Y, 2024, Acta Materia Medica, V3, DOI [10.15212/amm-2024-0001, DOI 10.15212/AMM-2024-0001] Lin XY, 2024, PHARMACOL THERAPEUT, V254, DOI 10.1016/j.pharmthera.2024.108593 Liu MJ, 2020, J ETHNOPHARMACOL, V255, DOI 10.1016/j.jep.2020.112776 Liu MJ, 2020, ANTIOXID REDOX SIGN, V33, P87, DOI 10.1089/ars.2019.7791 Liu MJ, 2017, EUR J PHARMACOL, V815, P1, DOI 10.1016/j.ejphar.2017.10.003 Lu R, 2023, DIABETES OBES METAB, V25, P13, DOI 10.1111/dom.15014 Ma Z, 2022, BIOMED PHARMACOTHER, V155, DOI 10.1016/j.biopha.2022.113834 Maina V, 2012, CLIN SCI, V122, P545, DOI 10.1042/CS20110366 Miura K, 2013, HEPATOLOGY, V57, P577, DOI 10.1002/hep.26081 Musso G, 2023, PROG LIPID RES, V91, DOI 10.1016/j.plipres.2023.101238 Negrin KA, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0107265 Ramachandran P, 2012, P NATL ACAD SCI USA, V109, pE3186, DOI 10.1073/pnas.1119964109 Ren C. 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Homol., V1 Ren ZT, 2023, CHIN J NAT MEDICINES, V21, P830, DOI 10.1016/S1875-5364(23)60469-8 Roszer T, 2015, MEDIAT INFLAMM, V2015, DOI 10.1155/2015/816460 Schuster S, 2018, NAT REV GASTRO HEPAT, V15, P349, DOI 10.1038/s41575-018-0009-6 Staels B, 2023, J HEPATOL, V79, P1302, DOI 10.1016/j.jhep.2023.07.004 Stienstra R, 2010, HEPATOLOGY, V51, P511, DOI 10.1002/hep.23337 Sun Y, 2024, J PERIODONTAL RES, V59, P431, DOI 10.1111/jre.13242 Tacke F, 2023, J HEPATOL, V79, P552, DOI 10.1016/j.jhep.2023.03.038 Takai S, 2020, INT J MOL SCI, V21, DOI 10.3390/ijms21207543 Tong C, 2021, HUM EXP TOXICOL, V40, pS310, DOI 10.1177/09603271211038741 van der Heide D, 2019, FRONT IMMUNOL, V10, DOI 10.3389/fimmu.2019.02852 Wang LX, 2019, J LEUKOCYTE BIOL, V106, P345, DOI 10.1002/JLB.3RU1018-378RR Wang XJ, 2023, INT J MOL SCI, V24, DOI 10.3390/ijms24065843 Wang ZL, 2020, P NATL ACAD SCI USA, V117, P30816, DOI 10.1073/pnas.2012745117 Wei SL, 2024, DRUG DISCOV TODAY, V29, DOI 10.1016/j.drudis.2024.103910 Weiskirchen R, 2019, MOL ASPECTS MED, V65, P2, DOI 10.1016/j.mam.2018.06.003 Wong VWS, 2023, J HEPATOL, V79, P842, DOI 10.1016/j.jhep.2023.04.036 Yang YQ, 2023, HELIYON, V9, DOI 10.1016/j.heliyon.2023.e17116 Yu Y, 2024, J ETHNOPHARMACOL, V328, DOI 10.1016/j.jep.2024.118135 NR 46 TC 0 Z9 0 U1 11 U2 11 PU ELSEVIER GMBH PI MUNICH PA HACKERBRUCKE 6, 80335 MUNICH, GERMANY SN 0944-7113 EI 1618-095X J9 PHYTOMEDICINE JI Phytomedicine PD NOV 25 PY 2025 VL 148 AR 157365 DI 10.1016/j.phymed.2025.157365 EA OCT 2025 PG 13 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 8PD4O UT WOS:001593989500003 PM 41072282 OA hybrid DA 2026-03-26 ER PT J AU Yu, QL Shao, PW Liu, XQ Wang, Y Luo, L Li, XR Zhao, S An, YQ Li, BH Pei, JH Liu, SY Yang, CS Wang, JS Cui, SN AF Yu, Qiulu Shao, Puwei Liu, Xiaoqin Wang, Ying Luo, Liu Li, Xinru Zhao, Si An, Yanqun Li, Bohan Pei, Jiahe Liu, Shiyi Yang, Changshui Wang, Junsong Cui, Shuna TI Ethyl acetate extract of Sargentodoxa cuneata and Patrinia villosa alleviates pelvic inflammation by shifting macrophages polarization SO PHYTOMEDICINE LA English DT Article DE Ethyl acetate extract of Sargentodoxa cuneata; and Patrinia villosa; Pelvic inflammatory disease; Glycolysis; Macrophage; HK-II; NF-kappa B pathway ID IMMUNE EVASION; PHOSPHORYLATION; EXPRESSION; APIGENIN AB Background: Pelvic inflammatory disease (PID) is a prevalent gynecological infection, that poses significant therapeutic challenges. Sargentodoxa cuneata and Patrinia villosa (S&P) demonstrate empirical efficacy in PID treatment within traditional Chinese medicine practice. However, their active components and precise antiinflammatory mechanisms should be systematically elucidated. Purpose: This study aimed to investigate the pharmacologically active components of S&P and decipher their anti-inflammatory mechanism through integrated multi-omics approaches. Materials and methods: CCK-8 and NO inhibition assays were used to screen the optimal extract from three solvent partitions (ethyl acetate [EtOAc], n-butanol [n-BuOH], and water). The chemical components of different extracts and S&P were detected by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The effects of EtOAc extract on PID were studied in an lipopolysaccharide (LPS) -induced PID murine model to evaluate uterine histopathology and macrophage phenotype. RNA sequencing was utilized to analyze the differentially expressed genes after EtOAc extract treatment. Cytokines and macrophage phenotype markers were detected by flow cytometry. LC-MS/MS-based metabolic analysis and western blotting were used to study the potential mechanism. Results: Bioactivity screening identified EtOAc extract as the most potent fraction, suppressing iNOS-mediated NO production without cytotoxicity. EtOAc extract inhibited the release of IL-6 and upregulated the M2 phenotypic marker CD206 in LPS induced RAW264.7 and THP-1 cells. In the murine PID model, EtOAc extract treatment alleviated LPS-induced pelvic inflammation, reduced uterine F4/80+ and CD86+ (M1) macrophages, and upregulated CD206+ (M2) subset. Transcriptomics of uterine tissue demonstrated that EtOAc extract upregulated genes related to M2 macrophages polarization, tissue repair and vascular remodeling, and endometrial receptivity and lactic acid metabolism, and downregulated genes involved in M1 macrophages, inflammation, and glycolysis and lactic acid synthesis. Metabolomics analysis showed that EtOAc extract ameliorated LPS-induced metabolic disorder. The differentially expressed metabolites were involved in the tricarboxylic acid (TCA) cycle, arginine and proline metabolism, pyruvate metabolism, and glycolysis or gluconeogenesis pathways. EtOAc extract inhibited the expression of glucose metabolism key proteins HKI, HKII, PKM2 and PD, and NF-kappa B and I kappa B-alpha phosphorylation, and synergized with HK-II inhibitor (2-deoxy-D-glucose). Conclusions: EtOAc extract alleviates LPS-induced PID via a novel immunometabolic axis, namely, by suppressing HK-II-mediated glycolysis through the NF-kappa B axis and balancing macrophages polarization. The mechanistic elucidation of macrophage immunometabolic reprogramming by S&P provides a molecular basis for phytotherapy in PID management. C1 [Yu, Qiulu; Shao, Puwei; Liu, Xiaoqin; Wang, Ying; Luo, Liu; Li, Xinru; An, Yanqun; Li, Bohan; Pei, Jiahe; Liu, Shiyi; Yang, Changshui; Cui, Shuna] Yangzhou Univ, Jiangsu Higher Educ Inst Integrated Tradit Chinese, Key Lab, Yangzhou 225009, Peoples R China. [Cui, Shuna] Yangzhou Univ, Affiliated Hosp, Dept Gynecol & Obstet, Yangzhou 225009, Peoples R China. [Liu, Xiaoqin] Chengdu Univ Tradit Chinese Med, Chengdu 610075, Peoples R China. [Zhao, Si] Yangzhou Univ, Huaian Hosp, The Peoples Hosp Huaian 5, Huaian 223300, Peoples R China. [Wang, Junsong] Nanjing Univ Sci & Technol, Sch Environm & Biol Engn, Xiao Ling Wei 200, Nanjing 210094, Peoples R China. C3 Yangzhou University; Yangzhou University; Chengdu University of Traditional Chinese Medicine; Yangzhou University; Nanjing University of Science & Technology RP Cui, SN (corresponding author), Yangzhou Univ, Jiangsu Higher Educ Inst Integrated Tradit Chinese, Key Lab, Yangzhou 225009, Peoples R China. EM sncui@yzu.edu.cn RI ; liu, shiyi/PFI-9517-2025 OI Liu, Xiaoqin/0009-0005-4527-7681; pei, jiahe/0009-0002-1856-1757; FU National Natural Science Foundation of China (NSFC) [82174432, 82575120]; Scientific Research Foundation of Jiangsu Province, China [BK20211327]; Jiangsu Province Qinglan Project; Yangzhou University "Top Talent" project; Natural Science Foundation of Jiangsu Higher Education Institutions of China [21KJA360004] FX This research was supported by the National Natural Science Foundation of China (NSFC) (82174432, 82575120) ; Scientific Research Foundation of Jiangsu Province, China (BK20211327) ; Jiangsu Province Qinglan Project (2022) ; Yangzhou University "Top Talent" project (2020) ; The Natural Science Foundation of Jiangsu Higher Education Institutions of China (21KJA360004) . 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In recent years, GLPs have attracted considerable attention owing to their broad pharmacological activities and favorable safety profile. Despite advances in therapeutic approaches that have improved survival rate, cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide. CVDs are characterized by a complex pathogenesis and multiple risk factors, including hyperglycemia, lipid metabolism disturbances, and chronic inflammation. Accumulating evidence has demonstrated that GLPs exhibit remarkable anti-inflammatory and antioxidant properties, while also exerting regulatory effects on glucose and lipid homeostasis. Additionally, GLPs have demonstrated therapeutic potential in ameliorating endothelial dysfunction, modulating angiogenesis, attenuating atherosclerosis, and mitigating chemical-induced cardiotoxicity. This review summarizes the fundamental pharmacological activities of GLPs and discusses their potential mechanisms in cardiovascular diseases, with the aim of providing a valuable reference for future research and clinical application. C1 [Wang, Yingzhuo; Zuo, Yingbing; Weng, Junfei; Peng, Xiaoping] Nanchang Univ, Affiliated Hosp 1, Jiangxi Med Coll, Dept Cardiol, Nanchang 330006, Jiangxi, Peoples R China. [Wang, Yingzhuo; Zuo, Yingbing; Weng, Junfei; Peng, Xiaoping] Nanchang Univ, Clin Med Coll 1, Jiangxi Med Coll, Nanchang 330006, Jiangxi, Peoples R China. [Peng, Xiaoping] Jiangxi Hypertens Res Inst, Nanchang 330006, Jiangxi, Peoples R China. [Peng, Xiaoping] Nanchang Univ, Affiliated Hosp 1, Jiangxi Med Coll, Dept Cardiol,Jiangxi Key Lab Neurol Dis, Nanchang 330006, Jiangxi, Peoples R China. [Peng, Xiaoping] Academician Workstat Cardiovasc Innovat Mat, Nanchang 330006, Jiangxi, Peoples R China. C3 Nanchang University; Nanchang University; Nanchang University RP Peng, XP (corresponding author), Nanchang Univ, Affiliated Hosp 1, Jiangxi Med Coll, Dept Cardiol, Nanchang 330006, Jiangxi, Peoples R China. EM ndyfy1784@ncu.edu.cn FU National Natural Science Foundation of China [82060067]; Chinese Cardiovascular Association-Natural lipid-lowering drugs fund [2023-CCA-NLD-604] FX This work was supported by the National Natural Science Foundation of China (82060067) and the Chinese Cardiovascular Association-Natural lipid-lowering drugs fund (2023-CCA-NLD-604) . 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PD NOV PY 2025 VL 330 AR 148001 DI 10.1016/j.ijbiomac.2025.148001 EA OCT 2025 PN 1 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 8IU5A UT WOS:001589679800007 PM 41033521 DA 2026-03-26 ER PT J AU Xing, XY Hu, HJ Hu, HD Chu, JH Li, SY Han, DX Zhao, B Li, S AF Xing, Xinyue Hu, Haojie Hu, Haodong Chu, Jiahong Li, Siyu Han, Dongxu Zhao, Bing Li, Shu TI Quercetin from Penthorum chinense Pursh protects against LPS-induced liver inflammation in chickens via suppressing pyroptosis-macrophage polarization crosstalk SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Quercetin; Liver inflammation; Oxidative stress; Pyroptosis; M1 polarization; Chicken AB Ethnopharmacological relevance: Penthorum chinense Pursh, a medicinal plant used in traditional Miao medicine, contains a variety of bioactive compounds and is well known for its significant hepatoprotective properties. Quercetin (QUE), one of the most widely investigated hepatoprotective flavonoids derived from P. chinense, has garnered considerable attention owing to its potent antioxidant and anti-inflammatory activities. Nevertheless, the precise molecular mechanisms through which QUE attenuates LPS-induced liver inflammation have not been fully elucidated. Aim of the study: This study aimed to explore the protective effect of QUE against LPS-induced inflammatory liver injury and to clarify the underlying molecular mechanisms. Materials and methods: A chicken model of liver inflammation was established via intraperitoneal injection of LPS (1.5 mg/kg). To assess the protective effects of QUE, the compound (10 mg/kg) was administered by oral gavage for six consecutive days prior to LPS challenge. Histopathological and ultrastructural changes in liver tissues were evaluated using hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM), respectively. Oxidative stress markers and antioxidant enzyme activities were also measured in liver tissues. Integrated network pharmacology and bioinformatics analyses were employed to identify core potential targets of QUE. Further validation experiments, including immunofluorescence co-localization, Western blotting, RTqPCR, and in vitro cell culture assays, were conducted to elucidate the molecular mechanisms underlying QUE mediated attenuation of LPS induced liver inflammation. Results: QUE effectively ameliorated LPS-induced inflammatory liver injury, as evidenced by a significant reduction in hepatic levels of the oxidative stress marker malondialdehyde (MDA) and a marked increase in the activities of key antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), and catalase (CAT). Furthermore, QUE administration significantly down-regulated the expression of pyroptosis-related proteins (NLRP3, GSDMD, ASC, and Caspase-1), restored the LPSinduced imbalance in macrophage M1/M2 polarization, and suppressed the expression of chemokines such as CCL4, CCL17, CCL19, and MIF. QUE treatment also significantly reduced the levels of pro-inflammatory cytokines (IL-18, IL-1 beta, TNF-alpha, and IL-6) while upregulating the anti-inflammatory cytokine IL-10. Moreover, QUE markedly inhibited the detrimental crosstalk between LPS-induced pyroptosis and M1 macrophage activation. Integrated network pharmacology and bioinformatics analyses predicted the core targets and pathways involved, and subsequent experimental validation confirmed that QUE attenuates hepatic inflammation primarily through inhibition of the ROS/NLRP3 signaling pathway. Conclusions: This study demonstrates that QUE alleviates LPS-induced liver injury in chickens by suppressing the ROS/NLRP3 pathway, thereby interrupting the pathological crosstalk between pyroptosis and M1 macrophage polarization. These findings offer a promising therapeutic strategy rooted in traditional medicine for the treatment and prevention of inflammatory liver diseases. C1 [Xing, Xinyue; Hu, Haojie; Hu, Haodong; Chu, Jiahong; Li, Siyu; Han, Dongxu; Zhao, Bing; Li, Shu] Northeast Agr Univ, Coll Vet Med, Harbin 150030, Peoples R China. [Li, Shu] Northeast Agr Univ, Coll Vet Med, Dept Heilongjiang Common Anim Dis Prevent & Treatm, Key Lab Prov Educ, Harbin 150030, Peoples R China. C3 Northeast Agricultural University - China; Northeast Agricultural University - China RP Zhao, B; Li, S (corresponding author), Northeast Agr Univ, Coll Vet Med, Harbin 150030, Peoples R China. EM zhaobing@neau.edu.cn; lishu@neau.edu.cn FU Natural Science Foundation of Heilongjiang Province, China [LH 2024C018] FX This work was supported by Natural Science Foundation of Heilongjiang Province, China (LH 2024C018) . 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Ethnopharmacol. PD JAN 30 PY 2026 VL 355 AR 120665 DI 10.1016/j.jep.2025.120665 EA OCT 2025 PN A PG 16 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 8GN9W UT WOS:001588148800003 PM 41033424 DA 2026-03-26 ER PT J AU Huang, MC Lan, MY Liu, X Lin, CL Zeng, LL Li, Y Li, F Dou, XT Zhao, Y Shi, Y Xu, XW Sun, JF Liang, G AF Huang, Mincong Lan, Mengyao Liu, Xin Lin, Cailu Zeng, Lulu Li, Ying Li, Feng Dou, Xiaotong Zhao, Yan Shi, Yuan Xu, Xiangwei Sun, Jinfeng Liang, Guang TI Isolinderalactone regulates macrophage polarization and efferocytosis by activating the LXRα pathway against ulcerative colitis SO CHINESE MEDICINE LA English DT Article DE Lindera aggregate; Isolinderalactone; Liver X receptor alpha; Macrophage polarization; Efferocytosis; Ulcerative colitis ID CELLS; EXPRESSION; RESOLUTION; IBD AB BackgroundUlcerative colitis (UC), a chronic inflammatory bowel disease, remains an unmet medical need. Lindera aggregata, a traditional Chinese medicine used in treating gastrointestinal disorders, has demonstrated anti-UC efficacy, though its bioactive components are poorly characterized. Isolinderalactone (ILDL), a characteristic sesquiterpene lactone isolated from Lindera aggregata, has been demonstrated anti-cancer properties. However, its therapeutic potential in UC remains unexplored.MethodsLipopolysaccharide (LPS)-induced RAW264.7 inflammatory cell model was used to screen the anti-inflammatory properties of Lindera aggregata's characteristic compounds in vitro. DSS induced UC mouse model was used to study the anti-UC efficacy of ILDL in vivo. Transcriptomic was used to explore the anti-inflammatory mechanism of ILDL. Drug affinity responsible target stability was used to identify the combination of the ILDL and LXR alpha. LXR-mediated effects were further assessed via flow cytometry and Western blotting.ResultsILDL effectively inhibits macrophage polarization and the production of inflammatory mediators in vitro, and improves symptoms and tissue lesions in acute UC mice in vivo. Transcriptomic analysis revealed the involvement of the LXR-mediated pathway in ILDL's effects. Furthermore, ILDL was able to bind to LXR alpha and to upregulate LXR alpha target genes expression such as ABCA1, suggesting that ILDL itself can activate the LXR alpha pathway. Genetic/pharmacological LXR alpha inhibition abrogated ILDL's anti-inflammatory effects, confirming an LXR alpha-dependent mechanism. In addition to inhibiting macrophage M1 polarization, the activation of LXR alpha by ILDL can also promote macrophage efferocytosis of apoptotic intestinal epithelial cells in the co-culture system.ConclusionsILDL activates the LXR alpha pathway, inhibiting macrophage M1 polarization, reducing pro-inflammatory mediators production, and promoting macrophage efferocytosis. ILDL is a promising candidate compound from Lindera aggregata for anti-inflammation and UC treatment. C1 [Huang, Mincong; Xu, Xiangwei; Sun, Jinfeng; Liang, Guang] Hangzhou Med Coll, Affiliated Yongkang First Peoples Hosp, Hangzhou 310014, Zhejiang, Peoples R China. [Huang, Mincong; Xu, Xiangwei; Sun, Jinfeng; Liang, Guang] Hangzhou Med Coll, Sch Pharm, Hangzhou 310014, Zhejiang, Peoples R China. [Huang, Mincong; Lan, Mengyao; Lin, Cailu; Zeng, Lulu; Li, Ying; Li, Feng; Dou, Xiaotong; Zhao, Yan; Shi, Yuan; Liang, Guang] Hangzhou Med Coll, Sch Pharm, Zhejiang TCM Key Lab Pharmacol & Translat Res Nat, Hangzhou 311399, Zhejiang, Peoples R China. [Liu, Xin] Hangzhou Med Coll, Zhejiang Prov Peoples Hosp, Affiliated Peoples Hosp, Dept Colorectal Surg, Hangzhou 310014, Zhejiang, Peoples R China. [Sun, Jinfeng] Yanbian Univ, Coll Pharm, Key Lab Nat Med Changbai Mt, Minist Educ, Yanji 133002, Jilin, Peoples R China. C3 Hangzhou Medical College; Hangzhou Medical College; Hangzhou Medical College; Hangzhou Medical College; Zhejiang Provincial People's Hospital; Yanbian University RP Huang, MC; Xu, XW; Sun, JF; Liang, G (corresponding author), Hangzhou Med Coll, Affiliated Yongkang First Peoples Hosp, Hangzhou 310014, Zhejiang, Peoples R China.; Huang, MC; Xu, XW; Sun, JF; Liang, G (corresponding author), Hangzhou Med Coll, Sch Pharm, Hangzhou 310014, Zhejiang, Peoples R China.; Huang, MC; Liang, G (corresponding author), Hangzhou Med Coll, Sch Pharm, Zhejiang TCM Key Lab Pharmacol & Translat Res Nat, Hangzhou 311399, Zhejiang, Peoples R China.; Sun, JF (corresponding author), Yanbian Univ, Coll Pharm, Key Lab Nat Med Changbai Mt, Minist Educ, Yanji 133002, Jilin, Peoples R China. EM hmc1218@163.com; 881012022209@hmc.edu.cn; liuxin_5633@163.com; 2075413651@qq.com; 2656938152@qq.com; 15200311200@163.com; ykyjacky@163.com; xtdou01@163.com; 2372348363@qq.com; 1509809062@qq.com; xuxiangwei@hmc.edu.cn; jfsun@ybu.edu.cn; wzmcliangguang@163.com OI lan, mengyao/0009-0003-9565-054X FU Natural Science Foundation of Zhejiang Province [LMS25H280001, LMS25H030001, Q24H280064]; The administration of traditional Chinese Medicine of Zhejiang province [GZY-KJS-ZJ-2025-080, 2024ZF056]; National Natural Science Foundation of China [82300589, 82360805]; Zhejiang Medical and Health Science and Technology Plan Project [2024KY917]; Basic Scientific Research Funds of Department of Education of Zhejiang Province [KYYB2023002, KYYB2023017]; Key Discipline of Zhejiang Province in Public Health and Preventive Medicine (First Class, Category A), Hangzhou Medical College FX This work was financially supported by the Natural Science Foundation of Zhejiang Province (LMS25H280001, LMS25H030001, Q24H280064), the administration of traditional Chinese Medicine of Zhejiang province (GZY-KJS-ZJ-2025-080, 2024ZF056), the National Natural Science Foundation of China (82300589, 82360805), Zhejiang Medical and Health Science and Technology Plan Project (2024KY917), Basic Scientific Research Funds of Department of Education of Zhejiang Province (KYYB2023002, KYYB2023017), Key Discipline of Zhejiang Province in Public Health and Preventive Medicine (First Class, Category A), Hangzhou Medical College. 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PD OCT 1 PY 2025 VL 20 IS 1 AR 152 DI 10.1186/s13020-025-01216-9 PG 18 WC Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine; Pharmacology & Pharmacy GA 8BV7X UT WOS:001584952100003 PM 41029870 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Li, BH Zhou, ZY Zhang, Y Zhu, J Liu, QY Ma, J Gong, ZB Xu, ZJ Shen, JS Zhu, WL Chen, J AF Li, Binghui Zhou, Zhaoyin Zhang, Yong Zhu, Jing Liu, Qiyuan Ma, Jing Gong, Zhangbin Xu, Zhijian Shen, Jingshan Zhu, Weiliang Chen, Jia TI Uncovering key anti-inflammatory constituents and mechanism of Wuwei Xiaodu Decoction by a combined strategy of phytochemistry, AIDD, network pharmacology, and in vitro and in vivo assay SO BMC COMPLEMENTARY MEDICINE AND THERAPIES LA English DT Article DE Wuwei xiaodu decoction; Active components; Anti-inflammation effect; RAW264.7 cells; Mouse model ID NITRIC-OXIDE; MACROPHAGE POLARIZATION; INFLAMMATION AB BackgroundWuwei Xiaodu decoction (WXD), a renowned prescription in traditional Chinese medicine, is widely used to treat various skin diseases, including atopic dermatitis. However, the bioactive constituents and anti-inflammatory mechanisms remain unclear.PurposeThe study was designed to investigate the most important bioactive components and the anti-inflammatory molecular mechanisms of WXD that have not been fully elucidated.Materials and methodsThe mixed herbs of WXD were extracted by different solvents, including ethyl-acetate (EA) and petroleum-ether (PE). HPLC/LC-MS and GC-MS were performed to identify the chemical composition of WXD-EA and WXD-PE, respectively. The RAW264.7 cell line was used to assess the inflammatory responses, while CCK8 assay was employed to assess the cytotoxicity. Nitric oxide (NO) levels were quantified using the Griess assay. The protein expression levels were evaluated by western blot analysis. Nuclear translocation of p-STAT3 were analyzed by immunofluorescence and western blot. The targets and pathways were predicted by open-source databases. 1-chloro-2,4-dinitrobenzene (DNCB)-induced BALB/c mice was utilized for evaluating inflammatory responses. H&E staining was performed to assess the histopathological changes.ResultsThe best anti-inflammatory active fractions of WXD were found to be WXD-PE and WXD-EA.123 compounds from WXD-PE and 7 representative compounds with high content from WXD-EA were successfully identified. The in vitro anti-inflammatory activity studies confirmed that both WXD-PE and WXD-EA can significantly inhibit the production of NO, TNF-alpha, IL-6, and IL-1 beta in LPS-induced RAW264.7 cells, leading to a downregulation of COX-2 and iNOS expression, as well as a reduction in the phosphorylation levels of ERK, p38, and JNK proteins. Notably, the nuclear expression levels of phosphorylated STAT3 were significantly downregulated. Additionally, WXD-H2O and WXD-EA significantly alleviated DNCB-induced acanthosis, lymphocyte and neutrophil infiltration, and collagen over-deposition in the skin of BALB/c mice.ConclusionWXD-PE and WXD-EA, are identified as the most potent anti-inflammatory constituents of WXD as these fractions can effectively inhibit the MAPK signaling pathway and prevent the nuclear translocation of phosphorylated STAT3 in LPS-stimulated RAW264.7 cells. They also showed significant anti-inflammatory activity in the DNCB-induced inflammatory mouse model. C1 [Li, Binghui] Henan Univ, Sch Pharm, Kaifeng 475004, Peoples R China. [Li, Binghui; Zhou, Zhaoyin; Zhang, Yong; Zhu, Jing; Liu, Qiyuan; Xu, Zhijian; Shen, Jingshan; Zhu, Weiliang] Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China. [Zhou, Zhaoyin] Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China. [Zhu, Jing; Gong, Zhangbin] Shanghai Univ Tradit Chinese Med, Shanghai 201203, Peoples R China. [Liu, Qiyuan; Xu, Zhijian; Shen, Jingshan; Zhu, Weiliang] Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China. [Ma, Jing; Chen, Jia] Shanghai Jiao Tong Univ, Sch Med, Shanghai Childrens Med Ctr, Dept Integrat Med Pediat, Shanghai 200120, Peoples R China. [Chen, Jia] Shanghai Jiao Tong Univ, Guizhou Hosp, Shanghai Childrens Med Ctr, Sch Med, Guiyang 550009, Peoples R China. C3 Henan University; Chinese Academy of Sciences; Shanghai Institute of Materia Medica, CAS; Nanjing University of Chinese Medicine; Shanghai University of Traditional Chinese Medicine; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Shanghai Jiao Tong University; Shanghai Jiao Tong University RP Zhang, Y; Shen, JS; Zhu, WL (corresponding author), Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China.; Shen, JS; Zhu, WL (corresponding author), Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China.; Chen, J (corresponding author), Shanghai Jiao Tong Univ, Sch Med, Shanghai Childrens Med Ctr, Dept Integrat Med Pediat, Shanghai 200120, Peoples R China.; Chen, J (corresponding author), Shanghai Jiao Tong Univ, Guizhou Hosp, Shanghai Childrens Med Ctr, Sch Med, Guiyang 550009, Peoples R China. EM zhangyong109@simm.ac.cn; shenjingshan@simm.ac.cn; wlzhu@simm.ac.cn; chenjia@scmc.com.cn RI Wang, Jinan/AEN-5023-2022; Shen, Jingshan/NGS-8258-2025; Xu, Zhijian/E-1309-2013 FU School of Medicine, Shanghai Jiao Tong University FX The authors would like to thank Samuel Jacob Bunu for valuable discussions. 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Med. Ther. PD SEP 30 PY 2025 VL 25 IS 1 AR 344 DI 10.1186/s12906-025-05072-w PG 20 WC Integrative & Complementary Medicine WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine GA 8DP4H UT WOS:001586147500007 PM 41029337 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Ma, YW Cao, D Han, X Hu, ZQ Ding, XY Wang, J AF Ma, Yiwen Cao, Di Han, Xue Hu, Zhiqiang Ding, Xiaoyun Wang, Jing TI Bruceine D promotes TNBC regression by inhibiting M2-like tumor-associated macrophage polarization induced Wnt3a/ β-catenin pathway SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Bruceine D; Tumor-associated macrophages; Wnt3a/(3-catenin; Metastasis; Triple-negative breast cancer ID HEPATOCELLULAR-CARCINOMA; PHENOTYPE; GROWTH AB Triple-negative breast cancer (TNBC) is distinguished by its marked invasiveness and high recurrence rate, making it the subtype of breast cancer with the most dismal prognosis. Effective treatment modalities for TNBC remains elusive. Tumor-associated macrophages (TAMs) are essential stromal components within the tumor microenvironment, significantly contributing to TNBC progression. Herein, we demonstrated that Bruceine D (BD), a natural quassinoid isolated from Chinese herb Brucea javanica (L.) Merr., diminished the secretion of Wnt3a and downregulated the expression of (3-catenin, thereby not only inhibiting the polarization of M2-like macrophages and enhancing the ratio of M1/M2 macrophage but also suppressing M2-like macrophage-promoted proliferation and metastasis of tumor cells. Importantly, BD impeded the polarization of infiltrating M2-like TAMs and inhibited the Wnt3a/(3-catenin signaling in tumors, consequently suppressing tumor growth and the formation of metastatic lesions in the lungs and livers of TNBC-bearing mice. This study highlights the promising therapeutic potential of BD in remodeling TAMs as a strategy to address TNBC. C1 [Ma, Yiwen; Cao, Di; Han, Xue; Wang, Jing] Ningxia Med Univ, Sch Pharm, 1160 Shengli St, Yinchuan 750004, Peoples R China. [Hu, Zhiqiang; Ding, Xiaoyun] Ningxia Med Univ, Oncol Hosp, Gen Hosp, 804 Shengli St, Yinchuan 750003, Peoples R China. [Wang, Jing] Minist Educ, Key Lab Protect Dev & Utilizat Med Resources Liupa, 692 Shengli St, Yinchuan 750001, Peoples R China. C3 Ningxia Medical University; Ningxia Medical University RP Wang, J (corresponding author), Ningxia Med Univ, Sch Pharm, 1160 Shengli St, Yinchuan 750004, Peoples R China.; Ding, XY (corresponding author), Ningxia Med Univ, Oncol Hosp, Gen Hosp, 804 Shengli St, Yinchuan 750003, Peoples R China. EM XiaoyunDing_2023@163.com; jingwang_2023@nxmu.edu.cn RI Hu, Zhiqiang/NDS-8122-2025; zhou, xinyue/JOJ-6874-2023 FU Natural Science Foundation of Ningxia, China [2025AAC030856]; Scientific Research Project of Ningxia Medical University [XM2025065] FX This study was supported by the Natural Science Foundation of Ningxia, China (Grant No. 2025AAC030856) and the Scientific Research Project of Ningxia Medical University (Grant No. XM2025065) . 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Immunopharmacol. PD DEC 3 PY 2025 VL 166 AR 115596 DI 10.1016/j.intimp.2025.115596 EA SEP 2025 PG 15 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA 7ST3Y UT WOS:001578784300001 PM 40991998 DA 2026-03-26 ER PT J AU Sun, YC Yuan, XH Huang, WL Li, QH Zhang, SF Hang, Y Huang, JY Li, JQ Qian, YC Zhang, W Li, L AF Sun, Yucen Yuan, Xinghua Huang, Weiling Li, Qiuhong Zhang, Shanfang Hang, Yu Huang, Jingyi Li, Jiaqi Qian, Yechang Zhang, Wei Li, Li TI Fuzheng Huayu recipe inhibits alveolar macrophage M2 polarization and oxidative phosphorylation via METTL3-mediated NDUFA2 m6A modification SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE Fuzheng huayu recipe (FZHYR); Pulmonary fibrosis; M2 macrophage polarization; METTL3; NDUFA2; Oxidative phosphorylation ID PULMONARY-FIBROSIS AB Clinical evidence points to the Traditional Chinese Medicine Fuzheng Huayu recipe (FZHYR) as an anti-fibrosis drug. Our previous studies have shown that FZHYR regulates macrophage polarization and the expression of NADH dehydrogenase (ubiquinone) 1 alpha subcomplex subunit 2 (NDUFA2) to inhibit pulmonary fibrosis. This study aims to explore the mechanism of FZHYR regulates macrophage polarization and NDUFA2 expression in the treatment of pulmonary fibrosis. NR8383 alveolar macrophages polarizing to M1 or M2 polarization by stimulation with LPS/IFN-gamma or IL-14/IL-13 and received FZHYR treatment. Macrophage polarization was verified by detecting the levels of transmembrane protein that specific expression using flow cytometry and levels of inflammatory factors. Oxidative phosphorylation change was reflected by mitochondrial ROS and oxygen consumption rate. The effect of FZHYR on m6A of Ndufa2 mRNA and the involvement of m6A modification enzymes (METTL3 and IGF2BP1) was investigated. FZHYR promoted macrophage M1 polarization and inhibited macrophage M2 polarization. FZHYR inhibited oxidative phosphorylation and NDUFA2 expression in M2 macrophages. Ndufa2 silencing inhibited macrophage M2 polarization and oxidative phosphorylation. M2 macrophage polarization and oxidative phosphorylation induced by Ndufa2 overexpression were reversed by FZHYR. Mechanistically, METTL3 induced Ndufa2 m6A methylation in an IGF2BP1-dependent manner in FZHYR-treated M2 macrophage. Moreover, the inhibition of METTL3 suppressed macrophage M2 polarization and oxidative phosphorylation. FZHYR inhibits M2 macrophage polarization through the inhibition of METTL3-mediated m6A modification and downregulation of NDUFA2 and oxidative phosphorylation. C1 [Sun, Yucen; Yuan, Xinghua; Huang, Weiling; Zhang, Shanfang; Hang, Yu; Huang, Jingyi; Li, Jiaqi; Qian, Yechang; Li, Li] Shanghai Univ Tradit Chinese Med, Shanghai Baoshan Dist Hosp Integrated Tradit Chine, Dept Resp Dis, Baoshan Hosp Affiliated, Baoshan Dist,181 You Yi Rd, Shanghai 201999, Peoples R China. [Li, Qiuhong] Tongji Univ, Shanghai Pulm Hosp, Sch Med, Dept Resp & Crit Care Med, Shanghai 200433, Peoples R China. [Zhang, Wei] Shanghai Univ Tradit Chinese Med, Dept Pulm Dis, ShuGuang Hosp Afffliated, 528 Zhangheng Rd,Pudong New Area, Shanghai 201203, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine; Tongji University; Shanghai University of Traditional Chinese Medicine RP Li, L (corresponding author), Shanghai Univ Tradit Chinese Med, Shanghai Baoshan Dist Hosp Integrated Tradit Chine, Dept Resp Dis, Baoshan Hosp Affiliated, Baoshan Dist,181 You Yi Rd, Shanghai 201999, Peoples R China.; Zhang, W (corresponding author), Shanghai Univ Tradit Chinese Med, Dept Pulm Dis, ShuGuang Hosp Afffliated, 528 Zhangheng Rd,Pudong New Area, Shanghai 201203, Peoples R China. EM zhangw1190a@sina.com; yefan718@163.com RI zhang, wei/ADK-0893-2022 OI zhang, wei/0000-0003-4816-8390 FU Shanghai Natural Science Foundation; Shanghai Huanghai Pharmaceutical Co., Ltd. FX The authors would like to thank the Shanghai Huanghai Pharmaceutical Co., Ltd. for preparing the FZHYR extracts. 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Bioenerg. Biomembr. PD DEC PY 2025 VL 57 IS 6 BP 453 EP 467 DI 10.1007/s10863-025-10074-x EA SEP 2025 PG 15 WC Biophysics; Cell Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biophysics; Cell Biology GA DC8BB UT WOS:001574863500001 PM 40974490 DA 2026-03-26 ER PT J AU Sun, P Zhao, XF Lin, YH Xu, ZC Jia, YQ Wang, JY Wang, JF Zhan, ZS AF Sun, Peng Zhao, Xiangfeng Lin, Yanhua Xu, Zichen Jia, Yuqi Wang, Jingyi Wang, Jiafeng Zhan, Zhaoshuang TI Combining metabolomics and network pharmacology to clarify the mechanism of Angelica sinensis-Sophora flavescens pills in treating atopic dermatitis through the sweet-bitter harmonization theory SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Angelica sinensis - Sophora flavescens pills; Atopic dermatitis; M1-type macrophage polarization; Metabolomics; Network pharmacology; Sweet-bitter harmonization theory ID RECEPTOR; CALCIUM; INFLAMMATION; HOMEOSTASIS; ACTIVATION; RESPONSES AB Ethnopharmacological relevance Rooted in "sweet-bitter harmonization" theory from Gu Jin Yi Jian (Vol. 9), Angelica sinensis-Sophora flavescens pills (ASP) have been traditionally used for inflammatory dermatoses. This study mechanistically validates ASP's efficacy against atopic dermatitis (AD) through calcium signaling and metabolic regulation. Aim of the study: To elucidate ASP's anti-inflammatory mechanisms targeting AD pathophysiology, focusing on calcium-dependent macrophage polarization and metabolic reprogramming. Materials and methods: A network pharmacology approach identified 27 bioactive compounds and 176 AD-related therapeutic targets. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) metabolomics was applied to characterize key serum metabolic alterations in 2,4-dinitrochlorobenzene (DNCB)-induced BALB/c AD mice treated with ASP at doses of 0.68-2.73 g/kg. Molecular docking analyses (AutoDock Vina) evaluated receptor-ligand binding affinities (threshold: Delta G < -3 kcal/mol). In vivo validation encompassed hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), Western blot (WB), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence. In vitro experiments were conducted using RAW264.7 macrophages, with cell viability assessed via Cell Counting Kit-8 (CCK-8), and calcium signaling (Fluo-4 AM probe), protein expression (WB, IF), and functional assays (CCK-8) performed to characterize molecular mechanisms. Results: ASP dose-dependently reduced AD symptoms (skin thickness, EASI scores, splenomegaly; P < 0.01 in comparison with the model group). Downregulated CaSR/IP3R/PLC beta axis and PI3K/AKT phosphorylation. Inhibited M1 polarization (downregulated CD86(+) macrophages, downregulated COX-2) and pro-inflammatory cytokines (IFN-gamma, IgE, IL-6; P < 0.05). Modulated metabolic biomarkers: upregulated nordihydroguaiaretic acid (anti-inflammatory), downregulated arachidonic acid/LysoPC 22:5 (pro-inflammatory). Molecular docking confirmed high-affinity binding of matrine/oxymatrine/ferulic acid to T1R2-T1R3/TAS2R38 taste receptors. In vitro experiments,RAW264.7 cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. And revealed that oxymatrine (OMT) and Ferulic acid (FA) can inhibit related pathways, exerting an effect similar to that of BAPTA(1,2-Bis(2-aminophenoxy)ethane-N,N,N ',N '-tetraacetic Acid) in suppressing calcium signaling, and inhibiting M1 polarization markers COX-2 and iNOS. They can also inhibit the anti-inflammatory effects of the IP3R/PLC beta and PI3K/AKT pathways. Conclusion: The therapeutic effects of ASP on AD are mediated through inhibition of M1 macrophage polarization, likely via suppression of the IP3R/PLC beta and PI3K/AKT signaling axes and restoration of dysregulated metabolic homeostasis. The "sweet-bitter harmonization" theoretical framework may underpin its multi-target synergistic effects, supporting ASP's potential as a novel candidate for AD treatment. C1 [Sun, Peng; Zhao, Xiangfeng; Lin, Yanhua; Jia, Yuqi; Wang, Jingyi; Wang, Jiafeng; Zhan, Zhaoshuang] Shandong Univ Tradit Chinese Med, Coll Chinese Med, Jinan 250355, Peoples R China. [Xu, Zichen] Shandong Univ Tradit Chinese Med, Sch Ophthalmol & Optometry, Jinan 250355, Peoples R China. C3 Shandong University of Traditional Chinese Medicine; Shandong University of Traditional Chinese Medicine RP Wang, JF; Zhan, ZS (corresponding author), Shandong Univ Tradit Chinese Med, 12 Daxue Rd 4655, Jinan, Peoples R China. EM wjfeng2000@126.com; zzshuang2000@126.com RI zichen, Xu/C-4823-2014 FU Traditional Chinese Medicine Science and Technology Project in Shandong Province [Z20241753-2]; Qilu Medical School of Traditional Chinese Medicine [LuWei Letter [2022] 93]; Qilu authentic Medicine processing Technology [LuWei Letter [2021] 45]; Shandong Postgraduate Education [SDYAL20053, SDYKC21047]; Shandong University of Traditional Chinese Medicine [YJSTZCX2025002] FX 1 Key Project of Traditional Chinese Medicine Science and Technology Project in Shandong Province (Z20241753-2).2 Qilu Medical School of traditional Chinese Medicine academic School inheritance Project (Qilu febrile Disease School Tongfu Syndrome differentiation and treatment of febrile Diseases TCM characteristic Technology: LuWei Letter [2022] 93;3. Qilu authentic Medicine processing Technology: LuWei Letter [2021] 45);4. Shandong Postgraduate Education quality courses and Professional degree Postgraduate Teaching case Base Project (No.SDYAL20053); 5. Shandong Postgraduate Education quality improvement Program (No.SDYKC21047).6.The Quality Enhancement and Innovation Project for Postgraduate Students of Shandong University of Traditional Chinese Medicine (Project Number: YJSTZCX2025002). 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Ethnopharmacol. PD JAN 30 PY 2026 VL 355 AR 120570 DI 10.1016/j.jep.2025.120570 EA SEP 2025 PN A PG 22 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 8AR8P UT WOS:001584165300001 PM 40935216 DA 2026-03-26 ER PT J AU Jin, X Li, A Dai, ZY Li, Y Feng, XC Qiu, F AF Jin, Xin Li, Ang Dai, Zhaoyuan Li, Yi Feng, Xinchi Qiu, Feng TI Resina Draconis Promotes Diabetic Wound Healing by Regulating the AGE-RAGE Pathway to Modulate Macrophage Polarization SO CURRENT ISSUES IN MOLECULAR BIOLOGY LA English DT Article DE Resina Draconis; diabetic wound; AGE-RAGE; macrophage polarization ID DRAGONS BLOOD; RECEPTOR AB Resina Draconis (RD), a traditional Chinese medicine, has been widely used in treating diabetic foot ulcers. However, its specific mechanisms of action remain incompletely understood. First, network pharmacology combined with GEO clinical sample data mining was employed to systematically analyze the therapeutic targets of RD in promoting diabetic wound healing. Second, an AGEs-induced RAW264.7 cell model was utilized to investigate the regulatory effects of RD and its primary active components on the AGE-RAGE signaling pathway, along with their anti-inflammatory and antioxidant activities. Finally, a diabetic wound mouse model was established to validate the efficacy of RD and further explore its underlying molecular mechanisms. Integrated analysis of network pharmacology and GEO database mining identified 492 potential therapeutic targets of RD in diabetic wound healing, primarily involving the AGE-RAGE pathway. In vitro, RD (6.25 mu g/mL) significantly suppressed AGE-induced inflammatory factors and ROS production while downregulating AGE-triggered RAGE protein overexpression. In vivo, RD hydrogel accelerated diabetic wound healing by modulating the AGE-RAGE axis and regulating macrophage polarization. RD effectively promotes diabetic wound healing through synergistic regulation of the AGE-RAGE pathway, oxidative stress suppression, and macrophage polarization modulation, providing a novel therapeutic strategy for diabetic wound management. C1 [Jin, Xin; Li, Ang; Dai, Zhaoyuan; Li, Yi; Feng, Xinchi; Qiu, Feng] Tianjin Univ Tradit Chinese Med, Sch Chinese Mat Med, Tianjin Key Lab Therapeut Subst Tradit Chinese Med, 10 Poyang Lake Rd, Tianjin 301617, Peoples R China. C3 Tianjin University of Traditional Chinese Medicine RP Feng, XC; Qiu, F (corresponding author), Tianjin Univ Tradit Chinese Med, Sch Chinese Mat Med, Tianjin Key Lab Therapeut Subst Tradit Chinese Med, 10 Poyang Lake Rd, Tianjin 301617, Peoples R China. EM jinxin041@163.com; lianghbkd@163.com; zhaoyuandai1024@163.com; 15369620697@163.com; xiaochi0211@163.com; fengqiu20070118@163.com RI jin, xin/JOJ-8551-2023 OI Qiu, Feng/0000-0001-5505-8670; Jin, Xin/0009-0008-5915-7543; Feng, Xinchi/0000-0002-3522-0471 FU National Natural Science Foundation of China; [81973565]; [82374140] FX This research was funded by the National Natural Science Foundation of China (Grant No.: 81973565 and 82374140). 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Issues Mol. Biol. PD SEP 11 PY 2025 VL 47 IS 9 AR 748 DI 10.3390/cimb47090748 PG 21 WC Biochemistry & Molecular Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology GA 7TZ8P UT WOS:001579631600001 PM 41020870 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Liu, Z Guo, LQ Jin, L Fang, YD AF Liu, Zhe Guo, Luoqin Jin, Li Fang, Yudong TI Effects of sini decoction-mediated cellular mitochondrial autophagy on M1 macrophage polarization and its impact on a mouse model of peripheral artery disease SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE Traditional chinese medicine sini decoction; Peripheral artery disease; Mitophagy; M1 macrophage polarization; Serum inflammatory markers AB This study aimed to investigate the therapeutic effects of Sini Decoction on a murine model of peripheral arterial disease (PAD) and to explore its potential mechanisms of action related to mitochondrial autophagy and M1 macrophage polarization. A total of 36 specific-pathogen-free Kunming mice were used to establish a PAD model and were randomly assigned into four groups: the experimental group (EG, administered Sini Decoction via gavage), the control group (CG, administered rapamycin via gavage), the model group (MG, administered 0.9% sodium chloride solution via gavage), and the normal group (NG, administered 0.9% sodium chloride solution via gavage). Serum inflammatory cytokines, mitochondrial autophagy-related proteins (LC3bII and p62), M1 macrophage markers (iNOS and COX2), key proteins in the mitochondrial autophagy pathway (PINK1 and Parkin), relative mitochondrial DNA (mtDNA) content, and mitochondrial function indicators [oxygen consumption rate (OCR) and extracellular acidification rate (ECAR)] were measured and analyzed. The serum levels of IL-6, IL-1 beta, TNF-alpha, IL-10, and MCP-1 were significantly decreased in both the EG and CG compared to the MG (P < 0.05), with the EG showing considerably greater reductions than the CG (P < 0.05). Compared with the CG, the EG exhibited significantly increased protein and mRNA expression levels of LC3bII, p62, iNOS, and COX2 (P < 0.05), considerably elevated mitochondrial OCR, and considerably reduced ECAR (P < 0.05). Additionally, the relative mtDNA content and the percentage of atherosclerotic lesion area were markedly lower in the EG than in the CG (P < 0.05). Moreover, the expression level of PINK1 and Parkin proteins were significantly increased in both the EG and CG compared to the MG (P < 0.05). Sini Decoction demonstrated superior efficacy in ameliorating PAD compared to the autophagy inducer rapamycin. Its therapeutic effects may be associated with the promotion of mitochondrial autophagy and the induction of M1 macrophage polarization. C1 [Liu, Zhe; Guo, Luoqin; Fang, Yudong] Shanghai TCM INTEGRATED Hosp, Dept Vasc, Shanghai 200082, Peoples R China. [Jin, Li; Fang, Yudong] Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Macau 999078, Taipa, Peoples R China. [Jin, Li; Fang, Yudong] Macau Univ Sci & Technol, Sch Pharm, Macau 999078, Taipa, Peoples R China. C3 Macau University of Science & Technology; Macau University of Science & Technology RP Fang, YD (corresponding author), Shanghai TCM INTEGRATED Hosp, Dept Vasc, Shanghai 200082, Peoples R China.; Fang, YD (corresponding author), Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Macau 999078, Taipa, Peoples R China.; Fang, YD (corresponding author), Macau Univ Sci & Technol, Sch Pharm, Macau 999078, Taipa, Peoples R China. EM post1901601@163.com FU Project of "Technology Young Eagle" Program of Shanghai Hospital of Integrated Traditional Chinese and Western Medicine [2024KJCY002]; Science and Technology Development Project of Shanghai University of Traditional Chinese Medicine [24KFL085]; Traditional Chinese Medicine Research Project of Shanghai Hongkou District Health Commission [HKQ-GYQY-ZYY-2023-02]; Key Clinical Specialty of Traditional Chinese Medicine Surgery during the 13th Five-Year Plan Period of Shanghai Municipal Health Commission [2019WJ009]; Construction Project of Traditional Chinese Medicine Specialty and Disease Alliance in East China Region and at Municipal Level of Shanghai Municipal Health Commission (Vascular Disease Specialty Alliance); National Natural Science Foundation of China [82174382] FX The research is supported by: Project of "Technology Young Eagle" Program of Shanghai Hospital of Integrated Traditional Chinese and Western Medicine (No. 2024KJCY002); Science and Technology Development Project of Shanghai University of Traditional Chinese Medicine (No. 24KFL085); Traditional Chinese Medicine Research Project of Shanghai Hongkou District Health Commission (No. HKQ-GYQY-ZYY-2023-02); Key Clinical Specialty of Traditional Chinese Medicine Surgery during the 13th Five-Year Plan Period of Shanghai Municipal Health Commission (No. 2019WJ009); Construction Project of Traditional Chinese Medicine Specialty and Disease Alliance in East China Region and at Municipal Level of Shanghai Municipal Health Commission (Vascular Disease Specialty Alliance);National Natural Science Foundation of China (No. 82174382). 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Bioenerg. Biomembr. PD DEC PY 2025 VL 57 IS 6 BP 437 EP 451 DI 10.1007/s10863-025-10072-z EA SEP 2025 PG 15 WC Biophysics; Cell Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biophysics; Cell Biology GA DC8BB UT WOS:001569217900001 PM 40928591 DA 2026-03-26 ER PT J AU Wei, KK Li, JM Yu, LT Chen, L Gao, J Zhu, CL Liu, M Li, M Shi, DZ Ma, XJ AF Wei, Kangkang Li, Jinming Yu, Lintong Chen, Li Gao, Jie Zhu, Chunlin Liu, Min Li, Min Shi, Dazhuo Ma, Xiaojuan TI A combination of tetramethylpyrazine and berberine prevents coronary microembolization in rats by regulating miR-34a-5p in platelet-derived exosomes SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Tetramethylpyrazine; Berberine; Coronary microembolization; MiR-34a-5p; Platelet-derived exosomes ID ISCHEMIA-REPERFUSION INJURY; EXTRACELLULAR VESICLES; LIGUSTRAZINE AB Ethnopharmacological relevance: Both chuanxiong rhizome and Coptis chinensis were first recorded in the Shennong's Classic of Materia Medica. Chuanxiong rhizome and Coptis chinensis are a classic herbal pair in Traditional Chinese Medicine (TCM), renowned for their effects in activating blood circulation and resolving toxicity. They are widely used to treat chest impediment and heart pain.Tetramethylpyrazine (TMP) and berberine (BBR) are the main active components isolated from Chuanxiong Rhizome and Coptis chinensis, respectively. Both components have been applied to the treatment of various cardiovascular diseases owing to their anti-platelet, anti-inflammatory, and endothelial-protective effects. It has been demonstrated that the combination of TMP with BBR produces more effective anti-thrombotic effects compared with the monotherapy based on either agent. Aim of the study: This study was designed to explore the potential role and mechanisms of TMP combined with BBR in reducing the formation of coronary microembolization (CME) in rats. Materials and methods: CME was induced by the injection of sodium laurate into the left ventricular of rats. CME formation and myocardial damage were examined using histopathology, while echocardiography was used to assess cardiac functions. Additionally, a series of in vitro experiments was performed to examine how plateletderived exosomes (PLT-exo) enriched with miR-34a-5p influence human umbilical vein endothelial cells (HUVECs) subjected to ox-LDL and macrophages stimulated with LPS.Moreover, TMP and BBR were added to observe their effects. Results: The combination of TMP and BBR significantly mitigated CME formation, myocardial injury, and left ventricular ejection fraction (LVEF) in rats. Besides, the pretreatment with TMP and BBR inhibited platelet activation, alleviated endothelial cell damage, and reduced the number of M1 macrophages. Additionally, the levels of miR-34a-5p in PLT-exo of CME rats were suppressed after the pretreatment with TMP and BBR. However, these effects of TMP and BBR were attenuated after the injection of agomiR-34a-5p in CME rats. Furthermore, TMP combined with BBR ameliorated in vitro HUVEC damage and M1-type macrophage polarization induced by an increase in miR-34a-5p in PLT-exo. Conclusions: Our study concluded that the combination of TMP and BBR prevented CME and improved cardiac functions in rats by suppressing miR-34a-5p in PLT-exo. C1 [Chen, Li; Gao, Jie; Shi, Dazhuo; Ma, Xiaojuan] China Acad Chinese Med Sci, Xiyuan Hosp, Natl Clin Res Ctr Chinese Med Cardiol, Beijing 100091, Peoples R China. [Wei, Kangkang] Shandong Univ Tradit Chinese Med, Affiliated Hosp, Jinan 250014, Peoples R China. [Li, Jinming] Shandong Prov Third Hosp, Jinan 250031, Peoples R China. [Yu, Lintong; Zhu, Chunlin; Liu, Min; Li, Min] Beijing Univ Chinese Med, Beijing 100029, Peoples R China. C3 China Academy of Chinese Medical Sciences; Xiyuan Hospital, CACMS; Shandong University of Traditional Chinese Medicine; Beijing University of Chinese Medicine RP Shi, DZ; Ma, XJ (corresponding author), China Acad Chinese Med Sci, Xiyuan Hosp, Natl Clin Res Ctr Chinese Med Cardiol, Beijing 100091, Peoples R China. EM shidztcm@163.com; abc_mxj@aliyun.com RI 李, 金明/GWZ-6274-2022; Wei, Kangkang/KVY-5709-2024 FU National Natural Science Foundation of China [82074418]; Key Project of Science and Technology Innovation Project of the China Academy of Chinese Med-ical Sciences [CI2021A00911] FX Funding This work was supported by the National Natural Science Foundation of China (grant number 82074418) ; the Key Project of Science and Technology Innovation Project of the China Academy of Chinese Med-ical Sciences (grant number CI2021A00911) . 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PD JAN 10 PY 2026 VL 354 AR 120549 DI 10.1016/j.jep.2025.120549 EA SEP 2025 PG 14 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 7XT5T UT WOS:001582172700001 PM 40915375 DA 2026-03-26 ER PT J AU Liu, CQ Yuan, JF Cheng, PP Yang, T Liu, Q Li, TS Li, CY Qu, HY Zhou, H AF Liu, Chunqiu Yuan, Jinfeng Cheng, Peipei Yang, Tao Liu, Qian Li, Tianshu Li, Chuyi Qu, Huiyan Zhou, Hua TI Modulation of Macrophage Polarization by Traditional Chinese Medicine in HFpEF: A Review of Mechanisms and Therapeutic Potentials SO PHARMACEUTICALS LA English DT Review DE macrophage; traditional Chinese medicine; heart failure with preserved ejection fraction; mechanisms; signaling pathway ID PRESERVED EJECTION FRACTION; HEART-FAILURE; INFLAMMATION; INHIBITION; INJURY; ACTIVATION; PHENOTYPE; PROMOTE; PATHWAY; DYSFUNCTION AB Heart failure with preserved ejection fraction (HFpEF) is a multifactorial cardiovascular disorder characterized by diastolic dysfunction, systemic inflammation, and myocardial fibrosis. Emerging evidence indicates that macrophage polarization imbalance plays a central role in HFpEF pathogenesis. Traditional Chinese medicine (TCM) has demonstrated therapeutic potential in modulating macrophage activity through pathways such as NO/cGMP/PKG, TGF-beta/Smads, and PI3K/Akt, thereby exerting anti-inflammatory, antifibrotic, and antioxidant effects. In this review, we conducted a literature search in PubMed, Google Scholar, Web of Science, and CNKI for studies published up to May 2025, using the terms "HFpEF", "Traditional Chinese Medicine", and "macrophage". A total of 19 relevant studies were included. We highlight representative TCM metabolites and TCM formulas, such as resveratrol, Qishen Yiqi Pill, Shenfu Injection, etc. And we summarize their mechanisms in regulating M1/M2 macrophage polarization. Finally, we identify current challenges, including limited HFpEF-specific models and insufficient mechanistic validation, and propose directions for future research. C1 [Liu, Chunqiu; Yuan, Jinfeng; Cheng, Peipei; Yang, Tao; Liu, Qian; Li, Tianshu; Li, Chuyi; Qu, Huiyan; Zhou, Hua] Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Inst Cardiovasc Dis Integrated Tradit Chinese & We, Shanghai 201203, Peoples R China. [Liu, Chunqiu; Yuan, Jinfeng; Cheng, Peipei; Yang, Tao; Liu, Qian; Li, Tianshu; Li, Chuyi; Qu, Huiyan; Zhou, Hua] Shanghai Univ Tradit Chinese Med, Branch Natl Clin Res Ctr Chinese Med Cardiol, Shuguang Hosp, Shanghai 201203, Peoples R China. [Qu, Huiyan; Zhou, Hua] Shanghai Univ Tradit Chinese Med, Dept Cardiovasc Dis, Shuguang Anhui Hosp, Hefei 230031, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine RP Qu, HY; Zhou, H (corresponding author), Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Inst Cardiovasc Dis Integrated Tradit Chinese & We, Shanghai 201203, Peoples R China.; Qu, HY; Zhou, H (corresponding author), Shanghai Univ Tradit Chinese Med, Branch Natl Clin Res Ctr Chinese Med Cardiol, Shuguang Hosp, Shanghai 201203, Peoples R China.; Qu, HY; Zhou, H (corresponding author), Shanghai Univ Tradit Chinese Med, Dept Cardiovasc Dis, Shuguang Anhui Hosp, Hefei 230031, Peoples R China. EM 18703311364@163.com; qhy1520043084@163.com; zhouhua@shutcm.edu.cn RI Zhou, Hua/E-7315-2010; 袁, 金锋/LZE-8341-2025; liu, chunqiu/MTD-7990-2025 OI Li, Tianshu/0009-0003-3693-1165; liu, chunqiu/0009-0005-8042-7817 FU Three-year Action Plan of the Major Clinical Research Program of Shanghai Shenkang Medical Development Center; National Natural Science Foundation of China [82274306, 81973656]; Shanghai Shenkang Medical Development Center Emerging Frontier Technology Joint Research Project [SHDC12018125]; Science and Technology Support Project of the Shanghai Science and Technology Commission [18401932800]; Construction Project for Well-known Elderly TCM Specialist Academic Experience Research of Shanghai [SGGZS-202236]; Anhui Provincial Health Research Program [2024Aa10040]; [SHDC2020CR1053B] FX This research was funded by the Three-year Action Plan of the Major Clinical Research Program of Shanghai Shenkang Medical Development Center (No. SHDC2020CR1053B), the National Natural Science Foundation of China (No. 82274306, 81973656), the Shanghai Shenkang Medical Development Center Emerging Frontier Technology Joint Research Project (No. SHDC12018125), the Science and Technology Support Project of the Shanghai Science and Technology Commission (No. 18401932800), the Construction Project for Well-known Elderly TCM Specialist Academic Experience Research of Shanghai (No. SGGZS-202236), and the Anhui Provincial Health Research Program (No. 2024Aa10040). 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However, the precise mechanisms underlying its therapeutic effects remain to be elucidated. Aim of the study: To investigate whether WYXZ alleviates renal fibrosis by modulating macrophage polarization via JAK2/STAT3 signaling. Materials and methods: Renal fibrosis was induced in C57BL/6J mice by 5/6 nephrectomy, followed by treatment with WYXZ (4.94 or 9.88 g/kg) or valsartan for 8 weeks. Kidney function (serum creatinine/blood urea nitrogen), histopathology (HE/Masson staining), and macrophage polarization (CD86+/CD206+ flow cytometry) were assessed. In vitro, RAW264.7 macrophages were polarized to M1/M2 phenotypes and treated with WYXZmedicated serum (2.5-7.5 %) +/- JAK2 agonist Butyzamide or STAT3 shRNA. Inflammatory responses (IL-6/IL-10 secretion by ELISA), polarization status (flow cytometry), and JAK2/STAT3 pathway activation (phosphorylatedJAK2/STAT3 by Western blot) were analyzed. Fibrosis markers (alpha-smooth muscle actin, alpha-SMA/collagen I, Col-I) were evaluated in RAW264.7/HK-2 co-cultures. Results: WYXZ significantly attenuated renal fibrosis and improved kidney function in 5/6 nephrectomized mice, concurrently suppressing M1 macrophage polarization while enhancing M2 polarization. In vitro, WYXZmedicated serum reduced inflammatory cytokine secretion and inhibited JAK2/STAT3 pathway activation in LPS-stimulated macrophages. These effects were reversed by JAK2 agonism with Butyzamide and abolished through STAT3 knockdown. Critically, in macrophage-renal tubular cell co-cultures, WYXZ diminished fibrotic marker expression via suppression of macrophage JAK2/STAT3 signaling. Conclusions: WYXZ attenuates renal fibrosis by reprogramming macrophage polarization through JAK2/STAT3 inhibition, validating its traditional use for CKD. C1 [Lin, Xiaomeng; Lu, Hanyu; Peng, Xin] Zhejiang Chinese Med Univ, Ningbo Municipal Hosp Tradit Chinese Med TCM, Ningbo Inst Chinese Med Res, Affiliated Hosp, Ningbo 315010, Peoples R China. [Yu, Kena; Duan, Jiamin; Zhong, Guanghui; Cai, Xudong] Zhejiang Chinese Med Univ, Ningbo Municipal Hosp Tradit Chinese Med TCM, Dept Nephrol, Affiliated Hosp, Ningbo 315010, Peoples R China. [He, Liqun] Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Shanghai 200120, Peoples R China. C3 Zhejiang Chinese Medical University; Zhejiang Chinese Medical University; Shanghai University of Traditional Chinese Medicine RP Cai, XD (corresponding author), Zhejiang Chinese Med Univ, Ningbo Municipal Hosp Tradit Chinese Med TCM, Dept Nephrol, Affiliated Hosp, Ningbo 315010, Peoples R China. EM xudongcai1979@hotmail.com RI He, Liqun/OVZ-4910-2025 FU Zhejiang Provincial Natural Science Foundation of China [LY20H270004]; Pioneer" and "Leading Goose" R & D Pro-gram of Zhejiang [2023C03038]; Ningbo Major Research and Development Plan Project [2022Z135, 2023Z165]; Ningbo public welfare science and technology plan project [2022S083]; Zhejiang Traditional Chinese Medicine Science and Technology Plan Project [2024ZL142]; Ningbo Clinical Research Center for Traditional Chinese medicine nephropathy [2024L001]; Ningbo Top Medical and Health Research Program [2022030309]; National Administration of Traditional Chinese Medicine and Zhejiang Province [GZY-ZI-KJ-23037] FX This study was supported by the following funds and projects: 1. Joint Funds of the Zhejiang Provincial Natural Science Foundation of China (LBY24H290002) ; 2. "Pioneer" and "Leading Goose" R & D Pro-gram of Zhejiang (2023C03038) ; 3. Ningbo Major Research and Development Plan Project (2022Z135, 2023Z165) ; 4. Ningbo public welfare science and technology plan project (2022S083) ; 5.Zhejiang Provincial Natural Science Foundation of China (LY20H270004) ; 6. Zhejiang Traditional Chinese Medicine Science and Technology Plan Project (2024ZL142) ; 7. Ningbo Clinical Research Center for Traditional Chinese medicine nephropathy (2024L001) ; 8. Ningbo Top Medical and Health Research Program (2022030309) ; 9. Major Joint Projects Sup-ported by the National Administration of Traditional Chinese Medicine and Zhejiang Province (GZY-ZI-KJ-23037) . 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PD JAN 10 PY 2026 VL 354 AR 120497 DI 10.1016/j.jep.2025.120497 EA SEP 2025 PG 15 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 7CU4C UT WOS:001567959300008 PM 40876793 OA hybrid DA 2026-03-26 ER PT J AU Lin, RF Zhu, Y Liu, YJ Guo, ZH Wei, JM Li, Y Yu, YF AF Lin, Ruifang Zhu, Yun Liu, Yongjun Guo, Zhihua Wei, Jiaming Li, Ya Yu, Yunfeng TI Sirtuins regulate macrophage polarization in heart failure: Metabolic reprogramming, epigenetic regulation, and immune cell interactions SO PHARMACOLOGICAL RESEARCH LA English DT Article DE Sirtuins; Macrophage polarization; Heart failure; Metabolic reprogramming; Epigenetic regulation; Immune cell interaction ID PRESERVED EJECTION FRACTION; POST MYOCARDIAL-INFARCTION; ORAL BIOAVAILABILITY; INFLAMMATION RESOLUTION; DIASTOLIC DYSFUNCTION; CARDIAC MACROPHAGES; OXIDATIVE STRESS; ASTRAGALOSIDE-IV; DNA-DAMAGE; M2 AB Heart failure (HF) is an end-stage cardiovascular syndrome caused by structural or functional cardiac abnormalities. Its high morbidity and mortality underscore the urgent need for novel therapeutic strategies. In recent years, the dynamic regulatory mechanisms underlying macrophage polarization in the onset and progression of HF have attracted widespread attention. The Sirtuin family, as NAD+-dependent deacetylases, has emerged as a key regulatory factor in reshaping the macrophage polarization phenotype by integrating metabolic reprogramming, epigenetic regulation, and immune cell interactions. This paper systematically elaborates the molecular mechanisms by which Sirtuins (SIRT1-SIRT7) regulate metabolic reprogramming (e.g., glucose metabolism, lipid metabolism, and glutamine metabolism), coordinate epigenetic modifications (e.g., DNA methylation, histone modifications, and non-coding RNA regulation), and mediate interactions between immune cells to dynamically balance macrophage polarization. Furthermore, this review summarizes recent advances in the active components of phytomedicines, such as resveratrol, pterostilbene, astragaloside IV, quercetin, dihydromyricetin, berberine, honokiol, ginsenoside Rc, ginsenoside Rg1, and ginsenoside Rg3, in targeting the Sirtuin-macrophage polarization axis for the prevention and treatment of HF. This review aims to provide a theoretical framework and translational guidance for developing HF-targeted therapeutic strategies based on Sirtuin-mediated macrophage polarization, as well as for the research and development of related natural products. C1 [Lin, Ruifang; Zhu, Yun; Liu, Yongjun; Wei, Jiaming; Yu, Yunfeng] Hunan Univ Chinese Med, Sch Tradit Chinese Med, Changsha 410208, Hunan, Peoples R China. [Lin, Ruifang; Guo, Zhihua; Wei, Jiaming] Hunan Univ Chinese Med, Hunan Key Lab Coll & Univ Intelligent TCM Diag & P, Changsha 410208, Hunan, Peoples R China. [Guo, Zhihua; Yu, Yunfeng] Hunan Univ Chinese Med, Clin Coll Chinese Med 1, Changsha 410208, Hunan, Peoples R China. [Li, Ya] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China. [Wei, Jiaming] Hunan Univ Chinese Med, Affiliated Hengyang Hosp, Changsha 410208, Hunan, Peoples R China. C3 Hunan University of Chinese Medicine; Hunan University of Chinese Medicine; Hunan University of Chinese Medicine; Hunan University of Chinese Medicine; Hunan University of Chinese Medicine RP Wei, JM; Yu, YF (corresponding author), Hunan Univ Chinese Med, Sch Tradit Chinese Med, Changsha 410208, Hunan, Peoples R China.; Li, Y (corresponding author), Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China. EM 004916@hnucm.edu.cn; 003872@hnucm.edu.cn; yuyunfeng1510@163.com RI Yu, Yunfeng/NVL-9814-2025 FU National Natural Science Foundation of China [82174343, 82405372]; Key Subject of Scientific Research Projects of Traditional Chinese Medicine in Hunan Province [A2023017]; Hunan Provincial Health Commission Research Project [D202303017861]; Key Research and Development Plan of Hunan Province [2022SK2012]; Changsha Science and Technology Bureau Project [kq2402175]; Scientific Research Project of Hunan University of Chinese Medicine [Z2023XJYB05]; Graduate Innovation Project of Hunan University of Chinese Medicine [2024CX036, 2024CX008, 2024CX019]; Postdoctoral Fellowship Program of CPSF [GZC20252636]; China Postdoctoral Science Foundation [2025M773968, 2025T181082] FX This work was supported by the National Natural Science Foundation of China (82174343, 82405372) , Key Subject of Scientific Research Projects of Traditional Chinese Medicine in Hunan Province (A2023017) , Hunan Provincial Health Commission Research Project (D202303017861) , Key Research and Development Plan of Hunan Province (2022SK2012) , Changsha Science and Technology Bureau Project (kq2402175) , Scientific Research Project of Hunan University of Chinese Medicine (Z2023XJYB05) , Graduate Innovation Project of Hunan University of Chinese Medicine (2024CX036, 2024CX008, 2024CX019) , Postdoctoral Fellowship Program of CPSF (GZC20252636) , and China Postdoctoral Science Foundation (2025M773968, 2025T181082) . 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Res. PD OCT PY 2025 VL 220 AR 107936 DI 10.1016/j.phrs.2025.107936 EA SEP 2025 PG 28 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 7AL4W UT WOS:001566372100001 PM 40889623 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Hu, J Ma, XM Xiao, YF Chen, CJ Liu, C Lu, J Wang, XQ Lu, FG AF Hu, Jue Ma, Xiangming Xiao, Yufeng Chen, Chunjing Liu, Chang Lu, Jun Wang, Xiaoqi Lu, Fangguo TI Mechanisms underlying the mitigating action of Maxing Shigan Decoction in acute lung injury caused by influenza virus based on UPLC-HRMS analysis and network pharmacology SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE Maxing Shigan Decoction; acute lung injury; UPLC-HRMS; blood-absorbed components; macrophage polarization ID POLARIZATION; IDENTIFICATION; PATHOGENESIS; INFLAMMATION AB Introduction Influenza A virus (IAV) infection is associated with high morbidity and mortality and can ultimately lead to acute lung injury (ALI). In traditional Chinese medicine, Maxing Shigan Decoction (MXSGD) can treat exogenous wind-cold, toxic heat invading the lungs, and heat-toxicity obstructing the lungs. However, the active components and underlying mechanisms of MXSGD in IAV-induced diseases remain largely unexplored. Therefore, we aimed to investigate the active constituents of MXSGD and its underlying mechanism of action in ALI.Methods Bioactive components of MXSGD in rat serum were identified using ultra-high-performance liquid chromatography and high-resolution mass spectrometry (UPLC-HRMS). Blood-absorbed MXSGD components (i.e., the constituents of MXSGD detectable in serum) in ALI were predicted through network pharmacology and molecular docking analyses. A mouse lung injury model was established using the influenza virus. The degree of lung injury, viral load in lung tissues, serum levels of inflammatory factors, gene expression levels of inflammation-related factors in lung tissue, and macrophage polarization in the lungs were then assessed.Results and discussion In the rat serum, 242 bioactive components were identified using UPLC-HRMS. Moreover, 56 ingredients, including glycyrrhizin, amygdalin, and ephedrine, were analyzed using network pharmacology, revealing 338 ALI-related targets and 99 core proteins in the protein-protein interaction network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted for core targets, and molecular docking confirmed the binding affinity of the main identified targets with their respective blood-absorbed components. Validation results demonstrated that MXSGD significantly ameliorated lung injury, mitigated lung congestion and inflammation, lowered viral load in mouse lung tissue, promoted macrophage polarization, and downregulated the expression of the PI3K/AKT pathway in IAV-infected mice. Overall, this study revealed the mechanisms and active ingredients underlying the therapeutic effects, highlighting of MXSGD its potential in treating IAV-induced ALI and regulating the polarization of macrophages. C1 [Hu, Jue; Ma, Xiangming; Xiao, Yufeng; Chen, Chunjing; Liu, Chang; Lu, Jun; Lu, Fangguo] Hunan Univ Chinese Med, Med Sch, Changsha, Peoples R China. [Wang, Xiaoqi] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha, Peoples R China. C3 Hunan University of Chinese Medicine; Hunan University of Chinese Medicine RP Lu, FG (corresponding author), Hunan Univ Chinese Med, Med Sch, Changsha, Peoples R China. EM 001196@hnucm.edu.cn RI Xiao, Yufeng/KGL-6687-2024 FU National Natural Science Foundation of China10.13039/501100001809 [82374266, 82405375]; National Natural Science Foundation of China [2023JJ10031]; Outstanding Youth Project of Hunan Provincial Natural Science Foundation [kq2209019]; Outstanding Innovative Youth Project of Changsha [21B0360]; Scientific Research Program of Hunan Education Department [2021XJJJ019]; Research Fund Project of Hunan University of Chinese Medicine [CX20240737]; Research and Innovation Program for postgraduates in Hunan Province FX The author(s) declare financial support was received for the research and/or publication of this article. This work was supported by the National Natural Science Foundation of China (grant no. 82374266, 82405375), Outstanding Youth Project of Hunan Provincial Natural Science Foundation (2023JJ10031), Outstanding Innovative Youth Project of Changsha (kq2209019), the Scientific Research Program of Hunan Education Department (grant no. 21B0360), the Research Fund Project of Hunan University of Chinese Medicine (grant no. 2021XJJJ019), Research and Innovation Program for postgraduates in Hunan Province (CX20240737). 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PD SEP 1 PY 2025 VL 16 AR 1634442 DI 10.3389/fimmu.2025.1634442 PG 24 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA 7HI3N UT WOS:001571034100001 PM 40959060 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Mao, ZL Gong, M Sun, XY Yang, CH AF Mao, Zhenlin Gong, Ming Sun, Xinyue Yang, Canhong TI Mechanisms of IGF1R signaling in type 2 diabetes-related neurodegeneration and therapeutic implications of exercise SO EUROPEAN JOURNAL OF MEDICAL RESEARCH LA English DT Article DE Type 2 diabetes; Neurodegeneration; IGF1R; Neuroinflammation; Traditional Chinese Medicine; Exercise ID AMYLOID-BETA; ALZHEIMERS-DISEASE; CROSS-TALK; INSULIN; BRAIN; ROLES; IGF-1; LINK AB BackgroundType 2 diabetes (T2D) is a chronic metabolic disorder associated with an elevated risk of neurodegenerative diseases (NDs), notably Alzheimer's disease (AD). The insulin-like growth factor 1 receptor (IGF1R) plays a key role in both T2D and ND pathogenesis by regulating neuroinflammation and neuronal survival. However, the precise molecular mechanisms linking T2D to NDs remain unclear.ObjectivesThis study investigates how IGF1R-mediated immunomodulatory pathways could be leveraged for therapeutic purposes in T2D-related neurodegeneration. It further explores the combined effects of Traditional Chinese Medicine (TCM) and structured exercise on IGF1R signaling and their potential to mitigate T2D-induced neurodegenerative changes.MethodsBioinformatics analyses and in vitro experiments were conducted using SH-SY5Y neuronal cells and primary mouse cortical neurons exposed to amyloid-beta (A beta) toxicity. IGF1R was overexpressed, and cells were treated with CS at varying concentrations. Cell viability, apoptosis, inflammatory cytokines, oxidative stress markers, and macrophage polarization were assessed using CCK-8, flow cytometry, ELISA, fluorescence microscopy, and related methods.ResultsElevated IGF1R expression reduced A beta-induced neuronal death and inflammation. CS administration increased IL-10 levels, suppressing pro-inflammatory cytokines (IL-1 beta, TNF-alpha), and promoted M2-like macrophage polarization, enhancing neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and anti-inflammatory responses.ConclusionsIGF1R is pivotal in regulating neuroinflammation and neuronal apoptosis in T2D-associated neurodegeneration. Combined TCM and structured exercise may beneficially modulate IGF1R-dependent signaling and protect neurons. Further clinical studies are needed to validate these findings and assess their therapeutic potential. C1 [Mao, Zhenlin] Jinan Univ, Affiliated Guangzhou Red Cross Hosp, Dept Neurol, Guangzhou, Guangdong, Peoples R China. [Gong, Ming] Inst Neurosci, Key Lab Neurogenet & Channelopathies Guangdong Pro, Dept Neurol, Guangzhou, Peoples R China. [Gong, Ming] Guangzhou Med Univ, Affiliated Hosp 2, Guangzhou, Guangdong, Peoples R China. [Sun, Xinyue] Heilongjiang Univ Chinese Med, Harbin, Heilongjiang Pr, Peoples R China. [Yang, Canhong] Southern Med Univ, Affiliated Hosp 3, Dept Neurol, 183 Zhongshan Rd West, Guangzhou, Guangdong, Peoples R China. C3 Jinan University; Guangzhou Medical University; Heilongjiang University of Chinese Medicine; Southern Medical University - China RP Yang, CH (corresponding author), Southern Med Univ, Affiliated Hosp 3, Dept Neurol, 183 Zhongshan Rd West, Guangzhou, Guangdong, Peoples R China. EM 916487904@qq.com FU Guangzhou Science and Technology Plan Project; [2024A04J4728] FX The authors gratefully acknowledge the support of the Guangzhou Science and Technology Plan Project (No. 2024A04J4728). Special thanks are extended to the language editing team for their valuable assistance in refining the manuscript. 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J. Med. Res. PD AUG 30 PY 2025 VL 30 IS 1 AR 825 DI 10.1186/s40001-025-03087-0 PG 20 WC Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine GA 6RT2A UT WOS:001560450900001 PM 40885996 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Lu, JH Zhang, TH Jiang, CY Hu, HT Fei, YX Yang, YQ An, H Qin, HX Zhu, ZH Yang, YZ Tian, SS Huang, LL Zhao, HJ AF Lu, Jiahui Zhang, Tinghuang Jiang, Chenying Hu, Hongtao Fei, Yunxuan Yang, Yaqin An, Hai Qin, Haixin Zhu, Zhihui Yang, Yanzi Tian, Shasha Huang, Lili Zhao, Huajun TI Ganoderic acid A regulates CSF1R to reprogram tumor-associated macrophages for immune therapy of hepatocellular carcinoma SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Ganoderic acid A (GAA); Colony stimulating factor 1 receptor (CSF1R); Tumor associated macrophages (TAMs); Immune therapy; Hepatocellular carcinoma (HCC) ID NATURAL-PRODUCTS; CANCER AB Background: The tumor microenvironment (TME) plays a crucial role in cancer progression, with tumorassociated macrophages (TAMs) constituting the core cell population of the tumor immune microenvironment. TAMs can differentiate into M1 or M2 types based on the TME, either inhibiting or promoting tumor development. Ganoderma lucidum, a medicinal and edible fungus, has a long history of use for extending lifespan and improving health. Ganoderic acid A (GAA), a bioactive compound extracted from G. lucidum, is considered the most abundant monomer among ganoderic acids and has wide applications in clinical anti-tumor therapies. Methods: In this study, the effects of GAA against hepatocellular carcinoma (HCC) by modulating TAMs were investigated. The orthotopic and subcutaneous HCC mouse models were established and administrated with GAA at doses of 30 mg/kg/day and 60 mg/kg/day. Additionally, the toxicity of GAA towards tumor cells and macrophages in vitro at concentrations ranging from 25 to 100 mu M were evaluated and the phagocytic capacity of macrophages against HCC cells were assessed. The polarization of macrophages was analyzed, along with the expression of CSF1R. Results: Our data demonstrated that GAA could suppress the growth of both orthotopic and subcutaneous HCC, which was closely associated with macrophage modulation, confirming that its anti-HCC activity was mediated by enhancing macrophage efficacy. GAA exhibited no significant toxicity to tumor cells and macrophages in vitro while enhancing the phagocytic capacity of macrophages against HCC cells. Furthermore, GAA promoted M1 polarization of macrophages while inhibiting M2 polarization. These effects were mechanistically linked to the suppression of CSF1R expression on macrophages, both in vivo and in vitro. Conclusion: Our findings suggest that GAA exerts immunotherapeutic effects in HCC by regulating macrophage polarization through CSF1R inhibition. As a promising natural bioactive compound with the potential to modulate the TME of HCC, GAA may provide novel insights into HCC immunotherapy through the reprogramming of TAMs. C1 [Lu, Jiahui; Zhang, Tinghuang; Jiang, Chenying; Hu, Hongtao; Fei, Yunxuan; Yang, Yaqin; Qin, Haixin; Zhu, Zhihui; Yang, Yanzi; Tian, Shasha; Zhao, Huajun] Zhejiang Chinese Med Univ, Sch Pharmaceut Sci, Gaoke Rd, Hangzhou 311402, Zhejiang, Peoples R China. [An, Hai; Zhao, Huajun] Zhejiang Chinese Med Univ, Acad Chinese Med Sci, Hangzhou 310053, Zhejiang, Peoples R China. [Huang, Lili] Hangzhou Third Peoples Hosp, Hangzhou 310009, Zhejiang, Peoples R China. C3 Zhejiang Chinese Medical University; Zhejiang Chinese Medical University RP Zhao, HJ (corresponding author), Zhejiang Chinese Med Univ, Sch Pharmaceut Sci, Gaoke Rd, Hangzhou 311402, Zhejiang, Peoples R China. EM zhj@zcmu.edu.cn RI Jiang, Chenying/MSZ-3905-2025; Zhu, Zhihui/NGS-1130-2025 FU Natural Science Foundation of Zhejiang Province [LQ24H280008]; Project of State Administration of Traditional Chinese Medicine of Zhejiang Province [2025ZR015]; National Natural Science Fundation of China [82474271]; Natural Science Foundation of Zhejiang Chinese Medical University [2021RCZXZK17] FX This research was financially supported by the Natural Science Foundation of Zhejiang Province (Grant No. LQ24H280008), the Project of State Administration of Traditional Chinese Medicine of Zhejiang Province (Grant No. 2025ZR015), the National Natural Science Fundation of China (Grant No. 82474271), and the Natural Science Foundation of Zhejiang Chinese Medical University (Grant No. 2021RCZXZK17). We appreciate the great experimental support from the Public Platform of Pharmaceutical Research Center, Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University. 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Immunopharmacol. PD AUG 28 PY 2025 VL 161 AR 114989 DI 10.1016/j.intimp.2025.114989 EA AUG 2025 PG 12 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA 3UF5B UT WOS:001509125500002 PM 40483831 OA hybrid DA 2026-03-26 ER PT J AU Zhang, SJ Li, BH Han, XQ Ruan, LL Fu, XX Chen, YL Wan, HT Zhu, XJ Liu, D Yi, B AF Zhang, Shujuan Li, Banghua Han, Xiaoqun Ruan, Linlin Fu, Xingxing Chen, Yanglin Wan, Hongtao Zhu, Xiaojian Liu, Dan Yi, Bo TI Sanren decoction ameliorates ulcerative colitis by modulating gut microbiota and macrophage polarization to enhance intestinal barrier function SO CHINESE MEDICINE LA English DT Article DE Sanren decoction; Ulcerative colitis; Gut microbiota; PTGS2; Macrophage polarization; Microbial dysbiosis ID INFLAMMATORY-BOWEL-DISEASE; MUC2; PERMEABILITY; GENETICS AB Sanren Decoction (SRD), a traditional Chinese medicine formula historically used to relieve damp-heat and gastrointestinal disorders, demonstrates targeted efficacy in ulcerative colitis (UC)-a disease marked by chronic inflammation and mucosal damage-by acting on multiple pathological pathways. This study employed an integrative methodology comprising network pharmacology, molecular docking, and in vivo experimentation to elucidate the underlying pharmacological mechanisms of SRD in the management of UC. The findings identified 87 genes targeted by SRD that are associated with UC, highlighting PTGS2 (Prostaglandin-Endoperoxide Synthase 2) as a crucial target involved in inflammatory processes. Molecular docking analysis confirmed significant interactions between the active compounds of SRD and PTGS2, suggesting a potential anti-inflammatory pathway. In vivo experiments utilizing a DSS-induced colitis mouse model demonstrated that SRD effectively ameliorates clinical symptoms and histopathological damage, enhances intestinal barrier integrity, and modulates macrophage polarization from a pro-inflammatory M1 state to an anti-inflammatory M2 phenotype. Furthermore, SRD was found to alter gut microbiota composition by increasing the abundance of beneficial bacteria and influencing metabolic pathways. These findings establish a strong scientific foundation for the potential of SRD as a comprehensive therapeutic approach for UC, offering promising prospects for its integration into clinical practice. C1 [Zhang, Shujuan; Ruan, Linlin; Chen, Yanglin; Wan, Hongtao; Zhu, Xiaojian; Yi, Bo] Jiangxi Canc Hosp, Affiliated Hosp 2, Nanchang Med Coll, Abdominal Surg Dept 2, Nanchang 330029, Jiangxi, Peoples R China. [Li, Banghua] Nanchang Univ, Ward Gastrointestinal Oncol 3, Jiangxi Med Coll, Sch Pharm,Dept Integrated Tradit Chinese & Western, Nanchang 330006, Peoples R China. [Zhang, Shujuan; Han, Xiaoqun] Yichun Univ, Sch Chem & Bioengn, Yichun 336000, Peoples R China. [Fu, Xingxing; Liu, Dan] Nanchang Univ, Jiangxi Med Coll, Sch Pharm, Nanchang 330006, Peoples R China. [Ruan, Linlin] Jiangxi Canc Hosp, Affiliated Hosp 2, Nanchang Med Coll, Dept Pharm, Nanchang 330029, Jiangxi, Peoples R China. [Zhang, Shujuan; Yi, Bo] Jiangxi Canc Hosp, Jiangxi Key Lab Oncol, Nanchang 330006, Peoples R China. C3 Nanchang Medical College; Nanchang University; Yichun University; Nanchang University; Nanchang Medical College RP Yi, B (corresponding author), Jiangxi Canc Hosp, Affiliated Hosp 2, Nanchang Med Coll, Abdominal Surg Dept 2, Nanchang 330029, Jiangxi, Peoples R China.; Liu, D (corresponding author), Nanchang Univ, Jiangxi Med Coll, Sch Pharm, Nanchang 330006, Peoples R China.; Yi, B (corresponding author), Jiangxi Canc Hosp, Jiangxi Key Lab Oncol, Nanchang 330006, Peoples R China. EM liudan1201jx@ncu.edu.cn; yibo@ncmc.edu.cn RI Ruan, Linlin/PGG-2700-2026 FU National Natural Science Foundation of China [81760587, 81760731]; Key Project of Jiangxi Provincial Administration of Traditional Chinese Medicine Science and Technology Plan [2022Z019]; Jiangxi province Health Commission [202310886]; Jiangxi Provincial Key Clinical SpecialtyConstruction Project-Gastrointestinal Tumor Surgery; Jiangxi Provincial Key Clinical Specialty Construction Project-Colorectal Cancer Center; The 2023 Annual Scientific Research Open Fund Project of Jiangxi Provincial Cancer Hospital [KFJJ2023YB08]; Technology Plan Project of Jiangxi Provincial Health Commission [202310875]; Gastrointestinal Tumors Diagnosis, Treatment, and Drug Resistance Research Team of Nanchang Medical College [NYTD202209]; Central Government Financial Subsidy for Enhancing Medical Service and Security Capacity (Section on Inheritance and Development of Traditional Chinese Medicine)-Collaborative "Flagship"Departments of Integrated Traditional Chinese and Western Medicine FX This work was supported by the National Natural Science Foundation of China (81760587, 81760731); Key Project of Jiangxi Provincial Administration of Traditional Chinese Medicine Science and Technology Plan (2022Z019); The Jiangxi province Health Commission (202310886); Jiangxi Provincial Key Clinical SpecialtyConstruction Project-Gastrointestinal Tumor Surgery; Jiangxi Provincial Key Clinical Specialty Construction Project-Colorectal Cancer Center; 2023 Annual Scientific Research Open Fund Project of Jiangxi Provincial Cancer Hospital(KFJJ2023YB08);Technology Plan Project of Jiangxi Provincial Health Commission (No. 202310875) and Gastrointestinal Tumors Diagnosis, Treatment, and Drug Resistance Research Team of Nanchang Medical College (NYTD202209); Central Government Financial Subsidy for Enhancing Medical Service and Security Capacity (Section on Inheritance and Development of Traditional Chinese Medicine)-Collaborative "Flagship"Departments of Integrated Traditional Chinese and Western Medicine. 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Med. PD AUG 20 PY 2025 VL 20 IS 1 AR 128 DI 10.1186/s13020-025-01183-1 PG 23 WC Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine; Pharmacology & Pharmacy GA 6II7P UT WOS:001554058500001 PM 40836347 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Wang, ZY Liu, YF Liu, YX Li, QC Wang, Z Mu, DL AF Wang, Ziyi Liu, Yafei Liu, Yuxin Li, Qingcheng Wang, Zhong Mu, Dongliang TI Sigmoidin B attenuates sepsis-associated encephalopathy through EZH2-AKT2-mediated regulation of microglial polarization SO MOLECULAR IMMUNOLOGY LA English DT Article DE Sepsis-associated encephalopathy (SAE); EZH2; Sigmoidin B; MS177; Macrophage polarization ID EZH2 AB Purpose: Enhancer of zeste homolog (EZH2) is a potential target in treatment of sepsis. The current study is aimed to screen a novel EZH2 degrader agent based on the Traditional Chinese Medicine Database YaTCM. This may provide an important clue for development of new drugs to treat sepsis-associated encephalopathy (SAE). Methods: Macrophage-specific EZH2 knockout mice were used to observe the effects of EZH2 on the survival rate, levels of inflammatory cytokines, S100B, CD86, and CD206 in sepsis mice. Sigmoidin B was screened as the novel EZH2 degrader based on the structure of MS177 using large-scale virtual high-throughput screening. Molecular dynamics simulations and MMGBSA analysis were used to assess the stability and binding characteristics of Sigmoidin B. The protective effect of MS177 and the novel EZH2 degrader were verified using in vivo and vitro experiments. Results: Macrophage-specific knockout of EZH2 had been shown to enhance the survival rate in mice with sepsis, reduce levels of CD86 and TNF-alpha, promote the expression of IL-10 and CD206, and mitigate the extent of brain injury. Sigmoidin B exhibited strong binding affinity to EZH2 and featured a flavonoid core structure along with an olefin side chain. Molecular validation experiments confirmed that Sigmoidin B could ameliorate cognitive dysfunction and modulate microglial polarization via the EZH2-AKT2 pathway. Notably, Sigmoidin B demonstrated superior efficacy compared to MS177 in alleviating inflammation. Conclusion: Natural compound Sigmoidin B was successfully screened and confirmed as a novel EZH2 degrader, which was a potential target for the development of new therapeutic for SAE. C1 [Wang, Ziyi; Liu, Yafei; Li, Qingcheng; Mu, Dongliang] Peking Univ First Hosp, Beijing, Peoples R China. [Wang, Ziyi; Wang, Zhong] Tsinghua Univ, Beijing Tsinghua Changgung Hosp, Sch Clin Med, Beijing, Peoples R China. [Liu, Yuxin] Capital Med Univ, Xuanwu Hosp, Beijing, Peoples R China. C3 Peking University; Tsinghua University; Capital Medical University RP Mu, DL (corresponding author), Peking Univ First Hosp, Beijing, Peoples R China.; Wang, Z (corresponding author), Tsinghua Univ, Beijing Tsinghua Changgung Hosp, Sch Clin Med, Beijing, Peoples R China. EM wz523@mail.tsinghua.edu.cn; mudongliang@bjmu.edu.cn RI Wang, Ziyi/OJS-7808-2025 FU National High-Level Hospital Clinical Research Funding (High-Quality Clinical Research Project of Peking University First Hospital) [2022CR74]; Research Seed Fund Project of Peking University First Hospital [2025SF012] FX This work was supported by National High-Level Hospital Clinical Research Funding (High-Quality Clinical Research Project of Peking University First Hospital, No. 2022CR74) and Research Seed Fund Project of Peking University First Hospital (No.2025SF012) . The sponsor has no role in the study design and conduct; the collection, management, analysis, and interpretation of the data; or the preparation and approval of the manuscript. 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Immunol. PD OCT PY 2025 VL 186 BP 95 EP 113 DI 10.1016/j.molimm.2025.08.010 EA AUG 2025 PG 19 WC Biochemistry & Molecular Biology; Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Immunology GA 6SV3I UT WOS:001561188500001 PM 40834508 DA 2026-03-26 ER PT J AU Li, K Liu, YF Gao, TT Pang, LJ Diao, YP Fan, SY AF Li, Kun Liu, Yifan Gao, Tiantian Pang, Lijie Diao, Yunpeng Fan, Shuyuan TI Exploring the Anti-inflammatory Molecular Mechanism of L-shikonin in Promoting Diabetic Wound Healing by Modulating the Janus Kinase/Phosphatidylinositol-3-kinase/Protein Kinase B/Vascular Endothelial Growth Factor Pathway Based on Network Pharmacology SO CHEMISTRY & BIODIVERSITY LA English DT Article DE anti-inflammatory and proliferative; bioactive small molecules from natural sources; diabetic foot ulcers; L-shikonin ID FOOT ULCERS; POLARIZATION; MACROPHAGES; PLASTICITY; TISSUE AB Diabetic foot ulcers (DFUs) exhibit impaired healing due to disrupted macrophage polarization, wherein persistent hyperglycemia inhibits the critical M1-to-M2 phenotypic transition, sustaining a pro-inflammatory microenvironment. This investigation elucidates the therapeutic potential of L-shikonin (L-SK), a bioactive phytochemical derived from comfrey with established immunomodulatory properties. In a streptozotocin-induced diabetic murine model, L-SK treatment significantly enhanced wound closure through coordinated anti-inflammatory effects (downregulation of CD86 and tumor necrosis factor-alpha) and pro-regenerative outcomes (increased collagen deposition and CD31-mediated angiogenesis). At the molecular level, L-SK administration facilitated macrophage polarization towards the regenerative M2 phenotype (upregulated CD163 expression) while activating the pivotal Janus Kinase/phosphatidylinositol-3-kinase/protein kinase B/vascular endothelial growth factor (JAK/PI3K/AKT/VEGF) signaling cascade, as evidenced by enhanced phosphorylation of AKT and PI3K alongside elevated VEGF production. Complementary in vitro studies using human monocytic leukemia cells-derived macrophages confirmed these mechanistic findings, demonstrating consistent modulation of macrophage differentiation markers and secretory profiles. These results position L-SK as a multifaceted therapeutic agent capable of concurrently addressing the immunological and vascular deficiencies characteristic of DFUs, through its dual capacity for macrophage phenotype reprogramming and angiogenic pathway activation. The study provides compelling preclinical evidence for L-SK's potential application in diabetic wound management strategies. C1 [Li, Kun; Liu, Yifan; Gao, Tiantian; Pang, Lijie; Fan, Shuyuan] Liaoning Normal Univ, Coll Chem & Chem Engn, Dalian, Peoples R China. [Diao, Yunpeng] Dalian Med Univ, Coll Pharm, Dalian, Peoples R China. [Diao, Yunpeng] Dalian Antiinfect Tradit Chinese Med Dev Engn Tech, Dalian, Peoples R China. C3 Liaoning Normal University; Dalian Medical University RP Li, K; Fan, SY (corresponding author), Liaoning Normal Univ, Coll Chem & Chem Engn, Dalian, Peoples R China.; Diao, YP (corresponding author), Dalian Med Univ, Coll Pharm, Dalian, Peoples R China.; Diao, YP (corresponding author), Dalian Antiinfect Tradit Chinese Med Dev Engn Tech, Dalian, Peoples R China. EM lslikun@163.com; diaoyp@163.com; fanfanshuyuan@163.com RI shuyuan, Fan/GXW-1596-2022; 高, 田田/JRY-4685-2023 OI shuyuan, Fan/0000-0002-6803-5723; FU Natural Science Foundation of Liaoning Province [2020-MS-246]; Scientific Research Foundation of the Department of Education of Liaoning Province [LJKZ0980, LZ2019069, LZ2020016]; Special Fund of Basic scientific Research Business expenses of undergraduate universities in Liaoning Province [20240072]; National College Students Innovation and Entrepreneurship Training Program [202110161006X, 202010161004X, 201910161064, S202010161001X, 2017161025] FX This research was supported by the Natural Science Foundation of Liaoning Province (2020-MS-246), the Scientific Research Foundation of the Department of Education of Liaoning Province (LJKZ0980, LZ2019069, and LZ2020016), Supported by the Special Fund of Basic scientific Research Business expenses of undergraduate universities in Liaoning Province (20240072) and the National College Students Innovation and Entrepreneurship Training Program (202110161006X, 202010161004X, 202010161004X, 201910161064, S202010161001X, and 2017161025), thank you very much for your support. 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Biodivers. PD DEC 1 PY 2025 VL 22 IS 12 AR e01224 DI 10.1002/cbdv.202501224 EA AUG 2025 PG 15 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry GA AA4YI UT WOS:001551793800001 PM 40825181 DA 2026-03-26 ER PT J AU Su, ZQ Li, YL Zhou, ZH Tang, LP Zhu, Y Chen, HM Feng, B Zheng, GJ AF Su, Zuqing Li, Yanlin Zhou, Zihao Tang, Lipeng Zhu, Ying Chen, Haiming Feng, Bing Zheng, Guangjuan TI Huanglian Wendan decoction alleviates metabolic syndrome by reprogramming macrophage polarization: Evidence from multi-omics integration SO PHYTOMEDICINE LA English DT Article DE Huanglian Wendan decoction; Metabolic syndrome; Macrophage polarization; Multi-omics integration ID GUT MICROBIOTA AB Background: The prevalence of metabolic syndrome has shown a progressive rise, while contemporary pharmacological treatments are often associated with significant adverse effects. Huanglian Wendan Decoction (HLWD), a traditional formulation in Traditional Chinese Medicine utilized for the management of metabolic syndrome, has an underlying mechanism that remains not yet well understood. Purpose: This research aims to thoroughly explore how HLWD alleviates metabolic syndrome through a comprehensive multi-omics approach, including liquid mass spectrometry, network pharmacology, gut microbiota, metabolomics, and liver proteomics. Methods: The constituents of HLWD were analyzed utilizing UPLC-MS. A metabolic syndrome mouse model was developed through the administration of a high-fat diet (HFD) along with streptozocin. Our research assessed the effects of HLWD on various metabolic parameters, including insulin sensitivity, body weight, hyperglycemia, hyperlipidemia, and hepatic fat accumulation. The mechanisms of HLWD on metabolic syndrome were investigated through a multi-omics approach, encompassing network pharmacology, 16S rRNA gene sequencing of gut microbiota, serum metabolomics, and liver tissue proteomics. Result: 123 constituents were characterized in HLWD. HLWD demonstrated a marked enhancement in insulin sensitivity, as well as reductions in obesity, hyperglycemia, hyperlipidemia, inflammatory responses, and hepatic steatosis in mice with metabolic syndrome. 16S rRNA analysis indicated that HLWD effectively reduced the prevalence of microbial communities that facilitate lipid accumulation and inflammatory responses. Serum metabolomics studies revealed that, following HLWD treatment, numerous metabolites related to lipid metabolism exhibited significant improvements. Results from proteomics, immunohistochemistry, and multicolor immunofluorescence confirmed that HLWD effectively inhibited the M1 polarization of macrophages while promoting M2 polarization. Conclusion: This study offers a comprehensive and detailed exploration of the potential molecular mechanisms by which HLWD may mitigate metabolic syndrome, and firstly reveals that HLWD ameliorates metabolic syndrome through reprogramming hepatic macrophage polarization in mice, thereby positioning it as a promising new therapeutic option. C1 [Su, Zuqing; Li, Yanlin; Zhou, Zihao; Chen, Haiming; Feng, Bing; Zheng, Guangjuan] Guangzhou Univ Chinese Med, Affiliated Hosp 2, State Key Lab Tradit Chinese Med Syndrome, Guangzhou 510006, Peoples R China. [Tang, Lipeng; Zheng, Guangjuan] Guangzhou Univ Chinese Med, Affiliated Hosp 2, State Key Lab Dampness Syndrome Chinese Med, Guangzhou, Peoples R China. [Su, Zuqing; Li, Yanlin; Zhou, Zihao; Tang, Lipeng; Zhu, Ying; Feng, Bing; Zheng, Guangjuan] Guangzhou Univ Chinese Med, Affiliated Hosp 2, Guangdong Prov Key Lab Chinese Med Prevent &, Guangzhou, Peoples R China. [Su, Zuqing; Li, Yanlin; Zhou, Zihao; Tang, Lipeng; Zhu, Ying; Feng, Bing; Zheng, Guangjuan] Guangzhou Univ Chinese Med, Affiliated Hosp 2, Guangdong Hong Kong Macau Joint Lab Chinese Med &, Guangzhou, Peoples R China. C3 Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine RP Chen, HM; Feng, B; Zheng, GJ (corresponding author), Guangzhou Univ Chinese Med, Affiliated Hosp 2, State Key Lab Tradit Chinese Med Syndrome, Guangzhou 510006, Peoples R China. EM hemin066@gzucm.edu.cn; fengbing3701@gzucm.edu.cn; zhengguangjuan@gzucm.edu.cn RI Zheng, Guangjuan/ABB-6496-2020; Tang, Lipeng/ABB-6481-2020 FU National Natural Science Foundation of Guangdong Province [2023KT15523, YN2023MB11]; Chinese Medicine Scientific Research and Technology Research Projects of Guangdong Provincial Hospital of Chinese Medicine [2024A1515010568]; [YN2024GZRPY073]; [YN2024GZRPY069]; [YN2024GZRPY081] FX This work was supported by grants from the State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (No. QZ2023ZZ39) , the Specific Fund of State Key Laboratory of Dampness Syndrome of Chinese Medicine under Grant (No. SZ2021ZZ20) , the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund (Guangdong-Hong Kong-Macau Joint Lab) (No. 2020B1212030006) , the Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases (No.2023KT15523 and YN2023MB11) , National Natural Science Foundation of Guangdong Province (No. 2024A1515010568) , the Chinese Medicine Scientific Research and Technology Research Projects of Guangdong Provincial Hospital of Chinese Medicine (No. YN2024GZRPY073, YN2024GZRPY069,YN2024GZRPY081) . 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J. Front. Med. Zhu XQ, 2024, GUT MICROBES, V16, DOI 10.1080/19490976.2024.2390136 NR 35 TC 1 Z9 1 U1 22 U2 30 PU ELSEVIER GMBH PI MUNICH PA HACKERBRUCKE 6, 80335 MUNICH, GERMANY SN 0944-7113 EI 1618-095X J9 PHYTOMEDICINE JI Phytomedicine PD OCT PY 2025 VL 146 AR 157119 DI 10.1016/j.phymed.2025.157119 EA AUG 2025 PG 22 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 7VB9G UT WOS:001580361800001 PM 40795588 DA 2026-03-26 ER PT J AU He, QM Xiang, L Luo, YY Wang, RR Zheng, C Gao, YX Yao, H AF He, Qingman Xiang, Li Luo, Yuanyuan Wang, Rongrong Zheng, Chuan Gao, Yongxiang Yao, Huan TI Tumor-associated macrophages in colon cancer immunotherapy: mechanisms, natural product interventions, and microenvironment remodeling SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE tumor-associated macrophages; colon cancer; phytochemicals; immune checkpoint; nanoparticle delivery ID POLARIZATION IN-VIVO; COLORECTAL-CANCER; METABOLIC-REGULATION; IMMUNE-RESPONSES; LIVER METASTASIS; M1 MACROPHAGE; MURINE MODEL; CELLS; TUMORIGENESIS; EXPRESSION AB Colon cancer persists as a major global health burden due to therapy resistance and metastasis, with tumor-associated macrophages (TAMs) in the microenvironment driving progression through immune evasion and angiogenesis. This review highlights plant-derived therapeutics targeting TAMs to disrupt protumor signaling. Key phytochemicals (e.g., Curcumin, Cucurbitacin B, Astragaloside IV) suppress M2 polarization via NF-kappa B/STAT3 inhibition, block VEGF/HIF-1 alpha-mediated angiogenesis, and enhance antitumor immunity by downregulating PD-L1. Cannabidiol, Hydroxygenkwanin regulate TAM metabolism. Dietary agents like sulforaphane and beta-glucans modulate TAM-gut microbiome crosstalk. Nanoparticle-encapsulated phytochemicals enhance TAM-targeted delivery, while clinical translation requires standardized phytopreparations and biomarker-guided trials. We propose integrating validated botanical adjuvants (e.g., Fucoidan for TLR4 inhibition, dihydroisotanshinone I for CCL2 suppression) with immunotherapies to remodel immunosuppressive niches. Phytotherapy offers a multifaceted strategy to overcome TAM-driven therapeutic barriers in colon cancer, emphasizing plant-based precision medicine to augment conventional treatments. C1 [He, Qingman; Xiang, Li; Luo, Yuanyuan; Gao, Yongxiang] Hosp Chengdu Univ Tradit Chinese Med, Dept Rheumatol & Immunol, Chengdu, Peoples R China. [Wang, Rongrong] Chengdu Univ Tradit Chinese Med, Coll Basic Med, Chengdu, Sichuan, Peoples R China. [Zheng, Chuan; Yao, Huan] Chengdu Univ Tradit Chinese Med, Sichuan Prov Engn Technol Res Ctr Nat Small Mol Dr, Tianfu Tradit Chinese Med TCM Innovat Harbor, Chengdu, Peoples R China. [Zheng, Chuan] Hosp Chengdu Univ Tradit Chinese Med, Tradit Chinese Med TCM Regulating Metab Dis Key La, Chengdu, Peoples R China. [Yao, Huan] Chengdu Univ Tradit Chinese Med, Sichuan Prov Engn Res Ctr Innovat Redev Famous Cla, Tianfu Tradit Chinese Med TCM Innovat Harbour, Chengdu, Peoples R China. C3 Chengdu University of Traditional Chinese Medicine; Chengdu University of Traditional Chinese Medicine; Chengdu University of Traditional Chinese Medicine; Chengdu University of Traditional Chinese Medicine; Chengdu University of Traditional Chinese Medicine RP Gao, YX (corresponding author), Hosp Chengdu Univ Tradit Chinese Med, Dept Rheumatol & Immunol, Chengdu, Peoples R China.; Zheng, C; Yao, H (corresponding author), Chengdu Univ Tradit Chinese Med, Sichuan Prov Engn Technol Res Ctr Nat Small Mol Dr, Tianfu Tradit Chinese Med TCM Innovat Harbor, Chengdu, Peoples R China.; Zheng, C (corresponding author), Hosp Chengdu Univ Tradit Chinese Med, Tradit Chinese Med TCM Regulating Metab Dis Key La, Chengdu, Peoples R China.; Yao, H (corresponding author), Chengdu Univ Tradit Chinese Med, Sichuan Prov Engn Res Ctr Innovat Redev Famous Cla, Tianfu Tradit Chinese Med TCM Innovat Harbour, Chengdu, Peoples R China. EM zhengchuan@cdutcm.edu.cn; drgaoyx@cdutcm.edu.cn; Huanyao6620@hotmail.com RI Huan, Yao/AAD-4719-2019 OI Huan, Yao/0000-0001-5076-2650; Gao, Yongxiang/0000-0002-8927-378X FU Sichuan Provincial Science and Technology Program Projects [2024JDRC0030] FX The author(s) declare financial support was received for the research and/or publication of this article. This work was supported by the Sichuan Provincial Science and Technology Program Projects (Grant Number: 2024JDRC0030). 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Immunol. PD AUG 12 PY 2025 VL 16 AR 1642091 DI 10.3389/fimmu.2025.1642091 PG 25 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA 6LQ3T UT WOS:001556299800001 PM 40873588 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Deng, H Li, M Fang, XL Tang, K Xu, SQ Ding, R Li, ZL AF Deng, Heng Li, Ming Fang, Xiaoli Tang, Kun Xu, Shuqing Ding, Rui Li, Zilong TI Zuoqing granules attenuate ulcerative colitis via macrophage polarization modulation: involvement of the PPAR-γ/NF-κB/STAT1 signaling axis SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE Zuoqing granules; ulcerative colitis; macrophage polarization; PPAR-gamma/NF-kappa B/STAT1 signaling; traditional Chinese medicine AB Background Although our prior clinical study demonstrated the efficacy of Zuoqing granules (ZQGs) in treating ulcerative colitis (UC), the underlying immunomodulatory mechanisms remained unclear. This study systematically investigated ZQG's therapeutic effects through macrophage polarization modulation and related signaling pathways using both in vivo and in vitro models.Methods In vivo, dextran sulfate sodium (DSS)-induced UC rats were divided into normal control, DSS model, and ZQG treatment groups (high/medium/low doses). Colon tissues were analyzed using histopathology [hematoxylin and eosin (HE) staining], macrophage phenotyping (CD86+/CD206+ immunofluorescence and flow cytometry), signaling pathway assessment (PPAR-gamma, NF-kappa B p65, p-NF-kappa B p65, and STAT1 through Western blot/qPCR), and cytokine profiling (TNF-alpha, IL-6, IL-10, IL-1 beta, and IL-4 using ELISA). In vitro, lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were treated with ZQG-conditioned medium and a PPAR-gamma antagonist (GW9662) to validate direct effects.Results ZQG treatment dose-dependently (1) ameliorated colonic mucosal damage, reducing histological scores by 52% compared to that in the model group, (2) modulated macrophage polarization by increasing the M2 phenotype (CD206+ cells, 3.25-fold increase) while decreasing M1 macrophages (CD86+ cells, 70% reduction), (3) upregulated PPAR-gamma expression (2.0-fold increase) while suppressing NF-kappa B activation (43% decrease in p-NF-kappa B) and STAT1 signaling (48% and 40% reductions in protein and mRNA levels, respectively), and (4) rebalanced inflammatory cytokines, with 55%-62% reductions in TNF-alpha, IL-6, and IL-1 beta and 185%-210% increases in IL-10 and IL-4. In vitro studies further confirmed that ZQG directly shifted macrophage polarization via PPAR-gamma, inhibiting M1 polarization (an effect abolished by GW9662).Conclusion ZQG ameliorates UC by modulating macrophage plasticity through the PPAR-gamma/NF-kappa B/STAT1 axis, a mechanism validated in vitro as PPAR-gamma-dependent. These findings elucidate its clinical efficacy and support its use as a multi-target UC therapy. C1 [Deng, Heng] Anhui Univ Chinese Med, Affiliated Hosp 2, Dept Anorectal Surg, Hefei, Peoples R China. [Li, Ming; Fang, Xiaoli; Tang, Kun; Xu, Shuqing; Ding, Rui; Li, Zilong] Anhui Univ Chinese Med, Affiliated Hosp 1, Dept Anorectal Med, Hefei, Peoples R China. C3 Anhui University of Chinese Medicine; Anhui University of Chinese Medicine RP Li, M (corresponding author), Anhui Univ Chinese Med, Affiliated Hosp 1, Dept Anorectal Med, Hefei, Peoples R China. EM liming23456789@outlook.com RI deng, Heng/GPW-6805-2022 OI deng, Heng/0000-0002-2199-8960 FU Anhui Province Clinical Medical Research Transformation Project [202427b10020009, 202427b10020014, 202427b10020037]; Clinical Research Project of Anhui University of Chinese Medicine [2024YFYLCZX33] FX The authors would like to thank the Anhui University of Chinese Medicine for providing laboratory facilities and technical support. 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Pharmacol. PD AUG 11 PY 2025 VL 16 AR 1646545 DI 10.3389/fphar.2025.1646545 PG 8 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 6TK6X UT WOS:001561590100001 PM 40860883 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Li, ZH Huang, ZY Liao, X Li, H AF Li, Zihao Huang, Ziyu Liao, Xin Li, Hao TI Columbianadin targets TRIM7 to maintain P2X7 palmitoylation, inhibiting cuproptosis in synovial M2 macrophages SO PHYTOMEDICINE LA English DT Article DE Columbianadin; Tripartite motif containing protein 7; Palmitoylation; Macrophage; Cuproptosis ID RECEPTOR AB Background: Traumatic synovitis often arises from sports injuries, and early intervention is crucial for preserving joint health. Columbianadin (CBN), a natural phytochemical, has demonstrated efficacy in inhibiting inflammatory progression through Chinese herbal injection therapy; however, its underlying mechanism remains unclear. Purpose: This study aims to investigate the molecular mechanism by which CBN maintains P2X7 palmitoylation, characterize TRIM7 as a novel cuproptosis-alert protein, and provide a theoretical foundation for the bench-tobedside translation of CBN in treating traumatic synovitis. Methods: A non-destructive anterior cruciate ligament tear model was established to induce knee joint instability in mice. TRIM7 conditional knockout mice were generated via tissue-specific gene knockout. Single-cell sequencing and bioinformatics analysis were used to screen and validate CBN targets and downstream signaling pathways. Subcellular localization changes of P2X7 were detected via fluorescence co-localization. Copper concentrations in cells and tissues were measured using inductively coupled plasma-mass spectrometry. Palmitoylation levels of P2X7 were analyzed via acyl-biotin exchange assay. Results: CBN effectively suppressed synovial inflammation in mice. Mechanistically, CBN directly bound to TRIM7 and downregulated its expression. TRIM7 knockout significantly attenuated CBN's anti-inflammatory effects. TRIM7 competed with P2X7 for binding to ZDHHC5, leading to ubiquitination-mediated degradation of ZDHHC5. This disrupted ZDHHC5-dependent palmitoylation of P2X7, preventing its membrane localization and subsequent copper efflux. Accumulated intracellular copper induced cuproptosis. Conclusion: CBN directly targets TRIM7 to preserve ZDHHC5-mediated P2X7 palmitoylation, thereby inhibiting M2 macrophage cuproptosis in synovial tissues. These findings provide a theoretical basis for developing precision drug delivery systems targeting traumatic synovitis. C1 [Li, Zihao; Li, Hao] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Hangzhou 310000, Zhejiang, Peoples R China. [Li, Zihao; Li, Hao] Zhejiang Univ, Orthoped Res Inst, Hangzhou 310000, Zhejiang, Peoples R China. 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The synovitis is crucial for initiation and exacerbation of OA. Muscone, the main bioactive compound found in musk, exhibits anti-inflammatory, antioxidant, and neuroprotective effects. Nevertheless, it is still uncertain whether Muscone alleviates the progression of OA by suppressing inflammation. Our research investigated how Muscone affected M1 macrophage polarization and joint inflammation in vitro, as well as its effects on OA progression in vivo. Our findings showed that Muscone significantly inhibited pro-inflammatory cytokine secretion and M1 polarization in LPS-induced RAW264.7 macrophages. Moreover, Muscone suppressed synovitis by impeding proinflammatory and M1-related factors in synovium of OA mice. Mechanistic investigations revealed Muscone directly bound Nrf2 and promoted its nuclear translation in LPS-induced RAW264.7 cells, while also simultaneously suppressing the phosphorylation of P65 and I kappa B alpha within the NF-kappa B signaling pathway. Moreover, the pharmacological blockade of Nrf2 partially mitigated the influence of Muscone on LPS-triggered M1 macrophage polarization and the NF-kappa B pathway. Furthermore, Muscone slowed down the degeneration of articular cartilage in OA mice by promoting chondrocyte anabolism and simultaneously inhibiting inflammation, catabolic processes, and apoptosis of chondrocytes. Overall, our findings indicate that Muscone mitigates the advancement of OA through the inhibition of M1 macrophage polarization and the protection of chondrocytes, thus highlighting its potential as a therapeutic candidate for OA treatment. C1 [Qian, Zhuang; Xu, Jie; Zhang, Lei; Miao, Zheng; Lv, Ziyan; Ji, Hongwei; Deng, Qian; Lv, Zhuangwei; Zhan, Heqin; Yu, Yang; Liu, Zichuan; Ren, Wenjie] Xinxiang Med Univ, Inst Hlth Cent Plain, Clin Med Ctr Tissue Engn & Regenerat, Xinxiang 453003, Henan, Peoples R China. [Yu, Yang] Peking Univ, Clin Stem Cell Res Ctr, Beijing 100083, Peoples R China. [Liu, Zichuan] Tianjin Univ, Sch Pharmaceut Sci & Technol, 92 Weijin Rd, Tianjin 300072, Peoples R China. C3 Henan Medical University; Peking University; Tianjin University RP Yu, Y; Liu, ZC; Ren, WJ (corresponding author), Xinxiang Med Univ, Inst Hlth Cent Plain, Clin Med Ctr Tissue Engn & Regenerat, Xinxiang 453003, Henan, Peoples R China.; Liu, ZC (corresponding author), Tianjin Univ, Sch Pharmaceut Sci & Technol, 92 Weijin Rd, Tianjin 300072, Peoples R China. EM yuyang_bysy@puh3.net.cn; zichuan.liu@tju.edu.cn; 221011@xxmu.edu.cn RI Ren, Wenjie/JFK-8231-2023 FU National Natural Science Foundation of China [82302655, 82471191] FX Funding This work was supported by National Natural Science Foundation of CR Atukorala I, 2016, ANN RHEUM DIS, V75, P390, DOI 10.1136/annrheumdis-2014-205894 Barreto G, 2020, OSTEOARTHR CARTILAGE, V28, P92, DOI 10.1016/j.joca.2019.10.011 Casper E, 2023, LIFE SCI, V330, DOI 10.1016/j.lfs.2023.122007 Crisman E, 2023, MED RES REV, V43, P237, DOI 10.1002/med.21925 Du YQ, 2018, AM J TRANSL RES, V10, P4235 Glasson SS, 2007, OSTEOARTHR CARTILAGE, V15, P1061, DOI 10.1016/j.joca.2007.03.006 Glasson SS, 2010, OSTEOARTHR CARTILAGE, V18, pS17, DOI 10.1016/j.joca.2010.05.025 Glyn-Jones S, 2015, LANCET, V386, P376, DOI 10.1016/S0140-6736(14)60802-3 He MC, 2020, AM J CHINESE MED, V48, P559, DOI [10.1111/anu.13064, 10.1142/S0192415X20500287] Kobayashi EH, 2016, NAT COMMUN, V7, DOI 10.1038/ncomms11624 Krenn V, 2006, HISTOPATHOLOGY, V49, P358, DOI 10.1111/j.1365-2559.2006.02508.x Latourte A, 2020, NAT REV RHEUMATOL, V16, P673, DOI 10.1038/s41584-020-00518-6 Li L, 2024, BIOCHEM BIOPH RES CO, V702, DOI 10.1016/j.bbrc.2024.149628 Li YS, 2017, FRONT IMMUNOL, V8, DOI 10.3389/fimmu.2017.00356 Liang QQ, 2010, CLIN ORTHOP RELAT R, V468, P1600, DOI 10.1007/s11999-009-1079-0 Liao JY, 2025, ADV HEALTHC MATER, V14, DOI 10.1002/adhm.202401985 Liu YJ, 2024, MOL BIOL REP, V51, DOI 10.1007/s11033-023-08916-1 Lv SQ, 2022, J ETHNOPHARMACOL, V284, DOI 10.1016/j.jep.2021.114799 Mahon OR, 2020, OSTEOARTHR CARTILAGE, V28, P603, DOI 10.1016/j.joca.2019.10.010 Oeckinghaus A, 2011, NAT IMMUNOL, V12, P695, DOI 10.1038/ni.2065 Park MD, 2022, CELL, V185, P4259, DOI 10.1016/j.cell.2022.10.007 Ren WH, 2022, PEERJ, V10, DOI 10.7717/peerj.13523 Sanchez-Lopez E, 2022, NAT REV RHEUMATOL, V18, P258, DOI 10.1038/s41584-022-00749-9 Wang L, 2022, FRONT IMMUNOL, V13, DOI 10.3389/fimmu.2022.967193 Yu SS, 2020, INT IMMUNOPHARMACOL, V82, DOI 10.1016/j.intimp.2020.106355 Zhang H, 2020, OSTEOARTHR CARTILAGE, V28, P555, DOI 10.1016/j.joca.2020.01.007 Zhou LY, 2020, J NEUROCHEM, V155, P154, DOI 10.1111/jnc.15011 Zhou Y, 2022, MOL NEUROBIOL, V59, P5891, DOI 10.1007/s12035-022-02948-7 NR 28 TC 1 Z9 1 U1 6 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD OCT PY 2025 VL 503 AR 117494 DI 10.1016/j.taap.2025.117494 EA AUG 2025 PG 12 WC Pharmacology & Pharmacy; Toxicology WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy; Toxicology GA 5UN8H UT WOS:001544666900003 PM 40744211 DA 2026-03-26 ER PT J AU Li, AH Niu, YX Xu, WH Liang, BQ Zhang, R Mei, RY Zhang, XY Zhang, T Gao, Y Yan, YZ AF Li, Anhong Niu, Yuxiao Xu, Weihua Liang, Bingqing Zhang, Rong Mei, Ruya Zhang, Xinyue Zhang, Tong Gao, Yun Yan, Yuzhong TI Sophora Flos extract ameliorates inflammatory bowel disease via inhibiting the PI3K/AKT/mTOR signaling pathway activation and modulating M1/M2 polarization in macrophages SO PHYTOMEDICINE LA English DT Article DE Inflammatory bowel disease; Sophora flos; Rutin; Anti-inflammatory activity; Network pharmacology; PI3K/Akt/mTOR pathway ID NETWORK PHARMACOLOGY; PHYTOCHEMISTRY; METHODOLOGY; MECHANISMS; FLAVONOIDS; MEDICINE; CELLS; RUTIN AB Background: Sophora flos (SF) is a medicinal plant with a rich history. Its principal bioactive constituents are flavonoids, which are known for their remarkable anti-inflammatory and antioxidant properties. Nevertheless, a thorough investigation of its potential regulatory mechanisms in the context of treating inflammatory bowel disease (IBD) is lacking. Purpose: This study comprehensively assessed the pharmacological effects of Sophora flos extract (SFE) both in vitro and in vivo, with a specific focus on its efficacy against IBD and the underlying mechanisms involved. Methods: UHPLC-LTQ-ESI-Orbitrap-MS was used to analyze the chemical composition of SFE. Mouse colitis models were induced with dextran sulfate sodium (DSS). SFE therapeutic efficacy was assessed by colon length, disease activity index (DAI) and histopathology score. Changes in inflammatory cytokines, tight junction proteins and the macrophage phenotype after SFE treatment were assessed. Furthermore, the anti-inflammatory, antioxidant and regulatory effects of SFE on the macrophage phenotype were evaluated in lipopolysaccharide (LPS)stimulated RAW 264.7 cells. Using systems biology methodologies, we predicted potential targets and signaling pathways and validated them through experiments. Results: UPLC-LTQ-Orbitrap-MS analysis revealed 59 compounds in SFE, and the most abundant of these compounds was rutin. Animal studies demonstrated that SFE treatment improved colon length, DAI, and colon inflammation while decreasing proinflammatory cytokine expression and increasing the expression of antiinflammatory cytokines and tight junction proteins. Immunofluorescence revealed that SFE treatment inhibited M1 macrophage polarization and promoted M2 macrophage polarization. Cellular experiments revealed that SFE treatment reduced ROS levels and modulated the release of inflammatory mediators and the balance of M1/ M2 macrophage polarization. Network pharmacology analyses revealed that SF comprises eight principal components and interacts with 123 potential targets involved in IBD treatment, which are intricately associated with signaling pathways such as the PI3K/Akt, mTOR, and TNF pathways. Molecular docking results confirmed that PIK3CA, AKT1, PIK3R1 and TNF had high affinities for the main active components of SF, with the strongest affinity for rutin. Western blot and Q-PCR experiments revealed that PI3K/Akt/mTOR and TNF alpha expression were increased after LPS or DSS induction, and SFE or rutin treatment reversed these changes. Conclusion: This study integrates UPLC-MS phytochemical profiling, network pharmacology, and experimental validation to elucidate the anti-IBD mechanisms of SFE. We identified 59 bioactive compounds in SFE and demonstrated their efficacy via the inhibition of PI3K/Akt/mTOR and TNF alpha signaling. Notably, this work is the first to reveal that SFE alleviates IBD by restoring intestinal barrier integrity and rebalancing M1/M2 macrophage polarization. Molecular docking/dynamics confirmed the high affinity of rutin for core targets (PIK3CA, AKT1, and TNF). These findings establish SFE as a multitarget IBD therapeutic, synergizing traditional use with mechanistic validation through integrative omics and experimental approaches. C1 [Li, Anhong; Zhang, Xinyue; Yan, Yuzhong] Shanghai Univ Tradit Chinese Med, Postgrad Sch, Shanghai, Peoples R China. [Li, Anhong; Niu, Yuxiao; Liang, Bingqing; Zhang, Rong; Mei, Ruya; Zhang, Xinyue; Zhang, Tong; Yan, Yuzhong] Shanghai Univ Med & Hlth Sci, Zhoupu Hosp, Shanghai Key Lab Mol Imaging, Shanghai, Peoples R China. [Niu, Yuxiao; Liang, Bingqing; Zhang, Rong; Mei, Ruya; Yan, Yuzhong] Xinxiang Med Univ, Postgrad Sch, Xinxiang, Peoples R China. [Zhang, Tong] Univ Shanghai Sci & Technol, Postgrad Sch, Shanghai, Peoples R China. [Yan, Yuzhong] Shanghai Univ Med & Hlth Sci, Zhoupu Hosp, Dept Sci Res, Shanghai, Peoples R China. [Xu, Weihua] Shanghai Univ Med & Hlth Sci, Zhoupu Hosp, Dept Pharm, Shanghai, Peoples R China. [Gao, Yun] Shanghai Univ Med & Hlth Sci, Zhoupu Hosp, Dept Clin Lab, Shanghai, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine; Shanghai University of Medicine & Health Sciences; Henan Medical University; University of Shanghai for Science & Technology; Shanghai University of Medicine & Health Sciences; Shanghai University of Medicine & Health Sciences; Shanghai University of Medicine & Health Sciences RP Yan, YZ (corresponding author), Shanghai Univ Tradit Chinese Med, Postgrad Sch, Shanghai, Peoples R China. EM zp_yanyz@sumhs.edu.cn RI Li, Anhong/NRY-7630-2025 FU Shanghai Pudong New Area Health Commission [PW2024D-10, YC-2023-0401]; Science and Technology Commission of Shanghai Municipality [PKJ2023-Y109] FX This study was supported by grants from Shanghai Pudong New Area Health Commission (Grant No. YC-2023-0401) , Science and Technology Commission of Shanghai Municipality (PKJ2023-Y109) and Shanghai Pudong New Area Health Commission (PW2024D-10) . 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Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 5RS3Q UT WOS:001542749400002 PM 40737847 DA 2026-03-26 ER PT J AU Han, XT Zheng, WY Sun, ZJ Luo, T Li, ZY Lai, WH Jing, MY Kuang, MQ Su, HX Tan, W Zhong, ZF AF Han, Xintong Zheng, Wenying Sun, Zijun Luo, Tong Li, Zhiyan Lai, Wenhui Jing, Muyang Kuang, Mingqing Su, Huanxing Tan, Wen Zhong, Zhangfeng TI Plant-derived exosomes: Unveiling the similarities and disparities between conventional extract and innovative form SO PHYTOMEDICINE LA English DT Article DE Natural product; Herbal medicine; Nanoparticles; Exosomes; Plant-derived exosomes ID DRUG-DELIVERY; EXTRACELLULAR VESICLES; OXIDATIVE STRESS; ULCERATIVE-COLITIS; INDUCED APOPTOSIS; NANOPARTICLES; GINGER; NANOVESICLES; MECHANISM; MEDICINE AB Background: Herbal medicine, historically valued for its multi-component therapeutic synergy, faces significant challenges in clinical translation due to crude raw materials, compositional complexity, and low bioavailability, as well as unclear effective substances and action targets. As an innovative form of herbal medicine, plantderived exosomes (PDEs) exhibit their therapeutic potential from a unique phospholipid bilayer structure, which encapsulates bioactive molecules including proteins, lipids, RNAs, and metabolites. Purpose and methods: This study aims to elucidate the components, bioavailability, drug delivery, and stability of PDEs by reviewing the keywords including exosome, nanoparticle, and vesicle regarding plants and herbs in the databases (e.g., PubMed, Web of Science, MEDLINE, and Google Scholar), specially focusing on the highfrequency medicinal species (e.g., Ginseng, Ginger, Pueraria root, Turmeric, and Wolfberry). Results: Unlike conventional extracts of herbal medicine, which lose critical compounds during drying or alcoholbased processing, PDEs derived from fresh plant tissues preserve native phytochemical integrity and enhance bioactivity. Advanced extraction techniques and cargo-loading strategies further amplify their therapeutic potential, enabling precise modulation of pathways such as macrophage polarization and immune checkpoint. Despite these advantages, hurdles in standardizing isolation protocols, ensuring storage stability, and validating clinical efficacy remain key obstacles to widespread adoption. The natural surface proteins of PDEs, which facilitate receptor-specific targeting without synthetic modification, exemplify their ability to bridge the synergy of herbal medicine with precision medicine. Conclusions: These advances position PDEs as transformative agents of herbal medicine in chronic disease management, offering a paradigm shift toward stable, targeted, and efficacious phytotherapy. C1 [Han, Xintong; Zheng, Wenying; Sun, Zijun; Luo, Tong; Li, Zhiyan; Lai, Wenhui; Jing, Muyang; Kuang, Mingqing; Su, Huanxing; Zhong, Zhangfeng] Univ Macau, Inst Chinese Med Sci, Macao Ctr Res & Dev Chinese Med, State Key Lab Qual Res Chinese Med, Taipa 999078, Macau, Peoples R China. [Tan, Wen] Lanzhou Univ, Sch Pharm, Lanzhou 730000, Gansu, Peoples R China. C3 University of Macau; Lanzhou University RP Tan, W (corresponding author), Lanzhou Univ, Sch Pharm, Lanzhou 730000, Gansu, Peoples R China.; Su, HX; Zhong, ZF (corresponding author), Univ Macau, Ave Univ, Taipa 999078, Macao, Peoples R China. EM huanxingsu@um.edu.mo; tanwen@lzu.edu.cn; zfzhong@um.edu.mo RI Su, Huanxing/X-3980-2019 FU Macao Science and Technology Development Fund [FDCT 0047/2025/ITP1, 0123/2022/A, 001/2023/ALC, 0006/2020/AKP, 0008/2023/RIC, 005/2023/SKL]; Outstanding Youth of the Fundamental Research Funds for the Central Universities [lzujbky-2021-ey21]; University of Macau [MYRG-GRG2023-00198-ICMS, SRG2022-00052-ICMS] FX This study was supported by the Macao Science and Technology Development Fund (FDCT 0047/2025/ITP1, 0123/2022/A, 001/2023/ALC, 0006/2020/AKP, 0008/2023/RIC, and 005/2023/SKL), the Outstanding Youth of the Fundamental Research Funds for the Central Universities (lzujbky-2021-ey21), and the Research Fund of University of Macau (MYRG-GRG2023-00198-ICMS and SRG2022-00052-ICMS). 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10.1016/j.biomaterials.2021.121178 NR 228 TC 19 Z9 19 U1 89 U2 103 PU ELSEVIER GMBH PI MUNICH PA HACKERBRUCKE 6, 80335 MUNICH, GERMANY SN 0944-7113 EI 1618-095X J9 PHYTOMEDICINE JI Phytomedicine PD SEP PY 2025 VL 145 AR 157087 DI 10.1016/j.phymed.2025.157087 EA JUL 2025 PG 22 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 5NS6O UT WOS:001540034500004 PM 40714420 DA 2026-03-26 ER PT J AU Yao, ZL He, JJ Hu, MY Yan, P Xu, Q Zhang, Q Lin, Y Liao, J Cai, X Liu, L AF Yao, Zhongliu He, Junjie Hu, Mingyue Yan, Ping Xu, Qian Zhang, Qin Lin, Ye Liao, Jing Cai, Xiong Liu, Liang TI Fuhu Lijie Tang treats rheumatoid arthritis through multitarget therapy from autoantigen formation to bone destruction SO PHYTOMEDICINE LA English DT Article DE Rheumatoid arthritis; Combination therapy; Traditional Chinese medicine; Fuhu Lijie Tang; Collagen II-induced arthritis ID QFGJS AB Background: Rheumatoid arthritis (RA) is an incurable, disabling autoimmune disease, and combination therapy with disease-modifying antirheumatic drugs targeting different pathological mechanisms is a therapeutic strategy to improve treatment outcomes. Traditional Chinese medicine (TCM) offers the advantage of multi-component, multi-target therapy for RA; however, its ability to simultaneously target multiple key pathological mechanisms of RA remains to be further investigated. Fuhu Lijie Tang (FHLJT) is a novel TCM formulation with potential therapeutic effects on RA, and its anti-arthritic mechanisms require systematic study. Objective: This study aimed to comprehensively investigate the anti-arthritic effects of FHLJT and its underlying molecular mechanisms, focusing on its potential to simultaneously target multiple key pathological mechanisms in the treatment of RA. Methods: Collagen II-induced arthritic (CIA) rats received FHLJT treatment, with therapeutic effects assessed through arthritis scoring, paw swelling measurement, inflammatory marker analysis, and histopathology. Synovial tissue transcriptomics identified differentially expressed genes, followed by validation through Western blot, immunohistochemistry, ELISA, and flow cytometry to validate these findings. Results: FHLJT significantly reduced joint inflammation and histopathological damage in CIA rats. Transcriptomic analyses showed that FHLJT downregulated multiple RA-associated pathways, including RA signaling, T cell receptor (TCR), B cell receptor (BCR), vascular endothelial growth factor, osteoclast differentiation, antigen presentation, phagosome, and protein modification pathways. Further interaction analysis identified the phosphoinositide 3-kinase (PI3K)-protein kinase B (Akt) and AMP-activated protein kinase (AMPK) signaling pathways as central to these processes. Experimental validation confirmed that FHLJT inhibited citrullinated proteins, peptidyl arginine deiminase 2 (PADI2), PADI4, interferon gamma inducible protein 30, and CD74 expression in joint tissues of CIA rats. It also suppressed phosphorylated zeta chain of T cell receptor associated protein kinase 70 (p-ZAP70)/ZAP70, inducible T cell costimulator, programmed cell death protein 1 (PD-1), interleukin-17 levels in the TCR pathway, and reduced phosphorylated tyrosine-protein kinase Lyn (p-LYN)/LYN, phosphorylated Ras-related C3 botulinum toxin substrate (p-Rac)/Rac, and anti-type II collagen antibody levels in the BCR pathway. Additionally, FHLJT decreased synovial fibroblast marker CD90 and angiogenesis proteins, and inhibited osteoclast markers. In vitro, FHLJT inhibited M1 macrophage differentiation and MHC II expression while promoting M2 differentiation. Conclusion: FHLJT exerts its therapeutic effects by simultaneously targeting multiple key pathological mechanisms of RA through 74 compounds (e.g., sinomenine) which modulate processes such as citrullinated protein production, antigen presentation, TCR and BCR signaling pathways, synovial hyperplasia, angiogenesis, osteoclast differentiation, and the PI3K-Akt and AMPK signaling pathways. C1 [Yao, Zhongliu; He, Junjie; Hu, Mingyue; Yan, Ping; Xu, Qian; Zhang, Qin; Lin, Ye; Liao, Jing; Cai, Xiong] Hunan Univ Chinese Med, Dept Rheumatol, Hosp 1, Changsha 410208, Hunan, Peoples R China. [Yao, Zhongliu; He, Junjie; Hu, Mingyue; Yan, Ping; Xu, Qian; Zhang, Qin; Lin, Ye; Liao, Jing; Cai, Xiong] Hunan Univ Chinese Med, Sch Chinese Med Sci, Changsha 410208, Hunan, Peoples R China. [Liu, Liang] Guangzhou Univ Chinese Med, State Key Lab Tradit Chinese Med Syndrome, Guangdong Prov Hosp Chinese Med, Affiliated Hosp Guangzhou 2,Guangdong Prov Acad Ch, Guangzhou 510006, Guangdong, Peoples R China. C3 Hunan University of Chinese Medicine; Hunan University of Chinese Medicine; Guangzhou University of Chinese Medicine RP Liao, J; Cai, X (corresponding author), Hunan Univ Chinese Med, Dept Rheumatol, Hosp 1, Changsha 410208, Hunan, Peoples R China.; Liao, J; Cai, X (corresponding author), Hunan Univ Chinese Med, Sch Chinese Med Sci, Changsha 410208, Hunan, Peoples R China.; Liu, L (corresponding author), Guangzhou Univ Chinese Med, State Key Lab Tradit Chinese Med Syndrome, Guangdong Prov Hosp Chinese Med, Affiliated Hosp Guangzhou 2,Guangdong Prov Acad Ch, Guangzhou 510006, Guangdong, Peoples R China. EM liaojing@hnucm.edu.cn; caixiong@hnucm.edu.cn; lliu@gzucm.edu.cn RI Cai, Xiong/PKQ-7330-2026 FU National Natural Science Foundation of China General Program [82274506, 82405235]; China Postdoctoral Science Foundation [2022M721128, 2024T170267]; Science and Technology Innovation Program of Hunan Province [2020SK1020, 2021RC4035]; Natural Science Foundation of Hunan [2023JJ30455, 2023JJ40477, 2024JJ5298]; Open-competing Disciple Construction Project of Hunan University of Chinese Medicine (HNUCM) [22JBZ003]; Furong Distinguished Scholar Program of Hunan [XJT [2020] 58]; The 121 Training Project for Innovative Talents of Hunan [XRSH [2019] 192]; Chinese Academy of Engineering Academician Liang Liu's Workstation of HNUCM (KH [KH [2023] 3-23YS001]; World First-class Discipline Incubation Project of HNUCM [XJF [2022] 57] FX This research was funded by the National Natural Science Foundation of China General Program (82274506, 82405235) , the China Postdoctoral Science Foundation (2022M721128, 2024T170267) , the Science and Technology Innovation Program of Hunan Province (2020SK1020, 2021RC4035) , the Natural Science Foundation of Hunan (2023JJ30455, 2023JJ40477, 2024JJ5298) , the Open-competing Disciple Construction Project of Hunan University of Chinese Medicine (HNUCM) (22JBZ003) , and was financially supported by the Furong Distinguished Scholar Program of Hunan (XJT [2020] 58) , the 121 Training Project for Innovative Talents of Hunan (XRSH [2019] 192) , the Chinese Academy of Engineering Academician Liang Liu's Workstation of HNUCM (KH [2023] 3-23YS001) , and the World First-class Discipline Incubation Project of HNUCM (XJF [2022] 57) . 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Sustained existence of inflammatory microenvironment is detrimental for peripheral nerve regrowth following crush injuries, which results in the pathogenesis of pain over time. Here, we report that madecassoside (MA), a major active component generated from Centella asiatica, remarkably accelerates neuronal repair post-crush. In the present study, we find that motor functional exacerbation and gastrocnemius muscle atrophy are notably reversed in vivo through intragastric administration of MA. We also find that MA administration triggers macrophage migration for recruitment and M2 phenotype polarization, both of which play key roles in modulating inflammatory microenvironment within damaged nerves. However, this regulated capacity of MA on macrophage functions can be blunted through macrophage depletion in vivo. Mechanistically, MA inhibits TXNIP/NLRP3/GSDMD signaling pathway, resulting in inflammatory factors downregulation post-damage and regeneration improvement. Additionally, inhibiting this pathway recapitulates the effects of MA on promoting M2 macrophage transition and nerve regrowth. Our results identify MA as a favorable agent for sciatic nerve regeneration. C1 [Li, Changqing; Li, Shengji; Wu, Qingyuan; Wang, Chengjing] Heilongjiang Univ Chinese Med, Clin Med Coll 1, 24 Heping Rd, Harbin 150006, Peoples R China. [Meng, Xianyu] Heilongjiang Univ Chinese Med, Affiliated Hosp 1, 26 Heping Rd, Harbin 150040, Peoples R China. C3 Heilongjiang University of Chinese Medicine; Heilongjiang University of Chinese Medicine RP Meng, XY (corresponding author), Heilongjiang Univ Chinese Med, Affiliated Hosp 1, 26 Heping Rd, Harbin 150040, Peoples R China. EM aobin1999@163.com; mengxianyu1973@yeah.net; 1519778090@qq.com; studenttcm@126.com; 985128308@qq.com RI 吴, 青原/GRO-4492-2022 FU Natural Science Foundation of Heilongjiang Province [PL2024H218] FX This work was supported by Natural Science Foundation of Heilongjiang Province (PL2024H218). 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Neurobiol. PD DEC PY 2025 VL 62 IS 12 BP 15687 EP 15700 DI 10.1007/s12035-025-05196-7 EA JUL 2025 PG 14 WC Neurosciences WE Science Citation Index Expanded (SCI-EXPANDED) SC Neurosciences & Neurology GA 9AH5A UT WOS:001534723000001 PM 40699487 DA 2026-03-26 ER PT J AU Song, SY Wen, XH Chen, FS Li, JT Shi, KY Lou, Y Xu, AY Wen, CP Shao, TJ AF Song, Siyue Wen, Xianghui Chen, Fusen Li, Jiatao Shi, Kaiyue Lou, Yu Xu, Anyi Wen, Chengping Shao, Tiejuan TI Qu-zhuo-tong-bi decoction exerts gouty arthritis therapy by skewing macrophage polarization through butanoate metabolism SO CHINESE MEDICINE LA English DT Article DE Qu-zhuo-tong-bi decoction; Gouty arthritis; Gut microbiome; Butanoate metabolism; Macrophage polarization; Glycolysis AB BackgroundQu-zhuo-tong-bi decoction (QZTBD), a traditional Chinese medicine (TCM), has demonstrated efficacy in the treatment of gouty arthritis. However, to date, the precise pharmacological mechanisms remain unclear.PurposeThe study aims to ascertain the therapeutic effects and the underlying mechanisms of QZTBD in the treatment of gouty arthritis.MethodsThe efficacy and safety of different doses of QZTBD were investigated in Uox-KO mice. Candidate active ingredients were identified using UHPLC-MS/MS. The potential therapeutic pathways of the active ingredients were predicted through network pharmacology. The mechanisms of QZTBD in alleviating gouty arthritis were explored via comprehensive analyses of gut microbiota, combined with RT-qPCR, western blot, immunofluorescence, ELISA, flow cytometry, and Seahorse assay. Fecal microbiota transplantation (FMT), bacterial culture experiment, butyrate-producing bacteria (BPB) and butyrate administration, and 2-DG intervention were conducted to explore the roles of BPB and butanoate metabolism in gout progression and therapeutic mechanisms of QZTBD. In vitro studies further validated the regulatory effects of butyrate and QZTBD on macrophage polarization through glycolysis modulation.Results18.0 g/kg/d of QZTBD effectively alleviated the symptoms of gouty arthritis with excellent hepatic and renal safety. UHPLC-MS/MS analysis and network pharmacology revealed that QZTBD exerts its effects on butanoate metabolism during gouty arthritis inflammation. QZTBD treatment increased the abundance of BPB, the levels of serum and colon butyrate, and the expression levels of Buk and But. The transplantation of QZTBD-treated microbiota reproduced the therapeutic effects of QZTBD. M1 macrophage polarization was suppressed after QZTBD intervention. The administration of BPB and butyrate attenuated gouty arthritis and orchestrated macrophage polarization. Inhibition of glycolysis regulated the phenotype of macrophage and attenuated inflammatory processes. In vitro analysis unveiled that QZTBD and butyrate modulated glycolysis to regulate macrophage polarization, thereby alleviating gouty arthritis.ConclusionQZTBD targeted butanoate metabolism to regulate macrophage polarization, thereby effectively alleviating intestinal inflammation and restoring immune homeostasis in gouty arthritis. These findings establish a mechanistic foundation for developing precision therapeutic strategies leveraging QZTBD to combat gouty arthritis. C1 [Song, Siyue; Wen, Xianghui; Chen, Fusen; Li, Jiatao; Shi, Kaiyue; Lou, Yu; Wen, Chengping; Shao, Tiejuan] Zhejiang Chinese Med Univ, Coll Basic Med Sci, Hangzhou 310053, Peoples R China. [Wen, Chengping; Shao, Tiejuan] Ctr Innovat Basic Res Autoimmune Dis Med, Hangzhou 310053, Peoples R China. [Xu, Anyi] Zhejiang Chinese Med Univ, Clin Med Coll 1, Hangzhou 310053, Peoples R China. C3 Zhejiang Chinese Medical University; Zhejiang Chinese Medical University RP Wen, CP; Shao, TJ (corresponding author), Zhejiang Chinese Med Univ, Coll Basic Med Sci, Hangzhou 310053, Peoples R China.; Wen, CP; Shao, TJ (corresponding author), Ctr Innovat Basic Res Autoimmune Dis Med, Hangzhou 310053, Peoples R China. EM wengcp@163.com; tiejuanshao@zcmu.edu.cn FU National Natural Science Foundation of China; Public Platform of Medical Research Centre, Academy of Chinese Medical Science, Zhejiang Chinese Medical University FX We appreciate the technical support from the Public Platform of Medical Research Centre, Academy of Chinese Medical Science, Zhejiang Chinese Medical University. 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Med. PD JUL 22 PY 2025 VL 20 IS 1 AR 115 DI 10.1186/s13020-025-01162-6 PG 20 WC Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine; Pharmacology & Pharmacy GA 5JK2C UT WOS:001537100800002 PM 40696369 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhao, YH Shen, X Li, N Huang, WH Li, XX Ye, Q Ruan, YQ Li, RH Zhu, HQ Xu, LL Gong, XY Xu, YD Dong, L AF Zhao, Yuhui Shen, Xiao Li, Na Huang, Wenhan Li, Xinxin Ye, Qiang Ruan, Yiqiu Li, Ruihan Zhu, Hanqin Xu, Linlin Gong, Xinyi Xu, Yongdong Dong, Lei TI Qidong Huoxue decoction protects against acute lung injury by promoting SIRT1-mediated p300 deacetylation SO PHYTOMEDICINE LA English DT Article DE Acute lung injury; Qidong Huoxue decoction; p300; Acetylation; SIRT1; Inflammation; Lipopolysaccharide ID HISTONE ACETYLTRANSFERASE DOMAIN; AUTOACETYLATION; PATHOGENESIS; ACETYLATION AB Background: Qidong Huoxue Decoction (QD), a traditional Chinese medicine, has been used clinically to treat acute lung injury (ALI); however, its anti-inflammatory mechanisms remain poorly understood. Purpose: This study aimed to elucidate the mechanism by which QD mitigates ALI, focusing on its antiinflammatory effects. Methods: A combination of serum pharmacochemistry, acetyl-proteomic sequencing, and experimental validation was used to investigate the therapeutic effects of QD on ALI. Liquid chromatography-mass spectrometry (LC-MS) was used to profile the constituents of QD extract and their bioavailability in ALI mouse serum. Mice were randomly assigned to control or lipopolysaccharide (LPS) groups and treated with QD low-, medium-, or highdose, or dexamethasone (DEX). Acetyl-proteomics was performed on lung tissues to identify key signaling pathways in LPS-induced ALI. RAW264.7 macrophages were used for in vitro confirmation of inflammation. Results: QD treatment markedly improved pulmonary function in ALI mice by reducing cytokine levels and inhibiting M1 macrophage polarization. Proteomic analysis revealed a significant downregulation of p300 acetylation in the QD-treated group, which was confirmed in vitro. Venn analysis of LC-MS data identified 298 constituents shared between the QD extract and drug-containing serum. Among these, resveratrol, a SIRT1 activator, was a major bioactive compound, suggesting its potential role in mediating the anti-inflammatory effects of QD. Conclusion: QD alleviates ALI by suppressing p300 acetylation, probably by SIRT1 activation. These findings highlight the therapeutic potential of QD for epigenetic regulation of inflammatory signaling in ALI. C1 [Zhao, Yuhui; Shen, Xiao; Li, Na; Huang, Wenhan; Ye, Qiang; Ruan, Yiqiu; Li, Ruihan; Zhu, Hanqin; Xu, Linlin; Gong, Xinyi; Xu, Yongdong] Zhejiang Chinese Med Univ, Sch Clin Med 2, Hangzhou 310053, Peoples R China. [Li, Xinxin] Zhejiang Chinese Med Univ, Coll Integrated Tradit Chinese & Western Med, Hangzhou 310053, Peoples R China. [Dong, Lei] Zhejiang Chinese Med Univ, Affiliated Hosp 2, Hangzhou 310005, Peoples R China. C3 Zhejiang Chinese Medical University; Zhejiang Chinese Medical University; Zhejiang Chinese Medical University RP Dong, L (corresponding author), Zhejiang Chinese Med Univ, Affiliated Hosp 2, Dept Resp & Crit Care Med, Hangzhou 310005, Zhejiang, Peoples R China. EM ramelei.1024@163.com RI ; Huang, Wenhan/AGR-4886-2022; Li, Ruihan/AFU-4032-2022 OI Ruan, YiQiu/0009-0002-9166-3215; FU Zhejiang Key Research and Development Program [2024C03215]; Zhejiang Provincial Natural Science Foundation of China [LY22H290001]; Zhejiang Yangtze River Delta Health Research Fund [2023CSJ-2-D004] FX This work was supported by the Zhejiang Key Research and Development Program (Grant No 2024C03215) , the Zhejiang Provincial Natural Science Foundation of China (Grant No LY22H290001) , and the Zhejiang Yangtze River Delta Health Research Fund (Grant No 2023CSJ-2-D004) . 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Despite significant progress in understanding its underlying mechanisms, translating this knowledge into effective prevention or treatment remains a major clinical challenge. Ferroptosis, a form of controlled cellular demise triggered by iron, involves the accumulation of lipid peroxides, resulting in irreversible membrane disintegration and oxidative metabolic failure. Emerging studies suggest that ferroptosis exacerbates PF progression by promoting macrophage polarization, fibroblast proliferation, and extracellular matrix deposition, ultimately leading to alveolar epithelial cell death and fibrotic tissue remodeling. Consequently, targeting ferroptosis presents a promising therapeutic approach, with traditional Chinese medicine (TCM) showing particular potential through its multi-dimensional and holistic mechanisms. TCM compounds, extracts, and bioactive monomers exhibit anti-inflammatory, antioxidant, and multi-target properties that demonstrate significant value in managing PF. To develop innovative therapeutic strategies for PF, this review synthesizes recent progress in elucidating ferroptosis pathways implicated in the pathogenesis of PF and underscores the therapeutic potential of TCM in PF management via ferroptosis inhibition. Moreover, this paper highlights the advantages of integrating nanotechnology with TCM for regulating ferroptosis in PF treatment. In general, this paper will provide new perspectives for advancing research and clinical applications of TCM in the treatment of PF. C1 [Fan, Xudong; Xu, Jiangxin; Wang, Yu; Cai, Xinjun] Zhejiang Hosp Integrated Tradit Chinese & Western, Dept Pharm, Hangzhou, Peoples R China. [Gao, Jinlong] Hangzhou Normal Univ, Sch Pharm, Hangzhou, Peoples R China. [Zhang, Jie; Shan, Yanni; Luo, Jingming] Zhejiang Chinese Med Univ, Sch Pharmaceut Sci, Hangzhou, Peoples R China. [Fei, Weidong] Zhejiang Univ, Womens Hosp, Sch Med, Hangzhou, Peoples R China. C3 Hangzhou Normal University; Zhejiang Chinese Medical University; Zhejiang University RP Cai, XJ (corresponding author), Zhejiang Hosp Integrated Tradit Chinese & Western, Dept Pharm, Hangzhou, Peoples R China.; Fei, WD (corresponding author), Zhejiang Univ, Womens Hosp, Sch Med, Hangzhou, Peoples R China. EM zjtcmcxj@zcmu.edu.cn; feiweidong@zju.edu.cn RI Fei, Weidong/ABI-2596-2020 FU Special Pharmacy Project of Zhejiang Pharmaceutical Association [2023ZYY30] FX The author(s) declare that financial support was received for the research and/or publication of this article. This research was funded by Special Pharmacy Project of Zhejiang Pharmaceutical Association (No. 2023ZYY30). 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PD JUL 18 PY 2025 VL 13 AR 1598924 DI 10.3389/fcell.2025.1598924 PG 19 WC Cell Biology; Developmental Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology; Developmental Biology GA 5PN9P UT WOS:001541276000001 PM 40756260 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhang, SY Chen, JJ Qiu, L Wu, XW Zhou, W Peng, RQ Feng, Y Zhou, R Huang, X Wu, DZ Lu, ZH AF Zhang, Shaoyan Chen, Jiajun Qiu, Lei Wu, Xianwei Zhou, Wei Peng, Ruoqing Feng, Ya Zhou, Rui Huang, Xing Wu, Dingzhong Lu, Zhenhui TI Bufei Jiedu Formula enhances CD40 activation and macrophage polarization to eliminate intracellular MRSA persisters SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE MRSA infection; persistent; intracellular; macrophage polarization; CD40; atractylenolide II ID STAPHYLOCOCCUS-AUREUS; INFECTION; VANCOMYCIN; IDENTIFICATION; METABOLISM AB Background Intracellular methicillin-resistant Staphylococcus aureus (MRSA) represents a complex infection in clinical practice, characterized by its refractory and recurrent nature, rendering it challenging to treat with conventional antibiotics. Bufei Jiedu Formula (BFJD) is a traditional Chinese medicine compound utilized for treating chronic lung infections; however, its mechanisms against intracellular MRSA infection are not yet fully understood.Methods An animal model with persistent MRSA infection was used to evaluate the efficacy of BFJD against chronic bacterial infections. Flow cytometry was employed to assess the regulatory effects of BFJD on macrophages. Transcriptomic sequencing and molecular biological experiments were utilized to explore and validate the regulatory targets and pathways of BFJD. Flow cytometry and molecular docking were used to clarify the possible binding mode of bioactive compounds with CD40.Results BFJD reduced bacterial loads in the lungs, liver, and kidneys of mice with persistent MRSA infection and promoted M1 polarization of macrophages in the lungs. In vitro, BFJD decreased intracellular MRSA persisters loads and enhanced macrophage M1 polarization and M2-to-M1 repolarization. Multi-time point cellular sequencing data revealed the transcriptomic characteristics of intracellular persistent MRSA infections, including the downregulation of cytokine activity and TNF signaling pathways. GO-KEGG enrichment analysis revealed that BFJD regulated signaling pathways related to response to reactive oxygen species (ROS), IL-1 beta and IL-6 production, NF-kappa B and TNF signaling. Further intersection analysis found that genes down-regulated in the persistence state were up-regulated by BFJD, among which pro-inflammatory genes including Il1b, Il6, Ccl2, and Cd40 were all reversed. Furthermore, we found BFJD enhanced the host-mediated intracellular killing of MRSA by macrophages via the CD40-ROS-NF-kappa B signaling cascade. Multiplex cytokine analysis showed that BFJD increased the levels of IL-1 beta, CCL-2, IL-6, and TNF-alpha in the serum of persistently infected mice. Further screening of active compounds revealed that atractylenolide II and formononetin exhibit high affinity with CD40 and decreased intracellular bacterial loads.Conclusion BFJD decreased organ bacterial loads in mice with persistent MRSA infection by regulating the CD40-ROS-NF-kappa B signaling pathway, thereby modulating macrophage immunophenotypes and exerting anti-MRSA persister effects. C1 [Zhang, Shaoyan; Chen, Jiajun; Qiu, Lei; Wu, Xianwei; Zhou, Wei; Peng, Ruoqing; Feng, Ya; Zhou, Rui; Huang, Xing; Wu, Dingzhong; Lu, Zhenhui] Shanghai Univ Tradit Chinese Med, Longhua Hosp, Inst Resp Dis, Shanghai, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine RP Lu, ZH (corresponding author), Shanghai Univ Tradit Chinese Med, Longhua Hosp, Inst Resp Dis, Shanghai, Peoples R China. EM Dr_luzh@shutcm.edu.cn RI Peng, Ruoqing/KWU-9881-2024 OI 吴, 显伟/0000-0003-4512-6208 FU Major National Science and Technology Projects of China [2024ZD0523000]; National Natural Science Foundation of China [82374436, 81873255]; Science and Technology Commission of Shanghai Municipality [22XD1423500, 23S21900600, 22Y11920200]; Shanghai Municipal Health Commission [2022CX010, 2022XD027, GWVI-11.1-08]; Shanghai Hospital Development Center [SHDC12023106] FX The author(s) declare that financial support was received for the research and/or publication of this article. This study was supported by Major National Science and Technology Projects of China (2024ZD0523000 to ZL); National Natural Science Foundation of China (NO. 82374436 to ZL, No. 81873255 to ZL); Science and Technology Commission of Shanghai Municipality (No. 22XD1423500 to ZL, NO. 23S21900600 to SZ, No. 22Y11920200 to DW); Shanghai Municipal Health Commission (No. 2022CX010 to ZL, No. 2022XD027 to ZL, GWVI-11.1-08); Shanghai Hospital Development Center (NO. SHDC12023106 to ZL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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PD JUL 17 PY 2025 VL 26 IS 14 AR 6855 DI 10.3390/ijms26146855 PG 20 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry GA 5HP0O UT WOS:001535871200001 PM 40725102 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Li, ZH Yang, WM Huang, Q Shi, GX Liu, CZ Zhang, YQ AF Li, Zhi-han Yang, Wen-min Huang, Qi Shi, Guang-xia Liu, Cun-zhi Zhang, Yu-qin TI Acupuncture activates vagus nerve-macrophage axis and improves cardiac electrophysiology and inflammatory response in rats with atrial fibrillation via a7nAChR-JAK2/STAT3 pathway SO JOURNAL OF INTEGRATIVE MEDICINE-JIM LA English DT Article DE alpha 7nAChR-JAK2/STAT3 signaling pathway; Acupuncture; Atrial fibrillation; Inflammation; Macrophages ID HEART-RATE-VARIABILITY; QUALITY-OF-LIFE; CATHETER ABLATION; NEUROMODULATION; STIMULATION; PROGRESSION; EFFICACY; THERAPY AB Objective: The occurrence and development of atrial fibrillation (AF) are influenced by the autonomic nervous system and inflammation. Acupuncture is an effective treatment for AF. This study explored the protective effects of acupuncture in a rat model of paroxysmal AF and investigated its mechanisms. Methods: Male Sprague-Dawley rats (n = 130) were randomly divided into blank control (Con), sham operation (Sham), AF, and acupuncture treatment (Acu) groups. A paroxysmal AF model was established by rapid atrial pacing through the jugular vein. Rats in the Acu group were immobilized to receive acupuncture treatment at Neiguan acupoint (PC6) for 20 min daily for seven days. The other groups were immobilized for the same duration over the treatment period but did not receive acupuncture. The AF induction rate, AF duration, cardiac electrophysiological parameters, and heart rate variability were evaluated by monitoring surface electrocardiogram and vagus nerve discharge signals. After the intervention, the rats were euthanized, and atrial morphology was assessed using haematoxylin and eosin staining. The expression of macrophage F4/80 antigen (F4/80) and cluster of differentiation (CD) 86 in atrial myocardial tissue was detected using immunohistochemistry, immunofluorescence and flow cytometry. The expression levels or contents of interleukin (IL)-1b, IL-6, tumor necrosis factor-a (TNF-a), a7 nicotinic acetylcholine receptor (a7nAChR), phosphorylated Janus kinase 2 (p-JAK2), and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in atrial myocardial tissue were detected using Western blotting, reverse transcription-quantitative polymerase chain reaction, or enzyme-linked immunosorbent assay. The role of a7nAChR in acupuncture treatment was verified by intraperitoneal injection of the a7nAChR antagonist methyllycaconitine (MLA). Results: Compared with the AF group, acupuncture significantly reduced AF duration and induction rate, improved cardiac electrophysiology by enhancing vagus nerve activity and regulating autonomic balance. It also decreased the pro-inflammatory M1 macrophage proportion, alleviating myocardial injury and infiltration. MLA weakened acupuncture's electrophysiological improvement and anti-inflammatory effect. Results suggest that acupuncture triggers the a7nAChR-JAK2/STAT3 pathway and exerts cardioprotection via neuroimmune regulation. Conclusion: Acupuncture significantly reduced the AF induction rate, shortened AF duration, improved cardiac electrophysiological parameters, enhanced vagus nerve activity, and decreased the expression of pro-inflammatory M1 macrophages and inflammatory factors in rats with paroxysmal AF. Its positive effects are related to the activation of the a7nAChR-mediated JAK2/STAT3 signalling pathway, indicating that the interaction between cardiac vagus nerve and macrophages may be a potential target for acupuncture in the prevention and treatment of AF. Please cite this article as: Li ZH, Yang WM, Huang Q, Shi GX, Liu CZ, Zhang YQ. Acupuncture activates vagus nerve-macrophage axis and improves cardiac electrophysiology and inflammatory response in rats with atrial fibrillation via a7nAChR-JAK2/STAT3 pathway. J Integr Med. 2025; 23(4): 398-414. (c) 2025 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies. C1 [Li, Zhi-han; Yang, Wen-min; Huang, Qi; Shi, Guang-xia; Liu, Cun-zhi; Zhang, Yu-qin] Beijing Univ Chinese Med, Sch Acupuncture Moxibust & Tuina, Beijing 100029, Peoples R China. [Li, Zhi-han; Huang, Qi; Shi, Guang-xia; Liu, Cun-zhi; Zhang, Yu-qin] Beijing Univ Chinese Med, Int Acupuncture & Moxibust Innovat Inst, Beijing 100029, Peoples R China. C3 Beijing University of Chinese Medicine; Beijing University of Chinese Medicine RP Zhang, YQ (corresponding author), Beijing Univ Chinese Med, Sch Acupuncture Moxibust & Tuina, Beijing 100029, Peoples R China. EM yuqin_zhang@bucm.edu.cn RI ; Liu, Cunzhi/J-9190-2017 OI Yang, Wenmin/0009-0004-8479-7340; FU National Key Research and Development Program of China [2019YFC1712100]; National Natural Science Foundation of China [82105017] FX Funding This study was supported by the National Key Research and Development Program of China (No. 2019YFC1712100) , and the National Natural Science Foundation of China (No. 82105017) . 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Med.-JIM PD JUL PY 2025 VL 23 IS 4 BP 398 EP 414 DI 10.1016/j.joim.2025.06.002 EA JUL 2025 PG 17 WC Integrative & Complementary Medicine WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine GA 5EP8U UT WOS:001533854100002 PM 40562587 DA 2026-03-26 ER PT J AU He, CX Lu, YJ Wang, T Zhang, BW Su, ZQ Tang, LP Tao, LT Zheng, GJ Li, LN Feng, B Zhu, Y AF He, Chunxia Lu, Yanjing Wang, Tong Zhang, Bowen Su, Zuqing Tang, Lipeng Tao, Lanting Zheng, Guangjuan Li, Liuning Feng, Bing Zhu, Ying TI Xiaoji decoction induces apoptosis in lung cancer cells and M1 Macrophage polarization via the JAK1/STAT3/PD-L1 pathway SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Xiaoji decoction; Lung cancer; Macrophage polarization; JAK1; STAT3; PD-L1 ID ACTIVATION; RESISTANCE; STAT3; SP1; INHIBITION; EXPRESSION; CASPASES; PROMOTES AB Ethnopharmacological relevance: Xiaoji Decoction (XJD), a traditional Chinese herbal formula, has been used for decades to effectively treat non-small cell lung cancer (NSCLC), improving patients' quality of life and prolonging overall survival. Nevertheless, the molecular mechanisms responsible for the effectiveness of XJD on NSCLC remain largely unexplored. Aim of the study: This study aims to investigate the therapeutic effects of XJD in NSCLC and to elucidate the molecular mechanisms involved. Materials and methods: In vitro experiments were conducted by treating A549 cells with XJD at concentrations of 0, 6.25, 12.5, 25, and 50 mg/mL, and H1975 cells with XJD at concentrations of 0, 10, 20, 30, and 40 mg/mL. Ruxolitinib was used at a concentration of 10 mu M. MTT assays were used to evaluate cell viability, and EdU assays were employed to measure cell proliferation. Apoptosis and cell cycle progression were analyzed by flow cytometry in vitro. The JAK1, p-STAT3, STAT3, PD-L1, BAX, Bcl-2, Cleaved Caspase-9, and Cleaved Caspase-3 were examined through Western blot analysis. In vivo experiments involved allocating mice into six groups (n = 5), including a saline control group, XJD treatment group (13.4 g/kg/day by gavage), alpha PD-L1 group (200 mg/ mouse), Ruxolitinib group (10 mg/kg/day by gavage), XJD + Ruxolitinib group, and XJD + alpha PD-L1 group. Animal weight and tumor size were recorded daily for two weeks, and on day 18, the animals were sacrificed for tumor and spleen analysis. The number of macrophages present in the abdominal cavity, fresh tumors, and spleen was also measured. Results: XJD effectively inhibited cell growth, triggered apoptosis, and induced cell cycle arrest in NSCLC cells. XJD was shown to downregulate JAK1 expression, inhibit the phosphorylation of STAT3, and reduce PD-L1 protein levels. It also decreased Bcl-2 expression while increasing the levels of BAX, Cleaved Caspase-9, and Cleaved Caspase-3, promoting cell apoptosis. Furthermore, inhibiting STAT3 phosphorylation alongside XJD treatment further amplified cell growth inhibition, induced stronger apoptosis, and more effectively arrested the cell cycle. Additionally, XJD enhanced the anti-cancer efficacy of alpha PD-L1, with tumor growth inhibition linked to reduced M2 macrophage infiltration and increased M1 macrophage presence. Mechanistically, combination therapies incorporating XJD with either Ruxolitinib or alpha PD-L1 exhibited dual therapeutic effects: 1) promotion of tumor apoptosis through enhanced caspase activation, and 2) effective suppression of the oncogenic JAK1/ STAT3 signalling axis and its downstream PD-L1 expression. Conclusions: Our results indicate that XJD suppresses NSCLC cell growth, induces cell cycle arrest, and promotes apoptosis by inhibiting the JAK1/STAT3/PD-L1 signaling pathway. XJD has been shown to enhance the anticancer efficacy of alpha PD-L1 and exerts its anti-tumor effects by modulating macrophage polarization. C1 [He, Chunxia; Tao, Lanting; Li, Liuning] Guangzhou Univ Chinese Med, Clin Coll 2, Dept Oncol, Guangzhou 510120, Peoples R China. [Lu, Yanjing; Wang, Tong; Zhang, Bowen; Su, Zuqing; Tang, Lipeng; Zheng, Guangjuan; Feng, Bing; Zhu, Ying] Guangzhou Univ Chinese Med, Clin Coll 2, Dept Pharmacol Tradit Chinese Med, Guangzhou 510120, Peoples R China. [Su, Zuqing; Tang, Lipeng; Zheng, Guangjuan; Feng, Bing; Zhu, Ying] Guangzhou Univ Chinese Med, Clin Coll 2, Guangdong Hong Kong Macau Joint Lab Chinese Med &, Guangzhou 510120, Peoples R China. [Su, Zuqing; Tang, Lipeng; Zheng, Guangjuan; Feng, Bing; Zhu, Ying] Guangzhou Univ Chinese Med, Affiliated Hosp 2, State Key Lab Dampness Syndrome Chinese Med, Guangzhou 510120, Peoples R China. C3 Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine RP Li, LN (corresponding author), Guangzhou Univ Chinese Med, Clin Coll 2, Dept Oncol, Guangzhou 510120, Peoples R China.; Feng, B; Zhu, Y (corresponding author), Guangzhou Univ Chinese Med, Clin Coll 2, Dept Pharmacol Tradit Chinese Med, Guangzhou 510120, Peoples R China. EM doctorlln@gzucm.edu.cn; fengbing3701@gzucm.edu.cn; zhuying3340@gzucm.edu.cn RI Tang, Lipeng/ABB-6481-2020; Zheng, Guangjuan/ABB-6496-2020 OI Lu, Yanjing/0009-0006-2888-4305; FU Guangzhou Science and Technology Plan Project [202201010863, 202102010294]; National Natural Science Foundation of Guangdong [2024A1515010568, 2018B030311061]; Chinese Medicine Scientific Research and Technology Research Projects of Guangdong Provincial Hospital of Chinese Medicine [YN2024GZRPY073, YN2024GZRPY069, YN2024GZRPY081]; Specific Fund of State Key Laboratory of Dampness Syndrome of Chinese Medicine [SZ2021ZZ20]; The 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund (Guangdong-Hong Kong-Macau Joint Lab) [2020B1212030006]; Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases [2018B030322012] FX This work was supported by Guangzhou Science and Technology Plan Project (No: 202201010863, 202102010294) , National Natural Science Foundation of Guangdong (2024A1515010568, 2018B030311061) , the Chinese Medicine Scientific Research and Technology Research Projects of Guangdong Provincial Hospital of Chinese Medicine (No. YN2024GZRPY073, YN2024GZRPY069, YN2024GZRPY081) , the Specific Fund of State Key Laboratory of Dampness Syndrome of Chinese Medicine under Grant (SZ2021ZZ20) , the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund (Guangdong-Hong Kong-Macau Joint Lab) (2020B1212030006) , and the Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases (No. 2018B030322012) . 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PD AUG 29 PY 2025 VL 352 AR 120240 DI 10.1016/j.jep.2025.120240 EA JUL 2025 PG 17 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 5ML6U UT WOS:001539174300001 PM 40617363 OA hybrid DA 2026-03-26 ER PT J AU Chen, LY Lin, HB Qin, LM Zhang, GF Chen, PS Jiang, ZB Xu, P Huang, DH Zhang, X AF Chen, Liangyu Lin, Haobo Qin, Linmang Zhang, Guangfeng Chen, Peisheng Jiang, Zebo Xu, Pan Huang, Donghui Zhang, Xiao TI Network pharmacology-based approach to research the effects and mechanisms of Salvia Miltiorrhiza injection against idiopathic pulmonary fibrosis SO FRONTIERS IN MEDICINE LA English DT Article DE Salvia Miltiorrhiza injection; idiopathic pulmonary fibrosis; network pharmacology; inflammation; fibroblast ID MACROPHAGE POLARIZATION; OXIDATIVE STRESS; GELATINASE-B; ALPHA; INFLAMMATION; INHIBITION; MMP-9; MATRIX-METALLOPROTEINASE-9; OVEREXPRESSION; PATHOGENESIS AB Background Idiopathic pulmonary fibrosis (IPF) is a progressive, life-threatening lung disease with limited treatment efficacy. Salvia miltiorrhiza (SM), a traditional Chinese medicine (TCM), is widely used in Chinese hospitals due to its antithrombotic, anti-inflammatory, and antioxidant properties. SM has also demonstrated potential as an anti-fibrotic agent. This study aims to investigate the therapeutic effects and mechanisms of SM injection in treating IPF.Methods Active components and targets of SM were acquired from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, while IPF-associated genes were obtained from the DisGeNET database. Venn analysis was applied to intersect SM targets with IPF-associated genes, identifying potential therapeutic targets. A protein-protein interaction (PPI) network of these targets was constructed using the STRING database and visualized with Cytoscape software, where the CytoHubba plug-in was utilized to determine core therapeutic targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the core targets were conducted via R language, and molecular docking was performed to predict the binding affinities of active compounds to the core targets. The core targets were further validated through qRT-PCR, Western blot (WB), and ELISA experiments.Results 70 potential target genes of SM injection for the treatment of IPF were identified, with MMP9, IL-6, and TNF-alpha as the core targets. These core targets were linked to pathways involving inflammation, oxidative stress, and extracellular matrix (ECM) remodeling. In vitro experiments indicated that SM injection alleviated pulmonary fibrosis by downregulating MMP9, IL-6, and TNF-alpha.Conclusion SM injection may effectively reduce pulmonary fibrosis through multi-target mechanisms, providing a new therapeutic strategy for IPF from the perspective of TCM. C1 [Chen, Liangyu; Zhang, Xiao] Macau Univ Sci & Technol, Fac Chinese Med, Taipa, Peoples R China. [Chen, Liangyu; Chen, Peisheng; Jiang, Zebo; Xu, Pan; Huang, Donghui] Zhuhai Hosp Integrated Tradit Chinese & Western Me, Dept Resp & Crit Care Med, Zhuhai, Peoples R China. [Lin, Haobo; Qin, Linmang; Zhang, Guangfeng] Guangdong Prov Peoples Hosp, Dept Rheumatol, Guangzhou, Peoples R China. [Lin, Haobo; Qin, Linmang; Zhang, Guangfeng] Guangdong Acad Med Sci, Guangzhou, Peoples R China. [Lin, Haobo; Qin, Linmang; Zhang, Guangfeng] Southern Med Univ, Guangzhou, Peoples R China. [Zhang, Xiao] Sun Yat sen Univ, Affiliated Hosp 8, Dept Rheumatol, Shenzhen, Peoples R China. C3 Macau University of Science & Technology; Guangdong Academy of Medical Sciences & Guangdong General Hospital; Guangdong Academy of Medical Sciences & Guangdong General Hospital; Southern Medical University - China; Sun Yat Sen University RP Zhang, X (corresponding author), Macau Univ Sci & Technol, Fac Chinese Med, Taipa, Peoples R China.; Huang, DH (corresponding author), Zhuhai Hosp Integrated Tradit Chinese & Western Me, Dept Resp & Crit Care Med, Zhuhai, Peoples R China.; Zhang, X (corresponding author), Sun Yat sen Univ, Affiliated Hosp 8, Dept Rheumatol, Shenzhen, Peoples R China. EM feidiexian4@gmail.com; dhhuang2010@yeah.net RI jiang, zebo/LXV-6641-2024; Chen, Peisheng/AAL-5382-2021 FU National Natural Science Foundation of China [81771734, 82271822]; Natural Science Foundation of Guangdong Province [2019A1515010927]; Chinese Traditional Medicine Foundation of Guangdong Province [20241007, 20241290, 20241285]; Zhuhai Medical Research Project [2220009000235]; Zhuhai Social Development Science and Technology Program Project [2320004000290] FX The author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by the National Natural Science Foundation of China (81771734 & 82271822); Natural Science Foundation of Guangdong Province (2019A1515010927); Chinese Traditional Medicine Foundation of Guangdong Province (20241007, 20241290 & 20241285); Zhuhai Medical Research Project (2220009000235); and Zhuhai Social Development Science and Technology Program Project (2320004000290). The funding foundations had no role in the study design, data collection, analysis, or publication of this manuscript. 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Med. PD JUN 24 PY 2025 VL 12 AR 1569590 DI 10.3389/fmed.2025.1569590 PG 18 WC Medicine, General & Internal WE Science Citation Index Expanded (SCI-EXPANDED) SC General & Internal Medicine GA 4PT0O UT WOS:001523742800001 PM 40630478 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Leng, MD Jiang, HQ Lan, HY Zhong, W Shi, HN Jia, J Bao, YX AF Leng, Maodong Jiang, Huiqin Lan, Haiyan Zhong, Wei Shi, Hongna Jia, Jing Bao, Yixi TI Immunoregulatory function and anticancer effects of Polygonatum sibiricum polysaccharides against hepatic carcinoma via macrophage phenotype modulation SO INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES LA English DT Article DE Polygonatum sibiricum polysaccharide; Macrophage phenotype; Immunoregulatory function ID CANCER; ANTIOXIDANT; MYD88 AB Polysaccharides extracted from traditional Chinese medicine are biological macromolecules and the main compounds responsible for immunoregulatory effects. The immunoregulatory properties and anticancer effects of Polygonatum sibiricum polysaccharide (PSP) were found to be attributed to modulation of the phenotype of tumor-associated macrophages (TAMs). The underlying molecular mechanisms were elucidated. PSP is a natural macromolecule consisting of different functional groups. In vitro findings suggested the immunoregulatory function of PSP and that it could transform the M2 phenotype of macrophages toward the M1 phenotype. Studies at the molecular level revealed that the immunoregulatory and macrophage phenotype-modulatory functions of PSP were mediated by the TLR4-mediated MyD88-dependent signaling pathway. In vivo, PSP exhibited a strong tumor-inhibitory effect on hepatic carcinoma, and PSP-treated tumor-bearing mice exhibited a lower tumor cell-proliferation index as determined using immunohistochemical assays. PSP could increase the number of CD86-positive TAMs and decrease the number of CD206-positive TAMs in tumor tissues as determined using immunofluorescence assays. PSP exerted its immunoregulatory and anticancer effects by modulating the phenotype of TAMs toward the M1 phenotype via the TLR4-mediated MyD88-dependent signaling pathway. Our findings provide a potential strategy for the treatment of hepatic carcinoma. C1 [Leng, Maodong; Lan, Haiyan; Zhong, Wei; Bao, Yixi] Chongqing Med Univ, Affiliated Hosp 2, Dept Clin Lab, 76 Linjiang Rd, Chongqing 400010, Peoples R China. [Leng, Maodong; Shi, Hongna; Jia, Jing] Zhengzhou Univ, Childrens Hosp, Henan Childrens Hosp, Dept Clin Lab,Zhengzhou Key Lab Childrens Infect &, Zhengzhou 450000, Peoples R China. [Jiang, Huiqin] Zhengzhou Univ, Inst Adv Biomed Sci, Innovat Ctr Basic Res Metab Associated Fatty Liver, Tianjian Lab Adv Biomed Sci,Minist Educ China, Zhengzhou 450000, Henan, Peoples R China. C3 Chongqing Medical University; Zhengzhou University; Zhengzhou University RP Bao, YX (corresponding author), Chongqing Med Univ, Affiliated Hosp 2, Dept Clin Lab, 76 Linjiang Rd, Chongqing 400010, Peoples R China. EM yixibao@cqmu.edu.cn FU Medical Science and Technology Project of Henan Province [LHGJ20240553] FX This study was supported by Medical Science and Technology Project of Henan Province (LHGJ20240553) . 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Macromol. PD AUG PY 2025 VL 319 AR 145423 DI 10.1016/j.ijbiomac.2025.145423 EA JUN 2025 PN 1 PG 14 WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 4KG3M UT WOS:001520014400003 PM 40545106 DA 2026-03-26 ER PT J AU Munkong, N Ontawong, A Thatsanasuwan, N Pengnet, S Makjaroen, J Pearngam, P Nanthawong, S Somparn, P Leelahavanichkul, N Thim-uam, A AF Munkong, Narongsuk Ontawong, Atcharaporn Thatsanasuwan, Natthaphon Pengnet, Sirinat Makjaroen, Jiradej Pearngam, Phorutai Nanthawong, Saharat Somparn, Poorichaya Leelahavanichkul, Natnisha Thim-uam, Arthid TI Hibiscus sabdariffa L. (Roselle flower) extract exerts protective effects against lipopolysaccharide-induced inflammation by ameliorating TLR4/NF-κB and NLRP3 inflammasome activation SO INFLAMMOPHARMACOLOGY LA English DT Article DE Hibiscus sabdariffa Linn; Roselle flower; NLRP3 inflammasome; Mitochondrial dysfunction; Anti-inflammation; M1/M2 macrophages ID ANTIINFLAMMATORY ACTIVITIES; ANTIOXIDANT; EXPRESSION; ITACONATE; INJURY; TLR9 AB The phytochemical constituents of various plant extracts have shown potential in mitigating oxidative stress and inflammation. Hibiscus sabdariffa L. (HS), known as the roselle flower, has demonstrated antioxidant and anti-inflammatory effects in several models. Our study aimed to evaluate the effects of aqueous HS extract on modulating the TLR4/MyD88/NF-kappa B and Caspase-11/NLRP3 inflammasome signaling pathways during lipopolysaccharide (LPS)-induced mitochondrial stress and inflammation in macrophages by several in vitro assays. The results demonstrated that compared with LPS alone, HS extract significantly reduced the production of ROS, nitric oxide and proinflammatory cytokines (IL-6, TNF-alpha, PG-E2, IL-1 beta, and IFN-gamma) by lowering the gene expression of p22phox and iNOS and suppressed I kappa B alpha-dependent NF-kappa B signaling. Furthermore, HS treatment induced the polarization of macrophages from the M1 phenotype to the M2 phenotype, as demonstrated by qPCR and flow cytometry. The proteomic data revealed that HS extract can downregulate the expression of several mitochondria-associated proteins and reduce mitochondrial DNA leakage during LPS activation, suppressing Caspase-11/Gasdermin-D /NLRP3 inflammasome activation. In summary, the protective effects of HS extract against LPS-induced inflammation, which is mediated through the TLR4/NF-kappa B/NLRP3 signaling pathway, may significantly promote anti-inflammatory responses and alleviate related diseases. C1 [Munkong, Narongsuk] Univ Phayao, Sch Med, Dept Pathol, Phayao 56000, Thailand. [Ontawong, Atcharaporn; Pengnet, Sirinat] Univ Phayao, Sch Med Sci, Div Physiol, Phayao 56000, Thailand. [Thatsanasuwan, Natthaphon] Univ Phayao, Sch Med Sci, Div Nutr, Phayao 56000, Thailand. [Makjaroen, Jiradej; Nanthawong, Saharat; Somparn, Poorichaya] Chulalongkorn Univ, Fac Med, Ctr Excellence Syst Biol, Bangkok 10400, Thailand. [Makjaroen, Jiradej] Chulalongkorn Univ, Fac Allied Hlth Sci, Dept Transfus Med & Clin Microbiol, Bangkok 10330, Thailand. [Pearngam, Phorutai] Mahidol Univ, Int Coll, Nakhon Pathom 73170, Thailand. [Leelahavanichkul, Natnisha] Chulalongkorn Univ, Fac Med, Dept Microbiol, Bangkok, Thailand. [Thim-uam, Arthid] Univ Phayao, Sch Med Sci, Div Biochem, Phayao 56000, Thailand. C3 University of Phayao; University of Phayao; University of Phayao; Chulalongkorn University; Chulalongkorn University; Mahidol University; Chulalongkorn University; University of Phayao RP Thim-uam, A (corresponding author), Univ Phayao, Sch Med Sci, Div Biochem, Phayao 56000, Thailand. EM Arthidth@gmail.com OI Thim-uam, Arthid/0000-0002-1321-9728 FU Thailand science research and innovation fund and the University of Phayao [FF66-RIM061, 229/2567]; School of Medical Sciences, University of Phayao [MS251001] FX This research was supported by the Thailand Science Research and Innovation Fund and the University of Phayao (Grant No. FF66-RIM061, 229/2567), and the School of Medical Sciences, University of Phayao (Grant No. MS251001). 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FACTOR-1-ALPHA; ANTIMALARIAL AGENT ARTESUNATE; ALPHA-INDUCED PRODUCTION; GM-CSF EXPRESSION AB Background: The pathogenesis of rheumatoid arthritis (RA) involves abnormal activation and interactions among various cell types. Traditional Chinese medicine (TCM) natural products show therapeutic potential with multitarget anti-inflammatory effects, but their specific impacts on RA-related cell types remain unclear. Purpose: This review aims to provide a comprehensive overview of the effects of natural products on key cell types in RA. Methods: We extensively searched PubMed, Web of Science, and Scopus until April 2025, using keywords like "natural products," "rheumatoid arthritis," "cellular mechanisms," and specific cell types. Studies on natural products' effects on RA-related cells were included and analyzed. Results: This review marks the first attempt to integrate cellular resolution in evaluating therapeutic mechanisms of natural products in RA. The key findings highlight the cell-type-specific effects and mechanistic underpinnings of natural products. Sinomenine preferentially inhibits fibroblast-like synoviocytes (FLS) proliferation via tolllike receptor 4 (TLR4) /MyD88/NF-kappa B blockade, whereas icariin reprograms macrophage polarization through ERK/HIF-1 alpha/GLUT1 signaling pathway. Besides, natural products exhibit shared mechanisms across different cell types, such as oxidative stress and inflammatory pathway regulation. Importantly, certain natural products exhibit pan-cellular effects, targeting multiple cell types involved in RA pathogenesis. For example, resveratrol acts on a wide range of cell types including FLS, human umbilical vein endothelial cells (HUVECs), T cells, osteoclasts, chondrocytes, macrophages, monocytes, osteoblasts, and neutrophils. Conclusions: Through an in-depth analysis of cellular mechanisms, this work highlights the specific regulatory effects of natural products on key cell types and their extensive influence across cellular networks. By examining C1 [Liao, Yang; Xiao, Xian; Wang, Yiyuan; Lu, Jiayan; Zhang, Jingtao; Zhang, Jiaqi; Liu, Peiyu; Liu, Liang; Pan, Hudan] Guangzhou Univ Chinese Med, Clin Med Coll 2, Guangzhou 510405, Peoples R China. [Liao, Yang; Xiao, Xian; Wang, Yiyuan; Lu, Jiayan; Zhang, Jingtao; Zhang, Jiaqi; Liu, Peiyu; Liu, Liang; Pan, Hudan] Guangzhou Univ Chinese Med, Affiliated Hosp 2, State Key Lab Tradit Chinese Med Syndrome, Guangzhou 510006, Peoples R China. [Cheng, Wen] Capital Med Univ, Beijing Hosp Tradit Chinese Med, Beijing 100010, Peoples R China. C3 Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine; Capital Medical University RP Liu, L; Pan, HD (corresponding author), Guangzhou Univ Chinese Med, Affiliated Hosp 2, Guangzhou Higher Educ Mega Ctr, State Key Lab Tradit Chinese Med Syndrome, 55 Neihuan West Rd, Guangzhou 510006, Peoples R China. EM lliu@gzucm.edu.cn; hdpan@gzucm.edu.cn RI Zhang, Jiaqi/PNG-1210-2026; Liu, peiyu/AAE-3641-2021; Pan, Hudan/KDO-1834-2024 OI Pan, Hudan/0000-0002-7287-9718 FU Young Scientist Program of National Key Research and Development Program of Ministry of Science and Technology of China [2023YFC3504700] FX This work was supported by the Young Scientist Program of National Key Research and Development Program of Ministry of Science and Technology of China (2023YFC3504700) . 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& Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 4GL0S UT WOS:001517422100005 PM 40541126 DA 2026-03-26 ER PT J AU Ran, JY Ai, YL Ni, JX Zhang, YH Chen, J Wang, TY Ma, J Zheng, JJ Li, RL Ma, X Wen, YQ Zeng, JH AF Ran, Jiayu Ai, Yanling Ni, Jingxin Zhang, Yuanhao Chen, Jie Wang, Tingyao Ma, Jia Zheng, Jijun Li, Ruilin Ma, Xiao Wen, Yueqiang Zeng, Jinhao TI Astragaloside IV: A Promising Drug to Prevent the Transition from Colitis to Colorectal Cancer SO AMERICAN JOURNAL OF CHINESE MEDICINE LA English DT Article DE Astragaloside IV (AS-IV); Inflammatory Bowel Disease (IBD); Colorectal Cancer; The Inflammation-to-Cancer Transition; Natural Products; Phytochemicals ID TUMOR-ASSOCIATED MACROPHAGES; INTESTINAL PERMEABILITY; OXIDATIVE STRESS; CELLS; INFLAMMATION; DISEASE; MICE; PHARMACOKINETICS; TUMORIGENESIS; ACTIVATION AB Colorectal cancer (CRC) remains a major threat to health worldwide, partly due to the lack of effective treatments targeting the transition from inflammatory bowel disease (IBD) to malignancy. Astragaloside IV (AS-IV) is a major bioactive component from the traditional herb Astragalus membranaceus, and it has strong immunomodulatory and gastrointestinal protective effects. In this review, we evaluate the therapeutic potential and mechanisms of AS-IV in addressing the three hallmark pathological phases of colorectal cancer development: IBD-related inflammation, the transition from inflammation to cancer, and IBD-associated colorectal cancer (IBD-CRC). During the inflammatory phase, AS-IV promotes M2 macrophage polarization, reducing mucosal inflammation and repairing the intestinal barrier. In the transition from inflammation to cancer, AS-IV prevents IBD-CRC transition by targeting immune signaling pathways (e.g., NF-kappa B and PPAR gamma signaling pathways), gut microbiota, and oxidative stress. At the IBD-CRC stage, AS-IV can promote the polarization of M1 macrophages, thereby suppressing tumor growth, inducing apoptosis, inhibiting metastasis, and enhancing chemosensitivity. These findings highlight the potential of AS-IV to bidirectionally modulate the M1/M2 macrophage ratio and its role in the prevention and treatment of IBD-CRC. The multi-target therapeutic effects of AS-IV at various stages of IBD also provide new strategies to guide future drug development. C1 [Ran, Jiayu; Ai, Yanling; Ni, Jingxin; Zhang, Yuanhao; Chen, Jie; Wang, Tingyao; Ma, Jia; Zheng, Jijun; Li, Ruilin; Zeng, Jinhao] Hosp Chengdu Univ Tradit Chinese Med, 39 Shi Er Qiao Rd, Chengdu 610072, Sichuan, Peoples R China. [Ran, Jiayu; Ai, Yanling; Ni, Jingxin; Chen, Jie; Zheng, Jijun; Li, Ruilin; Zeng, Jinhao] TCM Regulating Metab Dis Key Lab Sichuan Prov Hosp, Chengdu, Peoples R China. [Ran, Jiayu; Ai, Yanling; Zhang, Yuanhao; Chen, Jie; Wang, Tingyao; Ma, Jia; Zheng, Jijun; Li, Ruilin; Zeng, Jinhao] Chengdu Univ Tradit Chinese Med, Sch Clin Med, Chengdu, Peoples R China. [Ma, Xiao] Chengdu Univ Tradit Chinese Med, Sch Pharm, Chengdu, Peoples R China. [Wen, Yueqiang] Chengdu Univ Tradit Chinese Med, Sch Basic Med, Chengdu, Peoples R China. C3 Chengdu University of Traditional Chinese Medicine; Chengdu University of Traditional Chinese Medicine; Chengdu University of Traditional Chinese Medicine; Chengdu University of Traditional Chinese Medicine RP Zeng, JH (corresponding author), Hosp Chengdu Univ Tradit Chinese Med, 39 Shi Er Qiao Rd, Chengdu 610072, Sichuan, Peoples R China.; Ma, X (corresponding author), Chengdu Univ Tradit Chinese Med, Sch Pharm, Chengdu, Peoples R China.; Wen, YQ (corresponding author), Chengdu Univ Tradit Chinese Med, Sch Basic Med, Chengdu, Peoples R China. EM tobymaxiao@cdutcm.edu.cn; wenyueqiang@cdutcm.edu.cn; zengjinhao@cdutcm.edu.cn RI ; Ni, Jingxin/NRZ-0855-2025; zhang, yuanhao/ODJ-0087-2025; Ma, Xiao/D-9568-2015 OI Zeng, Jinhao/0000-0002-5860-3790; Li, Ruilin/0009-0006-6714-1862; Ni, Jingxin/0009-0004-4781-8835; wang, tingyao/0009-0005-6320-7222; zhang, yuanhao/0009-0001-2822-6912; Ran, Jiayu/0009-0004-4348-7194; Ma, Xiao/0000-0002-0261-0369 FU Program of Science and Technology Department of Sichuan Province [2023NSFSC0039]; Young Elite Scientists Sponsor-ship Program by CACM [2023-QNRC2-A01, 2024-QNRC2-A10] FX This work was supported by the Program of Science and Technology Department of Sichuan Province (Grant No. 2023NSFSC0039) and the Young Elite Scientists Sponsor-ship Program by CACM [CACM-(2023-QNRC2-A01)] and [CACM-(2024-QNRC2-A10)]. We thank Bullet Edits Limited for the linguistic editing and proofreading of the manuscript. 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PY 2025 VL 53 IS 04 BP 1065 EP 1091 DI 10.1142/S0192415X25500405 EA JUN 2025 PG 27 WC Integrative & Complementary Medicine; Medicine, General & Internal WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine; General & Internal Medicine GA 4IK7N UT WOS:001510549100001 PM 40530759 DA 2026-03-26 ER PT J AU Ding, SP Huang, CX Gao, JH Bi, C Zhou, YY Cai, ZH AF Ding, Shoupeng Huang, Chunxiao Gao, Jinghua Bi, Chun Zhou, Yuyang Cai, Zihan TI Exploring T-cell metabolism in tuberculosis: development of a diagnostic model using metabolic genes SO EUROPEAN JOURNAL OF MEDICAL RESEARCH LA English DT Article DE Tuberculosis; T-cell metabolism; Machine learning biomarkers; Metabolic gene signatures; Molecular subtypes ID MANNOSIDASE MAN1A1; N-GLYCOSYLATION; EXPRESSION; INFECTION AB Objectives The early diagnosis and immunoregulatory mechanisms of active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remain unclear, and the role of metabolic genes in host-pathogen interactions requires further investigation. Methods Single-cell RNA sequencing (scRNA-seq) was applied to analyze peripheral blood mononuclear cells (PBMCs) from 7 individuals, including 2 healthy controls (HC), 2 LTBI patients, and 3 ATB patients. We identified T-cell-associated metabolic differentially expressed genes (TCM-DEGs) through integrated differential expression analysis and machine learning algorithms (XGBoost, SVM-RFE, and Boruta). These TCM-DEGs were then used to construct a diagnostic model and evaluate its clinical applicability. Results The analysis revealed significant immunological alterations in TB patients, characterized by markedly elevated monocyte/macrophage populations (p < 0.001) accompanied by reduced T and NK cell counts. Notably, LTBI cases demonstrated an intermediate CD4+/CD8+ T-cell ratio, indicative of dynamic immune homeostasis. The TB cohort exhibited increased inflammatory T-cell populations, while CD8+ T-cell-mediated MHC-I and BTLA signaling pathways were identified as key regulators of immune clearance and modulation. Transcriptomic profiling identified five metabolically significant differentially expressed genes (FHIT, MAN1C1, SLC4C7, NT5E, AKR1C3; p < 0.05) that effectively distinguish between latent tuberculosis infection (LTBI) and active tuberculosis (TB). The machine learning-driven diagnostic framework demonstrated remarkable consistency across independent validation cohorts (GSE39940, GSE39939), exhibiting AUC values spanning 0.867-0.873. Molecular subtyping analysis delineated two distinct TB phenotypes: an immune-activated M1 macrophage-dominant subtype and a CD8 + T-cell infiltrated immunophenotype. Clinical validation substantiated the differential expression patterns of T-cell-related metabolic differentially expressed genes (TCM-DEGs; p < 0.05), while the nomogram predictive model achieved exceptional discriminative capacity (C-index = 0.944), demonstrating superior clinical applicability through decision curve analysis. Conclusions Our findings reveal that TCM-DEGs critically regulate TB progression through immune-metabolic reprogramming and cell-cell communication networks. The developed diagnostic model and molecular subtyping strategy enable precise TB-LTBI differentiation and inform immunotherapy optimization. C1 [Ding, Shoupeng; Huang, Chunxiao] Gutian Cty Hosp, Dept Lab Med, Gutian 352200, Peoples R China. [Zhou, Yuyang; Cai, Zihan] Siyang Hosp, Dept Med Lab, Siyang 237000, Peoples R China. [Bi, Chun; Zhou, Yuyang; Cai, Zihan] Siyang Hosp, Oncol & Lab Immunol Res Innovat Ctr, Siyang 237000, Peoples R China. [Gao, Jinghua] Peoples Hosp Chuxiong Yi Autonomous Prefecture, Ctr Precis Med, Chuxiong 675000, Peoples R China. RP Cai, ZH (corresponding author), Siyang Hosp, Dept Med Lab, Siyang 237000, Peoples R China.; Cai, ZH (corresponding author), Siyang Hosp, Oncol & Lab Immunol Res Innovat Ctr, Siyang 237000, Peoples R China. EM zihancai001@163.com RI cai, zihan/GWU-7100-2022; Huang, Changqin/AAD-4590-2020 FU Siyang Hospital and the Affiliated Hospital of Jiangsu University in the first session of the hospital science and technology programmed projects to set up the topic FX Not applicable. 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PD JUN 16 PY 2025 VL 30 IS 1 AR 483 DI 10.1186/s40001-025-02768-0 PG 24 WC Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine GA 3VO0N UT WOS:001510029000002 PM 40524207 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Mo, L Wang, Y Liang, XY Zou, T Chen, Y Tan, JY Wen, J Jian, XH AF Mo, Li Wang, Yuan Liang, Xin-Yue Zou, Tao Chen, Yan Tan, Jin-Yu Wen, Jie Jian, Xiao-Hong TI Progress of traditional Chinese medicine in the prevention and treatment of colorectal cancer SO WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY LA English DT Review DE Colorectal cancer; Traditional Chinese medicine; Acupuncture; Prescriptions; Anti-tumor mechanism ID PHARMACOLOGY-BASED PREDICTION; M2 MACROPHAGE POLARIZATION; NETWORK PHARMACOLOGY; GUT MICROBIOTA; POSTOPERATIVE ILEUS; IN-VIVO; ELECTROACUPUNCTURE; RESECTION; MECHANISM; EFFICACY AB Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide, ranking among the highest in both incidence and mortality rates. Traditional Chinese medicine, with a history spanning thousands of years, has demonstrated unique efficacy and advantages in the prevention and treatment of CRC, playing a pivotal role at all levels of China's healthcare system. This article provides a comprehensive analysis and summary of traditional Chinese medicine's contributions to CRC prevention, antitumor therapy, palliative care for advanced tumors, perioperative rehabilitation, and postoperative functional recovery. C1 [Mo, Li; Wang, Yuan; Liang, Xin-Yue; Zou, Tao; Tan, Jin-Yu] Hunan Univ Chinese Med, Affiliated Hosp 2, Dept Proctol, Changsha 410010, Hunan, Peoples R China. [Chen, Yan] Changsha Med Univ, Changsha 410219, Hunan, Peoples R China. [Wen, Jie] Hunan Normal Univ, Hunan Prov Peoples Hosp, Affiliated Hosp 1, Dept Pediat Orthoped, 61 Jiefang West Rd, Changsha 410013, Hunan, Peoples R China. [Jian, Xiao-Hong] Hunan Normal Univ, Sch Med, Dept Anat, Changsha 410005, Hunan, Peoples R China. C3 Hunan University of Chinese Medicine; Changsha Medical University; Hunan Normal University; Hunan Normal University RP Wen, J (corresponding author), Hunan Normal Univ, Hunan Prov Peoples Hosp, Affiliated Hosp 1, Dept Pediat Orthoped, 61 Jiefang West Rd, Changsha 410013, Hunan, Peoples R China. EM cashwj@qq.com RI Liang, Xinyue/ABE-6501-2021 FU Hunan Provincial Natural Science Foundation [2025JJ90028]; Changsha Natural Science Foundation Project [kq2502190] FX Supported by Hunan Provincial Natural Science Foundation, No. 2025JJ90028; and Changsha Natural Science Foundation Project, No. kq2502190. 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PD JUN 15 PY 2025 VL 17 IS 6 AR 105690 DI 10.4251/wjgo.v17.i6.105690 PG 25 WC Oncology; Gastroenterology & Hepatology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Gastroenterology & Hepatology GA 3VN7H UT WOS:001510020600005 PM 40547140 OA Green Accepted, gold DA 2026-03-26 ER PT J AU Ye, YM Xie, MF Nie, HY Zhang, GS Tu, LX Ao, MY Liang, XL Yang, C Huang, XT Mei, ZC Xie, YF Liu, Q AF Ye, Yumeng Xie, Mingfeng Nie, Heyun Zhang, Guosong Tu, Liangxin Ao, Meiying Liang, Xinli Yang, Chao Huang, Xuetao Mei, Zicheng Xie, Yanfei Liu, Qian TI Investigation of the effect and mechanism of Fei Re Pu Qing powder in treating acute lung injury (ALI) by modulating macrophage polarization via serum pharmacology and network pharmacology SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Acute lung injury; Fei Re Pu qing powder; UHPLC-Q exactive HFX; Network pharmacology; Macrophage polarization; NF-kappa B/p65 AB Ethnopharmacological relevance: Acute lung injury (ALI) is a clinical critical illness characterized by progressive pulmonary inflammatory response and high mortality. An increasing number of studies have confirmed that traditional Chinese medicine (TCM) and compound prescriptions hold considerable promise in the prevention and treatment of respiratory inflammatory diseases. Fei Re Pu Qing Powder (FRPQ) is an efficacious prescription used in clinical treatment of pneumonia in Tibet, China. Its potential effects and mechanisms on ALI are worthy of further study. Aim of the study: This study aims to characterize the bioactive constituents of FRPQ and elucidate its potential target sites and underlying mechanisms of action in ALI. Materials and methods: Firstly, the pharmacodynamic effects of FRPQ were assessed using an LPS-induced rat model of ALI. Subsequently, the optimal pharmacodynamic dose was determined for a time-course study to evaluate the onset and duration of FRPQ's pharmacological actions. Based on the identification of potential active components in FRPQ-containing serum using UHPLC-Q Exactive HFX, core components, key targets, and signaling pathways were systematically screened via network pharmacology approaches. Subsequently, molecular docking analysis was performed on the identified core components and key targets to validate their binding activity and affinity. Finally, the potential mechanism underlying its effect on ALI was further verified using the ALI rat model and the M1/M2 polarization model of NR8383 cells. Results: FRPQ exerts rapid and long-lasting effects on ALI rats. 63 prototype components of FRPQ were identified in the drug-containing serum, among which 25 have potential activity. An active components-intersection targets-ALI network was constructed, and 6 core components (Kaempferol, Piperine, Phloretin, etc.) were selected. PPI analysis identified 9 targets closely related to the therapeutic effect of ALI. GO/KEGG analysis indicated that FRPQ treatment of ALI is closely related to multiple inflammatory signaling pathways. Molecular docking showed that the binding energy of the 6 core components with the 9 core targets was <=-5.4 kcal/mol, indicating strong binding affinity. In vivo experiments showed that FRPQ could significantly reduce macrophage infiltration in the lung tissue of ALI rats, effectively down-regulate the expression of NF-kappa B/p65 protein, and the changes in the transcriptional levels of inflammatory mediators in lung tissue and the content of inflammatory factors in alveolar lavage fluid further verified the regulatory effect of FRPQ on the NF-kappa B signaling pathway. In vitro experiments showed that the drug-containing serum significantly inhibited the polarization of NR833 cells to the M1 phenotype and promoted their polarization to the M2 phenotype. The inhibition of M1 polarization may be achieved through negative regulation of the NF-kappa B signaling pathway, providing potential mechanism support for the treatment of ALI. C1 [Ye, Yumeng; Xie, Mingfeng; Nie, Heyun; Ao, Meiying; Yang, Chao; Huang, Xuetao; Liu, Qian] Jiangxi Univ Chinese Med, Integrated Chinese & Western Med Inst Children Hlt, Nanchang, Jiangxi, Peoples R China. [Zhang, Guosong; Tu, Liangxin; Liang, Xinli] Jiangxi Univ Chinese Med, Sch Pharm, Nanchang, Jiangxi, Peoples R China. [Mei, Zicheng; Xie, Yanfei] Jiangxi Univ Chinese Med, Translat Med Ctr, Nanchang, Jiangxi, Peoples R China. C3 Jiangxi University of Traditional Chinese Medicine; Jiangxi University of Traditional Chinese Medicine; Jiangxi University of Traditional Chinese Medicine RP Liu, Q (corresponding author), Jiangxi Univ Chinese Med, Integrated Chinese & Western Med Inst Children Hlt, Nanchang, Jiangxi, Peoples R China.; Xie, YF (corresponding author), Jiangxi Univ Chinese Med, Translat Med Ctr, Nanchang, Jiangxi, Peoples R China. EM 1047501830@qq.com; 20211008@jxutcm.edu.cn FU Jiangxi Provincial Department of Education Science and Technology Project [GJJ2400838]; National Key Laboratories Projects of Key Research and Development Independently Deployed [20243BCC31008]; Jiangxi Provincial Natural Science Foundation [20212BAB206008]; Key Discipline Construction Fund of Jiangxi University of Chinese Medicine [2024jzzdxk003]; Top Discipline of Jiangxi Province and Discipline of Chinese and Western Integrative Medicine, Jiangxi University of Chi-nese Medicine [ZXYYLXK20220103] FX This work was supported by the Jiangxi Provincial Department of Education Science and Technology Project (GJJ2400838) ; National Key Laboratories Projects of Key Research and Development Independently Deployed (20243BCC31008) ; the Jiangxi Provincial Natural Science Foundation (20212BAB206008) ; Project Supported by Key Discipline Construction Fund of Jiangxi University of Chinese Medicine (2024jzzdxk003) ; Top Discipline of Jiangxi Province and Discipline of Chinese and Western Integrative Medicine, Jiangxi University of Chinese Medicine (ZXYYLXK20220103) . 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PD JUL 24 PY 2025 VL 351 AR 120089 DI 10.1016/j.jep.2025.120089 EA JUN 2025 PG 21 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 3XD6G UT WOS:001511118700006 PM 40499803 DA 2026-03-26 ER PT J AU Zheng, GZ Xie, J Yan, ZM Zhu, Y Zhu, HN Zhang, YH Li, H Yan, RX Wang, YP Shi, YY Cheng, ZY Li, HL Liang, J Yong, H Xiong, QP AF Zheng, Guangzhen Xie, Juan Yan, Zhimin Zhu, Yong Zhu, Haonan Zhang, Yuhan Li, Heng Yan, Ruixue Wang, Yunpeng Shi, Yingying Cheng, Zhaoyan Li, Hailun Liang, Jian Yong, Hui Xiong, Qingping TI Uncovering the mechanism of Buyang Huanwu Decoction in regulating mitochondrial dysfunction to alleviate atherosclerosis: BTK, PREPL, and P2RX7 proteins play key roles SO INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES LA English DT Article DE Buyang Huanwu decoction; Atherosclerosis; Core protein pathway mechanism ID MACROPHAGE POLARIZATION; ASTRAGALUS-MEMBRANACEUS; METABOLISM; RECEPTOR; SUBSETS; CANCER AB The purpose of this study was to uncover key target proteins and corresponding active ingredients of Buxue Huanwu Decoction (BYHWD) on improving mitochondrial function to alleviate atherosclerosis (AS) via construction of a novel strategy based on in silico virtual screening, UHPLC-Q-TOF-MS/MS, and experimental verification. Firstly, 57 compounds of BYHWD were identified using UHPLC-Q-TOF-MS/MS technology, followed by the selection of 13 candidate compounds using Druggability predictions. Subsequently, a combination of differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA), and machine learning methods were employed to identify three hub genes associated with mitochondrial function and AS, including BTK, P2RX7 and PREPL. Meanwhile, batch molecular docking and molecular dynamics simulations were conducted to evaluate the interactions between the candidate compounds and the hub genes. The results demonstrated that 9 compounds in BYHWD, including Methylnissolin, Isomucronulatol, and others, exhibited strong binding affinities with these genes. Finally, in vivo and in vitro experiments confirmed that BYHWD could improve mitochondrial function by upregulating PREPL and downregulating BTK and P2RX7, thereby alleviating AS. Furthermore, the 9 compounds in BYHWD that formed stable interactions with the hub genes, such as Methylnissolin, Isomucronulatol, and others, may play a crucial role in this process. C1 [Zheng, Guangzhen; Zhu, Yong; Zhang, Yuhan; Li, Heng; Yan, Ruixue; Wang, Yunpeng; Shi, Yingying; Xiong, Qingping] Huaiyin Inst Technol, Jiangsu Key Lab Reg Specif Resource Pharmaceut Tra, Huaian 223003, Jiangsu, Peoples R China. [Zheng, Guangzhen; Liang, Jian] Guangzhou Univ Chinese Med, Sch Pharmaceut Sci, State Key Lab Tradit Chinese Med Syndrome, Guangzhou 510006, Guangdong, Peoples R China. [Xie, Juan; Li, Hailun] Xuzhou Med Univ, Affiliated Huaian Hosp, Dept Nephrol, Huaian 223002, Jiangsu, Peoples R China. [Cheng, Zhaoyan] Jiangsu Food & Pharmaceut Sci Coll, Sch Pharm, Huaian 223003, Peoples R China. [Yong, Hui] Yangzhou Univ, Huaian Hosp, Peoples Hosp Huaian 5, Dept Cardiol, Huaian 223000, Jiangsu, Peoples R China. [Yan, Zhimin] Nanjing Univ Tradit Chinese Med, Huaian Hosp Tradit Chinese Med, Affiliated Hosp, Dept Pharm, Huaian 223002, Jiangsu, Peoples R China. [Zhu, Haonan] Northeast Forestry Univ, Coll Life Sci, Harbin 150040, Heilongjiang, Peoples R China. C3 Huaian University; Guangzhou University of Chinese Medicine; Xuzhou Medical University; Jiangsu Food & Pharmaceutical Science College; Yangzhou University; Nanjing University of Chinese Medicine; Northeast Forestry University - China RP Xiong, QP (corresponding author), Huaiyin Inst Technol, Jiangsu Key Lab Reg Specif Resource Pharmaceut Tra, Huaian 223003, Jiangsu, Peoples R China.; Liang, J (corresponding author), Guangzhou Univ Chinese Med, Sch Pharmaceut Sci, State Key Lab Tradit Chinese Med Syndrome, Guangzhou 510006, Guangdong, Peoples R China.; Li, HL (corresponding author), Xuzhou Med Univ, Affiliated Huaian Hosp, Dept Nephrol, Huaian 223002, Jiangsu, Peoples R China.; Yong, H (corresponding author), Yangzhou Univ, Huaian Hosp, Peoples Hosp Huaian 5, Dept Cardiol, Huaian 223000, Jiangsu, Peoples R China. EM lihailun101@sina.com; ljyyq@gzucm.edu.cn; HAWYyonghui@163.com; qpxiong@gmail.com RI shi, yingying/E-1112-2015; Zhu, Haonan/GXD-8065-2022; LI, HAILUN/PDW-0878-2025; Zhang, Yan/G-7208-2016 FU Huai'an City Science and Technology Program Project of Jiangsu Province of China [2023B724]; Postgraduate Research & Practice Innovation Program of Jiangsu Province of China [HAB202211]; Huai'an Health Research Project of Jiangsu Province of China [SJCX24_2135]; [HAWJ2024033] FX This work was partly supported by the National Natural Science Foundation of China (No. 82474116 and No. 82474176) , Key Research and Development Program (Social Development) Project of Jiangsu Province of China (No. BE2023746) , Project of Science and Technology Development of Traditional Chinese Medicine in Jiangsu Province of China (No. MS2022157 and No. MS2022156) , China Postdoctoral Science Foundation (No. 2023M740019) , Anhui Province Postdoctoral Research Personnel Research Activity Funding Project of China (No.2023B724) , Huai'an City Science and Technology Program Project of Jiangsu Province of China (No. HAB202211) , Postgraduate Research & Practice Innovation Program of Jiangsu Province of China (NO. SJCX24_2135) , Huai'an Health Research Project of Jiangsu Province of China (NO. HAWJ2024033) . 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PD JUL PY 2025 VL 318 AR 145011 DI 10.1016/j.ijbiomac.2025.145011 EA JUN 2025 PN 2 PG 28 WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 3XW5Z UT WOS:001511614300003 PM 40494461 DA 2026-03-26 ER PT J AU Guo, YX Lin, XC Wang, PH Wang, YY Chen, MY Tang, SY Jin, L Mao, WY Liu, X Shou, QY Fu, HY AF Guo, Yingxue Lin, Xiaochen Wang, Penghao Wang, Yingying Chen, Mengyun Tang, Shuiyan Jin, Lu Mao, Weiye Liu, Xia Shou, Qiyang Fu, Huiying TI Smilax china L. Rhizome extract enhances anti-tumor immune responses by resetting M2-like macrophages and tumor-associated macrophages to M1-like via ERK1/2 signaling SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Smilax china L.; Tumor-associated macrophage; Breast cancer; Tumor microenvironment; ERK1/2 signaling pathway ID CANCER; APOPTOSIS AB Ethnopharmacological relevance: Smilax china L. is a traditional Chinese herb. Smilax china L. Rhizome (SCR) have historically been used in ethnomedicine for their anti-inflammatory, anti-tumor, and immunomodulatory properties. Aim of the study: This study aimed to evaluate the anti-tumor efficacy of SCR in the MMTV-PyMT mouse mammary tumor model and elucidate its immunomodulatory mechanisms within the tumor microenvironment (TME). Materials and methods: SCR was administered to MMTV-PyMT mice to assess its effects on tumor progression and metastasis. Immune cell profiling (M1/M2-like macrophages, CD8+ T cells) was conducted via flow cytometry. In vitro macrophage polarization assays under IL-4 stimulation and mechanistic studies (MAPK/ERK signaling) were performed using Western blot and pharmacological inhibitors. Diosgenin, a key SCR constituent, was identified and validated through phytochemical analysis and functional assays. Results: SCR treatment significantly slowed primary tumor growth and reduced lung metastases. SCR induces a shift in macrophage polarization from immunosuppressive M2-like to proinflammatory M1-like and promotes increased CD8+ T cell infiltration. In vitro, SCR inhibited IL-4-induced M2 polarization and suppressed ERK1/2 phosphorylation, a critical node in the MAPK pathway. Diosgenin was identified as a pivotal bioactive compound contributing to SCR's anti-tumor and immunomodulatory effects. Conclusions: These findings provide a theoretical basis for the potential clinical application of SCR in cancer treatment, highlighting its critical role in remodeling the tumor immune microenvironment. C1 [Guo, Yingxue; Jin, Lu; Liu, Xia; Shou, Qiyang; Fu, Huiying] Zhejiang Chinese Med Univ, Clin Med Coll 2, Jinhua Acad, Hangzhou 310053, Zhejiang, Peoples R China. [Wang, Penghao; Wang, Yingying; Chen, Mengyun; Mao, Weiye; Shou, Qiyang] Zhejiang Chinese Med Univ, Zhezhong Lab, Jinhua 310053, Zhejiang, Peoples R China. [Lin, Xiaochen; Wang, Penghao; Wang, Yingying; Chen, Mengyun; Tang, Shuiyan] Zhejiang Chinese Med Univ, Sch Pharmaceut Sci, Hangzhou 311402, Peoples R China. C3 Zhejiang Chinese Medical University; Zhejiang Chinese Medical University RP Shou, QY; Fu, HY (corresponding author), Zhejiang Chinese Med Univ, Clin Med Coll 2, Jinhua Acad, Hangzhou 310053, Zhejiang, Peoples R China.; Fu, HY (corresponding author), Zhejiang Chinese Med Univ, Jinhua Acad, Zhezhong Lab, Jinhua 310053, Zhejiang, Peoples R China. EM tcmzcmu2019@163.com; fhy131@126.com RI fu, huiying/GZG-2399-2022; Lin, Xiaochen/P-6460-2015; Wang, Yingying/A-4694-2011 FU National Natural Science Foundation of China [82274175, 82474168, 82174026]; Natural Science Foundation of Zhejiang Province [LY22H280012, LY23H280009]; Zhejiang Provincial Administration of Traditional Chinese Medicine Co-construction Key Project [GZY-ZJ-KJ-23069]; Zhejiang Province Traditional Chinese Medicine Science and Technology Project [2022ZA084]; Zhejiang Chinese Medical University Institutional Research Project: Affiliated Hospital Research Special Fund [2023FSYYZZ06]; Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talent FX This research was sponsored by the National Natural Science Foundation of China (Grant 82274175 and 82474168 to Q.Y.S., Grant 82174026 to H.Y.F.) , the Natural Science Foundation of Zhejiang Province (Grant LY22H280012 to H.Y.F. and LY23H280009 to X.L.) , Zhejiang Provincial Administration of Traditional Chinese Medicine Co-construction Key Project (Grant GZY-ZJ-KJ-23069 to Q.Y.S.) , Zhejiang Province Traditional Chinese Medicine Science and Technology Project (Grant 2022ZA084 to X.L) , Zhejiang Chinese Medical University Institutional Research Project: Affiliated Hospital Research Special Fund (Grant 2023FSYYZZ06 to X.L.) and Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talent. 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Ethnopharmacol. PD JUN 12 PY 2025 VL 349 AR 119983 DI 10.1016/j.jep.2025.119983 EA JUN 2025 PG 15 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 3JM8D UT WOS:001501839500010 PM 40383248 DA 2026-03-26 ER PT J AU Liu, YQ Song, LY Chen, SY Li, JJ Peng, XH Sun, JH Tian, Y Huang, CG Gong, LK Chen, J AF Liu, Yongqi Song, Luyao Chen, Shiyi Li, Jiajia Peng, Xionghua Sun, Jianhua Tian, Ying Huang, Chenggang Gong, Li-kun Chen, Jing TI Qingfeiyin decoction in idiopathic pulmonary fibrosis: Lung-targeted components and PI3K-AKT modulation SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Idiopathic pulmonary fibrosis; Qingfeiyin; Baicalin; Oroxylin a; Network pharmacology; Molecular docking; Molecular dynamic simulation ID TRADITIONAL CHINESE MEDICINE; NETWORK PHARMACOLOGY; RESPONSES AB Ethnopharmacological relevance: Qingfeiyin decoction (QFY), a well-documented traditional Chinese medicine formula, is used to treat a variety of lung diseases. However, the effect of QFY on idiopathic pulmonary fibrosis (IPF) is still unclear. Aim of the study: This study aimed to investigate the effect of QFY on IPF, identify its bioactive components, and reveal the possible mechanism. Materials and methods: A bleomycin-induced pulmonary fibrosis mouse model was established to evaluate the anti-IPF effects of QFY. The bioactive ingredients in QFY were identified by HPLC-MS, following which their in vitro effects were examined by the cell models of epithelial-to-mesenchymal transition, fibroblast-tomyofibroblast transition and macrophage polarization. Network pharmacology and clinical dataset (GSE110147) were integrated to predict the possible mechanism of the bioactive ingredients, which were verified by in vitro experiments, molecular docking and molecular dynamics simulation. Results: QFY demonstrated dose-dependent amelioration of IPF pathological phenotypes. Oroxylin A (OA), Geniposide (GDS), Baicalin (BCL), and Genipin-1-gentiobioside (GG) were identified with significant lung tissue enrichment, where OA and BCL exhibited obvious improvement in EMT, FMT, and macrophage polarization experiments. Network pharmacology and bioinformatics analyses revealed the association of OA/GDS/BCL/GG with the PI3K-AKT signaling pathway, which were confirmed by their effects on the migration and apoptosis of A549 and HFL1 cells. Concurrently, molecular docking and molecular dynamics simulations demonstrated strong binding affinities of BCL and OA for p110 alpha and p110 gamma subunits of PI3K. Conclusions: Our work demonstrates the potential of QFY in the treatment of IPF, which might due to the bioactive ingredients in the lung affecting the PI3K signaling pathway. C1 [Liu, Yongqi; Gong, Li-kun] Southern Med Univ, Sch Pharmaceut Sci, Guangzhou 510515, Peoples R China. [Liu, Yongqi; Sun, Jianhua; Tian, Ying; Gong, Li-kun] Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China. [Song, Luyao; Chen, Shiyi; Li, Jiajia; Peng, Xionghua; Sun, Jianhua; Huang, Chenggang; Gong, Li-kun; Chen, Jing] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China. C3 Southern Medical University - China; Chinese Academy of Sciences; Shanghai Institute of Materia Medica, CAS; Chinese Academy of Sciences; Shanghai Institute of Materia Medica, CAS RP Huang, CG; Gong, LK; Chen, J (corresponding author), Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China.; Huang, CG (corresponding author), Chinese Acad Sci, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China. EM cghuang@simm.ac.cn; lkgong@simm.ac.cn; jingchen@simm.ac.cn FU Shanghai Committee of Science and Technology, China [21S21901800] FX Funding This work is supported by the Shanghai Committee of Science and Technology, China (Grant No: 21S21901800) . 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Ethnopharmacol. PD JUL 24 PY 2025 VL 351 AR 120071 DI 10.1016/j.jep.2025.120071 EA JUN 2025 PG 14 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 3UI0I UT WOS:001509191800004 PM 40451494 DA 2026-03-26 ER PT J AU Yin, XJ Sun, XH Li, AX Ruan, JZ Niu, HX Zhou, Y Chen, G Guo, JB He, QY Ji, XM AF Yin, Xiangjun Sun, Xiaohui Li, Aoxiang Ruan, Jiazhao Niu, Hongxia Zhou, Yuan Chen, Guang Guo, Jianbo He, Qingyong Ji, Xuming TI Wenxia Changfu formula inhibits Lewis lung cancer metastasis by reprogramming tumor-associated macrophages through the PPAR-γ/CD36 pathway SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Wenxia Changfu formula; Lung cancer; Metastasis; Tumor-associated macrophage; Metabolism ID METABOLISM AB Ethnopharmacological relevance: Wenxia Changfu formula (WCF), a traditional Chinese herbal medicine, has shown therapeutic potential for treating lung cancer in clinical practice. Metastasis is the main cause of mortality in lung cancer patients, reprogramming tumor-associated macrophages (TAMs) represents a promising strategy. Aim of this study: This study aims to investigate the effects of WCF on metastasis of Lewis lung cancer (LLC) cells and to elucidate the underlying mechanisms. Methods: RAW264.7 cells were differentiated into M2 macrophages, and conditioned medium from macrophages with different interventions was used to culture LLC cells. The effects of WCF on tumor migration and invasion were evaluated. Specific markers of macrophage polarization, non-targeted metabolomics, lipid content, and the PPAR-gamma/CD36 pathway in macrophages were analyzed. To investigate the in vivo effects of WCF on metastasis, a mouse model was established using LLC-luciferase (LLC-Luc) cells, macrophages were depleted upon clodronate liposome administration. Results: WCF effectively inhibited M2-like polarization of macrophages, as evidenced by reduced expression of CD206 and Arg-1, while promoting M1-like polarization, with increased expression of CD86, IL-1 beta, and TNF-alpha. These changes were correlated with decreased migration and invasion of LLC cells. In vivo, WCF treatment significantly decreased the fluorescence intensity of LLC-Luc cells, with no significant difference observed between WCF and clodronate liposome interventions. Furthermore, WCF regulated fatty acid metabolism, decreased lipid accumulation, and suppressed the PPAR-gamma/CD36 pathway in M2 macrophages. Conclusion: WCF inhibits the metastasis of LLC cells by reprogramming TAMs, mediated by the PPAR-gamma/CD36 pathway and fatty acid metabolism. C1 [Yin, Xiangjun; Li, Aoxiang; Ruan, Jiazhao; Niu, Hongxia; Zhou, Yuan; Ji, Xuming] Zhejiang Chinese Med Univ, Sch Basic Med Sci, Hangzhou 310053, Zhejiang, Peoples R China. [He, Qingyong] China Acad Chinese Med Sci, Guanganmen Hosp, Dept Cardiol, Beijing 100032, Peoples R China. [Sun, Xiaohui] Zhejiang Chinese Med Univ, Sch Publ Hlth, Hangzhou 310053, Zhejiang, Peoples R China. [Chen, Guang; Guo, Jianbo] Univ Hong Kong, LKS Fac Med, Sch Chinese Med, Hong Kong, Peoples R China. C3 Zhejiang Chinese Medical University; China Academy of Chinese Medical Sciences; Guang'anmen Hospital, CACMS; Zhejiang Chinese Medical University; University of Hong Kong RP Ji, XM (corresponding author), Zhejiang Chinese Med Univ, Sch Basic Med Sci, Hangzhou 310053, Zhejiang, Peoples R China.; He, QY (corresponding author), China Acad Chinese Med Sci, Guanganmen Hosp, Dept Cardiol, Beijing 100032, Peoples R China. EM yinxiangjun2019@zcmu.edu.cn; 20191030@zcmu.edu.cn; lakeryoo@163.com; ruanjz1028@163.com; niuhongxia1985@163.com; zhouy@zcmu.edu.cn; gchen91@hku.hk; gambols@connect.hku.hk; heqingyongg@163.com; jixuming724@163.com RI ; CHEN, GUANG/PGT-9995-2026 OI Guo, Jianbo/0000-0001-6990-6175; FU Natural Science Foun-dation of Zhejiang Province [LQ22H270005, Z24H270005]; Na-tional Natural Science Foundation of China [82405232, 82274406]; Traditional Chinese Medicine Science and Technology Plan Project of Zhejiang Province [2023ZR088]; Foundation of Zhejiang Chi-nese Medical University [2023JKZKTS04] FX This work was supported by grants from the Natural Science Foun-dation of Zhejiang Province (LQ22H270005, Z24H270005) , the Na-tional Natural Science Foundation of China (82405232, 82274406) , Traditional Chinese Medicine Science and Technology Plan Project of Zhejiang Province (2023ZR088) , and the Foundation of Zhejiang Chi-nese Medical University (2023JKZKTS04) . CR Bi QY, 2020, FRONT PHARMACOL, V11, DOI 10.3389/fphar.2020.594744 Bray F, 2024, CA-CANCER J CLIN, V74, P229, DOI 10.3322/caac.21834 Cao Y, 2022, CELL MOL LIFE SCI, V79, DOI 10.1007/s00018-022-04319-w Chen SZ, 2023, SIGNAL TRANSDUCT TAR, V8, DOI 10.1038/s41392-023-01452-1 Gao J, 2022, FRONT IMMUNOL, V13, DOI 10.3389/fimmu.2022.888713 Geiger R, 2016, CELL, V167, P829, DOI 10.1016/j.cell.2016.09.031 Gerstberger S, 2023, CELL, V186, P1564, DOI 10.1016/j.cell.2023.03.003 Guo Z, 2019, CELL DEATH DIS, V10, DOI 10.1038/s41419-019-1618-x Hu J, 2023, NATURE, V616, P806, DOI 10.1038/s41586-023-05880-5 Huang YH, 2022, J HEMATOL ONCOL, V15, DOI 10.1186/s13045-022-01347-8 Leiter A, 2023, NAT REV CLIN ONCOL, V20, P624, DOI 10.1038/s41571-023-00798-3 Li QF, 2022, CLIN TRANSL MED, V12, DOI 10.1002/ctm2.1036 Li XL, 2019, MOL CANCER, V18, DOI 10.1186/s12943-019-1102-3 Li Z, 2023, CANCER SCI, V114, P2306, DOI 10.1111/cas.15760 Liu SQ, 2021, J IMMUNOTHER CANCER, V9, DOI 10.1136/jitc-2021-002548 Lu W, 2019, DEV CELL, V49, P361, DOI 10.1016/j.devcel.2019.04.010 Luo Q, 2020, CANCER SCI, V111, P4000, DOI 10.1111/cas.14616 Massagué J, 2021, CANCER DISCOV, V11, P971, DOI 10.1158/2159-8290.CD-21-0010 Miao YM, 2022, CELL COMMUN SIGNAL, V20, DOI 10.1186/s12964-022-00849-9 Miller KD, 2022, CA-CANCER J CLIN, V72, P409, DOI 10.3322/caac.21731 Niu ZY, 2017, NAT COMMUN, V8, DOI 10.1038/s41467-017-00523-6 Qian YJ, 2024, BIOMARK RES, V12, DOI 10.1186/s40364-023-00549-7 Schabath MB, 2019, CANCER EPIDEM BIOMAR, V28, P1563, DOI 10.1158/1055-9965.EPI-19-0221 Shao N, 2025, J ADV RES, V68, P99, DOI 10.1016/j.jare.2024.02.009 Su P, 2020, CANCER RES, V80, P1438, DOI 10.1158/0008-5472.CAN-19-2994 Taylor EN, 2021, METABOLITES, V11, DOI 10.3390/metabo11110727 Wang YN, 2023, J IMMUNOTHER CANCER, V11, DOI 10.1136/jitc-2023-007253 Wu L, 2020, CANCER IMMUNOL RES, V8, P710, DOI 10.1158/2326-6066.CIR-19-0261 Xia YQ, 2020, ADV MATER, V32, DOI 10.1002/adma.202002054 Xie SM, 2021, BIOMED PHARMACOTHER, V138, DOI 10.1016/j.biopha.2021.111450 Xu M, 2021, FRONT IMMUNOL, V12, DOI 10.3389/fimmu.2021.618501 Yang H, 2024, CURR OPIN IMMUNOL, V91, DOI 10.1016/j.coi.2024.102491 Yang P, 2022, NAT COMMUN, V13, DOI 10.1038/s41467-022-33349-y Yang YX, 2024, METABOLISM, V155, DOI 10.1016/j.metabol.2024.155905 Yin XJ, 2021, EVID-BASED COMPL ALT, V2021, DOI 10.1155/2021/9942462 NR 35 TC 5 Z9 5 U1 5 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-8741 EI 1872-7573 J9 J ETHNOPHARMACOL JI J. Ethnopharmacol. PD JUL 24 PY 2025 VL 351 AR 120103 DI 10.1016/j.jep.2025.120103 EA JUN 2025 PG 16 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 3UI0I UT WOS:001509191800003 PM 40482863 DA 2026-03-26 ER PT J AU Zhou, YW Wang, WB Gu, H Jiang, Y Wang, X Su, X Shao, ZX An, K Liang, R Ma, YZ Wang, R Luo, L AF Zhou, Yinwei Wang, Wenbo Gu, Han Jiang, Ying Wang, Xi Su, Xin Shao, Zhixiang An, Kang Liang, Rui Ma, Yuzhen Wang, Rui Luo, Lin TI Buzhongyiqi granules in ulcerative colitis Therapy: Integrated chemical composition, pharmacodynamic validation, and IL-6/STAT3 axis regulation SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Buzhongyiqi granules; Blood-absorbed components; Ulcerative colitis; IL-6/STAT3 axis; Traditional Chinese medicine ID INFLAMMATION; AUTOIMMUNITY; PATHWAY; BARRIER AB Ethnopharmacological relevance: Buzhongyiqi Granules (BZYQ), a classical herbal formulation derived from Pi Wei Lun, is traditionally used to regulate Qi and blood circulation while enhancing immune function, particularly for gastrointestinal disorders. However, its protective effects and mechanisms on ulcerative colitis (UC) remain unclear. Aim of the study: This study aimed to identify the blood-entering bioactive components of BZYQ and elucidate its immune-modulatory mechanisms in UC using an integrated strategy combining medicinal chemistry, bioinformatics analysis, molecular docking, and experimental validation. Materials and methods: The chemical profile and serum pharmacochemistry components (SPCs) of BZYQ were identified via UPLC-QE-Orbitrap mass spectrometry. Network pharmacology and molecular docking predicted UC-related targets and pathways. In vivo, experimental colitis was induced via 3 % dextran sulfate sodium solution administration for 7 days, followed by 10-day BZYQ treatment. Anti-inflammatory effects were validated through flow cytometry, qPCR, Western blotting, and in vitro bone marrow-derived macrophage (BMDM) cultures. Results: Fifty-four compounds were identified in BZYQ, with seven SPCs (astragaloside IV, licoflavone A, 18 beta glycyrrhizinic acid, glabrolide, ganoderic acid X, complanatuside, and isosakuranin) directly related to UC pathogenesis. Molecular docking confirmed high-affinity interactions between glabrolide and IL-6. BZYQ alleviated colitis by suppressing IL-6/STAT3 axis, reprogramming macrophage polarization, increasing regulatory T cell frequency, and suppressing naive CD4+ T cell differentiation. Conclusions: This study is the first to define BZYQ's component basis and cellular immunological mechanisms in UC alleviation. These findings contribute to the development and application of traditional Chinese medicine prescriptions. C1 [Zhou, Yinwei; Wang, Wenbo; Gu, Han; Jiang, Ying; Wang, Xi; Shao, Zhixiang; An, Kang; Liang, Rui; Ma, Yuzhen; Luo, Lin] Nantong Univ, Sch Pharm, 9 Seyuan Rd, Nantong 226019, Jiangsu, Peoples R China. [Wang, Wenbo] Jiangsu Univ, Affiliated Kunshan Hosp, Dept Pharm, Kunshan 25300, Jiangsu, Peoples R China. [Su, Xin] Tongling Fourth Peoples Hosp, Dept Pharm, Tongling 244000, Anhui, Peoples R China. [Wang, Rui] Dali Univ, Dali 671000, Yunnan, Peoples R China. C3 Nantong University; Jiangsu University; Dali University RP Luo, L (corresponding author), Nantong Univ, Sch Pharm, 9 Seyuan Rd, Nantong 226019, Jiangsu, Peoples R China.; Wang, R (corresponding author), Dali Univ, Dali 671000, Yunnan, Peoples R China. EM 101104@whit.edu.cn; luolin@ntu.edu.cn OI wang, xi/0009-0008-5340-921X FU Science and Technology Project of Nantong [JC2020039]; National Natural Science Foundation of China project [82170544]; Postgraduate Research & Practice Innovation Program of Jiangsu Province [KYCX24_3663] FX This study was supported by Science and Technology Project of Nantong (JC2020039) , National Natural Science Foundation of China project (No. 82170544) and the Postgraduate Research & Practice Innovation Program of Jiangsu Province (No. KYCX24_3663) . 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Ethnopharmacol. PD JUL 24 PY 2025 VL 351 AR 120083 DI 10.1016/j.jep.2025.120083 EA JUN 2025 PG 13 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 3TI4D UT WOS:001508518600001 PM 40466879 DA 2026-03-26 ER PT J AU Gong, YN Tian, XC Ma, XQ Xing, J Ji, ZW Gao, XY Chen, Z Hu, FZ Yin, DD Li, F Sheng, C Liu, YP Shi, SL AF Gong, Yining Tian, Xinchen Ma, Xiaoqing Xing, Jin Ji, Zongwen Gao, Xueying Chen, Zhi Hu, Fangzhi Yin, Dandan Li, Feng Sheng, Can Liu, Yaping Shi, Shulong TI New insights into the pharmacological mechanisms of Jinqi Jiangtang Tablets in the treatment of type 2 diabetes mellitus: A multi-omics approach combined with experimental validation SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Jinqi Jiangtang tablets; Type 2 diabetes mellitus; Multi-omics; Network pharmacology; Metabolomics; Intestinal microbiota ID INSULIN-RESISTANCE; LIVER-FUNCTION; INJURY; CELLS; DEPRESSION; RATS AB Ethnopharmacological relevance: Type 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic disorder characterized by impaired glucose homeostasis and insulin dysfunction. Despite ongoing efforts, the management of T2DM remains challenging due to its complex pathogenesis and the limited effectiveness of current treatments. Jinqi Jiangtang Tablets (JQJTT), a well-established Traditional Chinese Medicine (TCM) formula, have shown promising clinical benefits in regulating blood glucose levels and improving metabolic health in T2DM patients. However, the specific pharmacological mechanisms behind its efficacy are still not fully understood, prompting the need for deeper exploration into its therapeutic actions. Aim of the study: This study aims to elucidate the pharmacologically active ingredients and mechanisms of JQJTT in T2DM using multi-omics methods combined with experimental verification. Materials and methods: Liquid chromatography-mass spectrometry (LC-MS) identified the chemical profile of JQJTT, and targets were screened via SwissTargetPrediction database. T2DM-related targets were acquired from GeneCards and Gene Expression Omnibus (GEO) databases. Therapeutic targets were ascertained by intersecting JQJTT and T2DM targets, followed by Protein-Protein Interaction (PPI) network analysis. GO and KEGG pathway enrichment was performed, and the compound-target-pathway network was built using Cytoscape. Mendelian randomization, single-sample Gene Set Enrichment Analysis (ssGSEA), and CIBERSORT analyses were executed to explore immune cell involvement. Single-cell RNA sequencing (scRNA-seq) identified affected cell types, while molecular docking and molecular dynamics (MD) simulation assessed compound-target affinities. Metabolomics and 16S rDNA sequencing analyzed JQJTT's effects on metabolites and gut microbiota. Results: LC-MS identified 161 compounds in JQJTT. Through network pharmacology, 6 core targets (AKT1, MMP9, HSP90AA1, CASP3, IL-6, PTGS2) were screened, and PI3K/AKT, NF kappa B, and lipid metabolism were pinpointed as key regulatory pathways. Mendelian randomization linked 39 immune cell types to T2DM, while ssGSEA and CIBERSORT suggested JQJTT potentially modulated the proportion of immune cells. scRNA-seq indicated JQJTT may affect macrophage polarization. Tangeritin, isorhamnetin, and kaempferol were determined as the main active compounds with glucose-lowering effects confirmed in vitro. In vivo experiments validated the molecular mechanisms of JQJTT against T2DM. Metabolomics unearthed 56 differentially abundant metabolites, primarily in linoleic acid, arachidonic acid, and pyruvaldehyde metabolisms. JQJTT also improved gut microbiota diversity in T2DM. Conclusion: JQJTT treated T2DM through a multi-target, multi-pathway approach, including attenuating inflammation, reshaping macrophage polarization, enhancing insulin signaling, regulating metabolites, and restoring intestinal flora balance. C1 [Gong, Yining; Xing, Jin; Yin, Dandan] Jining Med Univ, Dept Clin Med, Jining 272067, Peoples R China. [Tian, Xinchen] Jining First Peoples Hosp, Clin Med Lab Ctr, Jining 272000, Peoples R China. [Ma, Xiaoqing; Ji, Zongwen; Gao, Xueying; Chen, Zhi; Hu, Fangzhi; Liu, Yaping; Shi, Shulong] Jining First Peoples Hosp, Dept Endocrinol, Jining 272000, Peoples R China. [Sheng, Can] Jining Med Univ, Dept Neurol, Affiliated Hosp, Jining 272000, Peoples R China. [Shi, Shulong] Cisen Pharmaceut Co Ltd, Jining 272000, Peoples R China. [Shi, Shulong] Shandong Univ, Cheeloo Coll Med, Sch Pharmaceut Sci, Jinan 250012, Peoples R China. C3 Jining Medical University; Jining Medical University; Shandong University RP Liu, YP; Shi, SL (corresponding author), Jining First Peoples Hosp, Dept Endocrinol, Jining 272000, Peoples R China.; Sheng, C (corresponding author), Jining Med Univ, Dept Neurol, Affiliated Hosp, Jining 272000, Peoples R China. EM gongyining0917@163.com; txc0817@126.com; 984654637@qq.com; 13176160715@163.com; 13562412687@163.com; gaoxueying7890@163.com; 1078353126@qq.com; hufangzhikaoyan123@163.com; 15689041145@163.com; canyeweiwu2013@163.com; canyeweiwu2013@163.com; 409972352@163.com; 529306267@qq.com RI Tian, Xinchen/HGA-4308-2022; Gao, Xueying/NXC-0635-2025; Gong, Yining/GZA-9216-2022 OI Tian, Xinchen/0000-0002-7517-3462; FU Traditional Chinese Medicine Science and Technology Development Plan of Shandong Province [Q-2022026]; Shandong Postdoctoral Science Foundation [SDCX-ZG-202302036]; Taishan Scholar Foundation of Shandong Province [tsqn202306401] FX Funding This research was supported by the Traditional Chinese Medicine Science and Technology Development Plan of Shandong Province (Q-2022026) , Shandong Postdoctoral Science Foundation (SDCX-ZG-202302036) , and Taishan Scholar Foundation of Shandong Province (tsqn202306401) . 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PD JUN 26 PY 2025 VL 350 AR 120020 DI 10.1016/j.jep.2025.120020 EA JUN 2025 PG 21 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 3QM1N UT WOS:001506581100001 PM 40449695 DA 2026-03-26 ER PT J AU Xu, J Hu, HK Jiang, HX Wei, QZ Zhang, HL Lu, QY AF Xu, Jie Hu, Haikun Jiang, Haixu Wei, Qiuzhu Zhang, Honglin Lu, Qingyi TI The therapeutic mechanisms of quercetin on inflammatory diseases: an update SO INFLAMMOPHARMACOLOGY LA English DT Review DE Quercetin; Inflammatory diseases; Anti-inflammation; Anti-oxidative stress ID FATTY LIVER-DISEASE; ACUTE LUNG INJURY; OXIDATIVE STRESS; DIABETIC-NEPHROPATHY; INSULIN-RESISTANCE; KAPPA-B; ENDOTHELIAL FUNCTION; CARDIOVASCULAR RISK; PULMONARY-FIBROSIS; INDUCED ARTHRITIS AB Bioactive compounds derived from medicinal plants have become a significant source of drugs for inflammatory diseases treatment, particularly those caused by immune system abnormalities. Quercetin, a flavonol found in a wide variety of herbs, fruits, and vegetables, has garnered attention for its diverse biological properties, including anti-inflammatory, anticancer, and antiviral activities. Numerous in vivo and ex vivo studies have validated quercetin's role in treating inflammatory diseases through multiple pathways, mainly involving anti-oxidative stress, modulation of metabolism, intestinal flora, apoptosis, endoplasmic reticulum stress, and macrophage polarization, indicating it a promising pharmaceutical candidate for managing inflammatory and autoimmune conditions. We aimed to systematically review quercetin's anti-inflammatory activity and the mechanisms of action across various inflammatory diseases in the digestive, respiratory, endocrine, neurological, and osteoarticular systems. By summarizing the therapeutic potential of quercetin in these multifaceted conditions, this review seeks to provide a solid foundation for future clinical research and application strategies involving quercetin. C1 [Xu, Jie; Hu, Haikun; Wei, Qiuzhu; Zhang, Honglin; Lu, Qingyi] Beijing Univ Chinese Med, Sch Life Sci, Beijing 102488, Peoples R China. [Jiang, Haixu] Beijing Univ Chinese Med, Sch Chinese Pharm, Beijing, Peoples R China. C3 Beijing University of Chinese Medicine; Beijing University of Chinese Medicine RP Lu, QY (corresponding author), Beijing Univ Chinese Med, Sch Life Sci, Beijing 102488, Peoples R China. EM lu_qingyi@126.com OI Lu, Qingyi/0000-0003-0738-8725 FU National Natural Science Foundation of China [82205068]; Research Program from Beijing University of Chinese Medicine [2021-JYB-XJSJJ-023, 2023-JYB-JBQN-019] FX This work was supported by the National Natural Science Foundation of China (Grant No. 82205068), and the Research Program from Beijing University of Chinese Medicine (Grant Nos. 2021-JYB-XJSJJ-023 and 2023-JYB-JBQN-019). Cartoons in Fig. 1 were created with BioRender.com. 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Zhu XH, 2018, FOOD CHEM TOXICOL, V114, P52, DOI 10.1016/j.fct.2018.02.019 NR 179 TC 1 Z9 1 U1 9 U2 12 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 0925-4692 EI 1568-5608 J9 INFLAMMOPHARMACOLOGY JI Inflammopharmacology PD JUN PY 2025 VL 33 IS 6 BP 3015 EP 3049 DI 10.1007/s10787-025-01795-x EA MAY 2025 PG 35 WC Immunology; Pharmacology & Pharmacy; Toxicology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy; Toxicology GA 4NZ1V UT WOS:001499198800001 PM 40448820 DA 2026-03-26 ER PT J AU Fang, JF Wu, W He, WF Wang, L Liu, SY AF Fang, Junfeng Wu, Wei He, Weifeng Wang, Lin Liu, Shiyi TI FOS as a biomarker for myocardial infarction treatment with Deng's Yangxin Decoction: a systems biology-based analysis SO FRONTIERS IN CARDIOVASCULAR MEDICINE LA English DT Article DE myocardial infarction; immune infiltration; bioinformatic analysis; single-cell analysis; network pharmacology; diagnostic biomarker ID MACROPHAGE POLARIZATION; C-FOS; EXPRESSION; CELLS; MONOCYTES; APOPTOSIS; AP-1 AB Background Deng's Yangxin Decoction (DYX) is a Chinese herbal formula used in clinical practice to treat patients with myocardial infarction (MI). However, its underlying mechanism remains unclear.Objective This study aims to explore potential biomarkers and associated mechanisms of DYX for MI.Methods Therapeutic targets for DYX were obtained based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Traditional Chinese Medicine Integrated Database, and UniProt databases. Key targets were screened using topological analysis. Differentially expressed genes (DEGs) between MI patients and controls were obtained using open-source datasets. Weighted gene co-expression network analysis (WGCNA) was utilized to screen MI-related genes in the expression array. Hub biomarkers were determined by intersecting DEGs, protein-protein interaction networks, and WGCNA results. Molecular docking validated interactions between DYX components and hub biomarkers. Immune infiltration was assessed via CIBERSORT. Single-cell RNA sequencing analyzed hub biomarker expression in coronary plaques.Results FOS was a core biomarker for DYX for MI. Molecular docking confirmed strong binding affinities between quercetin/baicalein and FOS. In addition, high expression of FOS was associated with immune infiltration of neutrophils, activated mast cells, activated dendritic cells, monocytes, and NK cells. FOS was also found to be expressed at high levels in mast and dendritic cells, monocytes, and some T cells in coronary plaques.Conclusion FOS is a target of DYX for the treatment of MI, and the mechanism of action may be related to the modulation of immune infiltration. C1 [Fang, Junfeng; Wang, Lin; Liu, Shiyi] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Dept Emergency Med, Guangzhou, Peoples R China. [Wu, Wei] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Dept Cardiovasc Med, Guangzhou, Peoples R China. [He, Weifeng] Guangzhou Univ Chinese Med, Clin Med Coll 1, Guangzhou, Peoples R China. C3 Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine RP Liu, SY (corresponding author), Guangzhou Univ Chinese Med, Affiliated Hosp 1, Dept Emergency Med, Guangzhou, Peoples R China. EM 13430256071@163.com FU Young Innovative Talents Project for General Colleges and Universities in Guangdong Province FX This work has benefited from GEO. We thank the GEO network for its generous sharing of large amounts of data. 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PD MAY 30 PY 2025 VL 12 AR 1488684 DI 10.3389/fcvm.2025.1488684 PG 17 WC Cardiac & Cardiovascular Systems WE Science Citation Index Expanded (SCI-EXPANDED) SC Cardiovascular System & Cardiology GA 3RT1Z UT WOS:001507444400001 PM 40520937 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhao, XM Xiao, YF Jiang, M Cao, Y AF Zhao, Xiaomei Xiao, Yangfan Jiang, Miao Cao, Yi TI Pharmacological and toxicological roles of Kruppel-like factors (KLFs) in the cardiovascular system: a review SO MOLECULAR BIOLOGY REPORTS LA English DT Review DE Kruppel-like factors (KLFs); Cardiovascular system; Transcription factors (TFs); Pharmacology; Toxicology ID SMOOTH-MUSCLE-CELLS; ENDOTHELIAL-CELLS; INDUCED CARDIOTOXICITY; PHENOTYPIC MODULATION; TRANSCRIPTION FACTOR; ATHEROSCLEROSIS; PROLIFERATION; FERROPTOSIS; ATTACHMENT; EXPRESSION AB Kruppel-like factors (KLFs) are transcription factors (TFs) increasingly implicated in cardiovascular pharmacology and toxicology through molecular mechanisms regulating endothelial function, macrophage polarization, and lipid metabolism. For example, KLF2/4 maintains endothelial homeostasis by modulating endothelial nitric oxide synthase (eNOS) activity and oxidative stress, and KLF4 additionally regulates smooth muscle cell phenotypic switch. KLF6 governs macrophage polarization and pyroptosis, while KLF15 modulates cardiomyocyte lipid metabolism, with dysregulation linked to cardiomyopathy. Not surprisingly, drugs such as statins and phytochemicals, as well as toxicants like ox-LDL, nanomaterials, and radiation, alter KLF expression via non-coding RNA (such as microRNA) or TFs, influencing endothelial cell activation, vascular smooth muscle cell phenotypic switch, macrophage inflammation, and cardiomyocyte apoptosis. KLF-dependent pathways intersect with key toxicological processes, such as autophagy, ferroptosis, and lipid dysregulation, culminating in atherosclerosis and heart failure. Despite preclinical advances demonstrating KLFs as therapeutic targets, clinical translation remains limited, with no KLF-targeted agents in active trials. Future studies should delineate tissue-specific KLF interactions, resolve KLFs' conflicting roles, and explore CRISPR-based KLF-targeting modulation. Bridging molecular mechanisms, such as KLF's regulation of phenotypic transformation pathways in smooth muscle cells, to drug discovery could yield novel therapies for cardiovascular diseases. The present review underscores the need for mechanistic and translational research to harness KLFs in cardiovascular pharmacotherapy and toxicant risk assessment. C1 [Zhao, Xiaomei; Xiao, Yangfan; Cao, Yi] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China. [Jiang, Miao] Univ South China, Inst Cardiovasc Dis, Hengyang Med Sch, Key Lab Arteriosclerol Hunan Prov,Hunan Int Sci &, Hengyang 421001, Peoples R China. 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GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0301-4851 EI 1573-4978 J9 MOL BIOL REP JI Mol. Biol. Rep. PD MAY 26 PY 2025 VL 52 IS 1 AR 506 DI 10.1007/s11033-025-10613-0 PG 14 WC Biochemistry & Molecular Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology GA 2ZN5W UT WOS:001495045500002 PM 40418318 DA 2026-03-26 ER PT J AU Qi, YF Yan, JN Huang, XX Jiang, XD Li, RR Wan, JY Li, YY Miao, ZM Song, ZY Liu, YQ Zhang, LY Zhang, ZM AF Qi, Yafeng Yan, Jingnan Huang, Xixi Jiang, Xiaodan Li, Rongrong Wan, Jiayi Li, Yangyang Miao, Zhiming Song, Zhongyang Liu, Yongqi Zhang, Liying Zhang, Zhiming TI Targeting tumor-associated macrophage polarization with traditional Chinese medicine active ingredients: Dual reversal of chemoresistance and immunosuppression in tumor microenvironment SO PHARMACOLOGICAL RESEARCH LA English DT Article DE Natural product; Tumor-associated macrophage (TAM); Chemoresistance; Immunosuppression; Therapeutic potential ID PROSTATE-CANCER; RESISTANCE; ANTITUMOR; TUMORIGENESIS; HETEROGENEITY; PROGRESSION; CARCINOMA; CELLS; MODEL AB Chemotherapy resistance and immunosuppression are major causes of tumor treatment failure. The polarization state of tumor-associated macrophages (TAMs) is a central regulatory hub for both processes. Traditional Chinese medicine (TCM) has the characteristics of multi-component, multi-target, and multi-pathway. It regulating M1/ M2 polarization is promising due to the high plasticity of TAMs. This review comprehensively explores the antitumor effects of TCM active components through multiple targets such as metabolic reprogramming. The mechanism includes regulating TAM's polarization, reversing chemotherapy resistance, and modulating immunosuppression. Furthermore, we also summarize the synergistic effects of TCM multi-component and the exploration of mechanisms promoted by new technologies. While most studies are still in the preclinical stage, these insights highlight the potential of TCM as a cancer treatment and highlight avenues for future research and clinical application to improve patient outcomes. C1 [Qi, Yafeng; Yan, Jingnan; Huang, Xixi; Jiang, Xiaodan; Li, Rongrong; Wan, Jiayi; Li, Yangyang; Miao, Zhiming; Song, Zhongyang; Liu, Yongqi; Zhang, Liying] Gansu Univ Chinese Med, Prov Level Key Lab Mol Med Major Dis & Prevent & T, Lanzhou, Peoples R China. [Liu, Yongqi] Gansu Univ Chinese Med, Key Lab Dunhuang Med & Transformat Prov & Minister, Lanzhou, Peoples R China. [Liu, Yongqi; Zhang, Liying] Gansu Univ Chinese Med, Coll Basic Med, Lanzhou, Peoples R China. [Zhang, Zhiming] Gansu Prov Hosp Tradit Chinese Med, Dept Oncol, Lanzhou 730000, Gansu, Peoples R China. C3 Gansu University of Chinese Medicine; Gansu University of Chinese Medicine; Gansu University of Chinese Medicine RP Liu, YQ; Zhang, LY (corresponding author), 35 Dingxi East Rd, Lanzhou 730000, Gansu, Peoples R China.; Zhang, ZM (corresponding author), 418 Guazhou Rd, Lanzhou 730000, Gansu, Peoples R China. EM 13519317645@163.com; liuyongqi73@163.com; zhangliying201212@163.com; zhangzhimingys@163.com RI song, zhongyang/NRX-7308-2025; jiayi, wan/LTF-5657-2024; Qi, Yafeng/LFU-8527-2024 OI Qi, Yafeng/0009-0005-6876-6242 FU Natural Science Foundation of Gansu Province [24JRRA570]; Science and Technology Program of Gansu Province [18JR2FA001]; National Natural Science Foundation of China [81160882] FX This work was supported by the Natural Science Foundation of Gansu Province (Grant No. 24JRRA570) ; The Science and Technology Program of Gansu Province (Grant No. 18JR2FA001) ; National Natural Science Foundation of China (Grant No. 81160882) . 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PD JUN PY 2025 VL 216 AR 107788 DI 10.1016/j.phrs.2025.107788 EA MAY 2025 PG 19 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 3NP1G UT WOS:001504618900001 PM 40414586 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Xiong, BB Zhuo, YM Wang, H Zheng, QL Tang, F Huang, Q Yao, M AF Xiong, Bei-Bei Zhuo, Yu-Mei Wang, Huan Zheng, Qiao-Ling Tang, Feng Huang, Qun Yao, Man TI Macrophage polarization in disease therapy: insights from astragaloside IV and cycloastragenol SO FRONTIERS IN PHARMACOLOGY LA English DT Review DE astragaloside IV; cycloastragenol; macrophage polarization; nano drug delivery; natural products ID TUMOR-ASSOCIATED MACROPHAGES; NF-KAPPA-B; SIGNALING PATHWAY; MOLECULAR-CLONING; EFFICIENT BIOTRANSFORMATION; SUBCHRONIC TOXICITY; GENE-EXPRESSION; UP-REGULATION; ACTIVATION; PHARMACOKINETICS AB Dysregulated activation and polarization of macrophages drive the pathogenesis of diverse diseases, including inflammatory, autoimmune, ischemic, metabolic disorders, and cancers. Despite therapeutic advances, precise regulation of macrophage polarization remains challenging. Natural products have recently emerged as promising therapeutic regulators. Astragaloside IV (AS-IV) and its hydrolysate cycloastragenol (CAG), which are bioactive compounds derived from Astragalus membranaceus, have garnered significant interest due to their notable pharmacological properties encompassing anti-inflammatory, immunomodulatory, and antitumor effects. Nevertheless, the intricate multi-pathway mechanisms through which AS-IV and CAG regulate macrophage polarization are still not fully understood. A systematic review of literature from PubMed, Google Scholar, and SciFinder (2013-2025) shows that AS-IV and CAG modulate macrophage polarization. These compounds target critical signaling pathways, including TLR4/NF-kappa B, PI3K-AKT, AMPK, and PPAR gamma. These compounds exhibit therapeutic potential by suppressing pro-inflammatory M1 phenotypes and promoting anti-inflammatory/reparative M2 phenotypes. Their activities include anti-inflammatory, tissue-regenerative, and antitumor effects, with applications in inflammatory diseases, autoimmune disorders, ischemic vascular pathologies, metabolic syndromes, and cancer therapy. Furthermore, the integration of nanotechnology has emerged as a transformative approach to significantly enhance the bioavailability and targeted delivery of AS-IV and CAG, thereby expanding their clinical applicability. Despite the significant therapeutic potential of AS-IV and CAG in various disease models, their clinical translation remains constrained by low bioavailability. Future advancements that incorporate gene-editing technologies, computer-aided drug design, and nanotechnology are anticipated to optimize their pharmacokinetics and clinical efficacy. These innovations may position AS-IV and CAG as transformative agents in future therapies. C1 [Xiong, Bei-Bei] First Peoples Hosp Shuangliu Dist, Dept Oncol, Chengdu, Peoples R China. [Zhuo, Yu-Mei; Wang, Huan] Chengdu Univ Tradit Chinese Med, Sch Pharm, Chengdu, Peoples R China. [Zheng, Qiao-Ling] First Peoples Hosp Shuangliu Dist, Dept Resp & Crit Care Med, Chengdu, Peoples R China. [Tang, Feng] Sichuan Prov Peoples Hosp, Sichuan Acad Med Sci, Chengdu, Sichuan, Peoples R China. [Huang, Qun] Hosp Chengdu Univ Tradit Chinese Med, Dept Ophthalmol, Chengdu, Peoples R China. [Yao, Man] Chengdu First Peoples Hosp, Dept Ophthalmol, Chengdu, Peoples R China. C3 Chengdu University of Traditional Chinese Medicine; Sichuan Provincial People's Hospital; Chengdu University of Traditional Chinese Medicine RP Yao, M (corresponding author), Chengdu First Peoples Hosp, Dept Ophthalmol, Chengdu, Peoples R China. EM myao202245303@126.com FX The author(s) declare that no financial support was received for the research and/or publication of this article. 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Pharmacol. PD MAY 23 PY 2025 VL 16 AR 1598022 DI 10.3389/fphar.2025.1598022 PG 29 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 3MI0I UT WOS:001503753200001 PM 40487409 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Niknejad, A Esmaealzadeh, N Peyrovinasab, A Sirouskabiri, S Gholami, M Pasha, AVK Shahri, S Büsselberg, D Abdolghaffari, AH AF Niknejad, Amirhossein Esmaealzadeh, Niusha Peyrovinasab, Amirreza Sirouskabiri, Shirin Gholami, Mahsa Pasha, Aytak Vahdat Khajeh Shahri, Saleh Busselberg, Dietrich Abdolghaffari, Amir Hossein TI Phytochemicals Alleviate Tumorigenesis by Regulation of M1/M2 Polarization: A Systematic Review of the Current Evidence SO PHYTOTHERAPY RESEARCH LA English DT Review DE cancer; M1/M2 polarization; macrophage polarization; phytopharmacology; tumor ID P53 TUMOR-SUPPRESSOR; MACROPHAGE POLARIZATION; MUTANT P53; TGF-BETA; OXIDATIVE STRESS; CAFFEIC ACID; WILD-TYPE; CANCER; TOXICITY; POLYPHENOLS AB Cancers are increasingly common and significantly impact patients' quality of life and longevity. The role of macrophages in tumorigenesis is critical, and natural compounds have long been recognized as valuable sources of bioactive agents for treating this condition. However, no systematic review has been performed on the role of phytochemicals impacting tumorigenesis by M1/M2 macrophage polarization. The aim of this study is to systematically review phytochemicals that relieve tumorigenesis by impacting M1/M2 macrophage polarization and investigate related signaling pathways. This systematic review adheres to PRISMA 2020 guidelines and statements. Scientific databases, MEDLINE, Scopus, and Web of Science, have been searched from inception to October 2023. This review includes English original articles on the role of phytochemicals, whole plant extracts, and polyherbal formulas in ameliorating tumorigenesis through M1/M2 polarization while excluding non-English articles, non-original research, and unrelated studies according to title, abstract, and full-text screening. Shreds of evidence were gathered from cellular and animal studies about the beneficial impacts of phytochemicals against tumorigenesis by impacting M1/M2 macrophage polarization. Critical assessment of in vitro and in vivo studies was performed by the CRIS and ARRIVE guidelines. Due to the high level of heterogeneity of the collected data, only a narrative synthesis was performed. Of 741 collected articles, only 35 remained. Polyphenols are the most highlighted group. Phytochemicals affect cytokines related to M1, such as CD80, CD86, CD64, and iNOS, and M2, like CXCR-1, CXCR-2, and TGF-beta, in various cancer models. Together, these compounds exerted protective effects against tumorigenesis in preclinical cancer models. Furthermore, high-quality clinical experiments are recommended to cover the limitations of the current study, which are reliance on preclinical evidence, lack of clinical trials, and exclusion of non-English and grey literature. C1 [Niknejad, Amirhossein; Peyrovinasab, Amirreza; Sirouskabiri, Shirin; Gholami, Mahsa; Pasha, Aytak Vahdat Khajeh; Shahri, Saleh; Abdolghaffari, Amir Hossein] Islamic Azad Univ, Dept Toxicol & Pharmacol, TeMS C, Tehran, Iran. [Niknejad, Amirhossein; Esmaealzadeh, Niusha; Peyrovinasab, Amirreza; Sirouskabiri, Shirin; Gholami, Mahsa; Pasha, Aytak Vahdat Khajeh; Abdolghaffari, Amir Hossein] Universal Sci Educ & Res Network USERN, GI Pharmacol Interest Grp GPIG, Tehran, Iran. [Esmaealzadeh, Niusha] Univ Tehran Med Sci, Sch Persian Med, Dept Tradit Pharm, Tehran, Iran. [Esmaealzadeh, Niusha] Univ Tehran Med Sci, Students Sci Res Ctr, Tradit Persian Med & Complementary Med PerCoMed St, Tehran, Iran. [Busselberg, Dietrich] Qatar Fdn, Weill Cornell Med Qatar, Dept Physiol & Biophys, Doha, Qatar. C3 Islamic Azad University; Universal Scientific Education & Research Network (USERN); Tehran University of Medical Sciences; Tehran University of Medical Sciences; Qatar Foundation (QF); Weill Cornell Medical College Qatar RP Abdolghaffari, AH (corresponding author), Islamic Azad Univ, Dept Toxicol & Pharmacol, TeMS C, Tehran, Iran.; Abdolghaffari, AH (corresponding author), Universal Sci Educ & Res Network USERN, GI Pharmacol Interest Grp GPIG, Tehran, Iran.; Büsselberg, D (corresponding author), Qatar Fdn, Weill Cornell Med Qatar, Dept Physiol & Biophys, Doha, Qatar. 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PD JUL PY 2025 VL 39 IS 7 BP 3105 EP 3147 DI 10.1002/ptr.8522 EA MAY 2025 PG 43 WC Chemistry, Medicinal; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 5AY1B UT WOS:001491185000001 PM 40393795 DA 2026-03-26 ER PT J AU Richter, HI Gover, O Hamburg, A Bendalak, K Ziv, T Schwartz, B AF Richter, Hadas Inbart Gover, Ofer Hamburg, Amit Bendalak, Keren Ziv, Tamar Schwartz, Betty TI Impact of Black Soldier Fly Larvae Oil on Immunometabolic Processes SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE black soldier fly larvae (BSFL); macrophage polarization; cytokines; toll-like receptor (TLR); nuclear factor kappa B (NF-kappa B); peroxisome proliferator-activated receptor (PPAR); immunometabolism ID NF-KAPPA-B; ACTIVATION; PHOSPHORYLATION; PROLIFERATION; INFLAMMATION; MACROPHAGES; KINASES AB The oil extract derived from black soldier fly (Hermetia illucens) larvae (BSFL) is characterized by a distinctive fatty acid composition and bioactive compounds with demonstrated anti-inflammatory properties, as shown in our previous work. The present study aims to mechanistically explore the immunomodulatory effects of a saponified form of BSFL oil (MBSFL) and its potential interaction with metabolic signaling pathways. Using Pam3CSK4-polarized M1 primary human peripheral blood mononuclear cells (PBMCs), we demonstrate that MBSFL phenotypically suppressed the secretion of pro-inflammatory cytokines TNF alpha, IL-6, IL-17, and GM-CSF (p < 0.01) without altering anti-inflammatory cytokine levels (TGF beta 1, IL-13, and IL-4). A phosphoproteomic analysis of Pam3CSK4-stimulated THP-1 macrophages revealed MBSFL-mediated downregulation of CK2 and ERK kinases (p < 0.05), key regulators of NF-kappa B signaling activation. We confirmed that MBSFL directly inhibits NF-kappa B p65 nuclear translocation (p < 0.05), using both immunofluorescence staining and a western blot analysis of nuclear and cytoplasmic fractions. In the context of metabolism, using a luciferase reporter assay, we demonstrate that MBSFL functions as a weak agonist of PPAR gamma and PPAR delta (p < 0.05), which are nuclear receptors involved in lipid metabolism and immune regulation. However, subsequent immunoblotting revealed a macrophage polarization-dependent regulation: MBSFL upregulated PPAR gamma in M0 macrophages but did not prevent its suppression upon Pam3CSK4 stimulation, whereas it specifically enhanced PPAR delta expression during M1 polarization (p < 0.05). This study provides novel experimental evidence supporting our hypothesis of MBSFL's role in immunometabolism. We demonstrate for the first time that MBSFL acts as a dual regulator by suppressing NF-kappa B-mediated inflammation while promoting PPAR delta activity-an inverse relationship with potential relevance to immunometabolic disorders. C1 [Richter, Hadas Inbart; Gover, Ofer; Hamburg, Amit; Schwartz, Betty] Hebrew Univ Jerusalem, Robert Smith Fac Agr Food & Environm H, Inst Biochem Food Sci & Nutr, Sch Nutr Sci, IL-7610001 Rehovot, Israel. [Bendalak, Keren; Ziv, Tamar] Technion Israel Inst Technol, Smoler Prote Ctr, IL-3200003 H_efa, Israel. C3 Hebrew University of Jerusalem; Technion Israel Institute of Technology RP Schwartz, B (corresponding author), Hebrew Univ Jerusalem, Robert Smith Fac Agr Food & Environm H, Inst Biochem Food Sci & Nutr, Sch Nutr Sci, IL-7610001 Rehovot, Israel. EM betty.schwartz@mail.huji.ac.il OI Richter, Hadas/0009-0002-3865-3472; Schwartz, Betty/0000-0002-9705-3162; Gover, Ofer/0000-0002-8341-6209 CR Adhikary T, 2015, NUCLEIC ACIDS RES, V43, P5033, DOI 10.1093/nar/gkv331 Alexander AF, 2021, CELL REP, V36, DOI 10.1016/j.celrep.2021.109728 Antonio MB, 2020, International Journal of Immunology and Immunotherapy, V7, DOI [10.23937/2378-3672/1410041, 10.23937/2378-3672/1410041, DOI 10.23937/2378-3672/1410041] Arthur JSC, 2013, NAT REV IMMUNOL, V13, P679, DOI 10.1038/nri3495 Barish GD, 2012, CELL METAB, V15, P554, DOI 10.1016/j.cmet.2012.02.012 Bhatt D, 2014, FRONT IMMUNOL, V5, DOI 10.3389/fimmu.2014.00071 Casado P, 2013, SCI SIGNAL, V6, DOI 10.1126/scisignal.2003573 Chen SZ, 2023, SIGNAL TRANSDUCT TAR, V8, DOI 10.1038/s41392-023-01452-1 Covarrubias AJ, 2016, ELIFE, V5, DOI 10.7554/eLife.11612 Dabbou S, 2020, ANIMALS-BASEL, V10, DOI 10.3390/ani10081292 Daniel B, 2023, MOL CELL, V83, P121, DOI 10.1016/j.molcel.2022.11.017 Dorrington MG, 2019, FRONT IMMUNOL, V10, DOI 10.3389/fimmu.2019.00705 Dowling JK, 2021, NAT COMMUN, V12, DOI 10.1038/s41467-021-21617-2 Funderburg NT, 2011, IMMUNOLOGY, V134, P151, DOI 10.1111/j.1365-2567.2011.03475.x Geiger MA, 2020, FRONT IMMUNOL, V11, DOI 10.3389/fimmu.2020.569358 Hoesel B, 2013, MOL CANCER, V12, DOI 10.1186/1476-4598-12-86 Hong JW, 2010, BMB REP, V43, P807, DOI 10.5483/BMBRep.2010.43.12.807 Jin Y, 2015, J BIOL CHEM, V290, P2099, DOI 10.1074/jbc.M114.599985 Kim YB, 2020, POULTRY SCI, V99, P3133, DOI 10.1016/j.psj.2020.01.018 Li ZZ, 2022, CELL DEATH DISCOV, V8, DOI 10.1038/s41420-022-01200-4 Liu LL, 2016, P NATL ACAD SCI USA, V113, P1564, DOI 10.1073/pnas.1518000113 Liu T, 2017, SIGNAL TRANSDUCT TAR, V2, DOI 10.1038/sigtrans.2017.23 Mariod A.A., 2004, Insect Oil as a Source of Nutraceuticals Mottis A, 2013, GENE DEV, V27, P819, DOI 10.1101/gad.214023.113 Orekhov AN, 2019, VESSEL PLUS, V2019, DOI [10.20517/2574-1209.2019.04, 10.20517/2574-1209.2019.04, DOI 10.20517/2574-1209.2019.04] Perkins ND, 1997, SCIENCE, V275, P523, DOI 10.1126/science.275.5299.523 Planavila A, 2005, CARDIOVASC RES, V65, P832, DOI 10.1016/j.cardiores.2004.11.011 Richter H., 2020, Patent No. [WO2020234884A1, 2020234884] Richter H, 2023, INT J MOL SCI, V24, DOI 10.3390/ijms241310634 Rodríguez-Calvo R, 2008, DIABETES, V57, P2149, DOI 10.2337/db08-0176 Sakowicz A, 2020, INT J MOL SCI, V21, DOI 10.3390/ijms21155574 Schevzov G, 2015, MOL BIOL CELL, V26, P2475, DOI 10.1091/mbc.E14-10-1453 Shumo M, 2019, SCI REP-UK, V9, DOI 10.1038/s41598-019-46603-z Strizova Z, 2023, CLIN SCI, V137, P1067, DOI 10.1042/CS20220531 Szklarczyk D, 2023, NUCLEIC ACIDS RES, V51, pD638, DOI [10.1093/nar/gkac1000, 10.1093/nar/gky1131] Tarcic O, 2016, CELL REP, V14, P1462, DOI 10.1016/j.celrep.2016.01.020 Tian Y, 2019, FRONT IMMUNOL, V10, DOI 10.3389/fimmu.2019.01895 Tobita Y, 2020, INT J MOL SCI, V21, DOI 10.3390/ijms21155296 Toobian D, 2021, FRONT IMMUNOL, V12, DOI 10.3389/fimmu.2021.783780 Verma S, 2019, MOL CELL BIOL, V39, DOI 10.1128/MCB.00415-18 Viatour P, 2005, TRENDS BIOCHEM SCI, V30, P43, DOI 10.1016/j.tibs.2004.11.009 Vogelpoel LTC, 2014, NAT COMMUN, V5, DOI 10.1038/ncomms6444 Wang SY, 2019, CANCER LETT, V452, P14, DOI 10.1016/j.canlet.2019.03.015 Wiredja DD, 2017, BIOINFORMATICS, V33, P3489, DOI 10.1093/bioinformatics/btx415 Yu LX, 2023, FRONT PHARMACOL, V14, DOI 10.3389/fphar.2023.1254317 Zabulione A, 2023, GELS-BASEL, V9, DOI 10.3390/gels9100793 Zhong HH, 2002, MOL CELL, V9, P625, DOI 10.1016/S1097-2765(02)00477-X NR 47 TC 0 Z9 0 U1 2 U2 5 PU MDPI PI BASEL PA MDPI AG, Grosspeteranlage 5, CH-4052 BASEL, SWITZERLAND SN 1661-6596 EI 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD MAY 19 PY 2025 VL 26 IS 10 AR 4855 DI 10.3390/ijms26104855 PG 20 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry GA 3BZ5U UT WOS:001496717000001 PM 40429995 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhang, S Tan, HB Zhang, ZH Wang, ZY Zhang, CY Zhang, JY Jia, ET AF Zhang, Shan Tan, Haibo Zhang, Zhihao Wang, Ziyu Zhang, Chenyang Zhang, Jianyong Jia, Ertao TI Sinomenine alleviates gouty inflammation by inhibiting macrophage M1 polarization and neutrophil extracellular trap formation SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE Sinomenine; Gouty inflammation; Macrophage polarization; Neutrophil extracellular traps AB Gout is a common inflammatory arthropathy characterized by the deposition of monosodium urate (MSU) crystals, leading to severe pain and swelling. Sinomenine (SIN) is the major active component of Sinomenium acutum. SIN has been demonstrated to exert preventive and therapeutic effects on arthritis in cell-based, animal, and clinical studies. The present study focused on the efficacy and role of SIN in relieving symptoms of gouty inflammation in vivo and in vitro. The anti-inflammatory effects of SIN were evaluated in mice with MSU-induced air-pouch via hematoxylin-eosin (HE) staining, and enzyme-linked immunosorbent assay (ELISA). Transcriptomic analysis revealed that SIN modulates a range of inflammatory pathways associated with gout pathogenesis. Notably, the NOD-like receptor pathway and neutrophil extracellular trap (NET) formation were significantly enriched with the occurrence of gout and significantly improved after SIN treatment. THP-1 macrophages were stimulated with PBS or MSU, with or without SIN. Immunofluorescence (IF) and western blotting (WB) results indicated that SIN suppressed NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/interleukin-1 beta (IL-1 beta) expression. Additionally, SIN inhibited macrophage M1 polarization and NET formation. In summary, SIN ameliorates gouty inflammation, likely by regulating the NLRP3/IL-1 beta pathway, M1 macrophage polarization, and NET formation. Thus, SIN is a promising drug for treating gout. C1 [Zhang, Shan; Tan, Haibo; Zhang, Jianyong] Nanjing Univ Chinese Med, Shenzhen Tradit Chinese Med Hosp, Shenzhen 518033, Peoples R China. [Zhang, Zhihao; Wang, Ziyu; Zhang, Chenyang; Jia, Ertao] Guangzhou Univ Chinese Med, Guangdong Hosp Tradit Chinese Med 2, Clin Coll 5, Dept Rheumatism, Guangzhou 510000, Peoples R China. [Zhang, Jianyong] Univ Chinese Med, Shenzhen Tradit Chinese Med Hosp, Clin Med Coll Guangzhou 4, Dept Rheumatism, Shenzhen 518033, Peoples R China. C3 Nanjing University of Chinese Medicine; Shenzhen Traditional Chinese Medicine Hospital; Guangzhou University of Chinese Medicine; Shenzhen Traditional Chinese Medicine Hospital RP Jia, ET (corresponding author), Guangzhou Univ Chinese Med, Guangdong Hosp Tradit Chinese Med 2, Clin Coll 5, Dept Rheumatism, Guangzhou 510000, Peoples R China. EM 15951835723@163.com; thb13265042784@163.com; zzhzzhzzh0929@163.com; wangziyu20000506@163.com; zhangchenyang0304@hotmail.com; 13823396319@163.com; sailing1980@163.com RI Tan, Haibo/HOF-0217-2023 OI Tan, Haibo/0000-0001-7021-8492 FU National Natural Science Foundation of China [82374338]; Natural Science Foundation of Hunan province [2022 JJ50302] FX This work was supported by the National Natural Science Foundation of China (82374338) and the Natural Science Foundation of Hunan province (2022 JJ50302). 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Pharmacol. PD NOV PY 2025 VL 398 IS 11 BP 15791 EP 15805 DI 10.1007/s00210-025-04161-4 EA MAY 2025 PG 15 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 9HD9M UT WOS:001489544800001 PM 40381009 DA 2026-03-26 ER PT J AU Wang, XZ Tan, LP Dong, Y Lin, Y Yin, LJ Shen, SN Dou, H Hou, YY AF Wang, Xiuzhu Tan, Liping Dong, Yue Lin, Yan Yin, Lijie Shen, Sunan Dou, Huan Hou, Yayi TI Vitamin D enhances the effect of Soufeng sanjie formula in alleviating joint inflammation in CIA mice through VDR-NOTCH3/DLL4 signaling in macrophages SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Soufeng sanjie formula; Rheumatoid arthritis; Macrophage; M2-type polarization; Vitamin D ID ARTHRITIS AB Ethnopharmacological relevance: Rheumatoid arthritis (RA), defined as Bi Zheng syndrome in traditional Chinese medicine (TCM), is a chronic inflammatory and autoimmune disease that can cause substantial articular degradation and impairment. In RA, the polarization of macrophages to a proinflammatoy phenotype contributes to chronic inflammation and joint injury. Soufeng sanjie formula (SF), a traditional Chinese formula used to treat RA, consists of Scolopendra subspinipes mutilans L. Koch, Buthus martensii Karsch, Astragalus membranaceus (Fisch), and Glycine max (L.) Merr seed coats and plays a role in the regulation of macrophage polarization. Vitamin D (VD), a specific activator of the vitamin D receptor (VDR), promotes the differentiation of M2 macrophages and significantly enhances the therapeutic effects of TCM on arthritis. However, whether SF can be combined with VD to regulate macrophage polarization and alleviate RA remains unclear. Aim of the study: In this study, we examined the regulatory mechanisms and therapeutic effects of the combination of SF and VD on macrophages in RA. Materials and methods: We used network pharmacology to analyze the targets and pathways of SF in RA. Clinical data were analyzed to confirm the expression of key targets. The RA immune landscape for cell-gene correlations was built using bioinformatics. A collagen-induced arthritis (CIA) model was established to evaluate the combined therapeutic effects of SF and VD on joint injury and inflammation. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting (WB), and immunofluorescence were used to assess the expression of key molecules in macrophages. Macrophage polarization was analyzed using flow cytometry. Results: SF acts on RA through multiple pathways, including hub genes, such as VDR, ABL1, DNMT1, and CXCR4. Immune infiltration analysis of RA showed that a reduction in the number of M2 macrophages significantly affected RA. Clinical data analysis and prognostic assessments corroborated the pivotal roles played by hub genes, such as VDR, ABL1, DNMT1, and CXCR4. Crucially, this study demonstrated a strong association between the key hub gene VDR and M2 macrophages. In vivo and in vitro models of RA showed that VD significantly improved the efficacy of SF against arthritis in CIA mice and stimulated macrophage polarization toward the M2 phenotype via modulation of the NOTCH3/DLL4 pathway. Furthermore, siRNA-mediated interference with the expression of VDR confirmed that the downregulation of VDR significantly activated the NOTCH3/DLL4 signaling pathway and blocked the regulation of SF combined with VD on the polarization of macrophages toward the M2 phenotype. Conclusions: Our results demonstrate that the combination of SF and VD markedly improves the therapeutic effect of SF on RA via M2 macrophage differentiation through the VDR-NOTCH3/DLL4 signaling pathway. The VDenhancing effect of SF in improving RA symptoms offers a new strategy and theoretical foundation for the clinical treatment of the condition. C1 [Wang, Xiuzhu; Tan, Liping; Dong, Yue; Lin, Yan; Yin, Lijie; Shen, Sunan; Dou, Huan; Hou, Yayi] Nanjing Univ, Med Sch, Div Immunol, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Peoples R China. [Wang, Xiuzhu; Tan, Liping; Dong, Yue; Lin, Yan; Yin, Lijie; Shen, Sunan; Dou, Huan; Hou, Yayi] Jiangsu Key Lab Mol Med, Nanjing 210093, Peoples R China. C3 Nanjing University RP Dou, H; Hou, YY (corresponding author), Nanjing Univ, Med Sch, Div Immunol, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Peoples R China. EM douhuan@nju.edu.cn; yayihou@nju.edu.cn RI Dou, Huan/AFR-7946-2022 OI Hou, Yayi/0000-0002-1152-9132 FU Key Program of the National Natural Science Foundation of China [82230120]; National Natural Science Foundation of China [32070883]; Affiliated Drum Tower Hospital, Medical School of Nanjing University, for Clinical Trial purposes [2022-LCYJ-MS-38]; Innovative Training Program for Undergraduates of Nanjing University [202410284160Z] FX This research was made possible through funding from a number of sources. We gratefully acknowledge the support of the Key Program of the National Natural Science Foundation of China (Grant No. 82230120) , as well as the National Natural Science Foundation of China (Grant No. 32070883) . Additional funding was provided by the Affiliated Drum Tower Hospital, Medical School of Nanjing University, for Clinical Trial purposes (Grant No. 2022-LCYJ-MS-38) , and by the Innovative Training Program for Undergraduates of Nanjing University (Grant No. 202410284160Z) . 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PD JUN 12 PY 2025 VL 349 AR 119932 DI 10.1016/j.jep.2025.119932 EA MAY 2025 PG 15 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 3AU0M UT WOS:001495895200001 PM 40350051 DA 2026-03-26 ER PT J AU Dong, ZW Xue, ZF Zhang, M Wang, LM Lu, QQ Zhao, H Wang, XL Nie, SS Wei, JJ Yan, HF Fan, GW Wang, YX Zhu, MJ AF Dong, Zhengwei Xue, Zhifeng Zhang, Min Wang, Liming Lu, Qianqian Zhao, Huan Wang, Xinlu Nie, Shanshan Wei, Jingjing Yan, Haifeng Fan, Guanwei Wang, Yongxia Zhu, Mingjun TI Lingguizhugan decoction inhibit pulmonary hypertension by regulating macrophage IL-6 secretion via IL-33/ST2 pathway SO PHYTOMEDICINE LA English DT Article DE Pulmonary hypertension; Macrophage; IL-33/ST2; IL-6; Lingguizhugan decoction ID ARTERIAL-HYPERTENSION AB Background: Lingguizhugan decoction (LGZG), a typical Chinese herbal formula, has remarkable clinical effects for treating pulmonary hypertension (PH) with unclear ingredients and mechanisms. This study aimed to evaluate the efficacy of LGZG and the mechanism of its active ingredients in treating PH. Methods: The PH patient phenotype was characterized by transcriptomic assay of peripheral blood mononuclear cells (PBMCs) and multiplex cytokine profiling of serum. The active ingredients of LGZG were identified by UPLC-Q-TOF-MS. The monocrotaline (MCT)-induced PH model was performed to evaluate the effects of LGZG and its active ingredients in vivo. The interleukin-33 (IL-33)-induced RAW264.7 cells and the mouse pulmonary artery smooth muscle cells (mPASMCs) were applied to explored phenotype and mechanism of the active ingredients of LGZG by immunofluorescence, western blotting and RT-qPCR in vitro. Results: Inflammatory receptor activity in PBMCs and serum interleukin-6 (IL-6) levels were elevated in PH patients. Porinic acid B, cinnamic acid, atractylenolide I and glycyrrhizin (PCAG) were characterized and combined to treat the PH, And the IL-33/Growth stimulation expressed gene 2 (ST2) pathway may be the potential mechanism by transcriptomic analysis of lung tissues. Both in vivo and in vitro experiments confirmed that PCAG inhibited the IL-33/ST2 pathway, reduced macrophage polarization, and suppressed IL-6 secretion. Moreover, ST2 overexpression in macrophages attenuated the inhibitory effect of PCAG. Using a co-culture system of macrophages and mPASMCs, we demonstrated that PCAG reduced mPASMCs phenotypic switching by suppressing macrophage-derived IL-6 secretion. Conclusion: The active ingredient of LGZG, PCAG, inhibits the progression of PH by preventing macrophage polarization and IL-6 secretion through the IL-33/ST2 pathway. C1 [Dong, Zhengwei; Zhang, Min; Wang, Xinlu; Nie, Shanshan; Wei, Jingjing; Yan, Haifeng; Wang, Yongxia; Zhu, Mingjun] Henan Univ CM, Heart Ctr, Natl Reg Tradit Chinese Med Cardiovasc Diag & Trea, Affiliated Hosp 1, Zhengzhou 450000, Peoples R China. [Xue, Zhifeng] Shanxi Med Univ, Shanxi Bethune Hosp, Shanxi Acad Med Sci, Tongji Shanxi Hosp,Hosp 3, Taiyuan 030032, Peoples R China. [Xue, Zhifeng] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China. [Wang, Liming] Tianjin Univ Tradit Chinese Med, Tianjin 301617, Peoples R China. [Lu, Qianqian; Fan, Guanwei] Tianjin Univ Tradit Chinese Med, Teaching Hosp 1, Tianjin, Peoples R China. [Zhao, Huan] Henan Univ Tradit CM, Zhengzhou 450046, Peoples R China. C3 Shanxi Medical University; Huazhong University of Science & Technology; Tianjin University of Traditional Chinese Medicine; Tianjin University of Traditional Chinese Medicine RP Wang, YX; Zhu, MJ (corresponding author), Henan Univ CM, Heart Ctr, Natl Reg Tradit Chinese Med Cardiovasc Diag & Trea, Affiliated Hosp 1, Zhengzhou 450000, Peoples R China.; Fan, GW (corresponding author), Tianjin Univ Tradit Chinese Med, Teaching Hosp 1, Tianjin, Peoples R China. EM guanwei.fan@tjutcm.edu.cn; wyxchzhq@hactcm.edu.cn; zhumingjun@hactcm.edu.cn RI Xue, Zhifeng/ACB-8038-2022; FAN, GUANWEI/GWV-6480-2022; zhu, mingjun/KMX-7346-2024; lu, qianqian/LTD-4900-2024; Wei, Jingjing/OMN-2004-2025 FU Foundation of China [82405380]; Natural Science Foundation of Henan Province [242300421526]; Henan Health Commission [2023ZXZX1130]; Shanxi Provincial Science and Technology Department planning project [202203021221238]; Research Project of Shanxi Administration of Traditional Chinese Medicine [2023ZYYB027]; Henan University of Chinese Medicine [HSRP-DFCTCM-2023-7] FX Foundation of China (No. 82405380) , Natural Science Foundation of Henan Province (No. 242300421526) , Henan Health Commission (No. 2023ZXZX1130) , Shanxi Provincial Science and Technology Department planning project (No. 202203021221238) , Research Project of Shanxi Administration of Traditional Chinese Medicine (No. 2023ZYYB027) , Henan University of Chinese Medicine (No. HSRP-DFCTCM-2023-7) .r Foundation of China (No. 82405380) , Natural Science Foundation of Henan Province (No. 242300421526) , Henan Health Commission (No. 2023ZXZX1130) , Shanxi Provincial Science and Technology Department planning project (No. 202203021221238) , Research Project of Shanxi Administration of Traditional Chinese Medicine (No. 2023ZYYB027) , Henan University of Chinese Medicine (No. HSRP-DFCTCM-2023-7) . 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Although Liang-Ge-San (LGS), a traditional Chinese medicine formula, is known to promote inflammation resolution and shorten hospitalization duration of ALI, the mechanism is still unclear. Our results demonstrated that LGS regulated the dynamic balance of macrophage polarization as reflected by up-regulating the expression of anti-inflammatory factors (CD206, Arg-1 and IL-10) in advance to counteract the high expression of proinflammatory factors (CD86, iNOS, IL-6 and TNF-alpha) in vitro. MiR-21 concentration was elevated in LPSchallenged RAW264.7 cells and ALI mice. Moreover, the overexpression of miR-21 mimicked the antiinflammatory effects of LGS, whereas a miR-21 inhibitor abolished the protective effects of LGS in vitro. Most importantly, LGS protected ALI mice from LPS which could be counteracted by the treatment of miR-21 antagomir. Furthermore, LGS could inhibit the transcriptional activity and protein expression of PTEN by upregulating miR-21. In summary, LGS functions by regulating the miR-21/PTEN axis to induce a shift in macrophages from a pro-inflammatory phenotype to an anti-inflammatory phenotype, thereby alleviating LPSinduced ALI. This study supports the clinical evidence of LGS in the treatment of ALI. C1 [Zheng, Zhuping] Southern Med Univ, Nanfang Hosp, Dept Pharm, Guangzhou 510515, Peoples R China. [Zheng, Zhuping; Yang, Tangjia; Cao, Huihui; Yu, Jingtao; Fang, Xiaochuan; He, Xuemei; Zou, Lifang; Tang, Dongkai; Lu, Zibin; Liu, Junshan; Yu, Linzhong] Southern Med Univ, Sch Tradit Chinese Med, Level Res Lab State Adm Tradit Chinese Med 3, Guangzhou 510515, Peoples R China. [Zheng, Zhuping; Yang, Tangjia; Cao, Huihui; Yu, Jingtao; Fang, Xiaochuan; He, Xuemei; Zou, Lifang; Tang, Dongkai; Lu, Zibin; Liu, Junshan; Yu, Linzhong] Int Joint Labaratory Zebrafish Models Human Dis &, Guangdong Basic Res Ctr Excellence Integrated Trad, Guangdong Prov Key Lab Chinese Med Pharmaceut, Guangzhou 510515, Peoples R China. [Yu, Linzhong] Southern Med Univ, Nanfang Hosp, Dept Tradit Chinese Med, Guangzhou 510515, Peoples R China. C3 Southern Medical University - China; Southern Medical University - China; Southern Medical University - China RP Lu, ZB; Liu, JS; Yu, LZ (corresponding author), Southern Med Univ, Sch Tradit Chinese Med, Guangzhou 510515, Peoples R China. EM huang624@smu.edu.cn; liujunshan@smu.edu.cn; yulzh@smu.edu.cn RI Fang, Xiaochuan/JAX-1804-2023; Lu, Zi-Bin/ABF-3245-2020 FU National Natural Science Foundation of China [82074317, 82274398]; Guangdong Basic and Applied Basic Research Foundation [2023A1515011106]; General Project of Guangdong Provincial Enterprise Joint Fund [2022A1515220081] FX The work was supported by the National Natural Science Foundation of China (82074317, 82274398) , Guangdong Basic and Applied Basic Research Foundation (2023A1515011106) , General Project of Guangdong Provincial Enterprise Joint Fund (2022A1515220081) . 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In traditional Chinese medicine (TCM), qi stagnation and blood stasis are linked to the HCC tumor microenvironment (TME), but few studies explore the effects of related TCM herbs on the TME. Calceolarioside B, a key phenylethanoid glycoside in Akebiae Fructus, has not been well studied for its pharmacological activities or molecular targets, and its role in HCC remains unclear. Purpose: This study aimed to investigate the effects of Calceolarioside B on TAMs in HCC and clarify its potential targets and regulatory mechanisms. Methods: Murine intrahepatic transplantation HCC models and macrophage-HCC cell co-culture systems were used to investigate the effects of Calceolarioside B on M2-like TAMs polarization and infiltration, and tumor growth. Cellular thermal shift assay, small molecular pull-down assay and surface plasmon resonance were utilized to identify the potential targets regulating M2-like TAMs. Single-cell RNA sequencing and TCGA dataset analyses clarified the differential expression, prognosis, and TAMs association of the potential targets in HCC. Results: Calceolarioside B reduces M2-like TAMs polarization and infiltration in the TME by binding to and inhibiting matrix metallopeptidase-12 (MMP12) form both macrophages and HCC cells, thereby preventing immunosuppressive effects. Public database analysis revealed that MMP12 overexpression promoted macrophage infiltration, with MMP12+ macrophages preferentially aggregating in primary and metastatic HCC tumors. Conclusion: Calceolarioside B is identified as a novel MMP12 inhibitor modulating TAMs in the TME, offering a potential TAM-targeting strategy for HCC therapy C1 [Cao, Linna; Jia, Dongwei; Lu, Wenli; Liang, Chao; Liu, Xiaomei; Pan, Zhiqiang; Peng, Peike] Shanghai Univ Tradit Chinese Med, Sch Tradit Chinese Med, Shanghai 201203, Peoples R China. [Shao, Miaomiao] Nanjing Univ Chinese Med, Sch Med, Nanjing 210023, Peoples R China. [Gu, Yifei; Hu, Jinquan] Naval Med Univ, Shanghai Changzheng Hosp, Dept Orthopaed, Shanghai 200003, Peoples R China. [Zhang, Yiwei] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Anesthesiol, Shanghai 200233, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine; Nanjing University of Chinese Medicine; Naval Medical University; Shanghai Jiao Tong University RP Pan, ZQ; Peng, PK (corresponding author), Shanghai Univ Tradit Chinese Med, Sch Tradit Chinese Med, Shanghai 201203, Peoples R China.; Hu, JQ (corresponding author), Naval Med Univ, Shanghai Changzheng Hosp, Dept Orthopaed, Shanghai 200003, Peoples R China.; Zhang, YW (corresponding author), Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Anesthesiol, Shanghai 200233, Peoples R China.; Peng, PK (corresponding author), Shanghai Univ Tradit Chinese Med, Sch Tradit Chinese Med, Dept Expt TCM, 1200 Cailun Rd, Shanghai 201203, Peoples R China. EM pzq527@163.com; 1030218497@sjtu.edu.cn; hjqspine@163.com; pengpeike@shutcm.edu.cn RI Liu, Xiaomei/PKR-6131-2026; Gu, Yifei/HTS-7141-2023 FU National Natural Science Foundation of China [82004000, 82102631]; Science and Technology Development Projects of Shanghai University of Traditional Chinese Medicine [24KFL012]; Basic Scientific Research Projects of Shanghai Sixth People's Hospital [YNQN202317] FX This work was supported by the National Natural Science Foundation of China (82004000, 82102631) , Science and Technology Development Projects of Shanghai University of Traditional Chinese Medicine (24KFL012) and Basic Scientific Research Projects of Shanghai Sixth People's Hospital (YNQN202317) . The authors would like to thank Jianrong Xu (Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine) for his assistance in SPR assays; Dongjie Deng (Sequanta Technologies Co., Ltd) for his assistance in scRNA-seq analyses. 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6 Z9 6 U1 11 U2 22 PU ELSEVIER GMBH PI MUNICH PA HACKERBRUCKE 6, 80335 MUNICH, GERMANY SN 0944-7113 EI 1618-095X J9 PHYTOMEDICINE JI Phytomedicine PD JUL PY 2025 VL 142 AR 156805 DI 10.1016/j.phymed.2025.156805 EA MAY 2025 PG 15 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 2SU4O UT WOS:001490456800001 PM 40347889 DA 2026-03-26 ER PT J AU Xia, YD Han, BB Zhang, FY Li, QR Feng, Q Zhang, SD Liu, D Lin, C Wang, DX Liu, B AF Xia, Yidan Han, Beibei Zhang, Fengyuan Li, Qirong Feng, Qiang Zhang, Shidong Liu, Da Lin, Chao Wang, Dongxu Liu, Bin TI Pae/exo@PF-127 promote diabetic wound healing through miR-424-5p SO PHYTOMEDICINE LA English DT Article DE MSC-exo; miR-424; Paeonol; PF-127; Diabetic wound healing ID MACROPHAGE POLARIZATION; EXOSOMES; ANGIOGENESIS; FORMULATION AB Background: Currently, chronic diabetic wound healing is one of the urgent clinical challenges. Choosing appropriate dressings loaded with stem cell-derived exosomes (exo) and traditional Chinese medicine extracts that promote healing is an effective method to accelerate skin healing in diabetes. Paeonol (Pae), possessing antiinflammatory properties and vascular enhancement functions, can serve as a therapeutic herbal extract for treating diabetic wounds. Methods: Exo were extracted from mesenchymal stem cells and loaded them with Pae (Pae/exo). The effects of Pae/exo on human skin fibroblasts (HSF) and human umbilical vein endothelial cells (HUVEC) were evaluated using CCK-8, migration, and transwell assays. Western blotting, qPCR, and immunofluorescence experiments were conducted to analysis the regulation of associated genes and proteins. Mimics and inhibitors of miR-424-5p were synthesized to further investigate its role in HUVEC and HSF. Additionally, diabetic mice models were constructed with the knockout of miR-322 (a homologous miRNA of miR-424) to validate the impact of miR424-5p knockout on diabetic skin healing in vivo. To better simulate clinical application, thermosensitive hydrogel Pluronic (R) F-127 (PF-127) was used as a carrier for Pae/exo, and the effect of Pae/exo@PF-127 on wound healing in diabetic mice was investigated. Results: This study confirmed that Pae/exo increased the proliferation and migration of HSF and HUVEC by promoting epithelial-mesenchymal transition (EMT) and angiogenesis. The expression of miR-424-5p was significantly upregulated upon treatment with Pae/exo, which correlated with the induction of EMT and angiogenesis. In vivo experiments demonstrated that the wound healing rate was significantly lower in miR-322knockout diabetic mice compared to wild-type diabetic mice; vascular production and epithelialization rate were also reduced in the knockout mice. Pae/exo@PF-127 significantly improved wound healing efficiency in diabetic mice by enhancing EMT and promoting blood vessel formation. The integration of pae, MSC-exo, and PF-127 harnesses their synergistic effects to significantly enhance wound healing and prolong the interval between dressing changes, thereby alleviating patient discomfort. Conclusion: Pae/exo@PF-127 promotes EMT and angiogenesis by upregulating miR-424-5p expression, thereby facilitating diabetic wound healing. C1 [Xia, Yidan; Han, Beibei; Zhang, Fengyuan; Liu, Bin] First Hosp Jilin Univ, Dept Hand & Foot Surg, Changchun 130021, Peoples R China. [Li, Qirong; Feng, Qiang; Wang, Dongxu; Liu, Bin] Jilin Univ, Coll Anim Sci, Lab Anim Ctr, Changchun, Peoples R China. [Xia, Yidan; Han, Beibei; Zhang, Fengyuan; Liu, Bin] Tissue Engn Biomat Engn Lab Jilin Prov, Changchun, Peoples R China. [Zhang, Shidong] ZHONGKEJUYAN Stem Cell Co Ltd, Changchun, Peoples R China. [Liu, Da] Changchun Univ Chinese Med, Dept Pharm, Changchun, Peoples R China. [Lin, Chao] Jilin Business & Technol Coll, Sch Grain Sci & Technol, Changchun, Peoples R China. [Li, Qirong; Feng, Qiang; Wang, Dongxu] Wenzhou Inst Technol, Intellectual Innovat Gene Editing Anim Model Res C, Wenzhou, Peoples R China. C3 Jilin University; Jilin University; Changchun University of Chinese Medicine; Jilin Business & Technology College RP Wang, DX; Liu, B (corresponding author), Jilin Univ, Coll Anim Sci, Lab Anim Ctr, Changchun, Peoples R China. EM wang_dong_xu@jlu.edu.cn; l_bin@jlu.edu.cn OI Xia, Yidan/0000-0002-9211-7745 FU Program of China [(10.13039/501,100,012,166) * 2022YFC2405805]; Jilin Province Development and Reform Commission Program [ZKJCFGW2023015]; Wenzhou Science & Technology Bureau Basic Public Welfare Research Program [Y20240006]; Jilin University young teachers and students cross-disciplinary training project [2023-JCXK-08] FX Research supported by: National Key Research and Development Program of China (10.13039/501,100,012,166) * 2022YFC2405805; Jilin Province Development and Reform Commission Program under Grant ZKJCFGW2023015; Wenzhou Science & Technology Bureau Basic Public Welfare Research Program under Grant Y20240006; and the Jilin University young teachers and students cross-disciplinary training project under Grant 2023-JCXK-08. 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Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 2SU4O UT WOS:001490456800002 PM 40347888 OA hybrid DA 2026-03-26 ER PT J AU Yuan, S Liu, BH Cheng, WW Meng, H Hou, XT Xue, JC Zhang, HM Zhang, QG AF Yuan, Shuo Liu, Bao-Hong Cheng, Wen-Wen Meng, Huan Hou, Xiao-Ting Xue, Jia-Chen Zhang, Hua-Min Zhang, Qing-Gao TI Polyphyllin VI modulates macrophage polarization through autophagy-NLRP3 inflammasome to alleviate inflammatory bowel disease SO PHYTOMEDICINE LA English DT Article DE Polyphyllin VI; Inflammatory bowel disease; Autophagy; NLRP3 inflammasome; Macrophage polarization ID ACTIVATION; MECHANISM; COLITIS AB Background: Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with a rising global prevalence. If left untreated, it can result in severe complications, including colon cancer. Key factors in IBD pathogenesis include macrophages, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and autophagy. Polyphyllin VI (PPVI), a metanoidal saponin derived from the traditional Chinese herb Chonglou, exhibits significant anti-inflammatory and anti-cancer properties, making it a compound of considerable therapeutic interest. Purpose: The present study investigated the relevant mechanism of PPVI on protecting IBD from the perspective of NLRP3 as well as macrophage immunomodulation and laid a theoretical foundation for the development of novel IBD therapeutic drugs. Methods: The IBD mice were prepared by dextran sodium sulfate, and RAW 264.7 inflammatory cells were established through LPS and ATP stimulation. The indicators of macrophage polarization, NLRP3, and autophagy were detected using Western Blot, RT-qPCR, H&E staining, immunofluorescence, and flow cytometry. Results: PPVI can enhance the inflammatory state of LPS-induced RAW264.7 macrophages, which can reduce weight loss, decrease DAI score, increase colon length, reduce oxidative stress, and decrease intestinal epithelial barrier damage, and thus diminish inflammatory injury in DSS-induced IBD mice. PPVI can modify intestinal inflammation and injury by modulating macrophage function. The administration of PPVI can maintain the balance between M1-type macrophages and M2-type macrophages while regulating the intestinal macrophage polarization via the NLRP3 inflammasome and autophagy through wildtype mice, cells, and Nlrp3-/- mice. Conclusion: PPVI can regulate macrophage polarization through autophagic modulation of NLRP3 inflammasome to promote the repair of intestinal epithelial damage and maintain the integrity of the mucosal barrier, which contributes to the attenuation of inflammatory injury in DSS-induced IBD mice and provides a database for the development of novel clinical drugs. Innovations: 1. This subject discovered the protective effect of PPVI on IBD mice. 2. This subject proved that macrophages have an important role in the intestinal protection of PPVI in IBD mice, and PPVI can inhibit the polarization of M1-type macrophages and promote the polarization of M2-type macrophages. 3. This subject demonstrated that PPVI could regulate macrophage polarization through NLRP3 inflammasome and ameliorate intestinal inflammation in vitro, in vivo, and in Nlrp3-/- mice. 4. This subject confirmed that PPVI could regulate macrophage polarization to alleviate inflammatory injury by inhibiting NLRP3 inflammasome through modulating autophagy in vitro, in vivo, and the application of inhibitors. C1 [Yuan, Shuo; Liu, Bao-Hong; Cheng, Wen-Wen; Meng, Huan; Hou, Xiao-Ting; Zhang, Qing-Gao] Dalian Univ, Coll Med, Chron Dis Res Ctr, Dalian 116622, Liaoning, Peoples R China. [Xue, Jia-Chen; Zhang, Hua-Min] Dalian Univ, Affiliated Zhongshan Hosp, Dalian 116001, Liaoning, Peoples R China. C3 Dalian University; Dalian University RP Zhang, QG (corresponding author), Dalian Univ, Coll Med, Chron Dis Res Ctr, Dalian 116622, Liaoning, Peoples R China. EM yuanqiqi0710@yeah.net; LiuBH0808@163.com; chengww0921@163.com; 15563776072@163.com; h52110609@163.com; 18640957697@163.com; zhm4481@163.com; zhangqinggao@dlu.edu.cn RI Cheng, Wenwen/OGP-2928-2025 FU Korea Food Research Institute [2017029]; National Natural Science Foundation of China [61671098] FX This paper was supported by the Korea Food Research Institute funded project (2017029) and the National Natural Science Foundation of China (61671098) . 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This study used liquid chromatography-tandem mass spectrometry (LC-MS) to profile the bioactive compounds of ginger-processed EC (G-EC), focusing on its absorbed constituents and metabolic fate in vivo . Network pharmacology identified geniposidic acid (GPA) as a key bioavailable compound in G-EC, potentially alleviating RA. In vivo , GPA significantly improved RA symptoms. Additionally, exosomes from inflammatory fibroblast-like synoviocytes (FLSs) (LPS-exo) promoted M1 macrophage polarization, glycolytic activation, and synovial inflammation. GPA inhibited glycolysis, reduced M1 polarization induced by LPS-exo, and downregulated H3K56la histone lactylation. Mechanistic analysis suggested these effects involve the regulation of ATP-citrate lyase (ACLY) and Histone deacetylase 6 (HDAC6) expression. This study supports the therapeutic potential of GPA in RA and provides a foundation for further clinical research. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies. C1 [Pan, Yijing; Deng, Chenxi; Liu, Xinyue; Wang, Shunshun; Xu, Kang] Hubei Univ Chinese Med, Hubei Prov Engn Technol Res Ctr Chinese Med Proc, Sch Pharm, Wuhan, Peoples R China. [Pan, Yijing; Deng, Chenxi; Liu, Xinyue; Wang, Shunshun; Chen, Lin; Li, Anzheng; Xu, Kang; Wang, Chunli] Hubei Shizhen Lab, Wuhan, Peoples R China. [Chen, Lin; Li, Anzheng; Wang, Chunli] Hubei Univ Chinese Med, Sch Lab Med, Wuhan, Peoples R China. [Shu, Jinsong] Hubei Univ Chinese Med, Sch Chinese Med, Wuhan, Peoples R China. [Ku, Xiong] Hosp Wuhan Univ Sci & Technol, Dept Rehabil Med, Wuhan, Peoples R China. C3 Hubei University of Chinese Medicine; Hubei University of Chinese Medicine; Hubei University of Chinese Medicine; Wuhan University of Science & Technology RP Ku, X (corresponding author), Hosp Wuhan Univ Sci & Technol, Dept Rehabil Med, Wuhan, Peoples R China.; Shu, JS; Xu, K; Wang, CL (corresponding author), Hubei Univ Chinese Med, Wuhan 430065, Peoples R China. EM sjs197844@hbucm.edu.cn; kangxu05@hbucm.edu.cn; kuxiong@wust.edu.cn; lilywang@cqu.edu.cn RI wang, Shunshun/LRB-4854-2024; Xu, Kang/AAB-5737-2019 OI Xu, Kang/0000-0002-8492-2058 FU Science and Technology Special Project of the National Administration of Traditional Chinese Medicine [GZY-KJS-2025-010]; Natural Science Foundation of Hubei Province, China [2025AFD483]; Young Elite Scientists Sponsorship Program by the China Association of Chinese Medicine [CACM-2023-QNRC2-B06]; Project of Hubei Province Traditional Chinese Medicine Innovation Team [ZY2025J002]; Hubei Provincial Science and Technology Plan Project [2025BCB043] FX This work was supported by the Science and Technology Special Project of the National Administration of Traditional Chinese Medicine (GZY-KJS-2025-010) , the Natural Science Foundation of Hubei Province, China (2025AFD483) , and the Young Elite Scientists Sponsorship Program by the China Association of Chinese Medicine (CACM-2023-QNRC2-B06) , Project of Hubei Province Traditional Chinese Medicine Innovation Team (ZY2025J002) , Hubei Provincial Science and Technology Plan Project (2025BCB043) . 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PD APR PY 2026 VL 150 AR 110213 DI 10.1016/j.jnutbio.2025.110213 EA APR 2025 PG 13 WC Biochemistry & Molecular Biology; Nutrition & Dietetics WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA AS0NL UT WOS:001655398000001 PM 41330460 DA 2026-03-26 ER PT J AU Shi, YY Zhang, YH Cai, YS Yan, ZM Jing, Y Zhu, Y Li, H Zheng, GZ Chen, J Yang, XY Huang, Y Gan, YM Han, Y Yong, H Xiong, QP AF Shi, Yingying Zhang, Yuhan Cai, Yisa Yan, Zhimin Jing, Yi Zhu, Yong Li, Heng Zheng, Guangzhen Chen, Jie Yang, Xiaoyao Huang, Yi Gan, Yimin Han, Yun Yong, Hui Xiong, Qingping TI Key proteins identification of Buyang Huanwu Decoction in regulating macrophage polarization to alleviate atherosclerosis via an integrated strategy combining network pharmacology, batch molecular docking and experimental verification SO INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES LA English DT Article DE Buyang Huanwu Decoction; Macrophage polarization and atherosclerosis; Core protein pathway mechanism AB Buyang Huanwu Decoction (BYHWD) effectively treats atherosclerosis (AS), but its unclear mechanism limits clinical use. Traditional mechanism research strategies overlook BYHWD's multi-target synergy, while conventional network pharmacology neglects its organelle-level Supplement Qi function. The purpose of this paper was to decipher the mechanism of BYHWD in regulating macrophage polarization to mitigate AS via a novel integrated strategies combining network pharmacology, batch molecular docking, and experimental verification. Firstly, BYHWD was confirmed to significantly improve macrophage polarization to reduce AS. Then, using network pharmacological analysis, TP53, AKT1, and BCL2 were identified as core targets of BYHWD in regulation of macrophage polarization to alleviate AS and its key biological processes was found be mitochondrial function and metabolism. Meanwhile, main material basis of BYHWD was clarified by batch molecular docking as 3-O-p-coumaroylquinic acid, D-mandelonitrile, Ellagic acid, Ferulic acid, 5-hydroxy-L-tryptophan zwitterion, Isoliquiritigenin, Senkyunolide-F, Anofinic acid, Trimethylhydroquinone and Senkyunolide-E. On this basis, in vitro experiments confirmed that TP53, AKT1, and BCL2 were critical targets in BYHWD that restore mitochondrial function and regulate macrophage polarization to alleviate AS. This study clarified BYHWD's mechanism and offered a novel approach for studying traditional Chinese medicine. Future work should advance clinical applications and develop BYHWD-based therapies targeting macrophage polarization in AS. C1 [Shi, Yingying; Zhang, Yuhan; Cai, Yisa; Jing, Yi; Zhu, Yong; Li, Heng; Zheng, Guangzhen; Chen, Jie; Yang, Xiaoyao; Huang, Yi; Xiong, Qingping] Huaiyin Inst Technol, Jiangsu Key Lab Reg Specif Resource Pharmaceut Tra, Huaian 223003, Jiangsu, Peoples R China. [Gan, Yimin] Xuzhou Med Univ, Affiliated Huaian Hosp, Dept Rehabil, Huaian 223002, Jiangsu, Peoples R China. [Yan, Zhimin] Nanjing Univ Tradit Chinese Med, Huaian Hosp Tradit Chinese Med, Affiliated Hosp, Dept Pharm, Huaian 223002, Jiangsu, Peoples R China. [Yong, Hui] Yangzhou Univ, Peoples Hosp Huaian 5, Huaian Hosp, Dept Cardiol, Huaian 223000, Jiangsu, Peoples R China. [Han, Yun] Binzhou Med Univ, Sch Tradit Chinese Med, Yantai 264003, Shandong, Peoples R China. C3 Huaian University; Xuzhou Medical University; Nanjing University of Chinese Medicine; Yangzhou University; Binzhou Medical University RP Xiong, QP (corresponding author), Huaiyin Inst Technol, Jiangsu Key Lab Reg Specif Resource Pharmaceut Tra, Huaian 223003, Jiangsu, Peoples R China.; Gan, YM (corresponding author), Xuzhou Med Univ, Affiliated Huaian Hosp, Dept Rehabil, Huaian 223002, Jiangsu, Peoples R China.; Yong, H (corresponding author), Yangzhou Univ, Peoples Hosp Huaian 5, Huaian Hosp, Dept Cardiol, Huaian 223000, Jiangsu, Peoples R China.; Han, Y (corresponding author), Binzhou Med Univ, Sch Tradit Chinese Med, Yantai 264003, Shandong, Peoples R China. EM ganyimin2008@163.com; hykh888@163.com; HAWYyonghui@163.com; qpxiong@gmail.com RI Yang, Xiaoyao/PFJ-2180-2025; Zhang, Yan/G-7208-2016; shi, yingying/E-1112-2015; Cai, Yisa/OXC-8879-2025; Zhu, Yong/HGU-1521-2022 FU National Natural Science Foundation of China [82474116]; Key Research and Development Program (Social Development) Project of Jiangsu Province of China [BE2023746]; Project of Science and Technology Development of Traditional Chinese Medicine in Jiangsu Province of China [MS2022157, MS2022156]; China Postdoctoral Science Foundation [2023M740019]; Research Activities for Postdoctoral Researchers in Anhui Province [2023B724]; Postgraduate Research & Practice Innovation Program of Jiangsu Province [SJCX24_135]; Project of Huaian city health research in Jiangsu Province of China [HAWJ2024033] FX This work was partly supported by the National Natural Science Foundation of China (No. 82474116) , Key Research and Development Program (Social Development) Project of Jiangsu Province of China (No. BE2023746) , Project of Science and Technology Development of Traditional Chinese Medicine in Jiangsu Province of China (No. MS2022157 and No. MS2022156) , China Postdoctoral Science Foundation (No. 2023M740019) , Research Activities for Postdoctoral Researchers in Anhui Province (No. 2023B724) , Postgraduate Research & Practice Innovation Program of Jiangsu Province (No. SJCX24_135) , Project of Huaian city health research in Jiangsu Province of China (No. HAWJ2024033) . 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PD MAY PY 2025 VL 310 AR 143380 DI 10.1016/j.ijbiomac.2025.143380 EA APR 2025 PN 3 PG 20 WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 2FY7M UT WOS:001481735600001 PM 40258538 DA 2026-03-26 ER PT J AU Li, JL Cao, JR Zhang, ZY Wang, SZ Zhu, M Yang, LL Ouyang, WH Ma, CZ AF Li, Jilei Cao, Jiarui Zhang, Zhenyu Wang, Sizhe Zhu, Meng Yang, Lili Ouyang, Wenhui Ma, Chunzheng TI Mechanism study on the treatment of ulcerative colitis by Gegen Qinlian nano-preparation through promoting M2 macrophage polarization SO FRONTIERS IN MOLECULAR BIOSCIENCES LA English DT Article DE ulcerative colitis; Gegen Qinlian nano-preparation; nanoparticle-targeted traditional Chinese medicine; macrophages; polarization AB Objective To address the core pathological features of intestinal barrier disruption and immune imbalance in ulcerative colitis (UC), we developed a nano-targeted formulation (GGQL nano-preparation) based on berberine, puerarin, baicalin, and glycyrrhizin by combining traditional Chinese medicine (TCM) and nanotechnology in this study. We aimed to investigate whether GGQL nano-preparation could promote M2 macrophage polarization, correct intestinal inflammation, and treat UC.Methods We used databases to identify M2 macrophage-related gene targets for GGQL nano-preparation in UC. Protein-protein interaction networks, topological analysis, and GO/KEGG enrichment analyses revealed GGQL nano-preparation's potential regulation of macrophage polarization via a specific pathway. We validated this using a dextran sulfate sodium (DSS)-induced UC model in C57BL/6 mice. Parameters assessed included the disease activity index (DAI), colon length, colitis macroscopic damage index (CMDI), spleen index, and pathological changes (via HE staining). Immunohistochemistry detected AMPK-PPAR axis factor changes to determine GGQL nano-preparation's impact on M2 macrophage polarization and intestinal inflammation.Results Our analyses suggested the GGQL nano-preparation reduced the DAI, enhanced colon length, improved CMDI scores, and mitigated splenic inflammation. HE staining showed GGQL nano-preparation alleviated inflammation in the spleen, lungs, and colon. Immunohistochemical findings indicated GGQL nano-preparation upregulated AMPK, PPAR, and SIRT1 expression. Mechanistically, GGQL nano-preparation promoted M2 macrophage polarization through the AMPK-PPAR gamma axis, achieving therapeutic objectives for UC.Conclusion The GGQL nano-preparation effectively promotes M2 macrophage polarization via the AMPK-PPAR gamma axis, treating UC. C1 [Li, Jilei; Ma, Chunzheng] Henan Univ Chinese Med, Henan Prov Hosp TCM, Affiliated Hosp 2, Zhengzhou, Henan, Peoples R China. [Cao, Jiarui; Zhang, Zhenyu; Wang, Sizhe; Zhu, Meng; Ouyang, Wenhui] Henan Univ Chinese Med, Clin Med Coll 2, Zhengzhou, Henan, Peoples R China. [Yang, Lili] Kaifeng Cent Hosp, Kaifeng, Henan, Peoples R China. C3 Henan University of Traditional Chinese Medicine; Henan University of Traditional Chinese Medicine RP Ma, CZ (corresponding author), Henan Univ Chinese Med, Henan Prov Hosp TCM, Affiliated Hosp 2, Zhengzhou, Henan, Peoples R China. EM 15670259809@163.com FU Henan Provincial Hospital of Traditional Chinese Medicine Doctoral Fund [2024BSJJ10]; Leading Talents of Henan Province [[2021]-8, 2024KYCX073] FX The authors used the services and facilities of the Central Laboratory of Henan Provincial Hospital of Traditional Chinese Medicine. 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Mol. Biosci. PD APR 25 PY 2025 VL 12 AR 1580874 DI 10.3389/fmolb.2025.1580874 PG 15 WC Biochemistry & Molecular Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology GA 2IW6S UT WOS:001483717200001 PM 40351533 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Wang, XJ Zhao, HY Lin, WY Fan, WX Zhuang, TX Wang, X Li, Q Wei, XH Wang, ZT Chen, KX Yang, L Ding, LL AF Wang, Xunjiang Zhao, Hanyang Lin, Wenyuan Fan, Wenxiang Zhuang, Tongxi Wang, Xu Li, Qi Wei, Xiaohui Wang, Zhengtao Chen, Kaixian Yang, Li Ding, Lili TI Panax notoginseng saponins ameliorate LPS-induced acute lung injury by promoting STAT6-mediated M2-like macrophage polarization SO PHYTOMEDICINE LA English DT Article DE Panax notoginseng saponins; Acute lung injury; Signal transducer and activator of transcription; M2-like macrophages ID ACTIVATION AB Background: Acute lung injury (ALI) is a severe inflammatory condition characterized by dysregulated immune responses and high mortality rates, with limited effective therapeutic options currently available. Panax notoginseng saponins (PNS), bioactive compounds derived from Panax notoginseng, have shown promise in mitigating lipopolysaccharide (LPS)-induced ALI. However, the molecular mechanisms underlying their therapeutic effects remain poorly understood. Given the critical role of M2-like macrophage polarization in resolving inflammation and promoting tissue repair, we investigated whether PNS exerts its protective effects in ALI by modulating this process. Furthermore, we explored the specific involvement of the signal transducer and activator of transcription 6 (STAT6) pathway in mediating these effects. Methods: Chemical profiling of PNS was performed using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), followed by quantitative analysis of its major bioactive components via high-performance liquid chromatography (HPLC). To evaluate the therapeutic efficacy of PNS and its principal constituents, we established an ALI mouse model through intratracheal administration of LPS. Comprehensive assessments included lung field shadowing, oxygen saturation levels, pulmonary function, and systematic histopathological examination. The regulatory effects of PNS on macrophage polarization were examined in THP-1 cells and bone marrow-derived macrophages (BMDMs), with cellular phenotypes analyzed by flow cytometry. To elucidate the mechanistic role of STAT6 in PNS-mediated protection, experiments were conducted using Stat6-deficient BMDMs and Stat6 knockout mice. Results: UPLC-Q-TOF-MS and HPLC identified and quantified the principal components of PNS: Notoginsenoside R1, Ginsenoside Rg1, Ginsenoside Re, and Ginsenoside Rb1. PNS treatment dose-dependently reduced inflammatory responses in LPS-induced ALI mice, as evidenced by decreased cytokine levels. Each of the four major PNS components independently alleviated ALI symptoms in mice. Pathway analysis revealed 56 potential ALIrelated targets, with Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment suggesting that PNS exerts its protective effects by modulating inflammatory signaling pathways. In vitro studies demonstrated that PNS promoted STAT6 phosphorylation and nuclear translocation, enhancing M2-like macrophage polarization and interleukin-10 (IL-10) secretion in a STAT6-dependent manner. Genetic ablation of Stat6 partially reversed the protective effects of PNS on ALI, macrophage polarization, and IL-10 production, confirming the pivotal role of STAT6 in mediating PNS activity. Conclusion: This study demonstrates that PNS alleviates LPS-induced ALI by promoting STAT6-dependent M2-like macrophage polarization, highlighting its potential as a therapeutic agent for ALI. These findings provide mechanistic insights into the anti-inflammatory actions of PNS and underscore the importance of STAT6 signaling in its protective effects. C1 [Wang, Xunjiang; Zhao, Hanyang; Fan, Wenxiang; Zhuang, Tongxi; Wang, Xu; Li, Qi; Wei, Xiaohui; Wang, Zhengtao; Chen, Kaixian; Yang, Li; Ding, Lili] Shanghai Univ Tradit Chinese Med, Shanghai Key Lab Complex Prescript, Shanghai 201203, Peoples R China. [Wang, Xunjiang; Zhao, Hanyang; Fan, Wenxiang; Zhuang, Tongxi; Wang, Xu; Li, Qi; Wei, Xiaohui; Wang, Zhengtao; Chen, Kaixian; Yang, Li; Ding, Lili] Shanghai Univ Tradit Chinese Med, Minist Educ MOE, Key Lab Standardizat Chinese Med, Shanghai 201203, Peoples R China. [Wang, Xunjiang; Zhao, Hanyang; Fan, Wenxiang; Zhuang, Tongxi; Wang, Xu; Li, Qi; Wei, Xiaohui; Wang, Zhengtao; Chen, Kaixian; Yang, Li; Ding, Lili] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, State Adm Tradit Chinese Med SATCM, Key Lab New Resources & Qual Evaluat Chinese Med, Shanghai 201203, Peoples R China. [Wang, Xunjiang; Fan, Wenxiang; Zhuang, Tongxi; Wang, Xu; Li, Qi; Wei, Xiaohui; Wang, Zhengtao; Chen, Kaixian; Yang, Li; Ding, Lili] Shanghai R&D Ctr Standardizat Tradit Chinese Med, Shanghai 201203, Peoples R China. [Lin, Wenyuan] Shanghai Univ Tradit Chinese Med, Shanghai Municipal Hosp Tradit Chinese Med, Endocrinol Dept, Shanghai 200071, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine RP Chen, KX; Yang, L; Ding, LL (corresponding author), Shanghai Univ Tradit Chinese Med, Inst Tradit Chinese Mat Med, Cai Lun Rd 1200, Shanghai 201203, Peoples R China. EM kxchen@simm.ac.cn; yl7@shutcm.edu.cn; liliding@shutcm.edu.cn RI Lin, Wenyuan/OGO-3924-2025; Wang, Zhengtao/AAH-7360-2019 OI Lin, Wenyuan/0009-0002-0121-3887; Wang, Zhengtao/0000-0003-2797-4625; Wang, Xunjiang/0009-0006-4973-3039 FU Na-tional Natural Science Foundation of China [U24A20792, 82122074, 81920108033, 82130115, 82274165]; Traditional Chinese Medicine Research Project of Shanghai Municipal Health Commission [2024PT007]; Organizational Key Research and Development Program of Shanghai University of Tradi-tional Chinese Medicine [2023YZZ01, 2023YZZ02] FX This work was supported by the following funding sources: the Na-tional Natural Science Foundation of China (grant nos U24A20792, 82122074, 81920108033, 82130115, and 82274165) , the Traditional Chinese Medicine Research Project of Shanghai Municipal Health Commission (grant no 2024PT007) , and the Organizational Key Research and Development Program of Shanghai University of Tradi-tional Chinese Medicine (grant nos 2023YZZ01 and 2023YZZ02) . 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Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA Y8T3U UT WOS:001434772500001 PM 40010033 DA 2026-03-26 ER PT J AU Zheng, ZM Du, YZ Jiang, H Shi, ZP Zhou, HL Jiao, LJ Liu, PF Gong, YB AF Zheng, Zongmei Du, Yizhao Jiang, Hua Shi, Zhenpeng Zhou, Hailun Jiao, Lijing Liu, Peifeng Gong, Yabin TI KAJF alleviated colorectal cancer liver metastasis by reshaping the gut microbiota and inhibiting M2-like macrophage polarization SO PHYTOMEDICINE LA English DT Article DE Colorectal cancer; Metastasis; Gut microbiota; Macrophages; Kang-Ai-Jing-Fang AB Background: Colorectal cancer liver metastasis (CRLM) represents one of the most severe complications of colorectal cancer (CRC), often associated with unfavorable prognosis. The herbal formulation Kang-Ai-Jing-Fang (KAJF) has been employed clinically against CRC for several decades, although its precise mechanism of action remains elusive. Purpose: This study investigates the anti-metastatic potential of KAJF in CRLM, focusing on its modulatory effects on gut microbiota and inhibition of M2-like macrophage activation. Methods: KAJF was administered orally to CRLM model mice established through intrasplenic injection of murine CRC cells. To elucidate the role of gut microbiota reshaped by KAJF, fecal microbiota transplantation (FMT) was utilized to assess its impact on CRLM inhibition. Core targets and active compounds were identified through network pharmacology and molecular docking. To characterize microbiota composition, metabolite profiles, and gene expression variations, 16S rRNA sequencing, untargeted liquid chromatography-mass spectrometry (LCMS/MS) metabolomics, and transcriptomics analyses were performed. Results: KAJF demonstrated significant inhibitory effects on CRLM and ameliorated gut microbiota dysbiosis by enhancing the abundance of butyrate-producing bacteria (Lactobacillus, Bacteroides, Bifidobacterium). The therapeutic efficacy of KAJF-induced bacterial alterations in delaying CRLM and promoting butyrate-producing microbiota enrichment was further substantiated by FMT. Network pharmacology identified active ingredients in KAJF, including asperulosidic acid, polyphyllin II, ganoderenic acid B, calycosin, and ganoderic acid C, which exhibit substantial interactions with TLR4, PPAR gamma, SIRT1, PTGS2, and TNF. Molecular dynamics simulations and surface plasmon resonance (SPR) analysis demonstrated that ganoderic acid C2 exhibits a strong binding affinity for PPAR gamma. Moreover, KAJF administration led to a marked reduction in F4/80+ CD206+ macrophages and their associated cytokines (CCL17, CCL22, IL10, IL4, TGF), accompanied by a decrease in CD4+ T cells and myeloidderived suppressor cells (MDSCs), while increasing CD8+ T cell populations. Conclusions: This study demonstrates that KAJF mitigates CRLM, primarily through the regulation of gut microbiota and microbial metabolites, alongside inhibition of M2-like macrophage polarization. By integrating metabolomics, transcriptomics, and network pharmacology, this research elucidates the molecular mechanisms underpinning KAJF's therapeutic effects against CRLM, offering a promising approach for clinical intervention. C1 [Zheng, Zongmei; Du, Yizhao; Jiang, Hua; Shi, Zhenpeng; Zhou, Hailun; Jiao, Lijing; Gong, Yabin] Shanghai Univ Tradit Chinese Med, Yueyang Hosp Integrated Tradit Chinese & Western M, Dept Oncol, Shanghai 200437, Peoples R China. [Liu, Peifeng] Shanghai Jiao Tong Univ, Renji Hosp, Shanghai Canc Inst, Sch Med,State Key Lab Syst Med Canc, Shanghai 200032, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine; Shanghai Jiao Tong University RP Gong, YB (corresponding author), Shanghai Univ Tradit Chinese Med, Yueyang Hosp Integrated Tradit Chinese & Western M, Dept Oncol, Shanghai 200437, Peoples R China.; Liu, PF (corresponding author), Shanghai Jiao Tong Univ, Renji Hosp, Shanghai Canc Inst, Sch Med,State Key Lab Syst Med Canc, Shanghai 200032, Peoples R China. EM lpf@sjtu.edu.cn; gongyabin@shutcm.edu.cn RI ; DU, YIZHAO/HDM-8789-2022; Liu, Pei-Feng/NRB-2244-2025 OI Zhou, Hailun/0009-0000-1701-1142; FU China Postdoctoral Science Foundation [2024M762104]; Project of Postdoctoral Fellowship Program of China Postdoctoral Science Foundation [GZC20231709]; Shanghai Postdoctoral Excellence Program [2023552]; Shanghai "Science and Technology Innovation Action Plan" medical innovation research special project of major difficult disease diagnosis and treatment strategy clinical research [22Y31920103] FX This work was supported by China Postdoctoral Science Foundation (No 2024M762104) , the project of Postdoctoral Fellowship Program of China Postdoctoral Science Foundation (No GZC20231709) , Shanghai Postdoctoral Excellence Program (No 2023552) , Shanghai "Science and Technology Innovation Action Plan" medical innovation research special project of major difficult disease diagnosis and treatment strategy clinical research (No 22Y31920103) . 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Emerging evidence highlights the intricate interplay between ROS, microRNAs (miRNAs), and exosomes within the tumor microenvironment (TME), forming a regulatory axis that modulates immune responses, angiogenesis, and therapeutic resistance. In particular, oxidative stress not only stimulates exosome biogenesis but also influences the selective packaging of redox-sensitive miRNAs (miR-21, miR-155, and miR-210) via RNA-binding proteins such as hnRNPA2B1 and SYNCRIP. These miRNAs, delivered through exosomes, alter gene expression in recipient cells and promote tumor-supportive phenotypes such as M2 macrophage polarization, CD8+ T-cell suppression, and endothelial remodeling. This review systematically explores how this ROS-miRNA-exosome axis orchestrates communication across immune and stromal cell populations under hypoxic and inflammatory conditions. Particular emphasis is placed on the role of NADPH oxidases, hypoxia-inducible factors, and autophagy-related mechanisms in regulating exosomal output. In addition, we analyze the therapeutic relevance of natural products and herbal compounds-such as curcumin, resveratrol, and ginsenosides-which have demonstrated promising capabilities to modulate ROS levels, miRNA expression, and exosome dynamics. We further discuss the clinical potential of leveraging this axis for cancer therapy, including strategies involving mesenchymal stem cell-derived exosomes, ferroptosis regulation, and miRNA-based immune modulation. Incorporating insights from spatial transcriptomics and single-cell analysis, this review provides a mechanistic foundation for the development of exosome-centered, redox-modulating therapeutics. Ultimately, this work aims to guide future research and drug discovery efforts toward integrating herbal medicine and redox biology in the fight against cancer. C1 [Park, Moon Nyeo; Kim, Myoungchan; Lee, Soojin; Kang, Sojin; Ahn, Chi-Hoon; Kim, Woojin; Kim, Bonglee] Kyung Hee Univ, Coll Korean Med, 1-5 Hoegidong, Seoul 02447, South Korea. [Tallei, Trina Ekawati] Univ Sam Ratulangi, Fac Math & Nat Sci, Dept Biol, Manado 95115, Indonesia. [Tallei, Trina Ekawati] Univ Sam Ratulangi, Fac Med, Dept Biol, Manado 95115, Indonesia. [Kim, Woojin; Kim, Bonglee] Kyung Hee Univ, Coll Korean Med, Korean Med Based Drug Repositioning Canc Res Ctr, Seoul 02447, South Korea. C3 Kyung Hee University; Universitas Sam Ratulangi; Universitas Sam Ratulangi; Kyung Hee University RP Kim, B (corresponding author), Kyung Hee Univ, Coll Korean Med, 1-5 Hoegidong, Seoul 02447, South Korea.; Kim, B (corresponding author), Kyung Hee Univ, Coll Korean Med, Korean Med Based Drug Repositioning Canc Res Ctr, Seoul 02447, South Korea. EM mnpark@khu.ac.kr; dongoorai@khu.ac.kr; lettergr@khu.ac.kr; bmb1994@khu.ac.kr; ach2565@khu.ac.kr; trina_tallei@unsrat.ac.id; wjkim@khu.ac.kr; bongleekim@khu.ac.kr RI Kim, Bonglee/AAH-9077-2020; Tallei, Trina Ekawati/U-1322-2019; Kim, Woojin/AAK-2464-2020 OI Kim, Bonglee/0000-0002-8678-156X; sojin, kang/0009-0009-4479-8724; Tallei, Trina Ekawati/0000-0002-7963-7527; Kim, Woojin/0000-0001-8494-4524; park, moon nyeo/0000-0002-9276-3894 FU Ministry of Education [NRF-2020R1I1A2066868]; Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [RS-2024-00350362]; National Research Foundation of Korea (NRF) - Korean government (MSIT) [RS-2020-KH087790, RS-2024-00507224]; Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea; Ministry of SMEs and Startups (MSS, Korea) FX This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2020R1I1A2066868), the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2020R1A5A2019413), a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: RS-2020-KH087790), the Starting Growth Technological R&D Program (TIPS Program, No. RS-2024-00507224) funded by the Ministry of SMEs and Startups (MSS, Korea) in 2024, and the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (RS-2024-00350362). 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SWITZERLAND EI 2076-3921 J9 ANTIOXIDANTS-BASEL JI Antioxidants PD APR 22 PY 2025 VL 14 IS 5 AR 501 DI 10.3390/antiox14050501 PG 25 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Food Science & Technology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Food Science & Technology GA 3AS7R UT WOS:001495861900001 PM 40427384 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Dabravolski, SA Popov, MA Utkina, AS Babayeva, GA Maksaeva, AO Sukhorukov, VN Orekhov, AN AF Dabravolski, Siarhei A. Popov, Mikhail A. Utkina, Aleksandra S. Babayeva, Gulalek A. Maksaeva, Anastasia O. Sukhorukov, Vasily N. Orekhov, Alexander N. TI Preclinical and mechanistic perspectives on adipose-derived stem cells for atherosclerotic cardiovascular disease treatment SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Review DE Atherosclerosis; Macrophage polarisation; Inflammation; Adipose-derived mesenchymal stem cells; Exosomes; Micrornas ID EXTRACELLULAR VESICLES; MYOCARDIAL-ISCHEMIA; ENDOTHELIAL-CELLS; M2 MACROPHAGES; STROMAL CELLS; RISK; INFLAMMATION; SECRETION; EXOSOMES; THERAPY AB Adipose-derived mesenchymal stem cells (AD-MSCs) are a promising therapeutic modality for cardiovascular diseases due to their immunomodulatory, anti-inflammatory, and pro-angiogenic properties. This manuscript explores the current status, challenges, and future directions of AD-MSC therapies, focusing on their application in atherosclerosis (AS), myocardial infarction (MI), and heart failure (HF). Preclinical studies highlight AD-MSC's ability to stabilise atherosclerotic plaques, reduce inflammation, and enhance myocardial repair through mechanisms such as macrophage polarisation, endothelial protection, and angiogenesis. Genetically and pharmacologically modified AD-MSCs, including those overexpressing SIRT1, IGF-1, and PD-L1 or primed with bioactive compounds, exhibit superior efficacy compared to unmodified cells. These modifications enhance cell survival, immunopotency, and reparative capacity, showcasing the potential for tailored therapies. However, clinical translation faces significant hurdles. While recent clinical trials have confirmed the safety of AD-MSC therapy, their efficacy remains inconsistent, necessitating further optimisation of patient selection, dosing strategies, and delivery methods. Donor variability, particularly in patients with co-morbidities like type 2 diabetes (T2D) or obesity, impairs AD-MSC efficacy. Emerging research on extracellular vesicles (EVs) derived from AD-MSC offers a promising cell-free alternative, retaining the therapeutic benefits while mitigating risks. Future perspectives emphasise the need for multidisciplinary approaches to overcome these limitations. Strategies include refining genetic modifications, exploring EV-based therapies, and integrating personalised medicine and advanced diagnostic tools. By addressing these challenges, AD-MSC therapies hold the potential to revolutionise the treatment of cardiovascular diseases, providing innovative solutions to improve patient outcomes. C1 [Dabravolski, Siarhei A.] Braude Acad Coll Engn, Dept Biotechnol Engn, Snunit 51,POB 78, Karmiel 2161002, Israel. [Popov, Mikhail A.; Maksaeva, Anastasia O.; Sukhorukov, Vasily N.] Inst Gen Pathol & Pathophysiol, 8 Baltiyskaya St, Moscow 125315, Russia. [Utkina, Aleksandra S.] Plekhanov Russian Univ Econ, Dept Commod Expertise & Customs Business, 36 Stremyanny Lane, Moscow 115054, Russia. [Babayeva, Gulalek A.] Natl Med Res Ctr Cardiol, Inst Expt Cardiol, 15A 3-rd Cherepkovskaya Str, Moscow 121552, Russia. [Maksaeva, Anastasia O.] Sechenov First Moscow State Med Univ, Bldg 2 8,Trubetskaya St, Moscow 119991, Russia. [Sukhorukov, Vasily N.] Petrovsky Russian Natl Ctr Surg, Inst Human Morphol, 2 Abrikosovsky Lane, Moscow 119991, Russia. [Orekhov, Alexander N.] Natl Res Univ Higher Sch Econ, Fac Biol & Biotechnol, 33 Profsoyuznaya St,Bldg 4, Moscow 117418, Russia. C3 Braude Academic College of Engineering; Russian Academy of Medical Sciences; Institute of General Pathology & Pathophysiology, RAMS; Plekhanov Russian University of Economics; National Medical Research Center of Cardiology; Sechenov First Moscow State Medical University; Russian Academy of Medical Sciences; Research Institute of Human Morphology; HSE University (National Research University Higher School of Economics) RP Dabravolski, SA (corresponding author), Braude Acad Coll Engn, Dept Biotechnol Engn, Snunit 51,POB 78, Karmiel 2161002, Israel. EM sergedobrowolski@gmail.com; popovcardio88@mail.ru; ytkinaas@yandex.ru; babaevagulyalek@gmail.com; omisuh86@gmail.com; vnsukhorukov@gmail.com; alexandernikolaevichorekhov@gmail.com RI Babayeva, Gulalek/AAV-2338-2021; Dabravolski, Siarhei/E-8303-2015; Sukhorukov, Vasily/H-6545-2016; Popov, Mikhail/HIR-7175-2022 FU Russian Science Foundation FX Not applicable. 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Cell. Biochem. PD AUG PY 2025 VL 480 IS 8 BP 4647 EP 4670 DI 10.1007/s11010-025-05285-0 EA APR 2025 PG 24 WC Cell Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology GA 5SF7I UT WOS:001467028100001 PM 40234340 DA 2026-03-26 ER PT J AU Mai, YY Huang, LH Qiao, Y Qin, Y Wang, LF Liao, HB AF Mai, Yuying Huang, Linhui Qiao, Yang Qin, Yuan Wang, Lufei Liao, Hongbing TI The Potential of Siraitia grosvenorii to Promote Bone Regeneration via Modulating Macrophage Polarization: A Network Pharmacology and Experimental Study SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE Siraitia grosvenorii; bone defect healing; network pharmacology; macrophage polarization; osteogenic differentiation AB Siraitia grosvenorii (SG), a traditional Chinese medicinal herb, possesses immunomodulatory and osteoinductive properties, yet its pharmacological mechanisms in bone defect repair remain largely unexplored. This study investigates the therapeutic potential of SG through a combination of network pharmacology and experimental approaches. Active compounds were identified using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) Platform, and protein interaction targets were predicted. Molecular docking and dynamics simulations assessed interactions between SG compounds and critical targets. In vitro, RAW 264.7 macrophages treated with SG-conditioned medium exhibited enhanced M2 polarization and reduced inflammation, promoting osteogenic differentiation of co-cultured MC3T3-E1 cells as evidenced by increased alkaline phosphatase activity. In vivo, scaffolds loaded with low-dose or high-dose SG (LSG/HSG) significantly improved bone regeneration in rat calvarial defects, with HSG achieving near-complete repair and mature trabeculae at 8 weeks, alongside decreased CD86 and TNF-alpha levels and increased IL-10 expression. Network pharmacology identified 33 shared targets related to bone regeneration and macrophage polarization, with kaempferol and beta-sitosterol demonstrating strong binding affinities to targets such as TNF, PTGS2, and CASP3. These findings highlight the potential of SG in enhancing bone defect repair and its implications for regenerative medicine. C1 [Mai, Yuying; Huang, Linhui; Qiao, Yang; Qin, Yuan; Wang, Lufei; Liao, Hongbing] Guangxi Med Univ, Coll Stomatol, Shuangyong Rd 22, Nanning 530021, Peoples R China. [Mai, Yuying; Huang, Linhui; Qiao, Yang; Qin, Yuan; Wang, Lufei; Liao, Hongbing] Guangxi Key Lab Oral & Maxillofacial Rehabil & Rec, Nanning 530021, Peoples R China. C3 Guangxi Medical University RP Wang, LF; Liao, HB (corresponding author), Guangxi Med Univ, Coll Stomatol, Shuangyong Rd 22, Nanning 530021, Peoples R China.; Wang, LF; Liao, HB (corresponding author), Guangxi Key Lab Oral & Maxillofacial Rehabil & Rec, Nanning 530021, Peoples R China. EM maiyuying@stu.gxmu.edu.cn; 202010151@sr.gxmu.edu.cn; qiaoyanggg@outlook.com; qinyuan777@126.com; wlfdentist@outlook.com; hongbing_liao@gxmu.edu.cn OI Mai, YuYing/0000-0002-6796-9970; Wang, Lufei/0000-0003-4691-2665 FU National Natural Science Foundation of China; Joint Project on Regional High-Incidence Diseases Research of Guangxi Natural Science Foundation [2023GXNSFBA026125]; Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction Research Open Project [GXKLOMRR2404]; [82360191] FX This work was supported by the National Natural Science Foundation of China (grant number 82160192), National Natural Science Foundation of China (grant number 82360191), Joint Project on Regional High-Incidence Diseases Research of Guangxi Natural Science Foundation (No. 2023GXNSFBA026125), and Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and Reconstruction Research Open Project (GXKLOMRR2404). 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J. Mol. Sci. PD APR 11 PY 2025 VL 26 IS 8 AR 3609 DI 10.3390/ijms26083609 PG 22 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry GA 1WI8P UT WOS:001475213700001 PM 40332137 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Li, XC Wang, ZM Chen, YR Yang, Y Shao, HR Feng, XZ Ren, YL AF Li, Xiaochen Wang, Zhimin Chen, Yiran Yang, Ying Shao, Hanrui Feng, Xiuzhi Ren, Yanling TI Regulation of monocyte polarization through nuclear factor Kappa B /inhibitor of Kappa B Alpha pathway by Cuscuta chinensis Lam. In postmenopausal osteoporosis SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Cuscuta chinensis lam. (CCL); Postmenopausal osteoporosis (PMOP); Nuclear factor Kappa B (NF-kappa B) /inhibitor of Kappa B Alpha (I kappa B alpha) signaling pathway; Mechanism ID MACROPHAGES; DIFFERENTIATION; INFLAMMATION AB Ethnopharmacological relevance: Cuscuta chinensis Lam. (CCL), is made from the dried mature seeds of a plant in the Convolvulaceae family. Predominantly distributed in China and several Asian countries, it has long been used to treat osteoporosis (OP) and other aging-related diseases. However, studies on the mechanisms of anti-OP compounds in CCL remain limited. Aim of the study: The objective of this study is to determine the bioactive constituents present in CCL and to elucidate their mechanisms of action in the prevention and treatment of postmenopausal osteoporosis (PMOP). This will be achieved by investigating the modulation of bone marrow macrophage polarization via the Nuclear Factor Kappa B (NF-kappa B)/Inhibitor of Kappa B Alpha (I kappa B alpha) signaling cascade. Materials and methods: CCL's chemical components were identified using UPLC-Q-TOF-MS. Blood components were analyzed for targets using databases. Pathway enrichment was performed via network pharmacology. We used an ovariectomy (OVX)-induced OP rat model to assess the effects of CCL extracts in comparison to a positive control drug. Osteogenic markers were analyzed. We utilized flow cytometry to assess macrophage marker expression, while quantitative PCR (qPCR) and Western blotting were employed to identify targets within the signaling pathways. Results: Seventeen chemical components were identified in CCL extracts, of which 14 were identified as prototype compounds absorbed into the bloodstream. Pathway enrichment analysis revealed that CCL's therapeutic effects on PMOP were closely associated with the NF-kappa B signaling pathway, specifically targeting NF-kappa B and I kappa B alpha proteins. Animal studies showed that high-dose CCL significantly lowered serum levels of tartrate-resistant acid phosphatase (TRACP) and c-terminal telopeptide of type I collagen (CTX) (p < 0.01) and increased levels of bone-specific alkaline phosphatase (BALP) and procollagen I c-terminal propeptide (PICP) (p < 0.01), indicating effective inhibition of bone resorption and promotion of bone formation. CCL treatment improved the microstructure of trabecular bone at the distal femur by reducing bone cavity spaces, increasing trabecular thickness, and enhancing trabecular alignment. CCL markedly enhanced the expression levels of osteoprotegerin (OPG), runt-related transcription factor 2 (Runx2), and alkaline phosphatase (ALP) genes and their corresponding proteins in the tibial tissue (p < 0.01), promoting osteoblast differentiation and function. Flow cytometry analysis showed that CCL modulated immune cell markers CD86 and CD163, supporting its anti-inflammatory effects in PMOP treatment. Furthermore, CCL regulated the NF-kappa B/I kappa B alpha signaling pathway by significantly decreasing NF-kappa B expression and increasing I kappa B alpha expression, thereby modulating inflammatory responses and bone metabolism. Conclusion: The active components in CCL effectively prevent and treat PMOP by modulating bone marrow macrophage polarization through the NF-kappa B/I kappa B alpha signaling pathway. C1 [Li, Xiaochen; Chen, Yiran; Yang, Ying; Shao, Hanrui; Feng, Xiuzhi; Ren, Yanling] Liaoning Univ Tradit Chinese Med, Coll Pharm, Shenyang 110000, Peoples R China. [Wang, Zhimin] Liaoning Univ Tradit Chinese Med, Affiliated Hosp, Shenyang 110000, Peoples R China. C3 Liaoning University of Traditional Chinese Medicine; Liaoning University of Traditional Chinese Medicine RP Feng, XZ; Ren, YL (corresponding author), Liaoning Univ Tradit Chinese Med, Coll Pharm, Shenyang 110000, Peoples R China.; Feng, XZ (corresponding author), Sch Liaoning Univ Tradit Chinese Med, Chongdong Rd 77, Shenyang 110000, Peoples R China. EM 215153259@qq.com; lnutcmwangzm@163.com; cyrlnutcm@163.com; 846081373@qq.com; 1547927532@qq.com; zgsyfxz@sina.com; lnutcmren@163.com FU National Natural Science Foundation project [82174260]; Liaoning Province Science and Technology Department joint fund doctoral research project [2023-BSBA-224] FX This study was supported by the National Natural Science Foundation project (NO.82174260) , Liaoning Province Science and Technology Department joint fund doctoral research project (NO:2023-BSBA-224). 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PD APR 25 PY 2025 VL 346 AR 119710 DI 10.1016/j.jep.2025.119710 EA APR 2025 PG 13 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 1GH6A UT WOS:001464338400001 PM 40154899 DA 2026-03-26 ER PT J AU Zhang, ZY Wang, Z Wan, WP Li, SM Yang, WZ Shi, XA AF Zhang, Zhiyun Wang, Zhen Wan, Weiping Li, Shumin Yang, Wenzhi Shi, Xinan TI KunMingShanHaiTang formula reprograms macrophage metabolism and promotes M2 polarization via the HIF-1α pathway to alleviate ulcerative colitis symptoms in a rat model SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE KMSHTF; HIF-1 alpha; Reprograms Metabolism; Macrophage polarization; Ulcerative colitis AB The KunMingShanHaiTang Formula (KMSHTF), adjusted by Professor Zhong Chuanhua for the treatment of ulcerative colitis (UC), is the work of a renowned veteran practitioner of Chinese medicine. However, its specific mechanism remains unknown. Consequently, it is intriguing to investigate the molecular mechanism by which KMSHTF treats UC. To elucidate the mechanism of KMSHTF in the treatment of UC in rats. Initially, the active ingredients and key target genes of KMSHTF in treating UC were analyzed using network pharmacology. Protein-Protein interaction and gene enrichment analyses were performed to predict key targets and pathways. Subsequently, UC rats were treated with KMSHTF, and the expression proteins in intestinal tissue were detected. Finally, the active compounds of KMSHTF intreating ulcerative colitis were further screened using Molecular Docking, and their pharmacological effects were validated through cell experiments. A total of 47 active compounds and 365 key target genes of KMSHTF for UC treatment were identified through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,along with the GeneCards database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Enrichment Analysis revealed that KMSHTF exerted its therapeutic effects on UC through regulating multiple pathways. In this study, the HIF-1 alpha pathway was selected as the main molecular pathway of KMSHTF treating UC, and further validation was conducted through in vivo and in vitro experiments.Animal studies revealed that KMSHTF significantly ameliorated UC symptoms in rats, including diarrhea,rectal bleeding and specific pathological alterations in the intestinal wall. Furthermore, KMSHTF reduced pro-inflammatory cytokines IL-6 and TNF-alpha, up-regulated IL-4 of M2 macrophages and down-regulated iNOS and IL-1 beta of M1 macrophages. Additionally, it decreased the expression levels of HKII and GLUT1 related HIF-1 alpha pathway. The three active compounds of KMSHTF, Baicalein, Palmatine and Triptonide-were selected based on their strong binding affinity with HIF-1 alpha and HKII through computational molecular docking. Cellular experiments demonstrated that each of these compounds downregulated the protein expression levels of HIF-1 alpha, HKII, GLUT1 and IL-6 in an intestinal wall cell model. Of Note, Baicalein exhibited the most pronounced effect. However, the overexpression of HIF-1 alpha reversed the Baicalein-induced downregulation of HKII, GLUT1 and IL-6 at the protein level in vitro. KMSHTF may modulate macrophage metabolism to promote M2 polarization through the HIF-1 alpha pathway, thereby contributing to its therapeutic efficacy in ulcerative colitis (UC). Baicalein, Palmatine, and Triptonide are the three core active compounds of KMSHTF that primarily contribute to this hypothesis. C1 [Li, Shumin; Shi, Xinan] Yunnan Univ Chinese Med, Kunming 650500, Peoples R China. [Zhang, Zhiyun; Wang, Zhen; Wan, Weiping; Yang, Wenzhi] Yunnan Univ Chinese Med, Clin Med Coll 3, Dept Anorectal, Kunming 650500, Peoples R China. C3 Yunnan University of Chinese Medicine; Yunnan University of Chinese Medicine RP Shi, XA (corresponding author), Yunnan Univ Chinese Med, Kunming 650500, Peoples R China. EM 17387105981@163.com RI Li, Shumin/AAO-8770-2021 FU Yunnan Provincial Science and Technology Department-Applied Basic Research Joint Special Funds of Chinese Medicine [202001AZ070001-066, 202101AZ070001-174, 202101AZ070001-095, 202101AZ070001-251, 202301AZ070001-085, 202401AZ070001-102] FX This work was supported by Yunnan Provincial Science and Technology Department-Applied Basic Research Joint Special Funds of Chinese Medicine [Grant Number 202001AZ070001-066 /202101AZ070001-174/202101AZ070001-095/202101AZ070001-251/202301AZ070001 -085/202401AZ070001-102)]. 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Bioenerg. Biomembr. PD JUN PY 2025 VL 57 IS 2-3 BP 119 EP 145 DI 10.1007/s10863-025-10056-z EA APR 2025 PG 27 WC Biophysics; Cell Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biophysics; Cell Biology GA 3VK3J UT WOS:001458515300001 PM 40172736 OA Green Submitted, hybrid DA 2026-03-26 ER PT J AU Wen, XR Wang, XL Yao, Q Chen, SM Li, CW Zheng, CY Huang, A Zhan, XY Bai, ZF Xiao, XH AF Wen, Xinru Wang, Xianling Yao, Qing Chen, Simin Li, Chengwei Zheng, Congyang Huang, Ang Zhan, Xiaoyan Bai, Zhaofang Xiao, Xiaohe TI Hypericin impedes M2 macrophage polarization and protects against Hepatocellular carcinoma SO MOLECULAR IMMUNOLOGY LA English DT Article DE M2 macrophage polarization; Hypericin; Hepatocellular carcinoma; PI3K/AKT signaling pathway AB Background: There has been increasing evidence that M2 polarization, which is essential for tumor growth, is present in most tumor-associated macrophages. Hypericin is the major component of the Traditional Chinese Medicine Hypericum perforatum. Hypericin exhibits antitumor activities, but its regulation on M2 macrophage polarization and the protective against Hepatocellular carcinoma (HCC) remains unknown. Methods: IL-4 was used to induce bone marrow-derived macrophages (BMDMs) to differentiate into M2 macrophages, the effect of hypericin on M2 polarization of BMDMs was investigated, mRNA level of M2-related genes was determined using RT-qPCR and flow cytometry. Furthermore, the effect of culture medium of M2 macrophage (M2-CM) pretreated with hypericin or not on the proliferation, migration, and invasion of Hepa1-6 cells was studied. To investigate the mechanism, the PI3K/AKT signaling pathway, which is critical in macrophage polarization was tested. A mouse model of HCC was established by subcutaneous implantation of H22 cells, the impact of Hyp on tumor growth and M2 macrophage polarization in tumor tissues was identified. Results: In the present study, we found that Hyp significantly inhibited M2 polarization of macrophages, as indicated by decreased expression of CD206 and M2-related markers, moreover, Hyp suppressed the M2-CMinduced proliferation, invasion and migration of Hepa1-6 cells. Hyp manifested an inhibitory effect on the PI3K/AKT signaling pathway during the differentiation of M2 macrophages. In vivo experiments showed that Hyp greatly suppressed tumor growth and reduced M2 macrophage polarization in tumor tissues. Conclusion: Hyp impedes the growth, proliferation, invasion and migration of HCC by inhibiting M2 macrophages polarization via the PI3K/AKT signaling pathway, our data demonstrate that hypericin may be a promising candidate for HCC treatment. C1 [Wen, Xinru; Yao, Qing; Zhan, Xiaoyan; Bai, Zhaofang; Xiao, Xiaohe] Southern Med Univ, Sch Tradit Chinese Med, Guangzhou 510515, Peoples R China. [Wen, Xinru; Wang, Xianling; Yao, Qing; Chen, Simin; Li, Chengwei; Zheng, Congyang; Zhan, Xiaoyan; Bai, Zhaofang; Xiao, Xiaohe] Chinese Peoples Liberat Army Gen Hosp, Med Ctr 5, Dept Hepatol, Beijing 100039, Peoples R China. [Bai, Zhaofang] State Key Lab Qual Ensurance & Sustainable Use Dao, Beijing 100700, Peoples R China. [Zhan, Xiaoyan; Bai, Zhaofang; Xiao, Xiaohe] Natl Key Lab Kidney Dis, Beijing 100005, Peoples R China. [Huang, Ang] Peoples Liberat Army Gen Hosp, Med Ctr 1, Dept Gastroenterol & Hepatol, Beijing, Peoples R China. C3 Southern Medical University - China; Fifth Medical Center of Chinese PLA General Hospital; Chinese People's Liberation Army General Hospital; Chinese People's Liberation Army General Hospital RP Zhan, XY; Bai, ZF; Xiao, XH (corresponding author), Peoples Liberat Army Gen Hosp, Med Ctr 5, Dept Hepatol, Beijing 100039, Peoples R China. EM xyzhan123@163.com; baizf2008@hotmail.com; pharmacy_302@126.com RI Bai, Zhaofang/ODN-0173-2025; Xiao, Xiaohe/LTF-2553-2024 OI Huang, Ang/0000-0001-8876-9903 FU Natural Science Foundation of Bei-jing, China [7232321]; Beijing Nova Program [20230484395]; National Natural Science Foundation of China [U23A20519, 82230118, 82070584] FX Funding This work was supported by the Natural Science Foundation of Bei-jing, China (Grant No. 7232321) , Beijing Nova Program (Grant No. 20230484395) , National Natural Science Foundation of China (Grant No. U23A20519, No. 82230118, No. 82070584) . 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Immunol. PD MAY PY 2025 VL 181 BP 160 EP 168 DI 10.1016/j.molimm.2025.03.012 EA MAR 2025 PG 9 WC Biochemistry & Molecular Biology; Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Immunology GA 0ZF7E UT WOS:001459534800001 PM 40153953 OA hybrid DA 2026-03-26 ER PT J AU Chen, JJ Liu, HL Fu, YF Chen, XL Zhang, SQ Yang, YQ Li, SW Wang, GX Lan, T AF Chen, Jiajia Liu, Huanle Fu, Yanfang Chen, Xiaolan Zhang, Shiqin Yang, Yongqi Li, Shengwen Wang, Guixiang Lan, Tian TI Kaempferol attenuates macrophage M1 polarization and liver fibrosis by inhibiting mitogen-activated protein kinase/nuclear factor kB signaling pathway SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article DE Liver fibrosis; Kaempferol; Macrophage polarization; Inflammation; MAPK/NF-kB ID INFLAMMATION; INJURY AB Chronic liver inflammation is a major cause of death in patients with liver fibrosis and cirrhosis, which pose a serious health threat worldwide, and there is no effective anti-hepatic fibrosis drug. Kaempferol (KA), a flavonoid polyphenol extracted from many edible plants and traditional Chinese medicine, has been reported to possess anti-inflammatory, antioxidant, and antitumor activities and has an ameliorating effect on liver fibrosis or other fibroproliferative diseases. However, the specific regulatory mechanism of KA-reversed macrophage M1 polarization is still obscure. This study aimed to investigate the protective effects of KA on carbon tetrachloride (CCl4)-induced liver fibrosis in mice through M1 polarization. C57BL/6 mice were intraperitoneally injected with CCl4 twice weekly to induce liver fibrosis. Male mice were randomly divided into 4 groups (n 1/4 5): the oil group, the CCl4 group, the low-dose KA-treatment CCl4 group (50 mg/kg/day KA), and the high-dose KA-treatment CCl4 group (100 mg/kg/day KA). An equal amount of solvent was given to each group by intraperitoneal injection. The results indicated that KA decreased liver pathologic changes, hepatic macrophage recruitment, and serum alanine aminotransferase levels. Notably, it reduced the activation of M1-type macrophages in the liver. The expression of proinflammatory cytokines and genes associated with M1 macrophages, such as tumor necrosis factor-a, interleukin-6, interleukin-1b, and inducible nitric oxide synthase, was also decreased. The core targets, signaling pathways, and possible mechanisms related to the M1 polarization of KA were analyzed by network pharmacology and molecular docking. Further analysis revealed that KA regulated mitogen-activated protein kinase (MAPK)/nuclear factor kB (NFkB) signaling pathways. Finally, the results indicated that KA regulates M1 macrophage activation by modulating the MAPK/NF-kB signaling pathways. This study revealed that KA ameliorated liver injury, inflammation, and fibrosis by inhibiting macrophage M1 polarization through the MAPK/NF-kB signaling pathway, highlighting KA as a potential novel agent for the prevention and treatment of liver fibrosis. Significance Statement: Chronic liver inflammation is a leading cause of mortality in patients with liver fibrosis and cirrhosis, presenting a significant global health threat. Kaempferol, as a traditional Chinese medicine, effectively suppresses M1 polarization of macrophages through the mitogen-activated protein kinase/nuclear factor kB signaling pathway, thereby ameliorating liver injury, inflammation, and fibrosis. These findings underscore the potential of kaempferol as an innovative therapeutic agent for the prevention and treatment of liver fibrosis. (c) 2025 American Society for Pharmacology and Experimental Therapeutics. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies. C1 [Chen, Jiajia; Liu, Huanle; Fu, Yanfang; Chen, Xiaolan; Zhang, Shiqin; Li, Shengwen; Wang, Guixiang; Lan, Tian] Guangdong Pharmaceut Univ, Sch Pharm, Guangzhou, Peoples R China. [Yang, Yongqi; Lan, Tian] Harbin Med Univ, Coll Pharm, Dept Pharmacol, Harbin, Peoples R China. C3 Guangdong Pharmaceutical University; Harbin Medical University RP Wang, GX; Lan, T (corresponding author), Guangdong Pharmaceut Univ, Guangzhou Higher Educ Mega Ctr, 280 Wai Huan Dong Rd, Guangzhou 510006, Peoples R China. EM wgx306@126.com; lantian012345@163.com RI fu, yanfang/MTE-6936-2025; Wang, Guixiang/KBQ-1374-2024 OI Lan, Tian/0000-0002-5783-6883; FU National Natural Science Foundation of China [82373930]; Guangdong Hong Kong Macao Joint Innovation Field Project [2024A0505040 025] FX This work was supported by grants from the National Natural Science Foundation of China (82373930) and Guangdong Hong Kong Macao Joint Innovation Field Project (2024A0505040 025) . 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Pharmacol. Exp. Ther. PD APR PY 2025 VL 392 IS 4 AR 103533 DI 10.1016/j.jpet.2025.103533 EA MAR 2025 PG 10 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 0VL8K UT WOS:001456982400001 PM 40139075 DA 2026-03-26 ER PT J AU Li, WX Wu, YA Zhang, YA Gao, WY Li, X Luo, HX Lu, MM Liu, ZH Luo, AP AF Li, Wenxin Wu, Yenan Zhang, Yanan Gao, Wenyan Li, Xin Luo, Haixia Lu, Mengmeng Liu, Zhihua Luo, Aiping TI Halofuginone Disrupted Collagen Deposition via mTOR-eIF2α-ATF4 Axis to Enhance Chemosensitivity in Ovarian Cancer SO ADVANCED SCIENCE LA English DT Article DE cancer-associated fibroblasts (CAFs); extracellular matrix; fibrosis; halofuginone; ovarian cancer ID TUMOR MICROENVIRONMENT REVEALS; CELLS; FIBROBLASTS; MACROPHAGES; METASTASIS; INHIBITION; EXPRESSION; FIBROSIS; IMPACT AB The interplay between cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM) mediates progress, metastasis, and therapy resistance. However, strategy of targeting ECM remodeling to enhance chemosensitivity in ovarian cancer remains elusive. Here, a 22-gene matrisome signature predicts chemotherapy response and survival in ovarian cancer. The dense, collagen-rich ECM secreted by CAFs harbors more M2 tumor-associated macrophages (TAMs) than the looser ECM based on single cell RNA-seq (scRNA-seq) of ovarian cancer, suggesting the promising approach of targeting collagen to remodel ECM. An integrated analysis identifies collagen type I alpha 1 chain (COL1A1) as a major component of the ECM that contributes to chemoresistance and poor prognosis, highlighting its potential as a therapeutic target. Halofuginone (HF), a clinically active derivative of febrifugine, is identified as a COL1A1-targeting natural compound by screening the Encyclopedia of Traditional Chinese Medicine (ETCM). Mechanistically, HF inhibits COL1A1 production via the mTOR-eIF2 alpha-ATF4 axis in CAFs. Notably, HF disrupts collagen deposition and promotes CD8+ T cell infiltration, partially via M2-M1 macrophage polarization to enhance chemosensitivity. Overall, the findings suggest that HF combined with chemotherapy is a promising and effective treatment for ovarian cancer. C1 [Li, Wenxin; Wu, Yenan; Gao, Wenyan; Li, Xin; Lu, Mengmeng; Liu, Zhihua; Luo, Aiping] Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, State Key Lab Mol Oncol, Natl Clin Res Ctr Canc,Canc Hosp, 17 Nanli Panjiayuan, Beijing 100021, Peoples R China. [Zhang, Yanan] Peking Univ Third Hosp, Dept Obstet & Gynecol, 38 Xueyuan Rd, Beijing 100191, Peoples R China. [Luo, Haixia] Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, Dept Gynecol Oncol, Natl Clin Res Ctr Canc,Canc Hosp, 17 Nanli Panjiayuan, Beijing 100021, Peoples R China. C3 Chinese Academy of Medical Sciences - Peking Union Medical College; Cancer Institute & Hospital - CAMS; Peking Union Medical College; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Cancer Institute & Hospital - CAMS RP Liu, ZH; Luo, AP (corresponding author), Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, State Key Lab Mol Oncol, Natl Clin Res Ctr Canc,Canc Hosp, 17 Nanli Panjiayuan, Beijing 100021, Peoples R China. EM liuzh@cicams.ac.cn; luoaiping@cicams.ac.cn RI ; Lu, Mengmeng/AGI-4309-2022 OI Wu, Yenan/0009-0001-0918-4534; FU National Natural Science Foundation of China; CAMS Innovation Fund for Medical Sciences [2023-I2M-2-004, 2021-I2M-1-018, 2022-I2M-2-001]; Shenzhen Medical Research Funds [C2303002]; [82188102] FX W.L., Y.W., and Y.Z. contributed equally to this work. The authors thank Prof. Li for donating the ovarian cancer tissue microarrays. This study was supported by funding from National Natural Science Foundation of China (82188102), the CAMS Innovation Fund for Medical Sciences (2023-I2M-2-004, 2021-I2M-1-018, 2022-I2M-2-001), and Shenzhen Medical Research Funds (C2303002). 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PD MAY PY 2025 VL 12 IS 19 DI 10.1002/advs.202416523 EA MAR 2025 PG 13 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary WE Science Citation Index Expanded (SCI-EXPANDED) SC Chemistry; Science & Technology - Other Topics; Materials Science GA 2VZ0O UT WOS:001450361200001 PM 40126173 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Chen, J Qu, BQ Yang, DY Wang, YZ Zhu, HY Wang, ZC Zhang, XW Ma, HK Zhao, N Zhao, L Zhou, LJM He, XJ Li, P AF Chen, Jia Qu, Baoquan Yang, Danyang Wang, Yazhuo Zhu, Haoyue Wang, Zhengchun Zhang, Xiawei Ma, Huike Zhao, Ning Zhao, Li Zhou, Lijiaming He, Xiujuan Li, Ping TI Combined metabolomics and network pharmacology to elucidate the mechanisms of Huiyang Shengji decoction in treating diabetic skin ulcer mice SO PHYTOMEDICINE LA English DT Article DE Diabetic skin ulcer; Huiyang Shengji decoction (HYSJD); Metabolomics; Macrophage polarization; Network pharmacology ID ACID; MACROPHAGES; REPAIR; TISSUE AB Background: Diabetic skin ulcer is a clinical disorder of glucose metabolism that has a long treatment period and is prone to recurrent episodes. Huiyang Shengji decoction (HYSJD) is an effective traditional Chinese medicine for its clinical treatment, but its metabolic effects in patients with diabetic skin ulcers have not been well studied. Purpose: Our study aimed to investigate the mechanism of pharmacological treatment of HYSJD in treating diabetic skin ulcers. Methods: The potential mechanism underlying diabetic wound treatment by HYSJD was screened using network pharmacology. Ultra-high performance liquid chromatography-MS/MS metabolomics analysis and correlation analysis were performed to investigate potential target pathways and genes. Furthermore, the db/db diabetic wound tissues and RAW264.7 macrophage inflammation model verified the mechanism using molecular biology experiments. Results: In network pharmacology, HYSJD played a mainly therapeutic effect by regulating PI3K/AKT signaling pathway, EGFR tyrosine kinase inhibitor resistance, metabolic pathway, and other related metabolic-related pathways. Metabolomics analysis disclosed that L-lysine content increased, while those of linoleic and deoxycholic acids decreased in plasma between the HYSJD-treated group and the control group, participating in biotin metabolism. Among them, PPAR gamma played an important role. The experiments conducted in db/db mice indicated that HYSJD facilitates VEGF secretion and PPAR gamma expression. In vitro experiments have revealed that HYSJD inhibits macrophage ROS production, augments mitochondrial ATP production, elevates mitochondrial membrane potential, and diminishes the mitochondrial ECAR rate. Furthermore, these effects culminate in promoting M2 macrophage polarization through PPAR gamma activation. The molecular docking results revealed that the active compounds from HYSJD were capable of binding to PPAR gamma protein primarily through hydrogen bonding interactions. Notably, all binding energies were found to be lower than -3 kcal/mol, indicating strong and favorable interactions between the active compounds and the target receptor. Conclusions: The findings suggested that HYSJD regulates biotin metabolism by reducing excess levels of linoleic and deoxycholic acids and increasing levels of L-lysine, which in turn promotes diabetic wound healing by promoting M2 macrophage polarization through PPAR gamma up-regulation. These findings indicated that HYSJD is a decoction that can effectively treat diabetic skin ulcers. C1 [Chen, Jia; Qu, Baoquan; Yang, Danyang; Wang, Yazhuo; Zhu, Haoyue; Wang, Zhengchun; Zhang, Xiawei; Ma, Huike; Zhao, Ning; Zhao, Li; Zhou, Lijiaming; He, Xiujuan; Li, Ping] Capital Med Univ, Beijing Hosp Tradit Chinese Med, Beijing Inst Tradit Chinese Med, 23rd Art Museum Back St, Beijing 100010, Peoples R China. [Chen, Jia; Zhao, Li] Wuhan Hosp Tradit Chinese & Western Med, Wuhan 430022, Peoples R China. C3 Capital Medical University RP He, XJ; Li, P (corresponding author), Capital Med Univ, Beijing Hosp Tradit Chinese Med, Beijing Inst Tradit Chinese Med, 23rd Art Museum Back St, Beijing 100010, Peoples R China. EM hexiujuan@bjzhongyi.com; liping@bjzhongyi.com OI Wang, Yazhuo/0009-0005-2035-8565 FU National Natural Science Foundation of China [81804093] FX This work was supported by the National Natural Science Foundation of China (No.81804093) . 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FCP has been used as an adjunctive treatment of silicosis, however, the complete comprehension of these molecular mechanisms remains elusive. Aim of the study: To study the molecular immunological mechanism by which FCP alleviate inflammation and fibrosis in silicosis based on macrophage polarization and High Mobility Group Box protein 1 (HMGB1)-Toll-like receptor 4 (TLR4)-Nuclear factor kappaB (NF-kappa B) pathway through in vivo and in vitro experiments. Materials and methods: A rat model of silicosis and a co-culture cell model (NR8383 and RFL-6) exposed to silica were established and then intervened with different levels of FCP and FCP-containing serum, respectively, to explore the impacts of FCP on silica-induced inflammation and fibrosis and macrophage polarization at different time points. Upon the application of glycyrrhizic acid (GZA) to suppress HMGB1, an extensive analysis was undertaken to elucidate the impact of HMGB1-TLR4-NF-kappa B axis on the macrophages polarization. Results: FCP reduced M1, M2 macrophage polarization, and the HMGB1 expression in the lung of silicosis rats. Suppression of HMGB1 led to a pronounced reduction in the polarization of M1 macrophages, whereas it exerted no significant influence on the polarization of M2 macrophages. FCP-containing serum reduced silica-induced inflammation and fibrosis in the co-culture cell system. FCP-containing serum also reduced M1 macrophage polarization and inhibited stimulation of the HMGB1-TLR4-NF-kappa B signaling axis in NR8383 cells. Conclusions: Reduction of M1, M2 macrophage polarization is an important mechanism by which FCP attenuates inflammation and fibrosis in silicosis, in which reduction of M1 macrophage polarization may be achieved by suppression of the HMGB1-TLR4-NF-kappa B signaling axis. C1 [Pu, Shuangshuang; Shi, Yushan; Huang, Ning; Zhang, Chunlai; Pang, Aimei] Shandong Univ Tradit Chinese Med, Affiliated Hosp, Jinan 250014, Shandong, Peoples R China. [Meng, Xiangjing; Shao, Hua; Jia, Qiang] Shandong First Med Univ & Shandong Acad Med Sci, Shandong Acad Occupat Hlth & Occupat Med, Jinan 250062, Shandong, Peoples R China. C3 Shandong University of Traditional Chinese Medicine; Shandong First Medical University & Shandong Academy of Medical Sciences RP Shao, H; Jia, Q (corresponding author), Shandong Acad Occupat Hlth & Occupat Med, 18877 Jingshi Rd, Jinan 250062, Shandong, Peoples R China. EM chinashaohua5888@163.com; jiaqiang5632@163.com RI ZHANG, CHUNLAI/OSH-1837-2025 OI Huang, Ning/0000-0002-0037-7727 FU Ministry of Science and Technology [2022YFC2503202]; Natural Science Foundation of Shandong Province [ZR2020MH394, ZR2022QH041]; Health Commission of Shandong Province [202312010678]; Science and Technology Bureau of Jinan [202430001] FX Funding This work was supported by the Ministry of Science and Technology (2022YFC2503202) , the Natural Science Foundation of Shandong Province (ZR2020MH394, ZR2022QH041) , the Health Commission of Shandong Province (202312010678) , and the Science and Technology Bureau of Jinan (202430001) . 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Ethnopharmacol. PD APR 9 PY 2025 VL 345 AR 119631 DI 10.1016/j.jep.2025.119631 EA MAR 2025 PG 13 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 0PB8O UT WOS:001452643100001 PM 40090429 DA 2026-03-26 ER PT J AU Wang, RY Jiang, J Song, PL Peng, Q Jin, XR Li, B Shen, J Han, X Ni, JB Hu, GY AF Wang, Ruiyan Jiang, Jing Song, Pengli Peng, Qi Jin, Xuerui Li, Bin Shen, Jie Han, Xiao Ni, Jianbo Hu, Guoyong TI Kinsenoside alleviates experimental acute pancreatitis by suppressing M1 macrophage polarization via the TLR4/STAT1 signaling pathway SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Kinsenoside; Acute pancreatitis; M1 polarization; Macrophages; TLR4/STAT1 ID INHIBITION; DIVERSITY; CELLS AB Ethnopharmacological relevance: Acute pancreatitis (AP) is an inflammatory disease that can progress to systemic immune responses and multi-organ damage in its severe forms. Anoectochilus roxburghii (Wall.) Lindl. (AR), a traditional Chinese medicinal plant, has been reported to exhibit anti-inflammatory, hypoglycemic, hepatoprotective, and analgesic properties. Kinsenoside (KD), the primary bioactive glycoside in AR, is responsible for many of its therapeutic effects. Given its anti-inflammatory and immunomodulatory properties, KD may have the potential to mitigate pancreatic inflammation in AP. However, its protective role in AP has not yet been investigated. Aim of the study: This study aimed to investigate the protective effects of the natural active compound KD against acute pancreatitis (AP) and its associated molecular mechanisms. Materials and methods: Two AP mouse models were established: one by intraperitoneal injection of caerulein combined with lipopolysaccharide (LPS) and the other by retrograde injection of sodium taurocholate (NaT) into the biliopancreatic duct. KD (2.5, 5, 10 mg/kg) was administered as a pre-treatment 1 h before the induction of AP. The severity of AP was evaluated through histopathological analysis, while macrophage infiltration and phenotypic changes in pancreatic tissues were examined using immunofluorescence staining and flow cytometry. Bone marrow-derived macrophages (BMDMs) were polarized into the M1 phenotype through two distinct methods: stimulation with LPS and interferon-gamma (IFN gamma) and indirect co-culture with pancreatic acinar cells. Changes in macrophage phenotype after KD supplementation (100, 200, and 400 mu M) were analyzed using quantitative Reverse Transcription PCR (qRT-PCR) and flow cytometry. Network pharmacology and transcriptomic sequencing were utilized to identify potential targets and pathways affected by KD, with validation of key signaling pathways performed through qPCR and Western blot analysis. Results: In two models of AP mice, KD at a high dose (10 mg/kg) significantly alleviated pancreatic damage. It reduced pancreatic edema, necrosis, and inflammatory cell infiltration, with a notable decrease in macrophage infiltration. Furthermore, KD (10 mg/kg) administration significantly reduced serum lipase by 53.62% in the Caerulein + LPS model and 41.14% in the NaT model, as well as amylase by 28.13% and 27.99%, respectively. Additionally, KD (10 mg/kg) administration mitigated systemic inflammation and lung injury during AP. Both in vivo and in vitro experiments demonstrated that KD (400 mu M) significantly reduced the proportion of M1 macrophages. Furthermore, KD (400 mu M) downregulated the mRNA expression of M1-associated genes, including Nos2, Tnf, Ilub, and Il6, in macrophages stimulated by both LPS + IFN gamma and pancreatic acinar cell-conditioned media. Network pharmacology and transcriptomic analyses identified toll-like receptor 4 (TLR4) as a potential target of KD in the context of AP. KD (400 mu M) was shown to inhibit the activation of the TLR4/STAT1 signaling pathway in macrophages exposed to inflammatory stimuli. Conclusions: KD administration mitigated experimental AP induced by diverse etiologies through the inhibition of M1 macrophage polarization via the TLR4/STAT1 signaling pathway. These findings highlight KD as a promising therapeutic candidate with potential clinical applications in the management of AP. C1 [Wang, Ruiyan; Jiang, Jing; Song, Pengli; Peng, Qi; Jin, Xuerui; Li, Bin; Shen, Jie; Han, Xiao; Ni, Jianbo; Hu, Guoyong] Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Sch Med, Dept Gastroenterol, 100 Haining Rd, Shanghai 200080, Peoples R China. [Wang, Ruiyan; Jiang, Jing; Song, Pengli; Peng, Qi; Jin, Xuerui; Li, Bin; Shen, Jie; Han, Xiao; Ni, Jianbo; Hu, Guoyong] Shanghai Jiao Tong Univ, Inst Pancreat Dis, Sch Med, Shanghai Key Lab Pancreat Dis, 100 Haining Rd, Shanghai 200080, Peoples R China. C3 Shanghai Jiao Tong University; Shanghai Jiao Tong University RP Ni, JB; Hu, GY (corresponding author), Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Sch Med, Dept Gastroenterol, 100 Haining Rd, Shanghai 200080, Peoples R China.; Ni, JB; Hu, GY (corresponding author), Shanghai Jiao Tong Univ, Inst Pancreat Dis, Sch Med, Shanghai Key Lab Pancreat Dis, 100 Haining Rd, Shanghai 200080, Peoples R China. EM wrydoctor@126.com; jiangjing990317@163.com; songpengli0528@163.com; pengqi1114@126.com; jxr0023@163.com; libin2015y@163.com; shenjiemd@163.com; hanxiao714@126.com; jianbo.ni@shgh.cn; huguoyongsh@sina.com RI Han, Xiao/JNS-3098-2023; ni, jianbo/GWU-7471-2022 FU Shanghai Pujiang Program [23PJD082]; Science and Technology Innovation Action Plan of the Shanghai Municipal Science and Technology Commission [23Y11902000] FX This work was supported by the Shanghai Pujiang Program (23PJD082) and the Science and Technology Innovation Action Plan of the Shanghai Municipal Science and Technology Commission (23Y11902000) to Jianbo Ni. Graphical abstract and Schematic illustrations of mouse models were created in BioRender. 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Ethnopharmacol. PD APR 9 PY 2025 VL 345 AR 119551 DI 10.1016/j.jep.2025.119551 EA MAR 2025 PG 14 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 0ED9O UT WOS:001445227300001 PM 39999939 DA 2026-03-26 ER PT J AU Li, H Chen, C Chen, XZ Liu, JL Luo, C Chen, HL Geng, XY Pan, Z AF Li, Huan Chen, Chang Chen, Xinzhu Liu, Jiale Luo, Chen Chen, Huilin Geng, Xiaoyu Pan, Zheng TI Identification of active ingredients from Lamiophlomis rotata that increase wound repair in mouse skin SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE iridoid glycosides; Lamiophlomis rotata; mass spectrometry imaging; quality markers; wound repair ID MASS-SPECTROMETRY; GENIPOSIDE; PHARMACOKINETICS; BIOAVAILABILITY; METABOLITES; ABSORPTION AB Background and PurposeWe previously showed that the iridoid glycoside extract of Lamiophlomis rotata (IGLR) induces M2 macrophage polarisation to accelerate wound healing. The potentially active compounds (quality markers) in IGLR that accelerate wound healing have not been elucidated; we here identified quality markers that accelerate wound healing. Experimental ApproachAfter IGLR gavage of dorsal excisional wound mice and normal mice for 7 days, the tissues were analysed using the matrix-assisted laser desorption/ionisation (MALDI) mass spectrometry imaging (MSI) method and were further validated by liquid chromatography/mass spectrometry (LC/MS) coupled with multivariate analyses to identify quality markers. Key ResultsUsing the MSI assay, Shanzhiside methyl ester (SM), 8-O-acetylshanzhiside methyl ester (ASM) and Phlorigidoside C (PhC) were identified as the quality markers in IGLR and overlapped with endogenous metabolites (lactate, citrate and itaconate) in the same class by UMAP manifold analysis. Additionally, the results were also confirmed by UPLC-Q/TOF-MS coupled with multivariate analyses of the skin tissues in normal and wound groups. MSI data from the livers and kidneys revealed that the accumulation of SM, ASM and PhC in the livers significantly increased in the model group, and the ion intensity of their glucuronide conjugates in the kidneys was decreased compared to the normal group. These results suggested that bioavailability of these compounds was improved in the wound group. Conclusions and ImplicationsThe overall data demonstrated that SM, ASM and PhC were selectively increased in new granulation tissues, and are most likely the quality markers that accelerate wound healing. C1 [Li, Huan; Chen, Xinzhu; Luo, Chen; Chen, Huilin; Geng, Xiaoyu; Pan, Zheng] Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing, Peoples R China. [Chen, Chang; Liu, Jiale] Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China. [Pan, Zheng] Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing Key Lab Tradit Chinese Med Prevent & Cur, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China. C3 Chongqing Medical University; Chongqing Medical University; Chongqing Medical University RP Pan, Z (corresponding author), Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing Key Lab Tradit Chinese Med Prevent & Cur, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China.; Chen, C (corresponding author), Chongqing Med Univ, Coll Pharm, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China. EM lh20230622@163.com; chenchang@cqmu.edu.cn; 102796@cqmu.edu.cn RI Li, Huan/NES-5003-2025 OI Li, Huan/0009-0004-8235-9881; Chen, Chang/0000-0003-3425-1118; Pan, Zheng/0000-0002-9727-7975 FU National Natural Science Foundation of China; Cure of Metabolic Diseases, Chongqing, China FX We are grateful to Mr Caiyuan Ren and Mrs Xiaohong Wu for their helpful work in the optimisation of MSI measurements, and to the staff members of Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing, China. 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J. Pharmacol. PD JUN PY 2025 VL 182 IS 12 BP 2754 EP 2771 DI 10.1111/bph.17452 EA MAR 2025 PG 18 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 2UL8Z UT WOS:001440958600001 PM 40065575 OA hybrid DA 2026-03-26 ER PT J AU Zeng, LM Zhang, JY Song, RR Dong, XH Wei, ZB Li, XY Zeng, XK Yao, J AF Zeng, Liming Zhang, Jieyu Song, Rongrong Dong, Xinhuai Wei, Zibo Li, Xiaoyan Zeng, Xiaokang Yao, Jie TI Laminarin Alleviates Acute Lung Injury Induced by LPS Through Inhibition of M1 Macrophage Polarisation SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE acute lung injury; laminarin; macrophage polarisation; sepsis ID RESPIRATORY-DISTRESS-SYNDROME AB The lipopolysaccharide-induced acute lung injury (ALI) mouse model is used to simulate human acute respiratory distress syndrome (ARDS), which has a high mortality rate. An imbalance between M1 and M2 macrophages, characterised by an increase in M1 macrophages, was observed in sepsis-induced ALI. We report that laminarin, an active ingredient found in algae, exhibits exceptional performance in a mouse model of sepsis-induced ALI. It ameliorates lung edema, enhances the survival rate of mice and reduces the levels of the inflammatory factors TNF-alpha and IL-6. Furthermore, laminarin reduced the expression of CD86, which are markers associated with M1 macrophages. Laminarin treatment reduces the secretion of TNF-alpha and IL-6 in LPS-stimulated macrophages. Laminarin treatment also decreases glucose uptake in LPS-stimulated macrophages. Transcriptome sequencing reveals that genes downregulated in LPS-stimulated macrophages following laminarin treatment are predominantly enriched in the HIF-1 alpha signalling pathway. Experimental validation confirms that laminarin treatment of LPS-stimulated macrophages reduces the expression of HIF-1 alpha and significantly decreases the expression of related indicators ROS and NLRP3. After using siRNA to knock down HIF-1 alpha in RAW264.7 cells, the inhibitory effect of laminarin on LPS-induced M1 polarisation of macrophages is abolished. This suggests that laminarin may potentially inhibit macrophage polarisation towards the M1 phenotype by downregulating the HIF-1 alpha signal. In conclusion, the data presented in our study demonstrate that laminarin can effectively reduce M1 macrophage polarisation by downregulating HIF-1 alpha signalling. This makes it a novel candidate drug for the treatment of LPS-induced ALI. C1 [Zeng, Liming; Zhang, Jieyu; Song, Rongrong; Dong, Xinhuai; Wei, Zibo; Zeng, Xiaokang; Yao, Jie] Southern Med Univ, Peoples Hosp Shunde 1, Shunde Hosp, Med Res Ctr, Foshan, Guangdong, Peoples R China. [Zeng, Liming; Zhang, Jieyu; Song, Rongrong; Dong, Xinhuai; Wei, Zibo; Zeng, Xiaokang; Yao, Jie] Southern Med Univ, Shunde Hosp, Peoples Hosp Shunde 1, Dept Lab Med, Foshan, Guangdong, Peoples R China. [Zhang, Jieyu; Song, Rongrong; Zeng, Xiaokang] South China Univ Technol, Affliated Hosp 6, Sch Med, Cent Lab, Foshan, Guangdong, Peoples R China. [Li, Xiaoyan] Southern Med Univ, Peoples Hosp Shunde 1, Shunde Hosp, Clin Lab, Foshan, Guangdong, Peoples R China. [Yao, Jie] South China Univ Technol, Affiliated Hosp 6, Sch Med, Clin Lab, Foshan, Guangdong, Peoples R China. C3 Southern Medical University - China; Southern Medical University - China; South China University of Technology; Southern Medical University - China; South China University of Technology RP Yao, J (corresponding author), Southern Med Univ, Peoples Hosp Shunde 1, Shunde Hosp, Med Res Ctr, Foshan, Guangdong, Peoples R China.; Yao, J (corresponding author), Southern Med Univ, Shunde Hosp, Peoples Hosp Shunde 1, Dept Lab Med, Foshan, Guangdong, Peoples R China.; Li, XY (corresponding author), Southern Med Univ, Peoples Hosp Shunde 1, Shunde Hosp, Clin Lab, Foshan, Guangdong, Peoples R China.; Yao, J (corresponding author), South China Univ Technol, Affiliated Hosp 6, Sch Med, Clin Lab, Foshan, Guangdong, Peoples R China. EM xiaoyanli@gzhmu.edu.cn; kangki@163.com; 13883274679@139.com OI Zeng, Xiaokang/0000-0002-6531-2502 FU Educational Commission of Guangdong Province, China; Guangdong Basic and Applied Basic Research Foundation [2022A1515220197]; Natural Science Foundation of Guangdong Province, China [2021A1515010928]; Medical Science and Technology Foundation of Guangdong Province [B2021121]; Scientific Research Start Plan of Shunde Hospital, Southern Medical University [YNZX0003, YNZX0002, SRSP2021015, SRSP2021002, SRSP2021006, SRSP2019009, SRSP2021012]; Medical Research Center, Shunde Hospital, Southern Medical University; Molecular Medical Engineering Technology Research Center, Foshan; Base of oncology prevention and treatment with integrated traditional Chinese and western medicine in Shunde Hospital of Southern Medical University Traditional Chinese Medicine Clinical S; [2020KTSCX024] FX Guangdong Basic and Applied Basic Research Foundation (2022A1515220197); Natural Science Foundation of Guangdong Province, China (2021A1515010928); Educational Commission of Guangdong Province, China (2020KTSCX024); The Medical Science and Technology Foundation of Guangdong Province (B2021121); The Scientific Research Start Plan of Shunde Hospital, Southern Medical University (YNZX0003, YNZX0002, SRSP2021015, SRSP2021002, SRSP2021006, SRSP2019009, SRSP2021012). In this work, the authors are thankful to the Medical Research Center, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde); Molecular Medical Engineering Technology Research Center, Foshan; Base of oncology prevention and treatment with integrated traditional Chinese and western medicine in Shunde Hospital of Southern Medical University & Traditional Chinese Medicine Clinical Science and Technology Innovation Base of Foshan. 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PD MAR 5 PY 2025 VL 29 IS 5 AR e70440 DI 10.1111/jcmm.70440 PG 13 WC Cell Biology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology; Research & Experimental Medicine GA Z4A9C UT WOS:001438366500001 PM 40045157 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Yang, XQ Zhang, H He, CL Wang, D Li, JJ Fu, CM Wang, YT Wu, YH Zhang, JM AF Yang, Xiaoqin Zhang, Heng He, Chenglin Wang, Di Li, Jingjing Fu, Chaomei Wang, Yitao Wu, Yihan Zhang, Jinming TI Gegen Qinlian decoction remodels tumor immune microenvironment and inhibits aerobic glycolysis with the synergistic combination of CPT-11 chemotherapy in colorectal cancer therapy SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Colorectal cancer; Gegen Qinlian decoction; Irinotecan (CPT-11); Tumor microenvironment; Glycolysis; Intestinal toxicity ID DENDRITIC CELLS; IRINOTECAN; TOXICITY AB Ethnopharmacological relevance: Although several traditional Chinese medicine formulas have demonstrated remarkable outcomes in suppressing the severe gastrointestinal toxicity induced by irinotecan (CPT-11), few studies have investigated whether enhanced anti-cancer efficacy and reduced intestinal toxicity can be achieved through co-administration. CPT-11, as a first-line drug for treating colorectal cancer, has the side effect of intestinal toxicity. Previous studies have primarily focused on using traditional Chinese medicine to alleviate diarrhea caused by CPT-11. The combination of the classic Chinese medicine prescription Gegen Qinlian decoction (GQD) extract and CPT-11 can significantly reduce its intestinal toxicity. However, the mechanism by which it enhances anti-cancer effects remains to be elucidated. Aim of study: To investigate the combined effects of GQD and CPT-11 on colorectal cancer progression and intestinal toxicity. Materials and methods: The CT-26 xenograft tumor-bearing mouse model was established to evaluate the synergistic antitumor effects of GQD extract and CPT-11. Tumor size and tumor tissue changes were assessed, and flow cytometry was employed to analyze immune cell populations, thereby evaluating the impact of the combined treatment on tumor growth inhibition and immune modulation. Under anaerobic glycolysis conditions, glucose uptake and cell viability of CT26 cells were measured, and Western blotting analysis was used to determine the protein expression of PKM2 and GAPDH in tumors, assessing the metabolic impact of GQD extract on cancer cells. Flow cytometry was also used to assess the polarization of macrophages in colon tissue, and ELISA was employed to measure cytokine levels in colon tissue, evaluating the protective effect of GQD extract on the colon. Results: The combination of GQD extract and CPT-11 significantly increased tumor growth suppression and decreased intestinal toxicity in the mouse model. The anti-cancer synergy was reduced Treg cell immunosuppression and increased CD4+ and CD8+ T cell populations. GQD extract regulated glucose uptake and cell viability in CT-26 cells under anaerobic glycolysis, potentially disrupting cancer cell glycolysis. GQD also alleviated intestinal toxicity by modulating cytokine levels and promoting macrophage polarization from M1 to M2 in colon tissues. Conclusion: The study indicates that GQD extract improves CPT-11 efficacy in treating colorectal cancer and provides insights into the synergistic effects of TCM formulas in cancer treatment. C1 [Yang, Xiaoqin; Zhang, Heng; He, Chenglin; Wang, Di; Fu, Chaomei; Wu, Yihan; Zhang, Jinming] Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, 1166 Liutai Ave, Chengdu 611137, Peoples R China. [Wang, Yitao] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Tradit Chinese Med, Macau 999078, Peoples R China. [Li, Jingjing] Hong Kong Polytech Univ, Fac Hlth & Social Sci, Dept Rehabil Sci, Hong Kong, Peoples R China. C3 Chengdu University of Traditional Chinese Medicine; University of Macau; Hong Kong Polytechnic University RP Wu, YH; Zhang, JM (corresponding author), Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, 1166 Liutai Ave, Chengdu 611137, Peoples R China. EM yihanwuone@126.com; cdutcmzjm@126.com RI Wang, Yitao/O-5184-2016 FU Innovation Team and Talents Cultiva-tion Program of National Administration of Traditional Chinese Medi-cine [ZYYCXTD-D-202209]; National Natural Science Foundation of China (NSFC) [82405145]; China Postdoctoral Science Founda-tion [GZC20230335, :2024m750289] FX This work was supported by Innovation Team and Talents Cultiva-tion Program of National Administration of Traditional Chinese Medi-cine. (No: ZYYCXTD-D-202209) , National Natural Science Foundation of China (NSFC) (No: 82405145) , China Postdoctoral Science Founda-tion (No: GZC20230335, No:2024m750289) . 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Ethnopharmacol. PD MAR 26 PY 2025 VL 344 AR 119538 DI 10.1016/j.jep.2025.119538 EA MAR 2025 PG 15 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA Z5R7B UT WOS:001439480500001 PM 40023342 DA 2026-03-26 ER PT J AU Long, D Mao, CH Zhang, W Zhu, Y Xu, Y AF Long, Dan Mao, Chenhan Zhang, Wei Zhu, Ying Xu, Yin TI Natural products for the treatment of ulcerative colitis: focus on the JAK/STAT pathway SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE Janus kinase (JAK); signal transducer and activator of transcription (STAT); ulcerative colitis; natural products; traditional herbal medicine ID CHRYSANTHEMUM-MORIFOLIUM FLOWERS; INFLAMMATORY-BOWEL-DISEASE; NDP-ALPHA-MSH; TRANSCRIPTIONAL REGULATION; MACROPHAGE POLARIZATION; INTESTINAL MACROPHAGES; GUT MICROBIOTA; LAMINA PROPRIA; CELLS; STAT3 AB Ulcerative colitis (UC) is an autoimmune disease with an incompletely understood pathogenesis. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway plays a key role in immune response and inflammation. More and more studies demonstrated that JAK/STAT signaling pathway is associated with the pathogenesis of UC. The JAK/STAT pathway affects UC in multiple ways by regulating intestinal inflammatory response, affecting intestinal mucosal barrier, modulating T cell homeostasis, and regulating macrophages. Encouragingly, natural products are promising candidates for the treatment of UC. Natural products have the advantage of being multi-targeted and rich in therapeutic modalities. This review summarized the research progress of JAK/STAT pathway-mediated UC. Furthermore, the latest studies on natural products targeting the JAK/STAT pathway for the treatment of UC were systematically summarized, including active ingredients such as arbutin, aloe polysaccharide, berberine, matrine, curcumin, Ginsenoside Rh2, and so on. The aim of this paper is to provide new ideas for drug development to regulate JAK/STAT signaling for treating UC. C1 [Long, Dan; Zhang, Wei; Zhu, Ying; Xu, Yin] Hunan Univ Chinese Med, Hosp 1, Dept Gastroenterol, Changsha, Hunan, Peoples R China. [Mao, Chenhan] Nanjing Univ Chinese Med, Affiliated Hosp Integrated Tradit Chinese & Wester, Nanjing, Jiangsu, Peoples R China. C3 Hunan University of Chinese Medicine; Nanjing University of Chinese Medicine RP Zhu, Y; Xu, Y (corresponding author), Hunan Univ Chinese Med, Hosp 1, Dept Gastroenterol, Changsha, Hunan, Peoples R China. EM zhuying089@126.com; 311118@hnucm.edu.cn FU National Natural Science Foundation of China [82374426]; Postgraduate Scientific Research Innovation Project of Hunan Province [CX20240748]; Postgraduate Scientific Research Innovation Project of Hunan University of Chinese Medicine [2024CX022]; Domestic First-class Construction Discipline of Chinese Medicine in Hunan University of Chinese Medicine; Construction Project of Inheritance Studio of National Famous Traditional Chinese Medicine Experts of National Administration of Traditional Chinese Medicine [75] FX The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was funded by the National Natural Science Foundation of China (No. 82374426), the Postgraduate Scientific Research Innovation Project of Hunan Province (CX20240748), the Postgraduate Scientific Research Innovation Project of Hunan University of Chinese Medicine (2024CX022), the Domestic First-class Construction Discipline of Chinese Medicine in Hunan University of Chinese Medicine, and the Construction Project of Inheritance Studio of National Famous Traditional Chinese Medicine Experts of National Administration of Traditional Chinese Medicine ((2022) No. 75). 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Immunol. PD FEB 26 PY 2025 VL 16 AR 1538302 DI 10.3389/fimmu.2025.1538302 PG 15 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA Z9E3S UT WOS:001441847600001 PM 40078988 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Yuan, L He, QF Zhang, Y Luo, HY Xiang, W Deng, CD Li, CL Li, XZ Yao, L Ke, DZ Wang, S Zhou, JJ Wang, JW AF Yuan, Ling He, Qifeng Zhang, Yi Luo, Hongyu Xiang, Wei Deng, Chendan Li, Chunli Li, Xuezhi Yao, Ling Ke, Dazhi Wang, Shang Zhou, Jianjun Wang, Jianwei TI 6-Gingerol microneedle promotes diabetic wound healing by regulating macrophage polarization SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE 6-Gingerol; Microneedle; Macrophage polarization; Diabetic wound healing; Anti-inflammatory; Therapeutic property ID INFLAMMATION; PATHWAY AB Diabetic wound-healing difficulties are common for patients with diabetes. Compared to normal wound healing processes, the hyperglycaemic environment in diabetic wounds increases the proportion of M1 macrophages significantly, thereby prolonging the inflammatory phase of wound healing. Consequently, treatment approaches targeting macrophages are gaining increasing attention in both research and clinical practice. 6-Gingerol (6-G), a natural compound derived from ginger, is recognized for its anti-inflammatory, anti-tumour, and antioxidant properties. However, its application in diabetic wound treatment has been limited by poor water solubility and low bioavailability. In this study, we developed a hydrogel microneedle system (6-G@MN) combining 6-G with polyethylene glycol, hyaluronic acid, and gelatin. Our results demonstrated that 6-G@MN effectively promotes angiogenesis and collagen deposition in diabetic wounds while rebalancing macrophage populations in diabetic mice. Additionally, 6-G was shown to inhibit lipopolysaccharide-induced M1 macrophage polarization in vitro and to activate the AMPK/mTOR signalling pathway. In conclusion, we developed 6-G@MN as a novel therapeutic approach that integrates the advantages of the traditional Chinese medicine component 6-G with modern microneedle technology. By targeting macrophage polarization, the system can offer a promising strategy for improving the healing of diabetic wounds. C1 [Yuan, Ling; He, Qifeng; Li, Chunli; Wang, Jianwei] Chongqing Med Univ, Coll Basic Med Sci, Chongqing 400016, Peoples R China. [Xiang, Wei; Deng, Chendan; Li, Xuezhi; Yao, Ling; Wang, Shang; Zhou, Jianjun; Wang, Jianwei] Chongqing Univ Chinese Med, Chongqing 402760, Peoples R China. [Luo, Hongyu; Wang, Shang; Wang, Jianwei] Chongqing Key Lab Tradit Chinese Med Prevent & Cur, Chongqing, Peoples R China. [Zhang, Yi; Ke, Dazhi] Chongqing Med Univ, Affiliated Hosp 2, Dept Gen Practice, Chongqing 400016, Peoples R China. C3 Chongqing Medical University; Chongqing Medical University RP Wang, JW (corresponding author), Chongqing Med Univ, Coll Basic Med Sci, Chongqing 400016, Peoples R China.; Wang, S; Zhou, JJ; Wang, JW (corresponding author), Chongqing Univ Chinese Med, Chongqing 402760, Peoples R China.; Wang, S; Wang, JW (corresponding author), Chongqing Key Lab Tradit Chinese Med Prevent & Cur, Chongqing, Peoples R China. EM 18594210227@163.com; 546984214@qq.com; wjwcq68@163.com FU Chongqing Traditional Chinese Medicine Inheritance and Innovation Team project [2023090006KJZX2022WJW008]; Chongqing Municipal Education Commission [KJZD-M202215101, KJQN202215112]; Chongqing Science and Technology Bureau Project [cstc2022ycjh-bgzxm0010]; Chongqing Bayu Qihuang Scholarship Project [[2023] 23-03]; Huapont Life Sciences CO.,LTD. FX This study was supported by grants from the Chongqing Traditional Chinese Medicine Inheritance and Innovation Team project [No. 2023090006KJZX2022WJW008] ; Chongqing Municipal Education Commission's major project [No. KJZD-M202215101; No. KJQN202215112] ; Chongqing Science and Technology Bureau Project [No. cstc2022ycjh-bgzxm0010] ; Chongqing Bayu Qihuang Scholarship Project [No. [2023] 23-03] ; Huapont Life Sciences CO.,LTD. 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Immunopharmacol. PD APR 4 PY 2025 VL 151 AR 114288 DI 10.1016/j.intimp.2025.114288 EA FEB 2025 PG 13 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA Y7F8R UT WOS:001433744400001 PM 40007376 OA hybrid DA 2026-03-26 ER PT J AU Liu, HQ Yang, RM Zhong, HY Zhang, YQ Wang, SY Guo, KY Jiang, ZS He, JJ Huang, YM Lin, Y Chen, XZ Lin, JM AF Liu, Haiqin Yang, Ruiming Zhong, Hangyan Zhang, Youquan Wang, Shunyong Guo, Kangyue Jiang, Zhishan He, Jiajun Huang, Yunmei Lin, Ying Chen, Xuzheng Lin, Jiumao TI Mechanism of Qingjie Fuzheng Granules in inhibiting colitis associated colorectal cancer by regulating TLR4 and IL-4R mediated macrophage polarization SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Qingjie Fuzheng Granules; Colitis associated colorectal cancer; Macrophage polarization; TLR4; IL-4R ID SIGNALING PATHWAY; ACTIVATION; SURVIVAL; PROTEIN; GROWTH; CELLS; AKT1 AB Ethnopharmacological relevance: Qingjie Fuzheng Granules (QFG), a herbal formula, has been employed as an adjuvant therapy for colitis-associated colorectal cancer (CAC), yet the underlying mechanisms by which QFG operates remain unclear. Aims of the study: The aim of this study is to investigate whether the potential mechanism of QFG against CAC is associated with macrophage polarization. Materials and methods: Non-targeted metabolomics and molecular docking assessed potential compounds of QFG to interact with targets associated with macrophage polarization. A model of AOM/DSS-induced CAC mice was established to analyze the effects of QFG on macrophage polarization using flow cytometry and immunohistochemical staining. In vitro experiments involved models of Ana-1 macrophages, either induced by varying QFG concentrations or with MD2 knockdown, to analyze M1-like phenotype. Meanwhile, M2-like macrophages models induced by IL-4 or culture supernatant of CT26 cells were utilized to assess the effects of QFG on M2-like macrophages. Finally, the mRNA expression of M1-like phenotype related to TLR4 pathways and the protein expression in IL-4R-mediated pathways were analyzed using RT-qPCR and Western blot, respectively. Results: Molecular docking confirmed the presence of binding sites between the ingredients of QFG and IL-4R or TLR4/MD2 receptor complex. QFG could induce a shift in macrophages towards an M1-like phenotype while inhibiting an M2-like phenotype in the colon with CAC mice and Ana-1 macrophages. QFG resulted in the upregulation of iNOS, IL-6, IL-1 beta, and TNF-alpha mRNA expression, which could be counteracted by TAK242, SR11302, INH14, PDTC, and LY294002, or by the knockdown of MD2. Meanwhile, QFG inhibited IL-4R-induced phosphorylation of STAT 6 and Akt. Conclusion: Various monomer components within QFG can bind to MD2 or IL-4R, respectively, thereby inducing macrophages towards an M1-like phenotype through TLR4-mediated NF-kappa B, MAPK, and PI3K/Akt pathway activation, or inhibiting macrophages towards an M2-like phenotype via IL-4R-mediated JAKs pathway inhibition, ultimately exerting an inhibitory effect on the occurrence and development of CAC. C1 [Liu, Haiqin; Yang, Ruiming; Zhong, Hangyan; Wang, Shunyong; Guo, Kangyue; Huang, Yunmei; Chen, Xuzheng; Lin, Jiumao] Fujian Univ Tradit Chinese Med, Coll Integrat Med, Fuzhou 350122, Fujian, Peoples R China. [Liu, Haiqin; Yang, Ruiming; Huang, Yunmei; Chen, Xuzheng; Lin, Jiumao] Fujian Univ Tradit Chinese Med, Acad Integrat Med, Fuzhou 350122, Fujian, Peoples R China. [Liu, Haiqin; Yang, Ruiming; Huang, Yunmei; Chen, Xuzheng; Lin, Jiumao] Fujian Key Lab Integrat Med Geriatr, Fuzhou 350122, Fujian, Peoples R China. [Zhong, Hangyan] Shanghang Hosp Tradit Chinese Med, Dept Proctol, Longyan 364200, Fujian, Peoples R China. [Zhang, Youquan] Fujian Univ Tradit Chinese Med, Peoples Hosp 2, Fuzhou 350001, Fujian, Peoples R China. [Jiang, Zhishan; He, Jiajun] Fujian Univ Tradit Chinese Med, Coll Pharm, Fuzhou 350122, Fujian, Peoples R China. [Lin, Ying] Fujian Med Univ, Shengli Clin Med Coll, Fuzhou 350001, Fujian, Peoples R China. [Lin, Ying] Fuzhou Univ, Affiliated Prov Hosp, Dept Pathol, Fuzhou 350001, Fujian, Peoples R China. C3 Fujian University of Traditional Chinese Medicine; Fujian University of Traditional Chinese Medicine; Fujian University of Traditional Chinese Medicine; Fujian University of Traditional Chinese Medicine; Fujian Medical University; Fuzhou University RP Chen, XZ; Lin, JM (corresponding author), Fujian Univ Tradit Chinese Med, Coll Integrat Med, Fuzhou 350122, Fujian, Peoples R China. EM 2003037@fjtcm.edu.cn; linjiumao@fjtcm.edu.cn RI He, Jiajun/LCE-2081-2024; lin, ying/GRE-7329-2022; wang, shunyong/LKN-9368-2024 FU Natural Science Foundation of Fujian Province, China [2022J01368]; Chen Ke-Ji Integrative Medicine Development Funds [CKJ2022006]; Innovation and entrepreneurship training program for Fujian university students [S202410393013, 202310393008] FX This study was supported by the Natural Science Foundation of Fujian Province, China (No. 2022J01368) , Chen Ke-Ji Integrative Medicine Development Funds (No. CKJ2022006) , Innovation and entrepreneurship training program for Fujian university students (No. S202410393013; No. 202310393008) . 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Ethnopharmacol. PD MAR 26 PY 2025 VL 344 AR 119511 DI 10.1016/j.jep.2025.119511 EA FEB 2025 PG 17 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA Y7A3A UT WOS:001433599500001 PM 39978444 DA 2026-03-26 ER PT J AU Li, JX Gao, K Liu, Y Ning, ZX Yang, XY Chen, W Shen, L AF Li, Jinxia Gao, Kun Liu, Ying Ning, Zixin Yang, Xiaoyu Chen, Wei Shen, Li TI Actinidia eriantha polysaccharide prevents gastric cancer invasion and metastasis via inhibition of PD-1/PD-L1 regulation of macrophage polarization SO INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES LA English DT Article DE Actinidia eriantha polysaccharide; Macrophage; Gastric cancer ID ROOTS; MICROENVIRONMENT; ANTITUMOR; PATHWAY; CELLS AB Actinidia eriantha polysaccharide (AEPS), an active component of the Chinese herbal medicine Radix Actinidia chinensis, has anticancer effects. Here, we investigated the therapeutic potential of AEPS in gastric cancer through in vivo, in vitro, and in silico analyses. In our gastric cancer xenograft mouse model, AEPS effectively reduced tumor volume and weight. In the human gastric adenocarcinoma cell line AGS, AEPS inhibited migration and invasion without affecting proliferation; this result was validated in a fluorescent-labeled lung metastasis mouse model. Mass cytometry revealed that AEPS enhanced macrophage proportions in gastric cancer tissues. Bioinformatics analysis revealed a strong increase in PD-1-regulated M2 macrophage proportions in patients with gastric cancer, shortening their survival time and worsening their prognosis. In the coculture system of interleukin-4-induced human monocytic leukemia cells and AGS cells, AEPS treatment downregulated PD-1/PDL1 and M2 macrophage-related marker expression but promoted TAM polarization toward the M1 phenotype. These findings facilitated the elucidation of the mechanism underlying the treatment effects of AEPS against gastric cancer. Finally, AEPS-PD-1 antibody combination therapy further enhanced the anticancer effects of AEPS in vivo, suggesting its potential as a basis to develop novel therapeutics for gastric cancer. C1 [Li, Jinxia] Hunan Univ Chinese Med, Changsha 410208, Peoples R China. [Li, Jinxia] Hunan Univ Chinese Med, Prov Key Lab TCM Diagnost, Changsha 410208, Peoples R China. [Gao, Kun; Ning, Zixin; Yang, Xiaoyu; Shen, Li] China Acad Chinese Med Sci, Inst Basic Theory TCM, Beijing 100700, Peoples R China. [Liu, Ying] China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China. [Chen, Wei] Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Gen Surg, Hangzhou 310016, Peoples R China. [Chen, Wei] Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Key Lab Accurate Diag & Treatment Abdominal Infect, Hangzhou 310016, Peoples R China. C3 Hunan University of Chinese Medicine; Hunan University of Chinese Medicine; Institute of Basic Theory for Chinese Medicine, CACMS; China Academy of Chinese Medical Sciences; China Academy of Chinese Medical Sciences; Institute of Chinese Materia Medica, CACMS; Zhejiang University; Zhejiang University RP Shen, L (corresponding author), China Acad Chinese Med Sci, Inst Basic Theory TCM, Beijing 100700, Peoples R China.; Chen, W (corresponding author), Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Gen Surg, Hangzhou 310016, Peoples R China. EM wei_chen@zju.edu.cn; shenli1116@126.com RI Li, Jinxia/AAG-2429-2019 OI Li, Jinxia/0000-0002-0949-8365 FU Scientific and Techno-logical Innovation Project of China Academy of Chinese Medical Science [CI2021A03809]; National Natural Science Foundation of China [82074398, 82104775]; Special Funds for Basic Research Expenses of Central Public Welfare Research Institutes [YZX-202407]; TCM Theory Inheritance and Innovation Project of CACMS Innovation Fund [KYG-202406]; Science and Technology Innovation Program of Hunan Province [2024RC3198]; Young Elite Scientists Sponsorship Program by China Association for Science and Technology [YESS20220451]; Outstanding Youth Program of Hunan University of Traditional Chinese Medicine [Z2023XJYQ04] FX This work was financially supported by the Scientific and Techno-logical Innovation Project of China Academy of Chinese Medical Science [grant number CI2021A03809] ; National Natural Science Foundation of China [grant numbers 82074398, 82104775] ; Special Funds for Basic Research Expenses of Central Public Welfare Research Institutes [grant number YZX-202407] ; TCM Theory Inheritance and Innovation Project of CACMS Innovation Fund (KYG-202406] ; Science and Technology Innovation Program of Hunan Province [grant number 2024RC3198] ; Young Elite Scientists Sponsorship Program by China Association for Science and Technology [grant number YESS20220451] ; and Outstanding Youth Program of Hunan University of Traditional Chinese Medicine [grant number Z2023XJYQ04] . 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PD APR PY 2025 VL 304 AR 140763 DI 10.1016/j.ijbiomac.2025.140763 EA FEB 2025 PN 1 PG 15 WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA X7R6N UT WOS:001427277900001 PM 39922338 OA hybrid DA 2026-03-26 ER PT J AU Huang, YM Wang, BZ Ma, ZJ Chen, TZ Zou, HT Chen, YT Dong, Z Chen, JY Zhang, H Ding, YJ Tan, Q AF Huang, Yumeng Wang, Beizhi Ma, Zhouji Chen, Tianzhe Zou, Haiting Chen, Yutong Dong, Zheng Chen, Jingyi Zhang, Hao Ding, Youjun Tan, Qian TI Sulforaphane promotes diabetic wound healing by regulating macrophage efferocytosis and polarization SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Sulforaphane; Diabetic wound healing; Efferocytosis; Macrophage polarization; Inflammation ID UP-REGULATION; EXPRESSION AB Background: Delayed wound healing frequently occurs as a complication of diabetes. Diabetic wounds that are difficult to heal are associated with chronic, persistent inflammation, characterized by impaired efferocytosis and a sustained pro-inflammatory state of macrophages at the wound site. Sulforaphane (SFN), a bioactive compound found in cruciferous vegetables, possesses anti-inflammatory and antioxidant activities. Numerous studies have shown that SFN can inhibit various inflammatory diseases such as atherosclerosis and psoriasis; however, its potential in treating diabetic wounds remains unknown. Purpose: This study investigates the effects and potential mechanisms of SFN on diabetic wound healing. Methods: Network pharmacology approaches were employed to identify potential targets of SFN for diabetic wound treatment. Additionally, an STZ-induced diabetic mouse model (C57/B6) was used in in vivo studies to examine SFN's impact on diabetic wound healing. Simultaneously, immunofluorescence staining, immunohistochemical staining, Western blotting, and qPCR analysis were employed to detect phenotypes associated with macrophage efferocytosis and M2 polarization. Subsequently, the mechanism underlying SFN treatment was explored through in vitro experiments utilizing the THP-1 human monocyte cell line. Results: The results demonstrated that topical SFN application accelerated wound healing in diabetic mice, partly through the enhancement of impaired macrophage efferocytosis and the promotion of M2 macrophage polarization, thereby reducing the inflammatory response at the wound site. SFN promoted the phagocytosis of apoptotic Jurkat cells by THP-1 differentiated macrophages, reducing the resulting inflammatory response. Mechanistic studies revealed that SFN promotes macrophage efferocytosis by activating nuclear factor E2-related factor 2 (Nrf2), leading to upregulation of heme oxygenase 1 (HO-1) expression and subsequent enhancement of mer proto-oncogene tyrosine kinase (MERTK), a recognition receptor for efferocytosis. Furthermore, SFN enhanced macrophage polarization toward the M2 phenotype and reduced the lipopolysaccharide (LPS)-induced inflammatory response in vitro. Conclusion: These data suggest that SFN could serve as an effective adjunct or novel therapeutic agent for treating chronic non-healing wounds in diabetes. C1 [Huang, Yumeng; Ding, Youjun; Tan, Qian] Jiangsu Univ, Clin Coll, Nanjing Drum Tower Hosp, Dept Burns & Plast Surg, Nanjing, Peoples R China. [Wang, Beizhi; Chen, Jingyi; Tan, Qian] Nanjing Univ Chinese Med, Nanjing Drum Tower Hosp, Clin Coll, Dept Burns & Plast Surg, Nanjing, Peoples R China. [Ma, Zhouji] Soochow Univ, Affiliated Hosp 2, Dept Plast & Aesthet Surg, Suzhou, Peoples R China. [Chen, Tianzhe; Zou, Haiting; Chen, Yutong; Dong, Zheng; Zhang, Hao; Tan, Qian] Nanjing Univ, Nanjing Drum Tower Hosp, Affiliated Hosp, Dept Burns & Plast Surg,Med Sch, Nanjing, Peoples R China. [Ding, Youjun] Jiangsu Univ, Zhenjiang Peoples Hosp 4, Affiliated Hosp 4, Dept Emergency Surg, Zhenjiang, Peoples R China. C3 Jiangsu University; Nanjing University; Nanjing University of Chinese Medicine; Nanjing University; Soochow University - China; Nanjing University; Jiangsu University RP Ding, YJ; Tan, Q (corresponding author), Jiangsu Univ, Clin Coll, Nanjing Drum Tower Hosp, Dept Burns & Plast Surg, Nanjing, Peoples R China. EM youjunding@126.com; smmutanqian@sina.com RI Ma, Zhouji/ISB-4061-2023; zhang, hao/AFS-1562-2022; 丁, 丁友军/HSH-1839-2023 OI Chen, Tianzhe/0000-0001-7036-7789; huang, yumeng/0009-0005-8240-8791 FU National Natural Science Foundation of China [81671922, 81974288]; Jiangsu Zhenjiang Social Development Project [SH2023031] FX Funding This work was supported by the National Natural Science Foundation of China (Grant Nos. 81671922, 81974288) and the Jiangsu Zhenjiang Social Development Project [Grant No. SH2023031] . 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PD MAR 26 PY 2025 VL 150 AR 114243 DI 10.1016/j.intimp.2025.114243 EA FEB 2025 PG 14 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA X6Q9P UT WOS:001426582200001 PM 39938166 OA hybrid DA 2026-03-26 ER PT J AU Li, YK Ai, SN Li, Y Ye, WY Li, R Xu, XL Liu, QQ AF Li, Yake Ai, Sinan Li, Yuan Ye, Wangyu Li, Rui Xu, Xiaolong Liu, Qingquan TI The role of natural products targeting macrophage polarization in sepsis-induced lung injury SO CHINESE MEDICINE LA English DT Review DE Traditional Chinese herbs; Natural products; Sepsis-induced acute lung injury; SALI; Macrophage polarization; M1; M2 ID MYOCARDIAL ISCHAEMIA/REPERFUSION INJURY; INHIBITING OXIDATIVE STRESS; PULMONARY-FIBROSIS; M2 POLARIZATION; ALTERNATIVE ACTIVATION; NLRP3 INFLAMMASOME; M1 POLARIZATION; INTENSIVE-CARE; TANSHINONE IIA; PROTEIN-KINASE AB Sepsis-induced acute lung injury (SALI) is characterized by a dysregulated inflammatory and immune response. As a key component of the innate immune system, macrophages play a vital role in SALI, in which a macrophage phenotype imbalance caused by an increase in M1 macrophages or a decrease in M2 macrophages is common. Despite significant advances in SALI research, effective drug therapies are still lacking. Therefore, the development of new treatments for SALI is urgently needed. An increasing number of studies suggest that natural products (NPs) can alleviate SALI by modulating macrophage polarization through various targets and pathways. This review examines the regulatory mechanisms of macrophage polarization and their involvement in the progression of SALI. It highlights how NPs mitigate macrophage imbalances to alleviate SALI, focusing on key signaling pathways such as PI3K/AKT, TLR4/NF-kappa B, JAK/STAT, IRF, HIF, NRF2, HMGB1, TREM2, PKM2, and exosome-mediated signaling. NPs influencing macrophage polarization are classified into five groups: terpenoids, polyphenols, alkaloids, flavonoids, and others. This work provides valuable insights into the therapeutic potential of NPs in targeting macrophage polarization to treat SALI. C1 [Li, Yake; Li, Rui; Xu, Xiaolong; Liu, Qingquan] Capital Med Univ, Beijing Hosp Tradit Chinese Med, Beijing 100010, Peoples R China. [Li, Yake; Li, Rui] Beijing Inst Chinese Med, Beijing 100010, Peoples R China. [Li, Yake; Li, Rui; Xu, Xiaolong; Liu, Qingquan] Capital Med Univ, Lab Clin Med, Beijing 100010, Peoples R China. [Ai, Sinan] China Japan Friendship Hosp, Beijing 100029, Peoples R China. [Li, Yuan] Henan Univ Chinese Med, Zhengzhou 450046, Peoples R China. [Ye, Wangyu] China Acad Chinese Med Sci, Guanganmen Hosp, Beijing 100053, Peoples R China. C3 Capital Medical University; Capital Medical University; China-Japan Friendship Hospital; Henan University of Traditional Chinese Medicine; Guang'anmen Hospital, CACMS; China Academy of Chinese Medical Sciences RP Xu, XL; Liu, QQ (corresponding author), Capital Med Univ, Beijing Hosp Tradit Chinese Med, Beijing 100010, Peoples R China.; Xu, XL; Liu, QQ (corresponding author), Capital Med Univ, Lab Clin Med, Beijing 100010, Peoples R China. EM xiaolong_xu3013@126.com; liuqingquan_2003@126.com RI Ai, Sinan/IUQ-4724-2023 OI Liu, Qingquan/0000-0003-0828-0361 FU National Natural Science Foundation of China [82141202, 82174348]; Key Discipline Construction Project of High-level Traditional Chinese Medicine of the State Administration of Traditional Chinese Medicine [ZYYZDXK-2023001]; National Multi- disciplinary Interdisciplinary Innovation Team Project ofTraditional Chinese Medicine [ZYYCXTD-D-202201] FX This study was supported in part by the National Natural Science Foundation of China (82141202, 82174348), the Key Discipline Construction Project of High-level Traditional Chinese Medicine of the State Administration of Traditional Chinese Medicine (ZYYZDXK-2023001), and the National Multi- disciplinary Interdisciplinary Innovation Team Project ofTraditional Chinese Medicine (ZYYCXTD-D-202201). 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Med. PD FEB 5 PY 2025 VL 20 IS 1 AR 19 DI 10.1186/s13020-025-01067-4 PG 30 WC Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine; Pharmacology & Pharmacy GA U8P9C UT WOS:001414356000002 PM 39910395 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zuo, CY Zhang, CS Zhang, HX Gou, CY Lei, H Tian, FW Wang, ZX Yin, HY Yu, SG AF Zuo, Chuan-yi Zhang, Cheng-shun Zhang, Han-xiao Gou, Chun-yan Lei, Hong Tian, Feng-wei Wang, Zhu-xing Yin, Hai-yan Yu, Shu-guang TI Moxibustion Alleviates Inflammation via SIRT5-mediated Post-translational Modification and Macrophage Polarization SO INFLAMMATION LA English DT Article DE Moxibustion; Inflammation; Macrophage; Sirt5 ID IL-1-BETA; GLUTAMINE; PAIN AB Macrophage polarisation is influenced by Sirtuin5 (SIRT5), which is crucial for regulating anti-inflammatory processes. Moxibustion, a traditional Chinese medicine therapy, exerts anti-inflammatory effects by altering the succinate/alpha-ketoglutarate (alpha-KG) ratio, an indicator of the M1 to M2 macrophage shift. Glutamate dehydrogenase 1 (GLUD1), a key enzyme involved in alpha-KG production, is desuccinylated by SIRT5. Currently, the potential influence of moxibustion on SIRT5-GLUD1-alpha-KG-mediated macrophage polarization in inflammatory diseases remains unexplored. C57BL/6 J and Sirt5 knockout mice were used as complete Freund's adjuvant (CFA)-induced adjuvant arthritis models. Moxibustion and acupoint injections of MC3482 were administered. Paw capacity asssays and ELISA were performed to quantify inflammatory effects and the expression of succinate, and alpha-KG expressions. Flow cytometry (FCM) and immunofluorescence were used to assesss the expression of M1- and M2-like macrophages. LC-MS/MS-based proteomic analysis was performed, and GLUD1 was identified desuccinylated protein associated with SIRT5. Western blotting and immunoprecipitation (IP) were used to detect SIRT5, GLUD1, and succinylated GLUD1expressions. Moxibustion and the SIRT5-mediated desuccinylation inhibitor MC3482 decreased inflammation by increasing the number of M2 macrophages and reducing the number of M1 macrophage in the CFA model. The potential mechanism may be related to the effects of moxibustion and SIRT5 inhibition, which inverted succinate and alpha-KG levels in the CFA group, resulting in low succinate, high alpha-KG, and increased GLUD1 succinylation after treatment. These findings suggest that the anti-inflammatory effects moxibustion are related to the impact of macrophage conversion after SIRT5-mediated post-translational modification. C1 [Zuo, Chuan-yi; Gou, Chun-yan; Lei, Hong; Tian, Feng-wei; Wang, Zhu-xing] Chongqing Tradit Chinese Med Hosp, Dept Acupuncture, Chongqing 400021, Peoples R China. [Zhang, Cheng-shun; Yin, Hai-yan; Yu, Shu-guang] Chengdu Univ Tradit Chinese Med, Acupuncture & Tuina Sch, Chengdu 610075, Sichuan, Peoples R China. [Zhang, Han-xiao] Univ Paris Saclay, Fac Med, F-94800 Villejuif, France. C3 Chengdu University of Traditional Chinese Medicine; Universite Paris Saclay RP Zuo, CY (corresponding author), Chongqing Tradit Chinese Med Hosp, Dept Acupuncture, Chongqing 400021, Peoples R China.; Yin, HY; Yu, SG (corresponding author), Chengdu Univ Tradit Chinese Med, Acupuncture & Tuina Sch, Chengdu 610075, Sichuan, Peoples R China. EM chuanyi_zuo@163.com; 20062066@cdutcm.edu.cn; ysg@cdutcm.edu.cn OI Yin, Haiyan/0000-0002-5442-5210 FU The 973 Program [2015CB554504]; National Natural Science Foundation of China [82105010]; Chongqing Postdoctoral Science Foundation [cstc2021jcyj-bshX0124]; Project for Performance Incentives and Guidance of Scientific Research Institutions of Chongqing [cstc2022jxjl120031]; Acupuncture and Chronobiology Key Laboratory of Sichuan Province Open Project [2021006] FX We would like to express our gratitude to the 973 Program (2015CB554504), National Natural Science Foundation of China (82105010), Chongqing Postdoctoral Science Foundation (cstc2021jcyj-bshX0124), Project for Performance Incentives and Guidance of Scientific Research Institutions of Chongqing (cstc2022jxjl120031), and the Acupuncture and Chronobiology Key Laboratory of Sichuan Province Open Project (2021006) for their financial support. 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WOS:001411623400001 PM 39899130 OA Green Submitted, hybrid DA 2026-03-26 ER PT J AU Cui, GL Wang, ML Liu, ZT Chang, C Wu, YY Li, XM Sun, ZG AF Cui, Guoliang Wang, Manli Liu, Zhiting Chang, Cheng Wu, Yuanyuan Li, Xiaoman Sun, Zhiguang TI Investigating the therapeutic effects and potential mechanisms of Zuojin Pill in the treatment of gastroesophageal reflux disease SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Gastroesophageal reflux disease; Zuojin pill; Network pharmacology; Traditional Chinese medicine ID NF-KAPPA-B; ADENOCARCINOMA SEQUENCE; ESOPHAGITIS; EXPRESSION; EXTRACT; PATHOPHYSIOLOGY; PATHWAY; BARRIER AB Ethnopharmacological relevance: Zuojin Pill (ZJP), a traditional Chinese medicinal formula, is widely recognized for its diverse pharmacological properties in the management of gastrointestinal disorders. However, the precise mechanisms underlying its therapeutic effects in gastroesophageal reflux disease (GERD) remain inadequately understood. Aim of the study: This study aims to investigate the therapeutic effects of ZJP in GERD and to elucidate the molecular mechanisms involved. Materials and methods: The chemical composition of ZJP was characterized using HPLC-Q-Exactive-MS. A rat model of GERD was established through esophagogastric anastomosis, and three different doses of ZJP were administered. Histological changes were assessed via hematoxylin-eosin (H&E) staining, while pro-inflammatory cytokines were quantified to evaluate the anti-inflammatory effects of ZJP. Network pharmacology combined with bioinformatics analysis was employed to predict potential therapeutic targets and signaling pathways of ZJP in GERD. Validation of the mechanisms was conducted through Western blotting, immunofluorescence (IF), transmission electron microscopy (TEM), and immunohistochemistry (IHC). Results: The results demonstrated that ZJP effectively alleviated pathological alterations and reduced pro- inflammatory cytokine levels in esophageal tissues of GERD rats. Western blotting and IF analysis of E-cadherin and claudin-1 confirmed that ZJP enhanced the integrity of the esophageal mucosal barrier. TEM imaging revealed that ZJP restored intercellular space (DIS), increased desmosome density, thereby protecting esophageal tissues from the detrimental effects of GERD. Furthermore, ZJP modulated macrophage polarization in the GERD rat model. Mechanistic investigations indicated that ZJP exerted its therapeutic effects by inhibiting MAPK/NF kappa B signaling pathway activation and downregulating the expression of prostaglandin-endoperoxide synthase 2 (PTGS2) and matrix metalloproteinase 2 (MMP2), consistent with predictions from network pharmacology analysis. Conclusions: This study provides comprehensive evidence for the therapeutic efficacy of ZJP in GERD, acting through modulation of inflammation, mucosal barrier integrity, and macrophage polarization. Additionally, ZJP downregulated PTGS2 and MMP2 expression and suppressed the activation of MAPK/NF-kappa B signaling pathways, underscoring its potential as a therapeutic intervention for GERD. C1 [Cui, Guoliang] Nanjing Univ Chinese Med, Sch Integrat Med, Nanjing 210023, Peoples R China. [Wang, Manli; Sun, Zhiguang] Nanjing Univ Chinese Med, Clin Med Coll 1, 138 Xianlin Ave, Nanjing 210023, Peoples R China. [Liu, Zhiting] Nanjing Univ Chinese Med, Jinling Clin Med Coll, Nanjing 210023, Peoples R China. [Chang, Cheng] Nanjing Univ Chinese Med, Jiangsu Prov Hosp Chinese Med, Affiliated Hosp, Nanjing 225200, Peoples R China. [Wu, Yuanyuan; Li, Xiaoman] Nanjing Univ Chinese Med, Sch Pharm, Jiangsu Key Lab Pharmacol & Safety Evaluat Chinese, 138 Xianlin Ave, Nanjing 210023, Peoples R China. C3 Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine RP Sun, ZG (corresponding author), Nanjing Univ Chinese Med, Clin Med Coll 1, 138 Xianlin Ave, Nanjing 210023, Peoples R China.; Wu, YY; Li, XM (corresponding author), Nanjing Univ Chinese Med, Sch Pharm, Jiangsu Key Lab Pharmacol & Safety Evaluat Chinese, 138 Xianlin Ave, Nanjing 210023, Peoples R China. EM cuiguoliang93@163.com; 20223056@njucm.edu.cn; liuzhiting1224@163.com; shizhe001@163.com; ywu@njucm.edu.cn; lixm@njucm.edu.cn; zhiguangsun@njucm.edu.cn OI Cui, Guoliang/0000-0002-0082-4742; Sun, Zhiguang/0009-0000-6491-1047 FU National Natural Science Foundation of China [82274399]; Postgraduate Research & Practice Innovation Program of Jiangsu Province [SJCX23_0806]; Open Project of Zhenjiang Traditional Chinese Medicine Spleen and Stomach Disease Clinical Medicine Research Center [SSPW2022-KF03] FX The project was supported by National Natural Science Foundation of China (Grant Nos. 82274399) , Postgraduate Research & Practice Innovation Program of Jiangsu Province (SJCX23_0806) and the Open Project of Zhenjiang Traditional Chinese Medicine Spleen and Stomach Disease Clinical Medicine Research Center (SSPW2022-KF03) . 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PD JAN 31 PY 2025 VL 340 AR 119230 DI 10.1016/j.jep.2024.119230 EA JAN 2025 PG 13 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA R4S3S UT WOS:001391362900001 PM 39662861 OA hybrid DA 2026-03-26 ER PT J AU Wan, LY Hao, WT Li, LL Wang, L Song, YZ AF Wan, Laiyi Hao, Wentao Li, Leilei Wang, Lin Song, Yanzheng TI Dissecting macrophage heterogeneity and kaempferol in lung adenocarcinoma: a single-cell transcriptomic approach and network pharmacology SO DISCOVER ONCOLOGY LA English DT Article DE Lung adenocarcinoma; Macrophage heterogeneity; Tumor microenvironment; Single-cell transcriptomics; Kaempferol ID CANCER AB BackgroundLung adenocarcinoma (LUAD) is a leading form of non-small cell lung cancer characterized by a complex tumor microenvironment (TME) that influences disease progression and therapeutic response. Tumor-associated macrophages (TAMs) within the TME promote tumorigenesis and evasion of immune surveillance, though their heterogeneity poses challenges in understanding their roles and therapeutic targeting. Additionally, traditional Chinese medicine (TCM) offers potential anti-cancer agents that could modulate the immune landscape.MethodsWe conducted single-cell RNA sequencing (scRNA-seq) on LUAD samples, performing an in-depth analysis of macrophage populations and their expression signatures. Network pharmacology was used to identify TCM components with potential TAM-modulatory effects, focusing on Astragalus membranaceus. Pseudotime trajectory analysis, immunofluorescence staining, and in vitro assays examined the functional roles of TAMs and the effects of selected compounds on macrophage polarization.ResultsOur scRNA-seq analysis identified notable heterogeneity among macrophages, revealing predominant M2-like phenotypes within TAMs. Network pharmacology highlighted active TCM ingredients, including quercetin, isorhamnetin, and kaempferol, targeting genes related to macrophage function. Survival analysis implicated AHSA1, CYP1B1, SPP1, and STAT1 as prognostically significant factors. Further experiments demonstrated kaempferol's efficacy in inhibiting M2 polarization, underlining a selective influence on TAM functionality.ConclusionsThis study delineates the diverse macrophage landscape in LUAD and suggests a pivotal role for STAT1 in TAM-mediated immunosuppression. Kaempferol, identified from TCM, emerges as an influential agent capable of altering TAM polarization, potentially enhancing anti-tumoral immunity. These findings underscore the translational potential of integrating TCM-derived compounds into immunotherapeutic strategies for LUAD. C1 [Wan, Laiyi; Hao, Wentao; Li, Leilei; Wang, Lin; Song, Yanzheng] Fudan Univ Shanghai, Shanghai Publ Hlth Clin Ctr, Dept Thorac Surg, Caolang Highway 2901, Shanghai, Peoples R China. [Song, Yanzheng] Fudan Univ, Shanghai Emerging & Re Emerging Infect Dis Inst, TB Ctr, Shanghai, Peoples R China. C3 Fudan University; Fudan University RP Wan, LY; Wang, L; Song, YZ (corresponding author), Fudan Univ Shanghai, Shanghai Publ Hlth Clin Ctr, Dept Thorac Surg, Caolang Highway 2901, Shanghai, Peoples R China.; Song, YZ (corresponding author), Fudan Univ, Shanghai Emerging & Re Emerging Infect Dis Inst, TB Ctr, Shanghai, Peoples R China. 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Oncol. PD JAN 30 PY 2025 VL 16 IS 1 AR 104 DI 10.1007/s12672-025-01832-9 PG 15 WC Oncology; Endocrinology & Metabolism WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Endocrinology & Metabolism GA U4P5W UT WOS:001411635400001 PM 39884998 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Mohanty, A Vekariya, V Yadav, S Agrawal-Rajput, R AF Mohanty, Aditya Vekariya, Vasu Yadav, Shivani Agrawal-Rajput, Reena TI Natural phytochemicals reverting M2 to M1 macrophages: A novel alternative leishmaniasis therapy SO MICROBIAL PATHOGENESIS LA English DT Article DE Leishmaniasis; Kala-azar; Macrophage polarisation; Natural bioactive compounds; M1 and M2 macrophages ID VITRO ANTILEISHMANIAL ACTIVITY; EXPERIMENTAL VISCERAL LEISHMANIASIS; IN-VITRO; OXIDATIVE STRESS; PROINFLAMMATORY CYTOKINES; IMMUNOMODULATORY ACTIVITY; ANTIOXIDANT PROPERTIES; MURINE LEISHMANIASIS; MOUSE MACROPHAGES; ARGINASE ACTIVITY AB Introduction: Leishmaniasis is a tropical parasitic disease caused by the protozoan Leishmania which remains a significant global health concern with diverse clinical manifestations. Transmitted through the bite of an infected sandfly, its progression depends on the interplay between the host immune response and the parasite. The disease outcome is linked to macrophage polarisation into M1 and M2 phenotypes. M1 macrophages are proinflammatory and promote parasite clearance, while M2 macrophages support tissue repair and parasite survival by facilitating promastigote entry and intracellular amastigote proliferation. Purpose: The review focuses on discovering novel phytochemicals that exploit the immunomodulatory properties of macrophages, which can serve as an alternative antileishmanial treatments due to their diverse chemical structures and ability to modulate immune responses. It examines the immunomodulatory effects of phytochemicals that directly or indirectly promote antileishmanial activity by influencing macrophage polarisation and cytokine secretion. They can induce M1 macrophage polarisation to directly combat leishmaniasis or suppress M2 macrophages, thereby exerting indirect antileishmanial activity by influencing the release of M1-and M2-related cytokines. Results & Discussion: Phytochemicals demonstrate antileishmanial effects through ROS production, M1 activation, and cytokine modulation. They regulate M1/M2-related cytokines and macrophage activity, influencing immune responses. Although their effects may be non-specific, targeted delivery strategies could overcome current therapeutic limitations, positioning phytochemicals as promising candidates for leishmaniasis treatment to counter the limitations of current medications. C1 [Mohanty, Aditya; Vekariya, Vasu; Yadav, Shivani; Agrawal-Rajput, Reena] Indian Inst Adv Res, Immunol Lab, Biotechnol & Bioengn, Gandhinagar 382426, Gujarat, India. RP Agrawal-Rajput, R (corresponding author), Indian Inst Adv Res, Immunol Lab, Biotechnol & Bioengn, Gandhinagar 382426, Gujarat, India. 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Pathog. PD MAR PY 2025 VL 200 AR 107311 DI 10.1016/j.micpath.2025.107311 EA JAN 2025 PG 17 WC Immunology; Microbiology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Microbiology GA U9K0K UT WOS:001414880200001 PM 39863089 DA 2026-03-26 ER PT J AU Liu, XG Zhao, P Wang, LM Wu, JY He, WR Wei, Y Chen, HR Li, JS AF Liu, Xinguang Zhao, Peng Wang, Liming Wu, Jinyan He, Wenrui Wei, Yu Chen, Hongrui Li, Jiansheng TI Screening effective-component compatibility from Jinshui Chenfei formula for silicosis treatment by serum-pharmacochemistry and feedback system control SO PHYTOMEDICINE LA English DT Article DE Effective-component compatibility; Feedback system control; Jinshui Chenfei formula; Silicosis; Synergistic combination ID LIQUID-CHROMATOGRAPHY; GLYCYRRHIZIC ACID; MASS-SPECTROMETRY; CLASSIFICATION; INDUCTION AB Background: The unclear chemical composition and mechanisms of action pose challenges for new drug development and quality control of traditional Chinese medicine (TCM) formulas. To address this, the concept of effective-component compatibility (ECC) was proposed to represent drug combination with equivalent efficacy to TCM formulas, along with clear composition and dosage. However, previous strategies for screening ECC have often overlooked the synergistic effects of its components. Purpose: This study proposed a strategy integrating serum pharmacochemistry and feedback system control (FSC) to identify synergistic combinations as ECC of TCM formulas. The strategy was applied to identify the ECC of Jinshui Chenfei formula (JCF) for silicosis treatment. Methods: A chemical library of JCF was constructed using ultra-high-performance liquid chromatography- quadrupole extractive orbitrap mass spectrometry (UHPLC-Q-Extractive Orbitrap MS). The library was then used to identify absorbed prototype compounds of JCF, and the serum levels of its main components were analyzed. Based on the primary absorbed prototypes, FSC was employed to screen the most effective synergistic combinations from JCF for inhibiting LPS- and IL-4-induced macrophage polarization. The pharmacological effects of ECC-JCF were further validated using a silica-induced silicosis mouse model, and its synergistic mechanisms were investigated through transcriptomics and molecular dynamic simulations. Results: A total of 437 compounds were identified in JCF, with 203 absorbed prototypes detected following oral administration. After three rounds of FSC iterative screening, a synergistic combination of isoliquiritin (180 mu g/ ml/0.43 mM), glycyrrhizic acid (180 mu g/ml/0.22 mM), and gallic acid (3.75 mu g/ml/0.02 mM) significantly inhibited the expression of TNF-alpha, IL-1 beta, IL-6, CD206, and Arg-1 mRNA in mouse alveolar macrophages. This combination also protected lung tissues from alveolar collapse, inflammatory cell infiltration, fibroblast proliferation, and fibrous nodule formation. In addition, the combination improved alveolitis and fibrosis scores in silicosis mice, outperforming both the original JCF formula and the sum of individual components. The synergistic effects of these compounds may regulate targets in inflammation and fibrosis formation pathways. Conclusion: This study identified an ECC of JCF with a well-defined composition and mechanism of action, facilitating the future development of JCF as a new drug. Compared with traditional ECC screening methods, this strategy reduces experimental workload while accounting for synergistic effects. C1 [Liu, Xinguang; Zhao, Peng; Wang, Liming; Wu, Jinyan; He, Wenrui; Wei, Yu; Chen, Hongrui; Li, Jiansheng] Henan Univ Chinese Med, Coconstruct Collaborat Innovat Ctr Chinese Med & R, Zhengzhou, Peoples R China. [Liu, Xinguang; Zhao, Peng; Wang, Liming; Wu, Jinyan; He, Wenrui; Wei, Yu; Chen, Hongrui; Li, Jiansheng] Henan Univ Chinese Med, Henan Key Lab Chinese Med Resp Dis, Zhengzhou, Peoples R China. [Liu, Xinguang; Zhao, Peng; Wang, Liming; Wu, Jinyan; He, Wenrui; Wei, Yu; Chen, Hongrui] Henan Univ Chinese Med, Acad Chinese Med Sci, Zhengzhou, Peoples R China. [Li, Jiansheng] Henan Univ Chinese Med, Affiliated Hosp 1, Dept Resp Dis, Zhengzhou, Peoples R China. C3 Henan University of Traditional Chinese Medicine; Henan University of Traditional Chinese Medicine; Henan University of Traditional Chinese Medicine; Henan University of Traditional Chinese Medicine RP Li, JS (corresponding author), Henan Univ Chinese Med, Zhengzhou 450046, Henan, Peoples R China. 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We previously reported the existence of Arg1-specific memory T cells among peripheral blood mononuclear cells (PBMCs) and described that Arg-1-based immune modulatory vaccines (IMVs) control tumor growth and alter the M1/M2 macrophage ratio in murine models of cancer. In the present study, we investigated how Arg1-specific T cells can directly target TAMs and influence their polarization.Methods Murine Arg1-specific CD4+T cells isolated from splenocytes of animals vaccinated with an Arg1-derived peptide in the adjuvant montanide were co-cultured with either in vitro M2-differentiated bone marrow-derived macrophages or ex vivo isolated F4/80+TAMs. Human Arg1-specific CD4+T cell clones were co-cultured with Arg1-expressing TAMs generated in vitro from either PBMC-derived CD14+cells or the myeloid cell lines MonoMac1 and THP-1. MHC class II-restricted Arg-1 peptide presentation by macrophages was confirmed by immunopeptidomics. T-cell-mediated changes in the macrophage immune phenotype and cytokine microenvironment were examined using flow cytometry, RT-qPCR and multiplex immunoassay. The effect of Arg1-derived peptide IMV on TAMs in vivo was assessed by multiplex gene analysis of F4/80+cells.Results We show that Arg1-based IMV-mediated tumor control was linked to a decrease in multiple immunosuppressive pathways in the TAM population of the treated animals. Tumor-conditioned media (TCM) derived from Arg1-vaccinated mice induced significantly higher upregulation of MHC-II on exposed myeloid cells compared with controls. Furthermore, murine CD4+Arg1-specific T cells were able to target TAMs and effectively reprogram their phenotype ex vivo by secreting IL2 and IFN gamma. Next, we established that human Arg1+TAMs present Arg1-derived peptides and are directly recognized by proinflammatory CD4+Arg1-specific T cell clones. These CD4+Arg1-specific T cells were able to reprogram TCM-conditioned macrophages as observed by increased expression of CD80 and HLA-DR.Conclusions TAMs may be directly targeted and modulated by Arg1-specific CD4+T cells. These findings provide a strong rationale for future clinical development of Arg1-based IMVs to alter the immune-suppressive TME by reprogramming TAMs and promoting a proinflammatory TME. C1 [Martinenaite, Evelina; Lecoq, Ines; Aaboe-Jorgensen, Mia; Ahmad, Shamaila Munir; Perez-Penco, Maria; Glockner, Hannah Jorinde; de la Torre, Lucia Lara; Romer, Anne Mette Askehoj; Andersen, Mads Hald] Herlev Hosp, Natl Ctr Canc Immune Therapy CCIT DK, Dept Oncol, Herlev, Denmark. [Martinenaite, Evelina; Lecoq, Ines; Chapellier, Marion; Pedersen, Ayako Wakatsuki] IO Biotech ApS, Copenhagen, Denmark. [Olsen, Lars Ronn] Tech Univ Denmark, Dept Hlth Technol, Sect Bioinformat, Lyngby, Denmark. [Andersen, Mads Hald] Univ Copenhagen, Dept Immunol, Copenhagen, Denmark. C3 University of Copenhagen; Herlev & Gentofte Hospital; Technical University of Denmark; University of Copenhagen RP Andersen, MH (corresponding author), Herlev Hosp, Natl Ctr Canc Immune Therapy CCIT DK, Dept Oncol, Herlev, Denmark.; Andersen, MH (corresponding author), Univ Copenhagen, Dept Immunol, Copenhagen, Denmark. EM evelina.martinenaite@regionh.dk; ines.lecoq.molinos@regionh.dk; miaaaboe@gmail.com; shamaila.munir.ahmad@regionh.dk; maria.perez.penco@regionh.dk; hannah.jorinde.gloeckner@regionh.dk; mc@iobiotech.com; lucia.lara.de.la.torre@regionh.dk; larsronnolsen@gmail.com; am.askehoej.roemer@gmail.com; awp@iobiotech.com; Mads.Hald.Andersen@regionh.dk OI Olsen, Lars Rønn/0000-0002-6725-7850; Askehøj Rømer, Anne Mette/0000-0002-5408-7020; Andersen, Mads Hald/0000-0002-2914-9605; Perez-Penco, Maria/0000-0003-4000-9184; Chapellier, Marion/0000-0003-1292-5695; Glöckner, Hannah Jorinde/0009-0008-9080-8033 FU Innovationfund Denmark [0153- 00059B, 8054- 00058B]; IO Biotech; Herlev and Gentofte Hospital; National Center for Cancer Immune Therapy (CCIT- DK); Research Council at Herlev and Gentofte Hospital FX This work was supported by Innovationfund Denmark (0153- 00059B and 8054- 00058B) and IO Biotech (N/A). In addition, it was supported by Herlev and Gentofte Hospital, and through a research funding agreement between IO Biotech ApS and National Center for Cancer Immune Therapy (CCIT- DK) (N/A) as well as Sundhedsstyrelsen (Danish Health and Medicines Authority) (4- 1612- 236/8) and The Research Council at Herlev and Gentofte Hospital (N/A). 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Immunother. Cancer PD JAN 29 PY 2025 VL 13 IS 1 AR e009930 DI 10.1136/jitc-2024-009930 PG 13 WC Oncology; Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Immunology GA U7C0D UT WOS:001413315600001 PM 39880485 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Huang, QT Ma, XD Zhang, JN Lin, WX Shen, XX Huang, ZW Zhang, X Wu, XY Dou, YX Su, ZR Su, JY Li, YC Liu, YH Xie, YL Lin, RF Huang, HY Zhang, QH Huang, XQ AF Huang, Qi-Ting Ma, Xing-Dong Zhang, Jia-Na Lin, Wei-Xiong Shen, Xue-Xia Huang, Zhuo-Wen Zhang, Xia Wu, Xiao-Yan Dou, Yao-Xing Su, Zi-Ren Su, Ji-Yan Li, Yu-Cui Liu, Yu-Hong Xie, You-Liang Lin, Rong-Feng Huang, Hai-Yang Zhang, Qi-Hui Huang, Xiao-Qi TI A Hepatic Oxidative Metabolite of Palmatine Ameliorates DSS-Induced Ulcerative Colitis by Regulating Macrophage Polarization Through AMPK/NF-κB Pathway SO AMERICAN JOURNAL OF CHINESE MEDICINE LA English DT Article DE Palmatine; Protoberberine; 8-Oxypalmatine; Ulcerative Colitis; Macrophage Polarization; Intestinal Mucosal Barrier; AMPK/NF-kappa B Pathway ID ACTIVATION; DISEASE; INFLAMMATION AB Palmatine (PAL) and berberine are both classified as protoberberine alkaloids, derived from several traditional Chinese herbs such as Coptis chinensis Franch. and Phellodendron chinense Schneid. These compounds are extensively used in treating dysentery and colitis. PAL is one of the crucial quality markers for these plants in the Chinese Pharmacopoeia. A key metabolite of PAL, 8-Oxypalmatine (OPAL), shows favorable anti-inflammatory activity and better safety compared to PAL, though its mechanisms in ulcerative colitis (UC) are not fully understood. This study used a dextran sodium sulfate-induced colitis mouse model to explore OPAL's effects. The results indicated that OPAL provided superior therapeutic effects to those of PAL, alleviating colitis symptoms and reducing colon inflammation by modulating pro-inflammatory (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6) and anti-inflammatory (transforming growth factor-beta and interleukin-10) cytokines. Additionally, OPAL helped rebuild the mucus barrier and upregulated tight junction proteins, thereby restoring intestinal integrity. Notably, OPAL inhibited the M1 macrophages infiltration while promoting M2 macrophage distribution in the colon. Its role in fostering M2 polarization and modulating the inflammatory cytokine profile was further confirmed in vitro. Importantly, the anti-inflammatory effects were primarily linked to AMP-activated protein kinase activation, which subsequently inhibited the nuclear factor-kappa B pathway. These findings highlight OPAL as a crucial active metabolite responsible for the therapeutic effects of PAL against UC, emphasizing its potential as a novel treatment for this condition. C1 [Huang, Qi-Ting; Ma, Xing-Dong; Zhang, Jia-Na; Lin, Wei-Xiong; Shen, Xue-Xia; Huang, Zhuo-Wen; Zhang, Xia; Wu, Xiao-Yan; Su, Zi-Ren; Li, Yu-Cui; Liu, Yu-Hong; Xie, You-Liang; Lin, Rong-Feng; Huang, Xiao-Qi] Guangzhou Univ Chinese Med, Sch Pharmaceut Sci, 232 Univ City Ring Rd East, Guangzhou 510006, Peoples R China. [Huang, Qi-Ting; Zhang, Jia-Na; Huang, Xiao-Qi] Guangzhou Univ Chinese Med, Dongguan Inst, 4 Libin Rd, Dongguan 523808, Peoples R China. [Ma, Xing-Dong] Huadu Dist Peoples Hosp Guangzhou, Guangzhou 510800, Peoples R China. [Dou, Yao-Xing] Guangdong Med Univ, Sch Ocean & Trop Med, Zhanjiang 524005, Peoples R China. [Su, Ji-Yan] Foshan Matern & Child Healthcare Hosp, Foshan 528000, Peoples R China. [Su, Ji-Yan] Southern Med Univ, Sch Pharmaceut Sci, Guangzhou 510515, Peoples R China. [Huang, Hai-Yang] Guangzhou Univ Chinese Med, Dongguan Hosp, Dongguan Hosp Tradit Chinese Med, Dongguan 523000, Peoples R China. [Zhang, Qi-Hui] Chongqing Univ, Sch Chem & Chem Engn, 55 Univ Town South Rd, Chongqing 400044, Peoples R China. C3 Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangdong Medical University; Southern Medical University - China; Guangzhou University of Chinese Medicine; Chongqing University RP Huang, XQ (corresponding author), Guangzhou Univ Chinese Med, Sch Pharmaceut Sci, 232 Univ City Ring Rd East, Guangzhou 510006, Peoples R China.; Huang, XQ (corresponding author), Guangzhou Univ Chinese Med, Dongguan Inst, 4 Libin Rd, Dongguan 523808, Peoples R China.; Zhang, QH (corresponding author), Chongqing Univ, Sch Chem & Chem Engn, 55 Univ Town South Rd, Chongqing 400044, Peoples R China. EM qhzhang@cqu.edu.cn; huangxiaoqi@gzucm.edu.cn RI Liu, Yuhong/AAT-9680-2021; Su, Jiyan/JMQ-1113-2023; 林, 伟雄/HNJ-1424-2023; Su, Zi-Ren/O-5014-2019; Xiaoqi, Huang/AAK-7124-2020 OI 黄, 卓文/0009-0001-3773-9867; Dou, Yaoxing/0000-0002-8606-7526; Su, Zi-Ren/0000-0002-7018-3207; Xiaoqi, Huang/0000-0003-3401-5000 FU National Natural Scientific Foundation of China [82374126]; Basic and Applied Basic Research Foundation of Guangdong Province [2021A1515220162, 2022A1515140124, 2023A1515220035]; National Undergraduate Innovation and Entrepreneurship Training Program [202310572018]; Research Project on Traditional Chinese Medicine by Guangdong Provincial Administration of Traditional Chinese Medicine [20241124] FX This work was supported by the National Natural Scientific Foundation of China (82374126); Basic and Applied Basic Research Foundation of Guangdong Province (2021A1515220162, 2022A1515140124 and 2023A1515220035); National Undergraduate Innovation and Entrepreneurship Training Program (202310572018) and Research Project on Traditional Chinese Medicine by Guangdong Provincial Administration of Traditional Chinese Medicine (20241124). 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PY 2025 VL 53 IS 01 BP 285 EP 307 DI 10.1142/S0192415X25500119 EA JAN 2025 PG 23 WC Integrative & Complementary Medicine; Medicine, General & Internal WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine; General & Internal Medicine GA Y6E6W UT WOS:001408495900001 PM 39880666 DA 2026-03-26 ER PT J AU Zhang, XS Yang, LQ Feng, KR Zhang, H Chen, YL Li, WX Wang, XY Zhang, ML Wu, YL Wei, ST Zheng, YJ Meng, GQ Meng, WT Chen, XF Tang, JF AF Zhang, Xiaoshuai Yang, Liuqing Feng, Kairui Zhang, Hui Chen, Yulong Li, Weixia Wang, Xiaoyan Zhang, Mingliang Wu, Yali Wei, Shiting Zheng, Yajuan Meng, Gaoquan Meng, Weiting Chen, Xiaofei Tang, Jinfa TI Shuxuening injection improves myocardial injury after myocardial infarction by regulating macrophage polarization via the TLR4/NF-κB and PI3K/Akt signaling pathways SO PHYTOMEDICINE LA English DT Article DE Shuxuening injection; Myocardial infarction; Macrophage polarization; TLR4/NF-kappa B pathway; PI3K/Akt pathway ID IN-VIVO; INFLAMMATION; ACTIVATION; APOPTOSIS; PROTECTS AB Background: Macrophage activation and polarization play pivotal roles in the inflammatory response and myocardial injury associated with myocardial infarction (MI). Modulating macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype is a promising therapeutic approach for MI. Shuxuening injection (SXNI) is extensively utilized in clinical settings for MI treatment and has demonstrated therapeutic efficacy. However, the effects of SXNI on macrophage polarization post-MI and its underlying mechanisms remain insufficiently understood. Aim of the study: This study is aimed to evaluate the effects of SXNI on macrophage polarization following MI and to elucidate its potential mechanisms of action. Methods: A rat model of MI was established by ligation of the left anterior descending coronary artery. The cardioprotective effects of SXNI were assessed through echocardiography, TTC staining, Masson's trichrome staining, HE staining, TUNEL staining, and western blotting (WB). Macrophage polarization was evaluated using ELISA, immunofluorescence staining, and WB. An in vitro model of oxygen-glucose deprivation (OGD) was utilized to simulate MI in macrophages, and qRT-PCR was employed to examine M1/M2 polarization markers. UPLC-Q-TOF/MS was used to identify active components in SXNI. Network pharmacology analysis and molecular docking were utilized to predict the key targets and pathways, which were subsequently validated through WB and immunohistochemistry. Results: SXNI improved cardiac function, reduced infarct size, and attenuated myocardial tissue damage and apoptosis in MI rats. Staining analyses indicated a reduction in M1 macrophages (CD86+/CD68+) and an increase in M2 macrophages (CD206+/CD68+) in SXNI-treated animals. In vivo and in vitro experiments demonstrated that SXNI decreased M1 markers and pro-inflammatory cytokines levels while increasing M2 markers and the production of anti-inflammatory and pro-angiogenic cytokines. UPLC-Q-TOF/MS analysis identified 18 active components in SXNI. Network pharmacology analysis and molecular docking implicated the TLR4/NF-kappa B and PI3K/Akt pathways as central mechanisms, which were further confirmed by WB and immunohistochemistry. SXNI inhibited the expression of TLR4 and phosphorylated NF-kappa B while enhancing phosphorylated PI3 K and Akt levels. Conclusions: SXNI modulates the TLR4/NF-kappa B and PI3K/Akt signaling pathways to promote the polarization of macrophages from the M1 to the M2 phenotype, thereby alleviating myocardial inflammation and injury. These findings provide a scientific basis for the clinical application of SXNI in MI management, and establish a scientific foundation for exploring novel therapeutic strategies for cardiovascular diseases based on macrophage polarization. C1 [Zhang, Xiaoshuai; Yang, Liuqing; Zhang, Hui; Li, Weixia; Wang, Xiaoyan; Zhang, Mingliang; Wu, Yali; Wei, Shiting; Zheng, Yajuan; Meng, Gaoquan; Meng, Weiting; Chen, Xiaofei; Tang, Jinfa] Henan Univ Chinese Med, Dept Pharm, Affiliated Hosp 1, Zhengzhou 450003, Henan, Peoples R China. [Yang, Liuqing; Zhang, Hui; Li, Weixia; Wang, Xiaoyan; Zhang, Mingliang; Wu, Yali; Chen, Xiaofei; Tang, Jinfa] Henan Prov Engn Res Ctr Safety Evaluat & Risk Mana, Henan Prov Engn Res Ctr Clin Applicat Evaluat & Tr, Henan Prov Key Lab Clin Pharm Tradit Chinese Med, Zhengzhou 450003, Henan, Peoples R China. [Zhang, Xiaoshuai; Li, Weixia; Wang, Xiaoyan; Wei, Shiting; Zheng, Yajuan; Meng, Gaoquan; Meng, Weiting; Tang, Jinfa] Henan Univ Chinese Med, Sch Pharm, Zhengzhou 450046, Henan, Peoples R China. [Feng, Kairui] Shandong Second Med Univ, Sch Pharm, Weifang 261053, Peoples R China. [Chen, Yulong] Tianjin Univ Tradit Chinese Med, Coll Pharmaceut Engn Tradit Chinese Med, Tianjin 301617, Peoples R China. C3 Henan University of Traditional Chinese Medicine; Henan University of Traditional Chinese Medicine; Shandong Second Medical University; Tianjin University of Traditional Chinese Medicine RP Yang, LQ; Chen, XF; Tang, JF (corresponding author), Henan Univ Chinese Med, Dept Pharm, Affiliated Hosp 1, 19 Renmin Rd, Zhengzhou 450046, Peoples R China. EM yangliuqqing@163.com; chenxiaofei5555@163.com; a0519@163.com RI chen, xiaofei/AAZ-6658-2021; xiaoshuai, zhang/MGW-2916-2025; WU, yali/PGF-1693-2026; Chen, Yulong/MVX-5272-2025 OI Feng (冯凯瑞）, Kairui/0009-0004-4260-7000; FU National Natural Science Founda-tion of China [82204838]; Key project of Henan Provincial Medical Science and Technology Research Plan [SBGJ202302100]; Henan Pro-vincial Health Commission National Clinical research base of traditional Chinese medicine research project [2022JDZX103]; Science and Technology Innovation Team in Universities of Henan Province [23IRTSTHN026] FX Acknowledgements This research was funded by the National Natural Science Founda-tion of China (82204838) , Key project of Henan Provincial Medical Science and Technology Research Plan (SBGJ202302100) , Henan Pro-vincial Health Commission National Clinical research base of traditional Chinese medicine research project (2022JDZX103) , and Science and Technology Innovation Team in Universities of Henan Province (23IRTSTHN026) . 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This study explores the therapeutic potential of Boswellia to treat recurrent aphthous ulcers by its anti-inflammatory and healing promotion effect in a rat oral ulcer model.MethodsNetwork pharmacology techniques were employed to elucidate Boswellia's active components and potential targets. Intersecting targets of Boswellia and oral ulcer-related genes were screened for protein-protein interaction network analysis and functional enrichment. An oral ulcer model in rats was used and rats were treated with Boswellia extract. The healing process was monitored by measuring the ulcer area and body weight changes. Histological analysis was performed, and the role of Boswellia in macrophage polarization was investigated through gene expression analysis and protein array tests. The underlying mechanism involving PPAR gamma activation was also explored.ResultsNetwork pharmacology analysis revealed Boswellia's interaction with key genes and pathways associated with inflammation and lipid metabolism, such as MAPK3, PPARG, and PTGS2. Boswellia extract significantly accelerated oral ulcer healing and recovered weight loss in rats. Histological examinations revealed reduced tissue swelling and inflammatory cell infiltration in treated groups. Furthermore, Boswellia extract decreased infiltration of M1 macrophage presence while increasing M2 macrophage, indicating an inflammation-resolving effect. In vitro studies showed that Boswellia extract enhanced M2-related gene expression and decreased pro-inflammatory cytokines, which is PPAR gamma dependent.ConclusionBoswellia extract promotes oral ulcer healing and resolves inflammation, primarily through the modulation of macrophage polarization via PPAR gamma activation. C1 [Zhao, Wei; Jia, Zhuoqun; Han, Jiao; Sun, Xiaojun] Shanxi Med Univ, Hosp 1, Dept Oral Med, Taiyuan, Peoples R China. C3 Shanxi Medical University RP Sun, XJ (corresponding author), Shanxi Med Univ, Hosp 1, Dept Oral Med, Taiyuan, Peoples R China. EM drsdyy@163.com FU Shanxi Provincial Health Commission Project; Fundamental Research Program of Shanxi Province [202203021221253]; [2023063] FX This study was supported by the Fundamental Research Program of Shanxi Province (202203021221253) and Shanxi Provincial Health Commission Project (2023063). 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Oral Pathol. Med. PD MAR PY 2025 VL 54 IS 3 BP 131 EP 140 DI 10.1111/jop.13609 EA JAN 2025 PG 10 WC Dentistry, Oral Surgery & Medicine; Pathology WE Science Citation Index Expanded (SCI-EXPANDED) SC Dentistry, Oral Surgery & Medicine; Pathology GA Z6U4F UT WOS:001406824100001 PM 39871413 DA 2026-03-26 ER PT J AU Zhang, FX Wang, F Zhao, LS Wang, LQ Li, WJ Huang, FH Wang, NN AF Zhang, Fanxuan Wang, Fang Zhao, Lisha Wang, Leqian Li, Wenjing Huang, Feihua Wang, Nani TI Yunvjian decoction attenuates lipopolysaccharide-induced acute lung injury by inhibiting NF-κB/NLRP3 pathway and pyroptosis SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE Yunvjian decoction; acute lung injury; active ingredients; NF-kappa B; NLRP3 AB Introduction Yunvjian (YNJ) decoction, a classic traditional Chinese medicine prescription for inflammatory diseases, has demonstrated good therapeutic effects in the clinical treatment of pneumonia. The aim of this study was to clarify the effective ingredients and mechanism of action of YNJ on lipopolysaccharide (LPS)-induced acute lung injury (ALI).Methods The effects of YNJ were evaluated in a mouse model of LPS-induced ALI and in LPS-treated MLE-12 murine lung epithelial cells and RAW264.7 macrophages in vitro. The mechanism of action of YNJ on these model systems was studied using RNA sequencing, immunohistochemical analysis, immunoblotting, immunofluorescence, ELISA, and polymerase chain reaction assays. Ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was applied to identify the absorbed components of YNJ.Results YNJ attenuated pulmonary damage in LPS-treated mice, as evidenced by reduced protein content in bronchoalveolar lavage fluid, decreased lung wet/dry weight ratio, and improved respiratory function. Analysis of pneumonia-related lung injury samples from patients in the Gene Expression Omnibus dataset GSE40012 indicated that NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis was a primary mechanism in ALI. YNJ reduced the phosphorylation of nuclear factor-kappa B (NF-kappa B) and decreased the expression levels of lung NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cleaved caspase-1, and interleukin-1 beta levels (IL-1 beta) in vivo. Administration of YNJ-containing mouse serum increased cell viability and decreased malondialdehyde and reactive oxidative species contents in LPS-stimulated MLE-12 cells. YNJ-containing serum also decreased the secretion of tumor necrosis factor-alpha, IL-6, and IL-1 beta in LPS-stimulated RAW264.7 macrophages, and promoted macrophage polarization toward an M2 phenotype. A total of 23 absorbed components were identified in YNJ-containing serum. Among those, network analysis and in vitro experiments indicated that diosgenin, timosaponin BII, and mangiferin are anti-inflammatory active substances.Conclusion YNJ attenuates LPS-induced ALI in mice by inhibiting pyroptosis of lung epithelial cells and macrophages via suppression of the NF-kappa B/NLRP3 pathway. Our findings provide novel insights into the therapeutic effects of YNJ on ALI. C1 [Zhang, Fanxuan; Li, Wenjing; Huang, Feihua] Zhejiang Chinese Med Univ, Clin Med Coll 2, Hangzhou, Zhejiang, Peoples R China. [Wang, Fang; Wang, Nani] Zhejiang Chinese Med Univ, Sch Pharm, Hangzhou, Zhejiang, Peoples R China. [Zhao, Lisha; Huang, Feihua; Wang, Nani] Zhejiang Chinese Med Univ, Tongde Hosp, Hangzhou, Zhejiang, Peoples R China. [Wang, Leqian] Hangzhou Normal Univ, Coll Pharm, Hangzhou, Zhejiang, Peoples R China. C3 Zhejiang Chinese Medical University; Zhejiang Chinese Medical University; Zhejiang Chinese Medical University; Hangzhou Normal University RP Huang, FH (corresponding author), Zhejiang Chinese Med Univ, Clin Med Coll 2, Hangzhou, Zhejiang, Peoples R China.; Wang, NN (corresponding author), Zhejiang Chinese Med Univ, Sch Pharm, Hangzhou, Zhejiang, Peoples R China.; Huang, FH; Wang, NN (corresponding author), Zhejiang Chinese Med Univ, Tongde Hosp, Hangzhou, Zhejiang, Peoples R China. EM hfhua238@sohu.com; wnn8511@163.com RI Li, Wenjing/LZG-4762-2025 FU Zhejiang Provincial Medicine Foundation [2022ZX002, GZY-ZJ-KJ-23006, 2024ZR001, 2024ZR007, 2024KY867]; Institute Specific Foundation for Zhejiang Provincial Department of Science and Technology [YSZX2401] FX The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research was funded by Zhejiang Provincial Medicine Foundation (2022ZX002, GZY-ZJ-KJ-23006, 2024ZR001, 2024ZR007, 2024KY867), and Institute Specific Foundation for Zhejiang Provincial Department of Science and Technology (YSZX2401). 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Pharmacol. PD JAN 24 PY 2025 VL 16 AR 1430536 DI 10.3389/fphar.2025.1430536 PG 16 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA U9Q2E UT WOS:001415042000001 PM 39925847 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Wang, WW Lin, FF Shi, SP Yu, YQ Lin, MY Lian, WL Chen, BY Qi, XY AF Wang, Wenwu Lin, Fangfeng Shi, Shuping Yu, Yunqiu Lin, Mengyan Lian, Wenliang Chen, Biyin Qi, Xiaoyan TI Investigating the Role of Quercetin, an Active Ingredient in Bazhen Decoction, in Targeting CXCL8 to Inhibit Macrophage M2 Polarization and Reshape the Immunological Microenvironment of Colorectal Cancer SO CHEMICAL BIOLOGY & DRUG DESIGN LA English DT Article DE colorectal cancer; CXCL8; macrophage M2 polarization; quercetin ID MEDICINE AB Bazhen Decoction (Eight Treasures Decoction) has demonstrated efficacy in the treatment of colorectal cancer (CRC), yet the active ingredients in it and the mechanisms underlying their anti-cancer properties are not well understood. Through network pharmacology, the effective components of Bazhen Decoction against CRC and their corresponding key genes were delineated. Molecular docking was executed to identify the active component targeting the key gene CXCL8, which led to the discovery of Quercetin. The cellular thermal shift assay method was then used to verify the binding interaction. CRC cells were treated with incremental concentrations of Quercetin, cell viability was evaluated by the Cell Counting Kit-8 assay to calculate the IC50, and apoptosis rates were determined by flow cytometry. Expression of the apoptosis-related proteins Bcl-2 and Cleaved caspase-3 was measured using western blot. The impact of Quercetin on macrophage polarization was studied by co-culturing the treated CRC cells with macrophages, assessing M1 and M2 macrophage distribution via flow cytometry, and quantifying cytokine levels (IL-6, IL-10, IL-12, and CXCL8) with enzyme-linked immunosorbent assay (ELISA). The active ingredient Quercetin from Bazhen Decoction exhibited a targeted binding affinity with the key gene CXCL8, which enabled it to inhibit the proliferation of CRC cells and induce cell apoptosis. The overexpression of CXCL8 was associated with the promotion of CRC malignancy, yet the presence of Quercetin could lessen the impact of CXCL8 overexpression on CRC cells. Moreover, the treatment with Quercetin leads to a diminished abundance of M2 macrophages and an increase in the levels of cytokines IL-6 and IL-12, while reducing the levels of IL-10 and CXCL8, which indicates that Quercetin has an inhibitory effect on macrophage M2 polarization. Quercetin, the active component in Bazhen Decoction that is known for anti-CRC effects, targets and inhibits CXCL8 to impede the malignant behaviors and the M2 polarization of macrophages. Thus, Quercetin may be utilized as an immunomodulatory agent in CRC treatment. C1 [Wang, Wenwu; Lin, Fangfeng; Shi, Shuping; Yu, Yunqiu; Lin, Mengyan; Lian, Wenliang; Chen, Biyin] Fujian Univ Tradit Chinese Med, Dept Oncol, Affiliated Peoples Hosp 3, Fuzhou, Peoples R China. [Qi, Xiaoyan] Zibo Cent Hosp, Dept Oncol, Zibo, Peoples R China. C3 Fujian University of Traditional Chinese Medicine RP Wang, WW (corresponding author), Fujian Univ Tradit Chinese Med, Dept Oncol, Affiliated Peoples Hosp 3, Fuzhou, Peoples R China.; Qi, XY (corresponding author), Zibo Cent Hosp, Dept Oncol, Zibo, Peoples R China. EM wwwwang882178@163.com; slhho1249@163.com FU Key laboratory of Integrative Medicine of Fujian Province University (Fujian University of Traditional Chinese Medicine) [KLIM2022005/CKJ2022005] FX This work was supported by the Key Laboratory of Integrative Medicine of Fujian Province University (Fujian University of Traditional Chinese Medicine) KLIM2022005/CKJ2022005. 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Biol. Drug Des. PD JAN 16 PY 2025 VL 105 IS 1 AR e70047 DI 10.1111/cbdd.70047 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA S3H9V UT WOS:001397188100001 PM 39821540 DA 2026-03-26 ER PT J AU Jiang, YS Cao, JY Li, R Yu, J Peng, Y Huang, Q Zuo, W Chen, JY AF Jiang, Yongsheng Cao, Jianye Li, Rui Yu, Jia Peng, Yan Huang, Qiong Zuo, Wei Chen, Junyue TI Tetrahydropalmatine ameliorates peripheral nerve regeneration by enhancing macrophage anti-inflammatory response SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Peripheral nerve injury; Tetrahydropalmatine; Anti-inflammatory response; Macrophage polarization ID ACTIVATION; STRESS AB Background: Peripheral nerve injury (PNI) is a common clinical problem that can result in partial or complete loss of sensory, motor, and autonomic functions. Tetrahydropalmatine (THP), a Corydalis yanhusuo-derived phytochemical alkaloid, possesses hypnotic, soothing, analgesic, and other effects, but little is known about the effect of THP on moderating peripheral nerve regeneration and its possible underlying mechanism of action. Purpose: In this study, we aim to elucidate the protective function of THP on PNI and further reveal the underlying pharmacological mechanisms. Methods: PNI rats were in suit injection of THP solution at doses of 40 mg/kg for consecutive 3, 7, or 28 days, followed by harvesting the sciatic nerve tissues. The protective effect of THP on PNI was evaluated by electrophysiological test, transmission electron microscopy, immunofluorescence (IF), and western blotting (WB). Macrophage polarization, the expression of inflammatory-related genes and cytokines, and its upstream signaling pathways were detected by IF, WB, enzyme-linked immunosorbent assay (ELISA), mRNA-seq, and WB. In vitro, the Raw 264.7 cells were treated with lipopolysaccharide containing with/without THP. The degree of inflammatory activation and its potential pharmacological mechanism were measured by ELISA, qRT-PCR, IF staining, flow cytometry, and WB. Additionally, a pharmacological agonist or inhibitor was added to the cell medium to further identify the role of THP's potential pharmacological mechanism in regulating inflammatory response via IF and ELISA technology. Results: Using the sciatic nerve crush model, we found that THP significantly enhanced the rate of axonal growth and functional recovery, and altered macrophage subtype transformation from the M1/M0 phenotype into the M2 phenotype, inducing the secretion of large amounts of anti-inflammatory factors. Moreover, THP significantly increased the phosphorylation level of PI3K, AKT, GSK3 beta, and I kappa Ba, and decreased the expression of TLR4 protein and NF-kappa B phosphorylation. Similarly, in vitro, THP also facilitated Raw 264.7 cell polarization to the M2 subtype under the condition of LPS stimulation. Meanwhile, the change of PI3K/AKT/GSK3 beta and TLR4/NF-kappa B signaling-related proteins in vitro was consistent with the results in vivo. Additionally, the THP-medicated antiinflammatory effect on Raw 264.7 cells was partly eliminated when pharmacological intervention of these two signaling pathways. Conclusions: THP has anti-inflammatory effects on facilitating M2-subtype macrophage polarization, which produces abundant anti-inflammatory cytokines to ameliorate peripheral nerve regeneration. Moreover, the potential mechanism of THP action may be intimately associated with activating the PI3K/AKT/GSK3 beta axis and inhibiting the TLR4/NF-kappa B pathway. C1 [Jiang, Yongsheng; Zuo, Wei; Chen, Junyue] Wenzhou Med Univ, Xiangshan Hosp, Ningbo 315700, Zhejiang, Peoples R China. [Li, Rui] Shenzhen Univ Med Sch, Sch Biomed Engn, Guangdong Key Lab Biomed Measurements & Ultrasound, Natl Reg KeyTechnol Engn Lab Med Ultrasound, Shenzhen 518060, Peoples R China. [Cao, Jianye] Wenzhou Med Univ, Wenzhou 325035, Peoples R China. [Yu, Jia; Peng, Yan] Hangzhou Inst Food & Drug Control, Hangzhou, Peoples R China. [Huang, Qiong] Xiangshan Maternal & Child Hlth Care Family Planni, Ningbo, Peoples R China. C3 Wenzhou Medical University; Shenzhen University; Wenzhou Medical University RP Zuo, W; Chen, JY (corresponding author), Wenzhou Med Univ, Xiangshan Hosp, Ningbo 315700, Zhejiang, Peoples R China.; Li, R (corresponding author), Shenzhen Univ, Sch Biomed Engn, Med Sch, Shenzhen, Peoples R China. EM xiaoerrui1989@163.com; zuowei196412@163.com; 68011336@qq.com RI Jiang, Yongsheng/AAB-7219-2022 FU National Natural Science Funding of China [81802238]; Zhejiang Pro-vincial Natural Science Foundation of China [LWQ20H170001] FX The research was financially supported by a research grant from the National Natural Science Funding of China (81802238) , Zhejiang Pro-vincial Natural Science Foundation of China (LWQ20H170001) . 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Immunopharmacol. PD FEB 6 PY 2025 VL 147 AR 114000 DI 10.1016/j.intimp.2024.114000 EA JAN 2025 PG 15 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA T9C0J UT WOS:001407886600001 PM 39765002 DA 2026-03-26 ER PT J AU Liu, ZH Gao, M Yan, FL Zhang, H Wang, L Zhao, YX Zhao, HR Xie, XZ Li, CX Dai, J Xiong, HB Zhang, JF AF Liu, Zhihong Gao, Min Yan, Fenglian Zhang, Hui Wang, Lin Zhao, Yuxuan Zhao, Hongru Xie, Xinzhou Li, Chunxia Dai, Jun Xiong, Huabao Zhang, Junfeng TI Cucurbitacin IIb mitigates concanavalin A-induced acute liver injury by suppressing M1 macrophage polarization SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE cucurbitacin IIb; M1 macrophage; concanavalin A; acute liver injury ID NF-KAPPA-B; CELLS AB Cucurbitacins are a class of triterpenoid compounds extracted from plants and possess various pharmacological applications. Cucurbitacin IIb (CuIIb), extracted from the medicinal plant Hemsleya amabilis (Cucurbitaceae), has served as a traditional Chinese medicine for the treatment of bacterial dysentery and intestinal inflammation. CuIIb has been shown to exhibit anti-inflammatory activity; however, the protective effect of CuIIb against concanavalin A (Con A)-induced acute liver injury (ALI) and the fundamental mechanism remain unelucidated. In this study, we established an acute liver injury mouse model using Con A to investigate the effects of CuIIb on ALI. The results revealed that CuIIb significantly reduced serum aminotransferase levels and increased the survival rate of mice. Additionally, CuIIb effectively attenuated hepatocyte apoptosis, hepatic histopathological damage, and oxidative stress. Notably, CuIIb inhibited the polarization of M1 macrophages in vivo and in vitro. Moreover, the expression levels of pro-inflammatory cytokines related to M1 macrophages, such as interleukin (IL)-12, IL-1 beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha), were reduced. CuIIb regulated M1 macrophage activation by modulating the nuclear factor (NF)-kappa B and mitogen-activated protein kinase (MAPK) signaling pathways. Conclusively, these results demonstrated that CuIIb significantly prevented Con A-induced ALI by suppressing M1 macrophage polarization via the MAPK and NF-kappa B signaling pathways, demonstrating the potential use of CuIIb for ALI treatment. C1 [Liu, Zhihong; Yan, Fenglian; Zhang, Hui; Wang, Lin; Zhao, Yuxuan; Zhao, Hongru; Li, Chunxia; Dai, Jun; Xiong, Huabao; Zhang, Junfeng] Jining Med Univ, Inst Immunol & Mol Med, Jining 272067, Peoples R China. [Liu, Zhihong] Shandong First Med Univ, Sch Basic Med, Jinan 271016, Peoples R China. [Gao, Min] Jining First Peoples Hosp, Clin Lab, Jining 272011, Peoples R China. [Yan, Fenglian; Zhang, Hui; Wang, Lin] Jining Med Univ, Jining Key Lab Immunol, Jining 272067, Peoples R China. [Xie, Xinzhou] Jining First Peoples Hosp, Dept Spine Surg, Jining 272011, Peoples R China. C3 Jining Medical University; Shandong First Medical University & Shandong Academy of Medical Sciences; Jining Medical University RP Xiong, HB; Zhang, JF (corresponding author), Jining Med Univ, Inst Immunol & Mol Med, Jining 272067, Peoples R China. EM xionghbl@163.com; zjfart001@163.com RI Yan, Fenglian/KBP-8427-2024; zhao, yuxuan/IUO-2639-2023 FU National Natural Science Foundation of China [82171810]; Research Fund for Academician Lin He New Medicine [JYHL2022ZD02, JYHL2021ZD01, JYHL2021MS06]; Doctoral Startup Fund of Jining Medical University [JY2016QD030] FX This work was supported by the National Natural Science Foundation of China [grant number 82171810]; the Research Fund for Academician Lin He New Medicine [grant numbers JYHL2022ZD02, JYHL2021ZD01, and JYHL2021MS06]; and the Doctoral Startup Fund of Jining Medical University [grant number JY2016QD030]. The funding bodies played no role in the study or decision to publish. 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There into, Huaier polysaccharides (HP), the major component of Trametes robiniophila Murr., as a preparation of Huaier granule, is recommended by clinical guidelines for Hepatocellular carcinoma (HCC). However, the anti-HCC mechanism remains unclear. Herein, we investigated whether HP could suppress HCC and revealed the underlying mechanism. Firstly, HP showed a weaker proliferation inhibitory effect on the mouse source and human HCC cells in vitro, but exhibited stronger anti-HCC effects in animals. And nude mice models confirmed that macrophages play an important role in the anti-HCC effect of HP. Then, we observed that HP reduced the polarization of M2 macrophages in tumor microenvironment and increased the secretion of pro-inflammatory factors by macrophages. Moreover, 16 s rRNA gene sequencing and non-targeted metabolomics analysis revealed that HP altered the gut microbiota and related metabolites. 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PD MAR PY 2025 VL 293 AR 139357 DI 10.1016/j.ijbiomac.2024.139357 EA JAN 2025 PG 15 WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA S9L5M UT WOS:001401349700001 PM 39743053 DA 2026-03-26 ER PT J AU Zhang, N Yang, XJ Liang, JF Zhu, CY Shen, GH Luo, C Wu, WB AF Zhang, Na Yang, Xinjia Liang, Jiefei Zhu, Chunyan Shen, Guohua Luo, Chao Wu, Weibin TI Tanshinone IIA Inhibits Alveolar Macrophage Polarization, Inflammation and Mitochondrial Damage by Regulating the PAPR-1 Signaling Pathway SO IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH LA English DT Article DE Tanshinone IIA; PARP-1; Inflammation; Alveolar Macrophage Polarization; Mitochondrial Damage ID POLY(ADP-RIBOSE) POLYMERASE-1; KAPPA-B; GENES AB Background: Alveolar macrophages (AMs) play a pivotal role in the initiation, resolution, and tissue repair processes of pulmonary inflammatory diseases. The regulation of poly (ADP-ribose) polymerase-1 (PARP-1) is closely associated with inflammatory mechanisms, including the expression of inflammatory mediators, macrophage polarization, and mitochondrial damage. Tanshinone IIA, the primary active component of the Chinese herb Salvia miltiorrhiza Bge., exhibits potent anti-inflammatory activity. Objectives: This study aims to elucidate the mechanism by which tanshinone IIA inhibits macrophage polarization, attenuates the inflammatory response, and prevents mitochondrial damage through regulation of the PARP-1 signaling pathway. Methods: We investigated the effects of tanshinone IIA on macrophage polarization, inhibition of inflammation and oxidative stress, and protection against mitochondrial damage via the PARP-1 signaling pathway using various experimental approaches, including enzyme-linked immunosorbent assay (ELISA), flow cytometry, western blot analysis, molecular docking, and molecular dynamics (MD) simulation studies. Results: Compared with the model group, tanshinone IIA significantly inhibited the phosphorylation and activation of nuclear factor kappa B (NF-kappa B, P < 0.05) in AMs by modulating PARP-1 (P < 0.05). This modulation led to suppression of NLRP3 inflammasome activation (P < 0.05 versus the model group), ultimately inhibiting the release of inflammatory mediators such as nitric oxide (NO), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha, P < 0.05). Simultaneously, tanshinone IIA suppressed cellular oxidative stress via the Nrf2/heme oxygenase-1 (HO-1) pathway (P < 0.05 versus the model group), resulting in decreased reactive oxygen species (ROS) release (P < 0.05) and reduced mitochondrial MitoSOX production (P < 0.05). By regulating PARP-1, tanshinone IIA also effectively inhibited mitochondrial damage (compared with the model group, JC-1 decreased and mitochondrial permeability transition (MPTP) increased, P < 0.05) and M1 polarization of AMs induced by lipopolysaccharide [LPS; expression of CD86, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) decreased; arginase-1 (ARG-1) and CD206 increased, P < 0.05]. Furthermore, it efficiently modulated signaling pathways involved in mitochondrial fission and fusion [optic atrophy 1 (OPA1), dynamin-related protein 1 (DRP1)] (P < 0.05). Conclusions: These findings suggest that the therapeutic effects of tanshinone IIA on pulmonary inflammation are closely related to its ability to inhibit inflammatory damage and oxidative stress, regulate AM polarization, and alleviate mitochondrial damage in AMs through modulation of the PARP-1 pathway. C1 [Zhang, Na; Yang, Xinjia; Luo, Chao] Shaoxing Inst Technol, Dept Med & Hlth, Shaoxing Key Lab Targeted Drug Delivery & Targeted, Shaoxing, Peoples R China. [Liang, Jiefei; Wu, Weibin] Zhaoqing Med Coll, Sch Basic Med, Zhaoqing, Peoples R China. [Zhu, Chunyan; Shen, Guohua] Shaoxing Univ, Affiliated Hosp, Shaoxing, Peoples R China. C3 Shaoxing Institute of Technology; Zhaoqing Medical College; Shaoxing University RP Luo, C (corresponding author), Shaoxing Inst Technol, Dept Med & Hlth, Shaoxing Key Lab Targeted Drug Delivery & Targeted, Shaoxing, Peoples R China.; Wu, WB (corresponding author), Zhaoqing Med Coll, Sch Basic Med, Zhaoqing, Peoples R China. EM luochao@usx.edu.cn; wuweibin@zqmc.edu.cn RI Wu, weibin/ABE-9268-2021 FU Zhejiang Provincial Natural Science Foundation of China [LTGY23H010 003]; Shaoxing Public Welfare Technology Application Research Project of China [2022A14033] FX Funding/Support: The authors acknowledge funding from the Zhejiang Provincial Natural Science Foundation of China (grant No. LTGY23H010 003) and the Shaoxing Public Welfare Technology Application Research Project of China (grant No. 2022A14033) . 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PD JAN-DEC PY 2025 VL 24 IS 1 AR e166272 DI 10.5812/ijpr-166272 PG 11 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA K7302 UT WOS:001628849300001 PM 41347221 OA hybrid DA 2026-03-26 ER PT J AU Zhang, Y Ruan, LJ Li, X Si, WM Yang, PW Ba, H Chen, Z AF Zhang, Yuan Ruan, Linjie Li, Xin Si, Waimei Yang, Peiwen Ba, He Chen, Zhen TI Modified Sijunzi Decoction Inhibits Pancreatic Cancer Progression and Improves Immune Suppression: Network Pharmacology and Experimental Validation SO DRUG DESIGN DEVELOPMENT AND THERAPY LA English DT Article DE Traditional Chinese Medicine; integrated pharmacology; macrophage polarization; molecular mechanism; Pancreatic Cancer ID GROWTH-FACTOR RECEPTOR; SRC KINASE; C-SRC; IMMUNOMODULATORY ACTIVITY; CELL-PROLIFERATION; STAT3; MACROPHAGES; EXPRESSION; STEM; POLYSACCHARIDE AB Purpose: This study aimed to assess the effectiveness of Modified Sijunzi Decoction (MSJZD) in pancreatic cancer (PC) treatment. Molecular mechanisms were elucidated and active ingredients were screened using network pharmacology, RNA sequencing, and in vivo experiments, providing a scientific foundation for the clinical application of MSJZD in PC treatment. Methods: We established an orthotopic PC mouse model and treated it with different MSJZD concentrations to evaluate its efficacy. Ultra-high-performance liquid chromatography Q-Exactive mass spectrometry was used to identify MSJZD components. Through integrated pharmacology analyses, the active ingredients, core targets, and signaling pathways were determined, and active ingredients targeting the core targets were screened using molecular docking simulations. RNA-sequencing analyses of the molecular mechanism of MSJZD in PC treatment were verified using immunohistochemistry and Western blotting. A multiplex immunofluorescence assay was used to detect macrophage and CD8+ T cell infiltration levels. Results: MSJZD effectively inhibited the growth of orthotopic pancreatic tumors in mice via JAK1-STAT3 pathway and reduced Ki-67 expression, with no discernible toxicity to the liver and kidneys. MSJZD relieved immunosuppression by decreasing M2 macrophage infiltration, increasing CD8+ T cell infiltration, and lowering the expression of immunosuppressive cytokines (interleukins 10 and 6). Network pharmacology analysis revealed that EGFR, SRC, AKT1, and STAT3 were the core MSJZD targets in PC treatment. Molecular docking revealed a strong binding affinity between wedelolactone and its core target proteins (EGFR, SRC, AKT1). Conclusion: MSJZD is a safe and effective decoction for PC that exerts anti-tumor effects by inhibiting JAK1-STAT3 pathway and improving immunosuppressive microenvironment by reducing M2 macrophage infiltration and increasing CD8+ T cell infiltration. This study reveals MSJZD therapeutic potential and offers a reference for further research. C1 [Zhang, Yuan; Ruan, Linjie; Li, Xin; Si, Waimei; Yang, Peiwen; Ba, He; Chen, Zhen] Fudan Univ, Shanghai Canc Ctr, Dept Integrat Oncol, 270 Dongan Rd, Shanghai 200032, Peoples R China. [Zhang, Yuan; Ruan, Linjie; Li, Xin; Si, Waimei; Yang, Peiwen; Ba, He; Chen, Zhen] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China. C3 Fudan University; Fudan University RP Chen, Z (corresponding author), Fudan Univ, Shanghai Canc Ctr, Dept Integrat Oncol, 270 Dongan Rd, Shanghai 200032, Peoples R China. EM zchenzl@fudan.edu.cn RI Chen, Zhen/M-3936-2017 OI Chen, Zhen/0000-0002-4502-0801; Si, Waimei/0000-0001-9026-5149 FU National Natural Science Foundation of China [81930115, 82174155] FX Funding This study received financial support from the National Natural Science Foundation of China. [grant number 81930115 and 82174155] . 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Dev. Ther. PY 2025 VL 19 BP 8949 EP 8966 DI 10.2147/DDDT.S520390 PG 18 WC Chemistry, Medicinal; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 8FA6C UT WOS:001587118300001 PM 41058947 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Lian, J Jin, GC Li, J Zhang, WJ Chang, YT Li, WW Zhi, H Tian, J Liang, C Su, JP AF Lian, Jie Jin, Guichun Li, Jing Zhang, Weijuan Chang, Yongtai Li, Wenwu Zhi, Hua Tian, Jiao Liang, Chen Su, Juanping TI Yuyang Decoction Regulates Macrophage Polarization and Repairs the Intestinal Mucosal Barrier via the TLRs/Tollip Signaling Pathway SO JOURNAL OF INFLAMMATION RESEARCH LA English DT Article DE Yuyang decoction; ulcerative colitis; occlusal protein; closure protein; TLRs/Tollip signaling pathway ID TOLL-LIKE RECEPTORS; ULCERATIVE-COLITIS AB Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing inflammation and impaired intestinal epithelial barrier. Current treatments have limitations, prompting interest in traditional Chinese medicine as potential alternatives. Yuyang Decoction (YYD) is a traditional formula with observed gastrointestinal protective effects, but its mechanisms remain unclear. Objective: To evaluate the therapeutic effects and underlying mechanisms of YYD on intestinal mucosal barrier repair in a UC mouse model. Methods: UC was induced in male C57/BL6 mice using 3% dextran sulfate sodium (DSS). Mice were randomly assigned to six groups: control, DSS model, low/medium/high-dose YYD, and mesalazine (positive control). Disease activity index (DAI), colon length, histopathology, cytokine levels, and tight junction protein expression were assessed. Tollip and IKK-beta levels were detected by Western blot and immunofluorescence. Active components in YYD-containing serum were identified by UPLC-Q-Tof-MS/MS. In vitro, Tollip knockdown in THP-1 macrophages examined YYD's effect on macrophage polarization and Caco-2 cell barrier integrity. Results: YYD significantly reduced DAI scores, reversed colon shortening, and alleviated histological damage. Expression of tight junction proteins (occludin, claudins, ZO-1) and Tollip was upregulated. YYD-containing serum suppressed LPS-induced M1 macrophage polarization and protected epithelial tight junctions in vitro. These effects were diminished upon Tollip silencing. Conclusion: YYD alleviates DSS-induced colitis by enhancing intestinal barrier repair and modulating immune responses. Its therapeutic effect may involve activation of the Tollip signaling pathway, which inhibits pro-inflammatory M1-like macrophage differentiation and reduces epithelial damage. C1 [Lian, Jie; Jin, Guichun; Li, Jing; Zhang, Weijuan; Chang, Yongtai; Li, Wenwu; Zhi, Hua; Tian, Jiao; Liang, Chen; Su, Juanping] Shanxi Tradit Chinese Med Hosp, Taiyuan, Peoples R China. 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Inflamm. Res. PY 2025 VL 18 BP 10499 EP 10518 DI 10.2147/JIR.S515902 PG 20 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA 5TP2R UT WOS:001544024500001 PM 40787257 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Liu, Y Zhang, J Gao, W Han, QC Xue, YT Liu, XJ AF Liu, Yi Zhang, Juan Gao, Wei Han, Quancheng Xue, Yitao Liu, Xiujuan TI Mechanistic Insights Into Qidan Yixin Decoction for Diabetic Cardiomyopathy via Macrophage Polarization SO JOURNAL OF DIABETES RESEARCH LA English DT Article DE diabetic cardiomyopathy; experimental validation; machine learning; macrophage polarization; network pharmacology AB Background: Diabetic cardiomyopathy (DCM) has a multifactorial etiology, and no specific treatment is available for its management. Qidan Yixin decoction (QDYXD) demonstrated encouraging clinical results in treating DCM; however, its underlying mechanics are yet unclear. Methods: Network pharmacology was applied to determine the active ingredients and targets of QDYXD. The GeneCards and GEO databases were used to retrieve genes associated with DCM and macrophage polarization. These targets were subjected to GO and KEGG enrichment analyses, immune infiltration study, and PPI network design. The core targets were further refined using SVM-RFE, LASSO, and random forest algorithms. Docking the core targets with the main active components followed. For experimental validation, rat models were created. Results: There were 48 potential targets in all. Quercetin, methyl palmitate, luteolin, and tanshinone IIA were identified as the primary active components. Enrichment analysis indicated that one of the key pathways associated with the potential targets was the signaling pathway of HIF-1. Machine learning techniques were used to identify two core targets, LDHA and PGK1. Animal experiments demonstrated that QDYXD can suppress the upregulation of PGK1, LDHA, and HIF1A; block the polarization of M1 macrophages; and considerably enhance DCM rats' cardiac function. Conclusion: QDYXD improves cardiac function in DCM by attenuating M1 macrophage polarization and inhibiting the HIF-1 signaling pathway, specifically through the modulation of PGK1, LDHA, and HIF1A. This study provides preliminary insights into how QDYXD modulates macrophage polarization during DCM treatment. Moreover, the identification of potential active components and core molecular targets of QDYXD offers promising directions for future drug development in DCM therapy. C1 [Liu, Yi; Han, Quancheng] Shandong Univ Tradit Chinese Med, Clin Med Coll 1, Jinan, Peoples R China. [Zhang, Juan; Gao, Wei; Xue, Yitao; Liu, Xiujuan] Shandong Univ Tradit Chinese Med, Dept Cardiol, Affiliated Hosp, Jinan, Peoples R China. C3 Shandong University of Traditional Chinese Medicine; Shandong University of Traditional Chinese Medicine RP Xue, YT; Liu, XJ (corresponding author), Shandong Univ Tradit Chinese Med, Dept Cardiol, Affiliated Hosp, Jinan, Peoples R China. EM 2022110637@sdutcm.edu.cn; 20221000059@sdutcm.edu.cn RI ; Han, Quancheng/NHP-0093-2025 OI liu, liuxiujuan/0000-0001-9718-2864; Liu, Yi/0000-0002-0223-5714; FU Young Scientists Fund FX The study was funded by Young Scientists Fund of the National Natural Science Foundation of China, No. 82305142. 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Diabetes Res. PY 2025 VL 2025 IS 1 AR 7578626 DI 10.1155/jdr/7578626 PG 19 WC Endocrinology & Metabolism; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Endocrinology & Metabolism; Research & Experimental Medicine GA 5QS0J UT WOS:001542060200001 PM 40778401 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhang, SZ Yan, M Liang, PP Zhang, Y Liu, JM Huang, H Li, GY Wu, HY AF Zhang, Shizhao Yan, Mei Liang, Pengpeng Zhang, Ye Liu, Jiamin Huang, Hai Li, Guiyun Wu, Hongyan TI Fu-Fang-Qi-Di-Hua-Yu-Tang Improves Diabetic Macrovascular Disease via PI3K/AKT Pathway Regulation SO DIABETES METABOLIC SYNDROME AND OBESITY LA English DT Article DE Fu Fang Qi Di Hua Yu Tang; diabetic macrovascular disease; insulin resistance; autophagy; ultra performance liquid chromatography quadrupole time of flight mass spectrometry AB Objective: This study aimed to investigate the active ingredients and mechanisms of Fu-Fang-Qi-Di-Hua-Yu-Tang (FFQD) in alleviating atherosclerosis and insulin resistance in diabetic macrovascular disease (DMD) mice. Methods: Chemical profiling of FFQD was performed using UPLC-Q-TOF-MS. Apoe-/- mice were injected with streptozotocin and fed a high-fat diet to establish DMD. Groups included control (C57BL/6), model (normal saline), low/medium/high-dose FFQD, and western medicine (atorvastatin + metformin). After 12 weeks, aortic morphology, blood glucose/lipid profiles, inflammatory factors, and PI3K/AKT pathway-related targets were analyzed. Results: FFQD contained 159 identified components. Treatment significantly reduced aortic plaque area, blood glucose, lipids, and lowered the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-1(3 (IL-1(3), oxidized low-density lipoprotein (ox-LDL), C-reactive protein (CRP), and monocyte chemoattractant protein-1 (MCP-1). It also reduced nitric oxide synthase 2 (NOS2) level, a marker of macrophage polarization, increased arginase 1 (Arg1) level, regulated macrophage polarization, and improved oxidative stress and inflammatory response. In addition, FFQD activated the receptor for advanced glycation end products (RAGE)/ PI3K/AKT/mammalian target of rapamycin (mTOR) pathway in the aorta, inhibited RAGE expression, promoted PI3K, AKT, and mTOR phosphorylation, down-regulated microtubule-associated protein 1A/1B-light chain 3-II/I (LC3 II/I) and nuclear factor kappa B (NF kappa B p65) expression, up-regulated SQSTM1 protein (p62) expression, inhibited excessive autophagy, and reduced vascular endothelial damage caused by long-term high glucose levels. In the liver, FFQD activated the Ras family small molecule G protein (RAP1)/PI3K/ AKT/forkhead box protein 01 (FOX01) pathway, inhibited RAP1 expression, promoted PI3K and AKT phosphorylation, suppressed FOX01 expression, and improved insulin resistance. Conclusion: FFQD may improve insulin resistance, regulate glucose and lipid metabolism, inhibit excessive autophagy, induce macrophage polarization, resist inflammation and oxidative stress, inhibit atherosclerosis, and ultimately improve DMD by activating the RAGE/PI3K/AKT/mTOR and RAP1/PI3K/AKT/FOX01 pathways. Therefore, FFQD may be a promising candidate for DMD treatment. C1 [Zhang, Shizhao; Liang, Pengpeng; Liu, Jiamin; Huang, Hai; Li, Guiyun; Wu, Hongyan] Shanghai Univ Tradit Chinese Med, Shenzhen Hosp, Shenzhen 518000, Peoples R China. [Yan, Mei; Wu, Hongyan] Jiangxi Univ Chinese Med, Sch Clin Med, Nanchang 330000, Peoples R China. [Zhang, Ye] Shenzhen Matern & Child Healthcare Hosp Coconstruc, Pediat TCM, Shenzhen 518000, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine; Jiangxi University of Traditional Chinese Medicine RP Wu, HY (corresponding author), Shanghai Univ Tradit Chinese Med, Shenzhen Hosp, Shenzhen 518000, Peoples R China.; Wu, HY (corresponding author), Jiangxi Univ Chinese Med, Sch Clin Med, Nanchang 330000, Peoples R China. EM wu.hy@163.com OI Huang, Hai/0000-0002-2376-0462 FU Science and Technology Development Project of Guangdong Province [2020A1515010217]; National Prestigious Chinese Medicine Doctor Project [[2022] 76]; Scientific research project of Guangdong Provincial Administration of Traditional Chinese Medicine [20222198] FX This study was supported by the Science and Technology Development Project of Guangdong Province (NO.2020A1515010217) , the National Prestigious Chinese Medicine Doctor Project ( [2022] 76) , the Scientific research project of Guangdong Provincial Administration of Traditional Chinese Medicine (No. 20222198) . 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Syndr. Obes. PY 2025 VL 18 BP 2247 EP 2265 DI 10.2147/DMSO.S515521 PG 19 WC Endocrinology & Metabolism WE Science Citation Index Expanded (SCI-EXPANDED) SC Endocrinology & Metabolism GA 4UF7S UT WOS:001526792600001 PM 40655167 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhang, YL Liu, JL Zhang, D Qian, HH AF Zhang, Yongli Liu, Jiali Zhang, Dan Qian, Haihua TI LianChuang ZhiXue Liquid Enema Modulates the Macrophage Polarization of Ulcerative Colitis via Inhibiting the Jagged-1/Notch1 Signaling Pathway SO DRUG DESIGN DEVELOPMENT AND THERAPY LA English DT Article DE LCZXL enema; M2 macrophage polarization; ulcerative colitis; Jagged-1/Notch1 signaling pathway ID NITRIC-OXIDE; NOTCH AB Objective: LianChuang ZhiXue Liquid (LCZXL) enema, one of the classic Chinese medicine prescriptions, in which herbal decoction enema acts directly on the intestines, is clinically effective in patients with ulcerative colitis (UC). However, its specific molecular mechanism has not been clarified to explore the underlying macular mechanism of LCZXL enema effect on UC, based on Jagged-1/Notch1 signaling pathway and the macrophage polarization. Methods: After modeling of UC mice, the experiment was conducted in two parts: Experiment I: Control, Model, Mesalazine, Low dose of LCZXL (LCZXL-L), High dose of LCZXL (LCZXL-H); Weight and Disease Activity Index (DAI) scores were recorded on days 1, 3, 5, 7, 9, 11, and 13. On day 14, the colon was taken off. Then the colon length was measured and the damage index (CMDI) score of colon mucosal was evaluated. Zonula occludens-1 (Zo-1) Immunohistochemistry (IHC) and Hematoxylin-Eosin (HE) staining were performed to visualize the colon injury. ELISA was used to detect cytokines content in serum. The M1 and M2 markers and Jagged-1/Notch1 signaling pathway-related genes/proteins were quantified by IF double staining, PCR, WB, and flow cytometry. Experiment II: Control, Model, Recombinant mouse Jagged-1 protein/ Fc Chimera Active (Jagged-1/Fc), LCZXL, Jagged-1/Fc +LCZXL. The M1 and M2 markers and Jagged-1 proteins were quantified by WB, and flow cytometry. Results: Our results indicated that LCZXL could reduce the colon injury of UC mice effectively, which expressed DAI and CMDI score reduction, and inhibited colon structure damage. DSS induced a significant up-regulation of CD86, iNOS, TNF-alpha, IL-1(3, and IL-6, and a down-regulation of Arg1, CD206, IL-4, IL-10 and increase of Jagged-1, Notch1, and Notch2. LCZXL enema treatment inhibiting the increase of UC modeling-induced CD86, TNF-alpha, IL-1(3, and IL-6 and increased CD206, Arg1, IL-4, and IL-10 expression level. Notch signaling pathway activator Jagged-1/Fc aggravated M1 macrophage polarization and activated the Jagged1/Notch1 signaling pathway. LCZXL treatment reversed this situation stop the activation of the Jagged-1/Notch1 signaling pathway. Conclusion: Our study proved that LCZXL Enema could inhibit the M1 Macrophage Polarization and promote M2 macrophage polarization of ulcerative colitis via regulating the Jagged-1/Notch1 signaling pathway. C1 [Zhang, Yongli; Liu, Jiali; Zhang, Dan; Qian, Haihua] Nanjing Univ Chinese Med, Affiliated Hosp, Dept Anorectal Surg, Qinhuai Rd 155, Nanjing 210029, Jiangsu, Peoples R China. [Zhang, Yongli] Xian Hosp Tradit Chinese Med, Dept Anorectal Surg, Xian 710016, Shaanxi, Peoples R China. C3 Nanjing University of Chinese Medicine RP Zhang, D; Qian, HH (corresponding author), Nanjing Univ Chinese Med, Affiliated Hosp, Dept Anorectal Surg, Qinhuai Rd 155, Nanjing 210029, Jiangsu, Peoples R China. EM danaezhang@163.com; qianhaihua_nzy@126.com RI l, jl/GQA-3435-2022 FU BioRender [GF282748QE] FX We express our gratitude to BioRender (https://BioRender.com /un7wvhw) for providing the graphical abstract services (ID:GF282748QE) . 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Hypoxia is related to poor prognosis and treatment resistance in cancer. Relevant studies have shown that a hypoxic microenvironment can promote the polarization of M2 macrophages and thus promote tumor development. Previous research has found that bufalin has a wide range of antitumor effects, but whether bufalin can reverse tumor resistance by improving the hypoxic tumor microenvironment is still unclear. In present research, it was found that high expression of SRC-3 in CRC cells under hypoxic conditions promoted the polarization of M2 and caused chemotherapy resistance, while bufalin, a monomeric drug used in Chinese medicine, reduced the level of SRC-3 and HIF-1 alpha, thereby reversing chemoresistance. In addition, overexpression of SRC-3 reduced the hypoxia-mitigating effect of bufalin on CRC cells to promote the polarization of M2. Bufalin also inhibits the polarization of M2 caused by hypoxic CRC cells. Therefore, bufalin has the potential to become a new adjuvant therapy that can be further explored in future studies on its treatment of CRC. C1 [Wang, Haijing; Jia, Linlin; Yu, Hongjie; Chi, Huabowen; Chen, Jinbao] Shanghai Univ Tradit Chinese Med, Putuo Hosp, Shanghai, Peoples R China. [Tang, Hui] Chongqing Med & Pharmaceut Coll, Chongqing, Peoples R China. [Zhang, Wei] Three Gorges Univ, Yichang, Peoples R China. [Zhang, Wei] Yichang Hosp Tradit Chinese Med, Yichang, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine; China Three Gorges University RP Chen, JB (corresponding author), Shanghai Univ Tradit Chinese Med, Putuo Hosp, Dept Med Oncol, 164 Lan Xi Rd, Shanghai 200062, Peoples R China.; Zhang, W (corresponding author), Three Gorges Univ, Coll Tradit Chinese Med, 2 Shengli 3rd Rd, Yichang 443000, Peoples R China.; Zhang, W (corresponding author), Yichang Hosp Tradit Chinese Med, 2 Shengli 3rd Rd, Yichang 443000, Peoples R China.; Chi, HBW (corresponding author), Shanghai Univ Tradit Chinese Med, Putuo Hosp, Intervent Canc Inst Chinese Integrat Med, 164 Lan Xi Rd, Shanghai 200062, Peoples R China. EM 1003960210@qq.com; 15926948882@163.com; cjb17317156680@163.com RI Yu, Hong-jie/GOE-3993-2022; Wang, Haijing/ODJ-1350-2025; jia, linlin/NIU-8117-2025 FU Shanghai Rising-Star Program (Sailing special Project) [22YF1441400]; Science and Technology Innovation Project of Shanghai Putuo District Health System [ptkwws202409]; Shanghai Sixth People's Hospital jointly established scientific research fund [23-LY-03]; Shanghai Famous Traditional Chinese Medicine Putuo Inheritance Studio Construction Project [ptzygzs2408]; TCM Scientific Research Project of Hubei Provincial Administration of Traditional Chinese Medicine Item [ZY2023M038] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was sponsored by the Shanghai Rising-Star Program (Sailing special Project, 22YF1441400), Science and Technology Innovation Project of Shanghai Putuo District Health System (ptkwws202409), Shanghai Sixth People's Hospital jointly established scientific research fund (23-LY-03), Shanghai Famous Traditional Chinese Medicine Putuo Inheritance Studio Construction Project (ptzygzs2408) and TCM Scientific Research Project of Hubei Provincial Administration of Traditional Chinese Medicine Item (No. ZY2023M038). 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Cancer Ther. PY 2025 VL 24 AR 15347354251325806 DI 10.1177/15347354251325806 PG 12 WC Oncology; Integrative & Complementary Medicine WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Integrative & Complementary Medicine GA 0BM6D UT WOS:001443421200001 PM 40071641 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Lin, MZ Piao, LH Zhao, ZD Liao, L Wang, DY Zhang, HW Liu, XD AF Lin, Mingzhang Piao, Linghua Zhao, Zhendong Liao, Li Wang, Dayong Zhang, Haiwen Liu, Xiande TI Therapeutic Potential of Cajanus cajan (L.) Millsp. Leaf Extract in Modulating Gut Microbiota and Immune Response for the Treatment of Inflammatory Bowel Disease SO PHARMACEUTICALS LA English DT Article DE IBD; Cajanus cajan leaf extract; inflammatory immune response; gut microbiota ID ULCERATIVE-COLITIS; EXTRAINTESTINAL MANIFESTATIONS; DOUBLE-BLIND; RESVERATROL; BARRIER AB Background/Objectives: Inflammatory bowel disease (IBD) is a persistent inflammatory condition affecting the gastrointestinal tract, distinguished by the impairment of the intestinal epithelial barrier, dysregulation of the gut microbiota, and abnormal immune responses. Cajanus cajan (L.) Millsp., traditionally used in Chinese herbal medicine for gastrointestinal issues such as bleeding and dysentery, has garnered attention for its potential therapeutic benefits. However, its effects on IBD remain largely unexplored. Methods: In this study, the major compounds from Cajanus cajan leaf extract (CCLE) were initially characterized by LCMS-IT-TOF. The IBD model was developed in C57BL/6 mice by administering continuous 4% (w/v) dextran sodium sulfate (DSS) aqueous solution over a period of seven days. The body weight, colon length, disease activity index (DAI), and histopathological examination using hematoxylin and eosin (H&E) staining were performed in the IBD model. The levels of the main inflammatory factors, specifically TNF-alpha, IL-1 beta, IL-6, and myeloperoxidase (MPO), were quantified by employing enzyme-linked immunosorbent assay (ELISA) kits. Additionally, the levels of tight junction proteins (ZO-1, Occludin) and oxidative stress enzymes (iNOS, SOD1, CAT) were investigated by qPCR. Subsequently, flow cytometry was employed to analyze the populations of various immune cells within the spleen, thereby assessing the impact of the CCLE on the systemic immune homeostasis of IBD mice. Finally, 16S rDNA sequencing was conducted to examine the composition and relative abundance of gut microbiota across different experimental groups. In addition, molecular docking analysis was performed to assess the interaction between the principal components of CCLE and the aryl hydrocarbon receptor (AHR). Results: We identified seven bioactive compounds in CCLE: catechin, cajachalcone, 2-hydroxy-4-methoxy-6-(2-phenylcinyl)-benzoic acid, longistylin A, longistylin C, pinostrobin, amorfrutin A, and cajaninstilbene acid. Our results demonstrated that oral administration of CCLE significantly alleviates gastrointestinal symptoms in DSS-induced IBD mice by modulating the balance of gut-derived pro- and anti-inflammatory cytokines. This modulation is associated with a functional correction in M1/M2 macrophage polarization and the Th17/Treg cell balance in splenic immune cells, as well as shifts in the populations of harmful bacteria (Erysipelatoclostridium and Staphylococcus) and beneficial bacteria (Odoribacter, unidentified Oscillospiraceae, Lachnoclostridium, and Oscillibacter) in the gut. Furthermore, cajaninstilbene acid, longistylin A, and longistylin C were identified as potential AhR agonists. Conclusions: The present results suggested that CCLE, comprising stilbenes like cajaninstilbene acid, longistylin A, and longistylin C, protects the epithelial barrier's structure and function against DSS-induced acute IBD by restoring gut microbiota balance and systemic immune response as AhR agonists. Overall, CCLE represents a promising natural product-based therapeutic strategy for treating IBD by restoring gut microbiota balance and modulating systemic immune responses. C1 [Lin, Mingzhang; Liu, Xiande] Hainan Univ, Sch Life & Hlth Sci, Collaborat Innovat Ctr One Hlth, Hainan Prov Key Lab One Hlth, 58 Renmin Ave, Haikou 570228, Peoples R China. [Piao, Linghua] Hainan Med Univ, Key Lab Trop Translat Med, Minist Educ, Haikou 570228, Peoples R China. [Piao, Linghua] Hainan Med Univ, Sch Basic Med & Life Sci, Key Lab Brain Sci Res Transformat Trop Environm Ha, Haikou 570228, Peoples R China. [Zhao, Zhendong] Hainan Univ, Analyt & Testing Ctr, Ctr Adv Studies Precis Instruments, Haikou 570228, Peoples R China. [Liao, Li; Zhang, Haiwen] Hainan Univ, Sch Trop Agr & Forestry, 58 Renmin Ave, Haikou 570228, Peoples R China. [Wang, Dayong] Hainan Univ, Sch Pharmaceut Sci, Haikou 570228, Peoples R China. C3 Hainan University; Hainan Medical University; Hainan Medical University; Hainan University; Hainan University; Hainan University RP Liu, XD (corresponding author), Hainan Univ, Sch Life & Hlth Sci, Collaborat Innovat Ctr One Hlth, Hainan Prov Key Lab One Hlth, 58 Renmin Ave, Haikou 570228, Peoples R China.; Zhang, HW (corresponding author), Hainan Univ, Sch Trop Agr & Forestry, 58 Renmin Ave, Haikou 570228, Peoples R China. EM 20071000110023@hainanu.edu.cn; zhaozhd898@126.com; liaoli@hainanu.edu.cn; wangdy@hainanu.edu.cn; hwzhang@hainanu.edu.cn; xiande_liu79@hainanu.edu.cn RI 朴, 伶华/IAO-1089-2023 OI Wang, Dayong/0000-0002-2086-1663 FU Natural Science Foundation of China; [32260854] FX Xiande Liu was supported by The Natural Science Foundation of China (No. 32260854). 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Med, V3, P47, DOI [10.13313/j.issn.1673-4890.2001.08.021, DOI 10.13313/J.ISSN.1673-4890.2001.08.021] NR 38 TC 7 Z9 8 U1 10 U2 19 PU MDPI PI BASEL PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND EI 1424-8247 J9 PHARMACEUTICALS-BASE JI Pharmaceuticals PD JAN PY 2025 VL 18 IS 1 AR 67 DI 10.3390/ph18010067 PG 15 WC Chemistry, Medicinal; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA T3C3C UT WOS:001403825700001 PM 39861130 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Deng, DZ Zhang, R Wu, JX Wang, LS Zhang, QL Zhang, JQ Tan, YF Chen, K Li, YH AF Deng, Dezhi Zhang, Rong Wu, Jiaoxia Wang, Lisha Zhang, Qiaoling Zhang, Junqing Tan, Yinfeng Chen, Kai Li, Yonghui TI A kidney protection nanoparticle based on Alpinia oxyphylla fructus polysaccharide by modulating macrophage polarization SO INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES LA English DT Article DE Nootkatone; Alpinia oxyphylla fructus polysaccharide; Nanoparticle; Acute kidney injury; Macrophage polarization ID PHYSICOCHEMICAL STABILITY; COMPOSITE NANOPARTICLES; DELIVERY-SYSTEMS; VITRO AB The use of natural polysaccharides from traditional Chinese medicine as carrier materials has great potentiality in drug delivery. Nootkatone (NKT) demonstrated good pharmacological activity in treating kidney injury, but its solubility and bioavailability are not very good which may affect the effectiveness of its therapeutic effect. Alpinia oxyphylla fructus polysaccharide (AOP), as a plant polysaccharide, has multiple pharmacological activities and may help to provide synergy for NKT. Therefore, AOP nanoparticles loaded with NKT (AOP-NKT NPs) were prepared for the prevention of acute kidney injury in this study. The sizes of AOP-NKT NPs are 291.60 +/- 3.73 nm, and the Zeta potential values are 35.2 +/- 0.65 mV. The nanoparticles exhibited excellent stability in pH, NaCl solution, temperature, and storage. The nanoparticles also improved the solubility and oral bioavailability of NKT. In biocompatibility experiments, AOP-NKT NPs showed lower macrophage toxicity than NKT, and the nanoparticles had good blood compatibility and in vivo biosafety. In vivo, prophylactic administration of this nanoparticle could enhance the ability of NKT in promoting macrophage M2 polarization, reducing renal inflammation and thus improve renal function and repair renal damage. In conclusion, the present study may provide the possibility for AOP as a nano delivery vehicle for renal injury protective drugs. C1 [Deng, Dezhi; Zhang, Rong; Wu, Jiaoxia; Wang, Lisha; Zhang, Qiaoling; Zhang, Junqing; Tan, Yinfeng; Chen, Kai; Li, Yonghui] Hainan Med Univ, Sch Pharm, Key Lab Trop Translat Med Minist Educ, Hainan Prov Key Lab Res & Dev Trop Herbs ,Haikou K, Haikou 571199, Peoples R China. C3 Hainan Medical University RP Tan, YF; Chen, K; Li, YH (corresponding author), Hainan Med Univ, Hainan Prov Key Lab R&D Trop Herbs, Haikou 571199, Peoples R China. EM hy0207059@hainmc.edu.cn; chenkai19910726@163.com; lyhssl@126.com RI Chen, Kai/GRF-3464-2022; zhang, qiaoling/GQB-2670-2022; 谭, 银丰/HMV-9593-2023 OI Chen, Kai/0000-0001-9680-6567; FU National Natural Science Founda-tion of China [82160826, 82160795]; Joint Program on Health Science & Technology Innovation of Hainan Province [WSJK2024MS156] FX This research was funded by the National Natural Science Founda-tion of China (NO. 82160826 and 82160795) and the Joint Program on Health Science & Technology Innovation of Hainan Province (WSJK2024MS156) . 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PD MAR PY 2025 VL 292 AR 139367 DI 10.1016/j.ijbiomac.2024.139367 EA DEC 2024 PG 16 WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA W9S9W UT WOS:001421890100001 PM 39743078 DA 2026-03-26 ER PT J AU Su, R Sun, L Ding, YF Pan, Z Yang, FY Fang, H Liao, XY Dong, L Wen, HQ AF Su, Rui Sun, Lei Ding, Yu-Fan Pan, Zhao Yang, Fei-Yu Fang, Hui Liao, Xiao-Yu Dong, Liang Wen, Hui-Qin TI In vitro studies on the effects of cryopreserved platelet-rich plasma on cells related to wound healing SO PLATELETS LA English DT Article DE Angiogenesis; cryopreserved platelet-rich plasma (cPRP); fibroblasts proliferation and migration; M1/M2 macrophage polarization; wound healing ID MACROPHAGE POLARIZATION; FRESENIUS COM.TEC; FENWAL AMICUS; EFFICACY; FUTURE; BLOOD AB Platelet-rich plasma (PRP) holds promise as a therapeutic modality for wound healing; however, immediate utilization encounters challenges related to volume, concentration, and consistency. Cryopreservation emerges as a viable solution, preserving PRP's bioactive components and extending its shelf life. This study explores the practicality and efficacy of cryopreserved platelet-rich plasma (cPRP) in wound healing, scrutinizing both cellular mechanisms and clinical implications. Fresh PRP and cPRP post freeze-thaw underwent assessment in macrophage, fibroblast, and endothelial cell cultures. The impact of cPRP on active component release and cell behavior pertinent to wound healing was evaluated. Varied concentrations of cPRP (1%, 5%, 10%) were examined for their influence on cell polarization, migration, and proliferation. The results showed minimal changes in cPRP's IL-1 beta levels, a slight decrease in PDGF-BB, and superior effects on macrophage M2 polarization and fibroblast migration, while no statistical significance was observed in endothelial cell angiogenesis and proliferation. Remarkably, 5% PRP exhibited the most significant stimulation among all cPRP concentrations, notably impacting cell proliferation, angiogenesis, and migration. The discussion underscores that cPRP maintains platelet phenotype and function over extended periods, with 5% cPRP offering the most favorable outcomes, providing a pragmatic approach for cold storage to extend post-thaw viability and amplify therapeutic effects. What is the context? Platelet-rich plasma (PRP) is a potential bioactive material for wound healing, but using it immediately faces issues like volume, concentration, and consistency.Low-temperature freezing is a method employed to preserve PRP. However, the current understanding of the effects of the freezing-thawing process on the components of PRP and its impact on cells relevant to wound healing remains unclear.What is new? This study explores the feasibility and effectiveness of using cryopreserved PRP at -80 degrees C for promoting wound healing. This research stands out for its focus on cellular responses and practical implications in therapeutic contexts.To understand their distinct impact on different cell types relevant to wound healing, the study meticulously examined various final concentrations of cPRP (1%, 5%, 10%).The study identified the superior effects of 5% cPRP on crucial cellular activities, notably in cell polarization, proliferation, angiogenesis, and migration.What is the impact? Low-temperature freezing can be considered an effective method for PRP preservation.Some bioactive components in cPRP exhibit subtle changes; however, these changes result in better effects on certain cell types related to healing.The study illustrates that all concentrations of cPRP effectively enhance cell proliferation, migration, and differentiation, emphasizing the comparable efficacy of cryopreserved PRP to non-cryopreserved PRP. C1 [Su, Rui; Sun, Lei; Ding, Yu-Fan; Wen, Hui-Qin] Anhui Med Univ, Dept Blood Transfus, Affiliated Hosp 1, Hefei, Peoples R China. [Pan, Zhao; Dong, Liang] Chinese Acad Sci, Zhejiang Canc Hosp, Hangzhou Inst Med HIM, Hangzhou 310022, Zhejiang, Peoples R China. [Yang, Fei-Yu; Fang, Hui; Liao, Xiao-Yu] Anhui Med Univ, Coll & Hosp Stomatol, Key Lab Oral Dis Res Anhui Prov, Hefei, Peoples R China. C3 Anhui Medical University; Chinese Academy of Sciences; Hangzhou Institute of Medicine, CAS; Zhejiang Cancer Hospital; Anhui Medical University RP Pan, Z; Dong, L (corresponding author), Chinese Acad Sci, Zhejiang Canc Hosp, Hangzhou Inst Med HIM, Hangzhou 310022, Zhejiang, Peoples R China. EM panzhao@him.cas.cn; dongliang@him.cas.cn; wenhuiqin@ahmu.edu.cn RI Ding, Yufan/OLR-6239-2025; pan, zhao/MSV-7851-2025; liao, xiaoyu/OGP-0488-2025; Su, Rui/C-7807-2017 FU National Natural Science Foundation of China [81801831, 22305254]; China Postdoctoral Science Foundation [2021M703067] FX This work was supported by the National Natural Science Foundation of China [Grants 81801831, 22305254], the China Postdoctoral Science Foundation [2021M703067]. 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Hematology WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology; Hematology GA PW9A3 UT WOS:001217224300001 PM 38722091 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhang, GF Qin, YM Liu, SB Chen, X Zhang, WW AF Zhang, Gaofeng Qin, Yanmei Liu, Shaobing Chen, Xi Zhang, Wenwen TI Bibliometric analysis of research trends and topic areas in traditional Chinese medicine therapy for lymphoma SO PHARMACEUTICAL BIOLOGY LA English DT Article DE Co-occurrence analysis; co-citation analysis; keywords analysis; trends; CiteSpace ID CELL-CYCLE ARREST; OXIDATIVE STRESS; APOPTOSIS; CANCER; CISPLATIN; PROLIFERATION; INHIBITION; EXPRESSION; EXTRACT AB ContextTraditional Chinese Medicine (TCM) is effective as a cancer treatment modality. However, this is the first bibliometric analysis of TCM in lymphoma treatment.ObjectiveThis study explores the current trends and research topics of TCM in treating lymphoma from 2000 to 2023.Materials and methodsWe searched within the Web of Science Core Collection (WoSCC) for publications on TCM in lymphoma treatment, spanning 2000 to 2023. Subsequently, we employed a comprehensive approach utilizing CiteSpace software and VOSviewer to visually analyze research trends, authors, institutions, co-cited references, and keywords.ResultsFrom January 1, 2000, to August 31, 2023, annual scientific publications on TCM for lymphoma treatment have steadily increased. Among the leading institutions in this field, the Beijing University of Chinese Medicine and the Fujian Medical University occupied the top positions. Regarding the authors, Jun Peng, Jiumao Lin, and Hongwei Chen emerged as the top three contributors. In the co-citation analysis of references, the top three co-cited references were authored by Hanahan D, Elmore S, and Livak KJ with citations numbered 13, 14, and 17, respectively. In particular, keywords reflecting current emerging trends included 'pathway', 'traditional Chinese medicine', 'oxidative stress', and 'macrophage polarization'.Discussion and conclusionsThis bibliometric analysis provides a comprehensive overview of TCM for lymphoma treatment. This analysis identified the predominant trends and research topics in the field. The findings are expected to be of significant value for researchers who focus on TCM in lymphoma treatment, helping them better understand the development of this field. C1 [Zhang, Gaofeng; Qin, Yanmei; Liu, Shaobing; Chen, Xi] Nanxishan Hosp Guangxi Zhuang Autonomous Reg, Dept Med Oncol, Guilin, Peoples R China. [Zhang, Wenwen] Guilin Municipal Hosp Tradit Chinese Med, Dept Pediat, Guilin, Peoples R China. [Zhang, Wenwen] Guilin Municipal Hosp Tradit Chinese Med, Guilin 541002, Peoples R China. [Chen, Xi] Nanxishan Hosp Guangxi Zhuang Autonomous Reg, Dept Med Oncol, Guilin 541002, Peoples R China. RP Zhang, WW (corresponding author), Guilin Municipal Hosp Tradit Chinese Med, Guilin 541002, Peoples R China.; Chen, X (corresponding author), Nanxishan Hosp Guangxi Zhuang Autonomous Reg, Dept Med Oncol, Guilin 541002, Peoples R China. 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Biol. PD DEC 31 PY 2024 VL 62 IS 1 BP 13 EP 21 DI 10.1080/13880209.2023.2288697 PG 9 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA CM7Y5 UT WOS:001125744600001 PM 38088354 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Xiong, SY Ding, XW Zhou, L Liu, ZQ Jiang, WY Ai, FR Cai, KY AF Xiong, Shiyu Ding, Xingwei Zhou, Ling Liu, Ziqian Jiang, Wenyan Ai, Fanrong Cai, Kaiyong TI An antibacterial and antioxidant rosmarinic acid hydrogel normalizes macrophage polarization to expedite diabetic wound healing SO JOURNAL OF COLLOID AND INTERFACE SCIENCE LA English DT Article DE Rosmarinic acid; Hydrogel; Antioxidation; Macrophage polarization; Diabetic wound healing AB The management of diabetic wounds (DW) is a significant challenge within the medical field. Effectively regulating the levels of reactive oxygen species (ROS) at the wound site and orchestrating the inflammatory response are effective strategies for DW treatment. In this study, a novel hydrogel was developed by cross-linking polyboronic acid-modified carboxymethyl chitosan with herbal active ingredient rosmarinic acid (RA), an active herbal ingredient, through dynamic boronic esters formation. In this RA hydrogel (RAgel), RA serves both as an active pharmaceutical ingredient and as a linker for the creation of a dynamic covalent hydrogel, which can decrease the potential toxicity of chemical crosslinking agents and improve the utilization of RA. RAgel demonstrated potential for controlling RA loading and responsiveness to ROS and glucose levels in a diabetic wound environment. Additionally, the intrinsic antioxidant and antibacterial properties of RA were effectively preserved and enhanced upon integration into RAgel. Furthermore, RAgel not only promoted the migration of L929 cells, a key aspect of tissue repair, but also induced M2 polarization in macrophages,while inhibiting the secretion of pro-inflammatory cytokines. In a murine model of diabetic wound healing, RAgel significantly enhanced the proliferation of both the epidermal and granulation tissues. It also exerts a marked antiinflammatory effect and promotes collagen deposition, thereby expediting the overall wound healing process. The reported RAgel formulation has potential to address the complex challenges associated with diabetic wound management. C1 [Xiong, Shiyu; Ding, Xingwei; Zhou, Ling; Liu, Ziqian; Jiang, Wenyan] Nanchang Univ, Inst Translat Med, Natl Engn Res Ctr Bioengn Drugs & Technol, Jiangxi Prov Key Lab Bioengn Drugs, Nanchang 330031, Jiangxi, Peoples R China. [Ai, Fanrong] Nanchang Univ, Sch Adv Mfg, Nanchang 330031, Jiangxi, Peoples R China. [Cai, Kaiyong] Chongqing Univ, Coll Bioengn, Key Lab Biorheol Sci & Technol, Minist Educ, Chongqing 400044, Peoples R China. C3 Nanchang University; Nanchang University; Chongqing University RP Ding, XW (corresponding author), Nanchang Univ, Inst Translat Med, Natl Engn Res Ctr Bioengn Drugs & Technol, Jiangxi Prov Key Lab Bioengn Drugs, Nanchang 330031, Jiangxi, Peoples R China.; Ai, FR (corresponding author), Nanchang Univ, Sch Adv Mfg, Nanchang 330031, Jiangxi, Peoples R China.; Cai, KY (corresponding author), Chongqing Univ, Coll Bioengn, Key Lab Biorheol Sci & Technol, Minist Educ, Chongqing 400044, Peoples R China. EM xwding@ncu.edu.cn; aifanrong@ncu.edu.cn; kaiyong_cai@cqu.edu.cn RI Cai, Kaiyong/G-1233-2011; , Xiongshiyu/PMF-8281-2026 OI Cai, Kaiyong/0000-0001-9029-680X; , Xiongshiyu/0009-0008-6581-7050 FU National Natural Science Foundation of China [32301186, 81760641, 51825302, 31960207]; National Key Research and Development Program of China [2022YFB3804400]; Jiangxi Province Key Research and Development Plan [20232BBE50017] FX This work was supported by the National Natural Science Foundation of China (32301186, 81760641, 51825302, 31960207) , National Key Research and Development Program of China (2022YFB3804400) and Jiangxi Province Key Research and Development Plan (20232BBE50017) . The authors would like to thank Dr. Jinlong Chen (School of Resources Environmental & Chemical Engineering, Nanchang University) for his help with NMR determination. 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Colloid Interface Sci. PD APR PY 2025 VL 683 BP 357 EP 371 DI 10.1016/j.jcis.2024.12.138 EA DEC 2024 PN 2 PG 15 WC Chemistry, Physical WE Science Citation Index Expanded (SCI-EXPANDED) SC Chemistry GA U2S8T UT WOS:001410364000001 PM 39736166 DA 2026-03-26 ER PT J AU Wu, ZQ Xu, KN Chen, MC Wang, SH Ma, Y AF Wu, Zhongqing Xu, Kanna Chen, Minchang Wang, Shihao Ma, Yong TI Protective role of Yougui Yin in experimental knee osteoarthritis: From the perspective of macrophage polarization SO PROSTAGLANDINS & OTHER LIPID MEDIATORS LA English DT Article DE Yougui Yin; Macrophages; Knee osteoarthritis; Anti-inflammation; Oxidative stress ID INFLAMMATION; PROGRESSION AB Knee osteoarthritis (KOA) refers to a prevalent musculoskeletal disorder, frequently complicated by substantial pain and physical disability. Yougui Yin (YGY) is a classic Chinese herbal mixture which has demonstrated potential in treating KOA. Considering that, its cryptic mechanism warrants to be deciphered, which is the subject of our present research. In vivo, H&E staining, Alcian blue staining and Masson staining assessed the histomorphology. Commercial kits and ELISA evaluated oxidative stress markers. ELISA also assayed serum inflammatory cytokines. TUNEL staining appraised apoptosis. Western blotting examined cartilage matrix degradation, apoptotic and NLRP3 inflammasome proteins. Immunofluorescence assay estimated macrophage polarization. In vitro, ELISA assayed oxidative stress markers and inflammatory cytokines. Immunofluorescence and flow cytometry assay estimated macrophage polarization. MTT and flow cytometry assays severally measured cell viability and apoptosis. DCFH-DA probe detected ROS formation. RT-qPCR and Western blotting examined chondrocyte markers, apoptotic and pyroptotic genes. YGY significantly eased the histomorphological damage, apoptosis and pyroptosis in the cartilage tissues of KOA mice. Besides, YGY exerted anti-oxidant and anti-inflammatory activities and drove M1-to-M2 polarization of macrophages both in vitro and in vivo. Further, the co-culture of macrophages treated by LPS and serum containing YGY improved the viability, eliminated the apoptosis, pyroptosis, inflammation, oxidative stress and cartilage degradation in TNF-alpha-exposed chondrocytes co-cultured with LPS-intervened macrophages. Overall, YGY might mediate macrophage polarization to impede the advancement of KOA. C1 [Wu, Zhongqing] Nanjing Univ Chinese Med, Sch Clin Med 1, Nanjing 210023, Peoples R China. [Wu, Zhongqing] First Peoples Hosp Huzhou, Dept Orthopaed, Huzhou 313000, Peoples R China. [Wu, Zhongqing; Chen, Minchang; Wang, Shihao] Huzhou Wuxing Dist Peoples Hosp, Dept Orthopaed, Huzhou 313008, Peoples R China. [Wu, Zhongqing; Chen, Minchang; Wang, Shihao] Huzhou Wuxing Dist Maternal & Child Hlth Hosp, Huzhou 313008, Peoples R China. [Xu, Kanna] First Peoples Hosp Huzhou, Emergency Dept, Huzhou 313000, Peoples R China. [Ma, Yong] Nanjing Univ Chinese Med, Sch Integrated Chinese & Western Med, 163 Xianlin Rd, Nanjing 210023, Peoples R China. C3 Nanjing University of Chinese Medicine; Huzhou University; Huzhou University; Nanjing University of Chinese Medicine RP Ma, Y (corresponding author), Nanjing Univ Chinese Med, Sch Integrated Chinese & Western Med, 163 Xianlin Rd, Nanjing 210023, Peoples R China. EM my0829doctor@163.com RI wu, zhongqing/HGU-0161-2022 FU Public Welfare Application Research Project of Huzhou Science and Technology Bureau [2023GYB33] FX Funding This research was supported by the Public Welfare Application Research Project of Huzhou Science and Technology Bureau (2023GYB33) . 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Activating and enhancing adaptive immunity through GSDME is a potential solution for anti-tumor therapy. Here we reported that berberine (BBR), a small molecule from traditional Chinese medicine, as a GSDME activator, induced caspase-3 (C-3)/GSDME pathway-mediated pyroptosis through the mitochondrial pathway, improved the immunosuppressive state of the tumor microenvironment, and thus promoted anti-tumor immunity. We determined the induction of pyroptosis of 4 T1 cells by BBR through various experiments, and investigated the immune activation effect of BBR by co-culture in vitro, which induced DCs maturation and macrophage polarization. Zebrafish embryo toxicity experiments were used to evaluate the in vivo safety of berberine. Furthermore, the in vivo antitumor and immune activation effects of BBR were investigated using 4 T1 orthotopic model mice, and the results showed that BBR could eliminate orthotopic tumor cells by activating local and systemic immunity. 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EM wuchengyu@sztu.edu.cn; lirui@cdutcm.edu.cn; zhaomengnan@cdutcm.edu.cn; shisanjuns@163.com RI Shi, Sanjun/L-2890-2019; Wu, Chengyu/HHM-6491-2022 OI Wu, Chengyu/0000-0003-1547-3516 FU Centrally Guided Local Science and Technology Development Project [2024ZYD0043]; National Natural Science Foundation of China [82003689]; Natural Science Foundation of Sichuan Province [25NSFSC2356] FX This study was financially supported by the Centrally Guided Local Science and Technology Development Project (2024ZYD0043) , the National Natural Science Foundation of China (82003689) and Natural Science Foundation of Sichuan Province (25NSFSC2356) . 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Immunol. PD FEB PY 2025 VL 408 AR 104908 DI 10.1016/j.cellimm.2024.104908 EA DEC 2024 PG 13 WC Cell Biology; Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology; Immunology GA R4P7L UT WOS:001391293700001 PM 39701005 DA 2026-03-26 ER PT J AU Vafadar, A Tajbakhsh, A Hosseinpour-Soleimani, F Savardshtaki, A Hashempur, MH AF Vafadar, Asma Tajbakhsh, Amir Hosseinpour-Soleimani, Fatemeh Savardshtaki, Amir Hashempur, Mohammad Hashem TI Phytochemical-mediated efferocytosis and autophagy in inflammation control SO CELL DEATH DISCOVERY LA English DT Review ID TRANSMEMBRANE CONDUCTANCE REGULATOR; FOAM CELL-FORMATION; APOPTOTIC CELLS; CYSTIC-FIBROSIS; PHOSPHATIDYLSERINE RECEPTOR; CHOLESTEROL ACCUMULATION; MACROPHAGE METABOLISM; CURCUMIN PRETREATMENT; PHAGOSOME MATURATION; MOLECULAR-MECHANISMS AB Efferocytosis, the clearance of apoptotic cells, is a critical process that maintains tissue homeostasis and immune regulation. Defective efferocytosis is linked to the development of chronic inflammatory conditions, including atherosclerosis, neurological disorders, and autoimmune diseases. Moreover, the interplay between autophagy and efferocytosis is crucial for inflammation control, as autophagy enhances the ability of phagocytic cells. Efficient efferocytosis, in turn, regulates autophagic pathways, fostering a balanced cellular environment. Dysregulation of this balance can contribute to the pathogenesis of various disorders. Phytochemicals, bioactive compounds found in plants, have emerged as promising therapeutic agents owing to their diverse pharmacological properties, including antioxidant, anti-inflammatory, and immunomodulatory effects. This review aims to highlight the pivotal role of phytochemicals in enhancing efferocytosis and autophagy and explore their potential in the prevention and treatment of related disorders. This study examines how phytochemicals influence key aspects of efferocytosis, including phagocytic cell activation, macrophage polarization, and autophagy induction. The therapeutic potential of phytochemicals in atherosclerosis and neurological diseases is highlighted, emphasizing their ability to enhance efferocytosis and autophagy and reduce inflammation. This review also discusses innovative approaches, such as nanoformulations and combination therapies to improve the targeting and bioavailability of phytochemicals. Ultimately, this study inspires further research and clinical applications in phytochemical-mediated efferocytosis enhancement for managing chronic inflammatory and autoimmune conditions. C1 [Vafadar, Asma; Savardshtaki, Amir] Shiraz Univ Med Sci, Sch Adv Med Sci & Technol, Dept Med Biotechnol, Shiraz, Iran. [Vafadar, Asma; Hosseinpour-Soleimani, Fatemeh] Shiraz Univ Med Sci, Student Res Comm, Shiraz, Iran. [Tajbakhsh, Amir] Shiraz Univ Med Sci, Pharmaceut Sci Res Ctr, Shiraz, Iran. [Hosseinpour-Soleimani, Fatemeh] Shiraz Univ Med Sci, Sch Adv Med Sci & Technol, Dept Appl Cell Sci & Tissue Engn, Shiraz, Iran. [Savardshtaki, Amir] Shiraz Univ Med Sci, Infertil Res Ctr, Shiraz, Iran. [Hashempur, Mohammad Hashem] Shiraz Univ Med Sci, Res Ctr Tradit Med & Hist Med, Sch Med, Dept Persian Med, Shiraz, Iran. C3 Shiraz University of Medical Science; Shiraz University of Medical Science; Tehran University of Medical Sciences; Shiraz University of Medical Science; Shiraz University of Medical Science; Shiraz University of Medical Science; Shiraz University of Medical Science RP Hashempur, MH (corresponding author), Shiraz Univ Med Sci, Res Ctr Tradit Med & Hist Med, Sch Med, Dept Persian Med, Shiraz, Iran. 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PD DEC 18 PY 2024 VL 10 IS 1 AR 493 DI 10.1038/s41420-024-02254-2 PG 23 WC Cell Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology GA P8B2J UT WOS:001380088800004 PM 39695119 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Qu, FF Xu, BQ Kang, HC Wang, HX Ji, JB Pang, LJ Wu, YQ Zhou, ZH AF Qu, Fanfan Xu, Baoqing Kang, Hongchang Wang, Hongxia Ji, Jianbin Pang, Lianjing Wu, Yaqian Zhou, Zhenghua TI The role of macrophage polarization in ulcerative colitis and its treatment SO MICROBIAL PATHOGENESIS LA English DT Article DE Macrophage; Ulcerative colitis; Macrophage polarization; Treatment ID PATHWAY AB Macrophages have great plasticity. Typically, there are two of activated macrophages: M1 macrophages and M2 macrophages. Of them, M1 macrophages play a major role in responses that are pro-inflammatory, while M2 macrophages play an important part in responses that are anti-inflammatory. Ulcerative colitis (UC) is a chronic, non-specific inflammatory disease of the intestine. The pathophysiology and course of UC are significantly influenced by the inflammatory response triggered by macrophage activation. M1 is a possible cause of increased inflammation in UC whereas M2 has a significant function in the healing of inflammation. The polarization imbalance of intestinal M1/M2 macrophages is closely linked to UC. Thus, by suppressing M1 polarization, encouraging M2 polarization, and reestablishing macrophage polarization balance, the treatment of UC based on macrophage polarization is beneficial for UC. Not only chemical drugs, but also traditional Chinese medicine compounds and herbal extracts have been shown to restore the balance of macrophage polarization, providing a new idea in the treatment of UC. C1 [Qu, Fanfan; Xu, Baoqing; Kang, Hongchang; Wang, Hongxia; Ji, Jianbin; Pang, Lianjing; Wu, Yaqian; Zhou, Zhenghua] Tianjin Univ Tradit Chinese Med, Teaching Hosp 1, Natl Clin Res Ctr Chinese Med Acupuncture & Moxibu, 88 Changling Rd, Tianjin 300381, Peoples R China. [Xu, Baoqing; Wu, Yaqian] Tianjin Univ Tradit Chinese Med, Tianjin, Peoples R China. C3 Tianjin University of Traditional Chinese Medicine; Tianjin University of Traditional Chinese Medicine RP Zhou, ZH (corresponding author), Tianjin Univ Tradit Chinese Med, Teaching Hosp 1, Natl Clin Res Ctr Chinese Med Acupuncture & Moxibu, 88 Changling Rd, Tianjin 300381, Peoples R China. EM zzh_tjtcm@163.com OI zhou, zhenghua/0009-0009-4703-6821; Xu, Baoqing/0009-0004-3411-0547 FU National Natural Science Foundation of China [82374351]; Tianjin Municipal Education Commission Scientific Research Program [2023KJ151]; New Works Project of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine [2023008] FX This work was supported by the National Natural Science Foundation of China (82374351) ; the Tianjin Municipal Education Commission Scientific Research Program (2023KJ151) ; and New Works Project of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine (Yard 2023008) . 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Pathog. PD FEB PY 2025 VL 199 AR 107227 DI 10.1016/j.micpath.2024.107227 EA DEC 2024 PG 12 WC Immunology; Microbiology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Microbiology GA R4C2O UT WOS:001390942600001 PM 39675441 DA 2026-03-26 ER PT J AU Dong, LN He, HY Chen, ZJ Wang, XX Li, YC Lü, GH Wang, B Kuang, L AF Dong, Lini He, Haoyu Chen, Zejun Wang, Xiaoxiao Li, Yunchao Lu, Guohua Wang, Bing Kuang, Lei TI Pharmacological Network Analysis of the Functions and Mechanism of Quercetin From Jisuikang (JSK) in Spinal Cord Injury (SCI) SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE Huangqi; Jisuikang; microglia; quercetin; spinal cord injury ID SIGNALING PATHWAY; GLIAL ACTIVATION; OXIDATIVE STRESS; RAT MODEL; EXPRESSION; PROMOTES; INTERLEUKIN-1; INFLAMMATION; ASTROCYTES; INDUCTION AB Neuroinflammation, especially microglia/macrophage activation, is a hallmark of spinal cord injury (SCI). Jisuikang (JSK) is a clinical experiential Chinese herbal formula for SCI therapy containing Huangqi (Astragali Radix), Danggui (Angelica sinensis Radix), Chishao (Paeoniae Radix Rubra), Dilong (earthworm, Pheretima aspergillum), Chuanxiong (Chuanxiong Rhizoma), Taoren (Persicae Seman) and Honghua (Carthami Flos). Eighteen active ingredients in 6 herbs of JSK were found to be correlated with inflammation, spinal injury and other diseases. These 18 active ingredients target 5464 genes according to the PubChem database. Through comparing differentially expressed genes between SCI and normal samples using GSE datasets, 50 hub genes were identified. These hub-genes were enriched in oxidative stress response and inflammation response. The herb-compound-target, herb-compound-signalling and compound-target-signalling networks were generated and quercetin was identified as the hub compound. A concentration of 25 mu M quercetin showed no cytotoxicity but significantly protected microglial cells from LPS-induced inhibition of cell viability. LPS stimulation elevated the levels of iNOS, IL-1 beta and TNF-alpha but decreased IL-10 levels, whereas quercetin significantly attenuated LPS-induced alterations in these factors. Moreover, quercetin targeted gene, IL1R1 was reduced by quercetin as predicted. Overexpression of IL1R1 further increased LPS-induced inflammation, which could be partly reversed by quercetin treatment. In vivo, quercetin improved histopathological alterations, inflammation and promoted M2 macrophage polarisation post-injury, whereas IL1R1 overexpression partially attenuated the beneficial effects of quercetin on the rat SCI model. Collectively, quercetin, the main ingredient compound of JSK, protects against LPS-induced cell viability inhibition and cellular inflammation, which could be partially attenuated by IL1R1 overexpression. C1 [Dong, Lini] Cent South Univ, Xiangya Hosp 2, Dept Geriatr, Changsha, Hunan, Peoples R China. [He, Haoyu; Chen, Zejun; Wang, Xiaoxiao; Li, Yunchao; Lu, Guohua; Wang, Bing; Kuang, Lei] Cent South Univ, Xiangya Hosp 2, Dept Spinal Surg, Changsha, Hunan, Peoples R China. C3 Central South University; Central South University RP Kuang, L (corresponding author), Cent South Univ, Xiangya Hosp 2, Dept Spinal Surg, Changsha, Hunan, Peoples R China. EM lei.kuang@csu.edu.cn RI ; Kuang, Lei/AAX-2989-2021; Li, Yunchao/F-8846-2014 OI Lini, Dong/0009-0004-0301-6814; FU Scientific Research Plan Project of Hunan Provincial Health Commission FX This study was supported by the Key Research and Development and Transformation Plan Project, the Science and Technology Department of Qinghai Province (No. 2023- SF- 118), the Natural Science Foundation of Hunan Province (No. 2022JJ30812) and the Scientific Research Plan Project of Hunan Provincial Health Commission (No. 202204073380). 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Cell. Mol. Med. PD DEC 16 PY 2024 VL 28 IS 24 AR e70269 DI 10.1111/jcmm.70269 PG 22 WC Cell Biology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology; Research & Experimental Medicine GA P5D7L UT WOS:001378117400001 PM 39679746 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Qiao, YR He, CE Xia, YX Ocansey, DKW Mao, F AF Qiao, Yaru He, Changer Xia, Yuxuan Ocansey, Dickson Kofi Wiredu Mao, Fei TI Intestinal mucus barrier: A potential therapeutic target for IBD SO AUTOIMMUNITY REVIEWS LA English DT Article DE Intestinal mucus barrier; IBD; MUC2; GCs; Chinese herbs ID GUT MICROBIOTA; FAECALIBACTERIUM-PRAUSNITZII; MACROPHAGE POLARIZATION; MOUSE STOMACH; GOBLET CELLS; CROHNS; MUCIN; COLITIS; EXPRESSION; LAYERS AB Intestinal mucus, a viscoelastic medium with mucin2 (MUC2) as its main component, covers the surface of intestinal epithelial cells and protects the intestine from invasion, forming the first barrier of the intestinal tract. Unlike the small intestine, where the mucus layer is a single layer, the colonic mucus layer can be divided into a sterile inner layer and an outer layer with bacterial colonization. Many of the substances in the mucus layer have beneficial effects on the intestinal epithelium, but the mucus layer is often affected by a variety of factors, mainly microbiological, dietary, and immunological. Inflammatory bowel disease (IBD) is a disease of increasing morbidity worldwide, with a complex etiology and a high relapse rate. In recent years, the mucus barrier in IBD has received increasing attention and is considered a key factor in the pathogenesis of IBD. Loss of goblet cells (GCs) and changes in the composition and properties of the mucus layer material are commonly found in the colon of IBD patients. Damage to the mucus layer may make it easier for microorganisms to access the intestinal epithelium and cause inflammation. There are currently a number of herbs and other therapies that can be used to treat IBD and repair the damaged mucus barrier. This review highlights the important role of the mucus layer in IBD and the therapies that target the mucus layer in IBD. C1 [Qiao, Yaru; Xia, Yuxuan; Ocansey, Dickson Kofi Wiredu; Mao, Fei] Jiangsu Univ, Sch Med, Key Lab Med Sci & Lab Med, Zhenjiang 212013, Peoples R China. [He, Changer] Nantong Univ, Affiliated Danyang Hosp, Peoples Hosp Danyang, Zhenjiang 212399, Jiangsu, Peoples R China. [Ocansey, Dickson Kofi Wiredu] Univ Cape Coast, Coll Hlth & Allied Sci, Sch Allied Hlth Sci, Dept Med Lab Sci, Cape Coast CC0959347, Ghana. C3 Jiangsu University; Nantong University RP Mao, F (corresponding author), Jiangsu Univ, Sch Med, Key Lab Med Sci & Lab Med, Zhenjiang 212013, Peoples R China. EM maofei2003@ujs.edu.cn RI Ocansey, Dickson/AAO-5984-2020; xia, yuxuan/KUC-8359-2024 FU Zhenjiang key research and development plan (social development) [SH2023050]; Teacher specialty leading person senior research project in a higher vocational college of Jiangsu province [2022GRFX069]; Henan province 2024 science and technology development plan [242102310081]; Open topic at the university level of Shangqiu Medical College [KFKT23005]; Jiangsu Provincial Medical Key Discipline Cultivation Unit [JSDW202241] FX Zhenjiang key research and development plan (social development) (Grant no. SH2023050) , Teacher specialty leading person senior research project in a higher vocational college of Jiangsu province (Grant No. 2022GRFX069) , Henan province 2024 science and technology development plan (Grant No. 242102310081) , the open topic at the university level of Shangqiu Medical College in 2023 (Grant No. KFKT23005) , and Jiangsu Provincial Medical Key Discipline Cultivation Unit (Grant No. JSDW202241) . 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Autoimmun. Rev. PD JAN 31 PY 2025 VL 24 IS 2 AR 103717 DI 10.1016/j.autrev.2024.103717 EA DEC 2024 PG 14 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA R0L8F UT WOS:001388485100001 PM 39662652 DA 2026-03-26 ER PT J AU Wang, N Yang, YT Wang, HN Li, YY Wang, M Li, QL AF Wang, Ning Yang, Yuting Wang, Hainan Li, Yueyue Wang, Meng Li, Qinglin TI Cinobufagin modulates vasculogenic mimicry and tumor-associated macrophages to inhibit ovarian cancer progression SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE Cinobufagin; Ovarian cancer; Vasculogenic mimicry; Tumor-associated macrophages; FOXS1; CCL2/CCR2 pathway ID FEATURES AB Background: Ovarian cancer is among the most prevalent malignant tumors affecting women. While conventional therapies like surgery do provide some measure of disease control, they are accompanied by evident side effects that may readily result in drug resistance. Cinobufagin (HCS) is a water-soluble active component extracted from the dried skin of the Bufo gargarizans. Clinical studies have demonstrated its significant anti-tumor effects. Methods: Transcriptome sequencing identified Forkhead Box S1 (FOXS1)-related targets, and Western blot analysis evaluated the expression levels of vasculogenic mimicry (VM)-related proteins and pathway proteins after cinobufagin intervention. Immunofluorescence and ELISA were used to detect the effects of cinobufagin on M1 and M2 macrophage markers. Additionally, a co-culture model of Skov3 cells and macrophages was established to study the effects of cinobufagin on tumor-associated macrophage polarization. Results: Cinobufagin significantly inhibited the growth of Skov3 ovarian cancer cells both in vitro and in vivo. Additionally, cinobufagin decreased the expression levels of VM-related proteins, thereby affecting vasculogenesis both in vitro and in vivo. Transcriptomic analysis revealed that the regulation of the FOXS1 gene contributed to this inhibitory effect. In the co-culture system, we found that cinobufagin inhibited IL-4-induced M2 macrophage polarization. Overexpression of FOXS1 in Skov3 cells enhanced the activity of the C-C motif chemokine ligand 2/receptor 2 (CCL2/CCR2) pathway, which was suppressed by cinobufagin, thus affecting the tumor microenvironment. Conclusion: Cinobufagin suppressed vasculogenic mimicry by regulating the FOXS1 gene and inhibited M2 macrophage polarization through the CCL2/CCR2 pathway, thereby affecting the tumor microenvironment. C1 [Wang, Ning; Yang, Yuting; Wang, Hainan; Li, Yueyue; Wang, Meng; Li, Qinglin] Anhui Univ Tradit Chinese Med, Key Lab Xinan Med, Anhui Prov Key Lab R&D Chinese Med, Minist Educ, 103 Meishan Rd, Hefei 230038, Anhui, Peoples R China. [Li, Qinglin] Anhui Acad Tradit Chinese Med Bozhou Branch, Bozhou 236800, Anhui, Peoples R China. C3 Anhui University of Chinese Medicine RP Wang, M; Li, QL (corresponding author), Anhui Univ Tradit Chinese Med, Key Lab Xinan Med, Anhui Prov Key Lab R&D Chinese Med, Minist Educ, 103 Meishan Rd, Hefei 230038, Anhui, Peoples R China. EM wangmeng@ahtcm.edu.cn; liqinglin@ahtcm.edu.cn OI Wang, Ning/0009-0005-9777-0662 FU National Natural Science Foundation of China [82305023]; Key projects of natural science research in Anhui Universities [2022AH050529]; Postdoctoral Research Project of Anhui Province [2024C835]; Anhui University of Chinese medicine [2022rcyb016] FX This work was supported by the National Natural Science Foundation of China [Grant No. 82305023 to Meng Wang] , Key projects of natural science research in Anhui Universities [Grant No. 2022AH050529 to Meng Wang] , Postdoctoral Research Project of Anhui Province in 2024 [Grant No. 2024C835 to Meng Wang] and The first batch of talent support plan projects of Anhui University of Chinese medicine in 2022 [Grant No. 2022rcyb016 to Meng Wang] . CR Ando Y, 2019, ADV HEALTHC MATER, V8, DOI 10.1002/adhm.201900001 Angara K, 2017, TRANSL ONCOL, V10, P650, DOI 10.1016/j.tranon.2017.04.007 Armstrong DK, 2021, J NATL COMPR CANC NE, V19, P191, DOI 10.6004/jnccn.2021.0007 Banerjee S, 2021, LANCET ONCOL, V22, P1721, DOI 10.1016/S1470-2045(21)00531-3 Bouris P, 2018, MATRIX BIOL, V74, P35, DOI 10.1016/j.matbio.2018.05.011 Conductier G, 2010, J NEUROIMMUNOL, V224, P93, DOI 10.1016/j.jneuroim.2010.05.010 Contreras-Sanzón E, 2023, TRANSL ONCOL, V33, DOI 10.1016/j.tranon.2023.101680 Dai CL, 2023, J PHARM PHARMACOL, V75, P1141, DOI 10.1093/jpp/rgad059 Fein MR, 2020, J EXP MED, V217, DOI 10.1084/jem.20181551 Feng WD, 2022, ACTA BIOCHIM POL, V69, P825, DOI 10.18388/abp.2020_6245 Gadducci A, 2019, CRIT REV ONCOL HEMAT, V135, P103, DOI 10.1016/j.critrevonc.2019.01.006 Garcia J, 2020, CANCER TREAT REV, V86, DOI 10.1016/j.ctrv.2020.102017 Guo L, 2012, MED ONCOL, V29, P1656, DOI 10.1007/s12032-011-0068-9 Hao WD, 2021, ARCH GYNECOL OBSTET, V303, P1589, DOI 10.1007/s00404-021-05967-2 Herrera-Vargas AK, 2021, CYTOKINE GROWTH F R, V62, P23, DOI 10.1016/j.cytogfr.2021.10.006 Kuroki L, 2020, BMJ-BRIT MED J, V371, DOI 10.1136/bmj.m3773 Liu Q, 2022, CELL DEATH DIS, V13, DOI 10.1038/s41419-022-04814-9 Luo QX, 2020, J HEMATOL ONCOL, V13, DOI 10.1186/s13045-020-00858-6 Mantovani A, 2022, NAT REV DRUG DISCOV, V21, P799, DOI 10.1038/s41573-022-00520-5 Miyamoto T, 2022, CANCER IMMUNOL RES, V10, P56, DOI 10.1158/2326-6066.CIR-21-0407 Miyauchi JT, 2018, CANCER RES, V78, P685, DOI 10.1158/0008-5472.CAN-17-1435 Morand S, 2021, INT J MOL SCI, V22, DOI 10.3390/ijms22126532 Na YR, 2018, CANCER LETT, V413, P46, DOI 10.1016/j.canlet.2017.10.044 Park JH, 2003, CLIN CANCER RES, V9, P433 Rong XM, 2016, ONCOTARGET, V7, P83976, DOI 10.18632/oncotarget.6930 Shen ZL, 2018, MOL MED REP, V17, P7435, DOI 10.3892/mmr.2018.8788 Siegel RL, 2021, CA-CANCER J CLIN, V71, P7, DOI 10.3322/caac.21654 Sokolov DI, 2017, B EXP BIOL MED+, V163, P148, DOI 10.1007/s10517-017-3756-4 Tavazoie SF, 2008, NATURE, V451, P147, DOI 10.1038/nature06487 Timar Jozsef, 2000, Magy Onkol, V44, P105 Wang J, 2022, FRONT IMMUNOL, V13, DOI 10.3389/fimmu.2022.1016612 Wang MY, 2023, BIOCHEM PHARMACOL, V218, DOI 10.1016/j.bcp.2023.115893 Wang S, 2019, SCI REP-UK, V9, DOI 10.1038/s41598-019-41717-w Webb PM, 2017, BEST PRACT RES CL OB, V41, P3, DOI 10.1016/j.bpobgyn.2016.08.006 Wei XX, 2021, MOL CANCER, V20, DOI 10.1186/s12943-020-01288-1 Wu M, 2022, CLIN TRANSL ONCOL, V24, P145, DOI 10.1007/s12094-021-02676-9 Xu MS, 2021, CELL PROLIFERAT, V54, DOI 10.1111/cpr.13115 Yan SS, 2023, J CANCER, V14, P3309, DOI 10.7150/jca.86544 Yang JP, 2016, ANGIOGENESIS, V19, P191, DOI 10.1007/s10456-016-9500-2 Yu WW, 2019, ONCOGENE, V38, P1225, DOI 10.1038/s41388-018-0463-1 Yuan ZT, 2017, ONCOTARGET, V8, P48012, DOI 10.18632/oncotarget.18225 Zhang L, 2017, ONCOTARGET, V8, P819, DOI 10.18632/oncotarget.13661 Zhao LQ, 2019, ONCOL REP, V41, P3209, DOI 10.3892/or.2019.7115 NR 43 TC 6 Z9 8 U1 0 U2 6 PU ELSEVIER PI AMSTERDAM PA RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS SN 0014-2999 EI 1879-0712 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JAN 15 PY 2025 VL 987 AR 177157 DI 10.1016/j.ejphar.2024.177157 EA DEC 2024 PG 13 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA Y8A8Y UT WOS:001434291800001 PM 39617163 DA 2026-03-26 ER PT J AU Wang, WD Fan, XY Wei, XQ Chai, WJ Li, FH Gao, K Liu, B Guo, SZ AF Wang, Wen-Di Fan, Xin-Yi Wei, Xiao-Qi Chai, Wang-Jing Li, Fang-He Gao, Kuo Liu, Bin Guo, Shu-Zhen TI Synergistic combinations of Angelica sinensis for myocardial infarction treatment: network pharmacology and quadratic optimization approach SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE Z-ligustilide; chlorogenic acid; myocardial infarction; network pharmacology; quadratic phenotypic optimization platform; cardiomyocyte apoptosis; macrophage polarization ID DRUG; IDENTIFICATION; MACROPHAGES; APOPTOSIS; DANGGUI; PAIRS AB Background and aim Angelica sinensis (Oliv.) Diels (Danggui, DG), exhibits potential in myocardial infarction (MI) treatment. However, research on its synergistic combinations for cardioprotective effects has been limited owing to inadequate approaches. Experimental procedure We identified certain phenolic acids and phthalein compounds in DG. Network pharmacology analysis and experimental validation revealed the components that protected H9c2 cells and reduced lactate dehydrogenase levels. Subsequently, a combination of computational experimental strategies and a secondary phenotypic optimization platform was employed to identify effective component combinations with synergistic interactions. The Chou-Talalay and Zero Interaction Potency (ZIP) models were utilized to quantify the synergistic relationships. The optimal combination identified, Z-Ligustide and Chlorogenic acid (Z-LIG/CGA), was evaluated for its protective effects on cardiac function and cardiomyocytes apoptosis induced by inflammatory in a mouse model of induced by left anterior descending coronary artery ligation. Flow cytometry was further utilized to detect the polarization ratio of M1/M2 macrophages and the expression of inflammatory cytokines in serum was measured, assessing the inhibition of inflammatory responses and pro-inflammatory signaling factors by Z-LIG/CGA. Key results Quadratic surface analysis revealed that the Z-LIG/CGA combination displayed synergistic cardioprotective effects (combination index value <1; ZIP value >10). In vivo, Z-LIG/CGA significantly improved cardiac function and reduced the fibrotic area in mice post-MI, surpassing the results in groups treated with Z-LIG or CGA alone. Compared to the MI group, the Z-LIG/CGA group exhibited decreased ratios of the myocardial cell apoptosis-related proteins BAX/Bcl-2 and Cleaved Caspase-3/Caspase-3 in mice. Further research revealed that Z-LIG/CGA treatment significantly increased IL-1R2 levels, significantly decreased IL-17RA levels, and inhibited the activation of p-STAT1, thereby alleviating cell apoptosis after MI. Additionally, the Z-LIG/CGA combination significantly inhibited the ratio of M1/M2 macrophages and suppressed the expression levels of pro-inflammatory cytokines IL-1 beta, IL-6, IL-17, and TNF-alpha in the serum. Conclusion and implications We successfully identified a synergistic drug combination, Z-LIG/CGA, which improves MI outcomes by inhibiting cardiomyocyte apoptosis and inflammatory damage through modulating macrophage polarization and regulating the IL-1R2/IL-17RA/STAT1 signaling pathway. This study provides a charming paradigm to explore effective drug combinations in traditional Chinese medicine and a promising treatment for MI. C1 [Wang, Wen-Di; Chai, Wang-Jing; Liu, Bin] Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing, Peoples R China. [Fan, Xin-Yi; Wei, Xiao-Qi; Li, Fang-He; Gao, Kuo; Guo, Shu-Zhen] Beijing Univ Chinese Med, Sch Tradit Chinese Med, Beijing, Peoples R China. [Liu, Bin] State Adm Tradit Chinese Med, Key Res Lab Exploring Effect Subst Class & Famous, Beijing, Peoples R China. C3 Beijing University of Chinese Medicine; Beijing University of Chinese Medicine RP Liu, B (corresponding author), Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing, Peoples R China.; Gao, K; Guo, SZ (corresponding author), Beijing Univ Chinese Med, Sch Tradit Chinese Med, Beijing, Peoples R China.; Liu, B (corresponding author), State Adm Tradit Chinese Med, Key Res Lab Exploring Effect Subst Class & Famous, Beijing, Peoples R China. EM gk@bucm.edu.cn; liubinyn67@163.com; guoshz@bucm.edu.cn RI fan, xinyi/MTD-8376-2025; wang, wendi/HJA-8574-2022 FU National Natural Science Foundation of China [82174206] FX The authors thank the National Natural Science Foundation of China (No. 82174206) for financial support and thank Beijing University of Chinese Medicine for providing the necessary infrastructure to perform this research. 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Pharmacol. PD DEC 9 PY 2024 VL 15 AR 1466208 DI 10.3389/fphar.2024.1466208 PG 21 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA Q1Z5A UT WOS:001382750400001 PM 39717556 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Gao, J Su, G Liu, JF Song, JY Chen, W Chai, M Xie, XD Wang, MX Liu, JX Zhang, ZC AF Gao, Juan Su, Gang Liu, Jifei Song, Jinyang Chen, Wei Chai, Miao Xie, Xiaodong Wang, Manxia Liu, Junxi Zhang, Zhenchang TI A Novel Compound Ligusticum Cycloprolactam Alleviates Neuroinflammation After Ischemic Stroke via the FPR1/NLRP3 Signaling Axis SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE FPR1; ischemic stroke; LIGc; macrophages; microglia; neuroinflammation; NLRP3 ID POLARIZATION; INFLAMMATION; ACTIVATION; AUTOPHAGY; DIAGNOSIS; MOUSE AB BackgroundMicroglia/macrophages, as pivotal immune cells in the central nervous system (CNS), play a critical role in neuroinflammation associated with ischemic brain injury. Targeting their activation through pharmacological interventions represents a promising strategy to alleviate neurological deficits, thereby harboring significant implications for the prevention and treatment of ischemic stroke. Ligusticum cycloprolactam (LIGc), a novel monomeric derivative of traditional Chinese medicine, has shown potential as a therapeutic agent; however, its specific role in cerebral ischemic injury remains unclear.MethodsIn vitro experiments utilized lipopolysaccharide (LPS)-induced inflammation models of RAW264.7 cells and primary mouse microglia. In vivo studies employed LPS-induced neuroinflammation models in mice and a transient middle cerebral artery occlusion (tMCAO) mouse model to evaluate the impact of LIGc on neuroinflammation and microglia/macrophage phenotypic alterations. Further elucidation of the molecular mechanisms underlying these effects was achieved through RNA-Seq analyses.ResultsLIGc exhibited the capacity to attenuate LPS-induced production of pro-inflammatory markers in macrophages and microglia, facilitating their transition to an anti-inflammatory phenotype. In models of LPS-induced neuroinflammation and tMCAO, LIGc ameliorated pathological behaviors and neurological deficits while mitigating brain inflammation. RNA-seq analyses revealed formyl peptide receptor 1 (FPR1) as a critical mediator of LIGc's effects. Specifically, FPR1 enhances the pro-inflammatory phenotype of microglia/macrophages and inhibits their anti-inflammatory response by upregulating NLR family pyrin domain protein 3 (NLRP3) inflammasomes, thus aggravating inflammatory processes. Conversely, LIGc exerts anti-inflammatory effects by downregulating the FPR1/NLRP3 signaling axis. Furthermore, FPR1 overexpression or NLRP3 agonists reversed the effects of LIGc observed in this study.ConclusionOur findings suggest that LIGc holds promise in improving ischemic brain injury and neuroinflammation through modulation of microglia/macrophage polarization. Mechanistically, LIGc attenuates the pro-inflammatory phenotype and promotes the anti-inflammatory phenotype by targeting the FPR1/NLRP3 signaling pathway, ultimately reducing inflammatory responses and mitigating neurological damage. C1 [Gao, Juan; Liu, Jifei; Song, Jinyang; Chen, Wei; Chai, Miao; Wang, Manxia; Zhang, Zhenchang] Lanzhou Univ, Hosp 2, Dept Neurol, Lanzhou, Gansu, Peoples R China. [Gao, Juan; Liu, Jifei; Song, Jinyang; Chen, Wei; Chai, Miao; Wang, Manxia; Zhang, Zhenchang] Lanzhou Univ, Clin Med Sch, Lanzhou, Gansu, Peoples R China. [Su, Gang; Xie, Xiaodong] Lanzhou Univ, Sch Basic Med Sci, Inst Genet, Lanzhou, Gansu, Peoples R China. [Liu, Junxi] Chinese Acad Sci, Lanzhou Inst Chem Phys, Key Lab Chem Northwestern Plant Resources, Lanzhou, Gansu, Peoples R China. [Liu, Junxi] Chinese Acad Sci, Lanzhou Inst Chem Phys, Key Lab Nat Med Gansu Prov, Lanzhou, Gansu, Peoples R China. C3 Lanzhou University; Lanzhou University; Lanzhou University; Chinese Academy of Sciences; Lanzhou Institute of Chemical Physics, CAS; Chinese Academy of Sciences; Lanzhou Institute of Chemical Physics, CAS RP Zhang, ZC (corresponding author), Lanzhou Univ, Hosp 2, Dept Neurol, Lanzhou, Gansu, Peoples R China.; Zhang, ZC (corresponding author), Lanzhou Univ, Clin Med Sch, Lanzhou, Gansu, Peoples R China.; Liu, JX (corresponding author), Chinese Acad Sci, Lanzhou Inst Chem Phys, Key Lab Chem Northwestern Plant Resources, Lanzhou, Gansu, Peoples R China.; Liu, JX (corresponding author), Chinese Acad Sci, Lanzhou Inst Chem Phys, Key Lab Nat Med Gansu Prov, Lanzhou, Gansu, Peoples R China. 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Ther. PD DEC 9 PY 2024 VL 30 IS 12 AR e70158 DI 10.1111/cns.70158 PG 20 WC Neurosciences; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Neurosciences & Neurology; Pharmacology & Pharmacy GA O7A6I UT WOS:001372613100001 PM 39654367 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Wang, Q Xiong, XY Chen, L Zhu, FH Yang, XQ Zhao, WM He, SJ Zuo, JP Lin, ZM AF Wang, Que Xiong, Xiaoyu Chen, Li Zhu, Fenghua Yang, Xiaoqian Zhao, Weimin He, Shijun Zuo, Jianping Lin, Zemin TI Periplosides Extract from Cortex periplocae Improve Collagen Antibody-Induced Arthritis by Regulating Macrophage Polarization SO CURRENT ISSUES IN MOLECULAR BIOLOGY LA English DT Article DE rheumatoid arthritis; Cortex periplocae; pregnane glycosides; anti-arthritic activity; collagen antibody-induced arthritis; macrophage polarization AB Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized primarily by the synovial infiltration of inflammatory cells. Macrophage infiltration in the joint synovium is one of the early hallmarks of RA disease activity. Cortex periplocae, which has been widely employed in traditional Chinese medicine (TCM) to alleviate RA, harbors a bioactive compound known as Periploca sepium periplosides (PePs). In this study, collagen antibody-induced arthritis (CAIA) was established in mice through the administration of collagen antibodies and lipopolysaccharide (LPS), followed by treatment with PePs. The therapeutic effects of PePs were evaluated by measuring paw thickness, clinical arthritis scores, and histological changes in joint tissues. Flow cytometry and qRT-PCR were used to assess macrophage polarization in vivo and in vitro. The findings indicate that PePs effectively attenuated CAIA by suppressing the polarization of RAW264.7 cells towards the M1 phenotype while promoting their polarization towards the M2 phenotype. These results provide valuable insights into the scientific significance of PePs as a potential therapeutic agent for RA. C1 [Wang, Que; Zuo, Jianping; Lin, Zemin] Shanghai Univ Tradit Chinese Med, Expt Ctr Sci & Technol, Shanghai 201203, Peoples R China. [Xiong, Xiaoyu; Chen, Li; Zhu, Fenghua; Yang, Xiaoqian; Zuo, Jianping; Lin, Zemin] Chinese Acad Sci, Shanghai Inst Materia Med, Lab Immunopharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China. [Zhao, Weimin] Chinese Acad Sci, Shanghai Inst Materia Med, Dept Nat Prod Chem, Shanghai 201203, Peoples R China. [He, Shijun] Shanghai Univ Tradit Chinese Med, Innovat Res Inst Tradit Chinese Med, Shanghai 201203, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine; Chinese Academy of Sciences; Shanghai Institute of Materia Medica, CAS; Chinese Academy of Sciences; Shanghai Institute of Materia Medica, CAS; Shanghai University of Traditional Chinese Medicine RP Zuo, JP; Lin, ZM (corresponding author), Shanghai Univ Tradit Chinese Med, Expt Ctr Sci & Technol, Shanghai 201203, Peoples R China.; Zuo, JP; Lin, ZM (corresponding author), Chinese Acad Sci, Shanghai Inst Materia Med, Lab Immunopharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China. EM 18616833881@163.com; xiongxiaoyu@simm.ac.cn; chenli@simm.ac.cn; fhzhu@simm.ac.cn; xqyang@simm.ac.cn; wmzhao@simm.ac.cn; jpzuo@simm.ac.cn; linzemin@simm.ac.cn RI lin, zemin/ADR-2173-2022 OI lin, zemin/0000-0002-3665-874X FU National Natural Science Foundation of China; Shanghai Municipal Science and Technology Major Project; State Key Laboratory of Drug Research Program [SIMM1903ZZ-03]; CAS Interdisciplinary Innovation Team; Major projects for fundamental research of Yunnan province [202201BC070002]; [82374108]; [22177123] FX This work was supported by the National Natural Science Foundation of China (82374108 and 22177123), the Shanghai Municipal Science and Technology Major Project, the State Key Laboratory of Drug Research Program (SIMM1903ZZ-03), the CAS "Light of West China" Program and CAS Interdisciplinary Innovation Team, and the Major projects for fundamental research of Yunnan province (202201BC070002). CR Boutet MA, 2021, AUTOIMMUN REV, V20, DOI 10.1016/j.autrev.2021.102758 Cheng Y, 2021, INT IMMUNOPHARMACOL, V99, DOI 10.1016/j.intimp.2021.107988 Cutolo M, 2022, FRONT IMMUNOL, V13, DOI 10.3389/fimmu.2022.867260 Faustino C, 2023, LIFE-BASEL, V13, DOI 10.3390/life13071514 Fukui S, 2018, FRONT IMMUNOL, V8, DOI 10.3389/fimmu.2017.01958 Kung CC, 2020, MOL BIOL REP, V47, P3423, DOI 10.1007/s11033-020-05422-6 Li T, 2021, PEST MANAG SCI, V77, P1925, DOI 10.1002/ps.6220 Lin ZM, 2021, J ETHNOPHARMACOL, V265, DOI 10.1016/j.jep.2020.113345 Lin ZM, 2016, SCI REP-UK, V6, DOI 10.1038/srep38115 Lins FSV, 2022, MOLECULES, V27, DOI 10.3390/molecules27185992 Mertz P, 2023, AUTOIMMUN REV, V22, DOI 10.1016/j.autrev.2023.103391 Murdaca G, 2024, BIOMEDICINES, V12, DOI 10.3390/biomedicines12051023 Radu AF, 2023, AGEING RES REV, V87, DOI 10.1016/j.arr.2023.101927 Rui K, 2023, CELL MOL IMMUNOL, V20, P548, DOI 10.1038/s41423-023-01004-1 STAINES NA, 1994, BRIT J RHEUMATOL, V33, P798 Tao J, 2023, BIOMED PHARMACOTHER, V157, DOI 10.1016/j.biopha.2022.113997 Wan J, 2008, INT IMMUNOPHARMACOL, V8, P1248, DOI 10.1016/j.intimp.2008.05.001 Weyand CM, 2021, NAT IMMUNOL, V22, P10, DOI 10.1038/s41590-020-00816-x Wu MF, 2021, CANCER IMMUNOL IMMUN, V70, P1435, DOI 10.1007/s00262-020-02781-8 Yang ZH, 2023, PHYTOMEDICINE, V115, DOI 10.1016/j.phymed.2023.154816 Zhu YN, 2006, J PHARMACOL EXP THER, V318, P1153, DOI 10.1124/jpet.106.105445 NR 21 TC 3 Z9 3 U1 2 U2 7 PU MDPI PI BASEL PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND SN 1467-3037 EI 1467-3045 J9 CURR ISSUES MOL BIOL JI Curr. Issues Mol. Biol. PD DEC PY 2024 VL 46 IS 12 BP 14095 EP 14105 DI 10.3390/cimb46120843 PG 11 WC Biochemistry & Molecular Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology GA Q3O1K UT WOS:001383809000001 PM 39727971 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Jie, LS Zhang, L Fu, HY Kang, JF Huang, ZL Zhu, ZS Yin, SJ Wu, P Wang, PM Mei, W Li, XC AF Jie, Lishi Zhang, Li Fu, Houyu Kang, Junfeng Huang, Zeling Zhu, Zaishi Yin, Songjiang Wu, Peng Wang, Peimin Mei, Wei Li, Xiaochen TI Xibining inhibition of the PI3K-AKT pathway reduces M1 macrophage polarization to ameliorate KOA synovial inflammation and nociceptive sensitization SO PHYTOMEDICINE LA English DT Article DE PI3K-AKT pathway; Intrinsic immunity; Macrophage polarization; Dorsal root ganglion; Knee osteoarthritis; TRP ion channels AB Background: Pain is the most critical symptom of knee osteoarthritis(KOA), which seriously affects the quality of life of patients. Xibining (XBN), a traditional herbal compound, has achieved good results in the clinical treatment of KOA, and its mechanism of action is worth exploring in depth. Objective: In vivo and in vitro models of KOA were constructed, and the potential drug action mechanism of XBN in improving osteoarthritis pain was explored in combination with transcriptomics. Methods: In vitro experiments were also conducted to explore the effects of different treatments of BMDMs on TRP channels in DRG neurons by constructing a coculture system of BMDMs and DRG neurons. The specific mechanism by which XBN affects BMDMs was explored via participatory transcriptomics. Results: Our results showed that KOA aggravated macrophage infiltration in synovial tissues and DRG tissues and increased the transcriptional and translational levels of TRPA1, TRPV1, and TRPM8 in synovial tissues and DRG tissues; XBN treatment improved inflammation in synovial tissues and macrophage infiltration in DRG tissues, and it decreased the transcriptional and translational levels of TRPA1, TRPV1, and TRPM8, consistent with the results of behavioral tests to improve nociceptive sensitization induced by KOA. The results from in vitro experiments showed that promoting macrophage M1-type polarization exacerbated TRP channel activation in DRG neurons and that XBN acted by inhibiting macrophage M1-type polarization. A reference transcriptome study showed that XBN may play a role in inhibiting M1 macrophage-type polarization in KOA by suppressing the PI3K-AKT pathway in BMDMs. We verified the conclusions obtained from transcriptomics via in vitro experiments. We place greater emphasis on the role that the intrinsic immune system plays in the area of pain control in osteoarthritis. Conclusion: XBN improve KOA nociceptive sensitization by modulating the PI3K/Akt signaling pathway, attenuating the level of synovial inflammation and inhibiting M1-type macrophage polarization in synovial and DRG tissues in KOA mice. C1 [Jie, Lishi; Zhang, Li; Fu, Houyu; Kang, Junfeng; Yin, Songjiang; Wu, Peng; Wang, Peimin; Mei, Wei; Li, Xiaochen] Nanjing Univ Chinese Med, Jiangsu Prov Hosp Tradit Chinese Med, Affiliated Hosp, Dept Orthopaed & Traumatol, Nanjing 210023, Peoples R China. [Jie, Lishi; Fu, Houyu; Kang, Junfeng; Huang, Zeling; Zhu, Zaishi] Nanjing Univ Chinese Med, Jiangsu Prov Hosp Tradit Chinese Med, Coll Clin Med 1, Key Lab Metab Dis Chinese Med, Nanjing 210023, Peoples R China. [Kang, Junfeng] Shanxi Univ Tradit Chinese Med, Affiliated Hosp, Taiyuan 030002, Peoples R China. [Huang, Zeling; Zhu, Zaishi] Suzhou Hosp Tradit Chinese Med, Dept Orthopaed & Traumatol, Suzhou, Peoples R China. [Wang, Peimin] Jiangsu Prov Engn Res Ctr TCM External Medicat Dev, Nanjing, Peoples R China. C3 Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine RP Mei, W; Li, XC (corresponding author), Nanjing Univ Chinese Med, Dept Orthopaed & Traumatol, Affiliated Hosp, 155,Hanzhong Rd, Nanjing, Jiangsu, Peoples R China. EM mei1899@163.com; drlixiaochen@njucm.edu.cn RI Mei, Wei/AFI-8243-2022; HUANG, ZELING/JVN-2020-2024 OI Wang, Peimin/0000-0002-5454-878X FU National Natural Science Foundation of China [82305276]; Project of Science and technology development of traditional Chinese medicine in Jiangsu province [QN202105]; Natural Science Research Project of Jiangsu Province Colleges and Universities [22KJB360008]; Excellent Young Doctoral Program of Jiangsu Province Hospital of Chinese Medicine [2023QB0118]; Peak Academic Talent Project of Jiangsu Province Hospital of Chinese Medicine [y2021rc48]; Clinical Medical Innovation Center for Knee Osteoarthritis in Jiangsu Province Hospital of Chinese Medicine [Y2023zx05]; Jiangsu Provincial Medical Key Discipline (Laboratory) Cultivation Unit [JSDW202252] FX This research was supported by the National Natural Science Foundation of China (82305276) , Project of Science and technology development of traditional Chinese medicine in Jiangsu province (QN202105) , Natural Science Research Project of Jiangsu Province Colleges and Universities (22KJB360008) , Excellent Young Doctoral Program of Jiangsu Province Hospital of Chinese Medicine (2023QB0118) , the Peak Academic Talent Project of Jiangsu Province Hospital of Chinese Medicine (y2021rc48) , Clinical Medical Innovation Center for Knee Osteoarthritis in Jiangsu Province Hospital of Chinese Medicine (Y2023zx05) , the Jiangsu Provincial Medical Key Discipline (Laboratory) Cultivation Unit (JSDW202252) . 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Luteolin (Lut) is a major bioactive component of LJF, demonstrating a regulatory role in immune disorders. However, the specific role of Lut in regulating macrophage-mediated intestinal inflammation and its underlying molecular mechanisms have not yet been fully explored. Aim of the study: This study was designed to explore whether Lut alleviates Ulcerative colitis (UC) in mice and to elucidate its underlying mechanism in intestinal inflammation. Materials and methods: Mice were administered Dextran sodium sulfate (DSS) for 7 d to establish a UC model, followed by oral administration of Lut (12.5, 25, and 50 mg/kg body weight). RNA-sequencing (RNA-Seq) was used to screen signaling pathways. RAW264.7 cells were cultured and treated with Lut (6.25, 12.5, and 25 mu M) and lipopolysaccharide (LPS, 1 mu g/mL) for 24 h. To examine the role of the AMP-activated protein kinase (AMPK)/Peroxisome proliferator-activated receptor gamma (PPAR gamma) signaling pathway, the cells were treated with compound C (an AMPK inhibitor) and GW9662 (a PPAR gamma antagonist). Results: Lut suppressed the inflammation of DSS-induced colitis in vivo, attenuated DSS-induced clinical manifestations, reversed colon length reduction, and reduced histological injury. Lut induced a shift in the macrophage phenotype from classical (M1) to alternative (M2) by suppressing M1 marker gene expression and enhancing M2 marker gene expression following DSS or LPS induction. RNA-seq revealed that PPAR gamma was involved in the regulation of macrophages by Lut. Furthermore, the polarization effect of Lut on macrophages was shown to be mediated through the AMPK-PPAR gamma signaling pathway. Conclusion: These findings indicate that Lut effectively ameliorates UC in mice through the activation of the AMPK-PPAR gamma signaling pathway, leading to the inhibition of macrophage M1 polarization and promotion of M2 polarization. This study provides insight into future research on the utilization of Lut-rich TCM dietary supplements as a prophylactic treatment strategy in the prevention of UC. C1 [Yang, Shuai; Duan, Hongwei; Zeng, Jianlin; Yan, Zhenxing; Niu, Tian; Ma, Xiaofei; Zhang, Yong; Hu, Junjie; Zhang, Lihong; Zhao, Xingxu] Gansu Agr Univ, Coll Vet Med, Lanzhou 730070, Gansu, Peoples R China. [Yang, Shuai; Duan, Hongwei; Zeng, Jianlin; Yan, Zhenxing; Niu, Tian; Ma, Xiaofei; Zhang, Yong; Hu, Junjie; Zhang, Lihong; Zhao, Xingxu] Gansu Key Lab Anim Generat Physiol & Reprod Regula, Lanzhou 730070, Gansu, Peoples R China. C3 Gansu Agricultural University RP Zhang, LH; Zhao, XX (corresponding author), Gansu Agr Univ, Coll Vet Med, Lanzhou 730070, Gansu, Peoples R China. EM zhanglih@gsau.edu.cn; zhaoxx@gsau.edu.cn RI Ma, Xiaofei/KFA-3269-2024 FU National Natural Science Foundation of China [32202873]; Fuxi Young Talents Fund of Gansu Agricultural University [Gaufx-05Y07]; Scientific Research Start-up Funds for Openly Recruited Doctors of Gansu Agricultural University [GAU-KYQD-2021-09] FX This work was supported by the National Natural Science Foundation of China (32202873) , The Fuxi Young Talents Fund of Gansu Agricultural University (Grant No.Gaufx-05Y07) , and Scientific Research Start-up Funds for Openly Recruited Doctors of Gansu Agricultural University (GAU-KYQD-2021-09) . The drawing platform of the graphic abstract is provided by Figdraw. 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ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-8741 EI 1872-7573 J9 J ETHNOPHARMACOL JI J. Ethnopharmacol. PD JAN 13 PY 2025 VL 339 AR 119157 DI 10.1016/j.jep.2024.119157 EA NOV 2024 PG 13 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA Z9I6A UT WOS:001441958500001 PM 39603400 DA 2026-03-26 ER PT J AU Yan, FL Li, WB Sun, XY Wang, L Liu, ZH Zhong, ZM Guo, ZR Liu, ZY Gao, M Zhang, JF Wang, CY Dong, GJ Li, CX Chen, S Xiong, HB Zhang, H AF Yan, Fenglian Li, Wenbo Sun, Xueyang Wang, Lin Liu, Zhihong Zhong, Zhaoming Guo, Zhengran Liu, Ziyu Gao, Min Zhang, Junfeng Wang, Changying Dong, Guanjun Li, Chunxia Chen, Shang Xiong, Huabao Zhang, Hui TI Sappanone A Ameliorates Concanavalin A-induced Immune-Mediated Liver Injury by Regulating M1 Macrophage Polarization SO INFLAMMATION LA English DT Article DE Sappanone A; Concanavalin A; Macrophage polarization; Immune-mediated liver injury; Oxidative stress; Inflammation ID INDUCED HEPATITIS; KUPFFER CELLS; INFLAMMATION; MODULATION; MECHANISMS; PROTECTS; MICE AB Sappanone A (SAP), a high-isoflavone compound derived from the traditional Chinese medicine Sumu, exhibits various pharmacological activities, including anti-inflammatory and anti-oxidant effects. However, its protective effects on the liver have rarely been reported. The aim of this study was to investigate the effects of SAP on immune-mediated liver injury induced by concanavalin A (Con A) in mice and to explore the underlying molecular mechanisms. Mice were administered SAP intraperitoneally (50 mg/kg body weight). Three hours later, Con A (18 mg/kg) was injected via the tail vein to induce liver damage. Livers and blood were collected 12 h after Con A challenge. Liver cell apoptosis, oxidative stress, and M1 macrophage activation in vivo were investigated. Bone marrow-derived macrophages were used to confirm the effects of SAP on M1 polarization in vitro. The results indicated that SAP decreased transaminase levels, inhibited apoptosis, and improved oxidative stress in mouse livers. Furthermore, SAP significantly reduced the proportion of macrophages, inhibited the expression of CD86, and downregulated the expression of M1 macrophage-related inflammatory cytokines. Moreover, SAP-treated macrophages alleviated liver damage caused by Con A compared to non-SAP-treated macrophages. Mechanistically, SAP inhibited the phosphorylation of key molecules in the MAPK and NF-kappa B signaling pathways in macrophages, resulting in an inhibitory effect on M1 macrophage activation. Taken together, SAP alleviates immune-mediated liver injury induced by Con A by suppressing M1 macrophage polarization, which is partially associated with NF-kappa B and MAPK signaling pathways. C1 [Yan, Fenglian; Li, Wenbo; Sun, Xueyang; Wang, Lin; Liu, Zhihong; Zhong, Zhaoming; Guo, Zhengran; Liu, Ziyu; Zhang, Junfeng; Wang, Changying; Dong, Guanjun; Li, Chunxia; Xiong, Huabao; Zhang, Hui] Jining Med Univ, Inst Immunol & Mol Med, Jining, Shandong, Peoples R China. [Yan, Fenglian; Li, Wenbo; Sun, Xueyang; Wang, Lin; Liu, Zhihong; Zhong, Zhaoming; Guo, Zhengran; Liu, Ziyu; Zhang, Junfeng; Wang, Changying; Dong, Guanjun; Li, Chunxia; Xiong, Huabao; Zhang, Hui] Jining Med Univ, Jining Key Lab Immunol, Jining, Shandong, Peoples R China. [Gao, Min] Jining First Peoples Hosp, Clin Lab, Jining, Shandong, Peoples R China. [Chen, Shang] Jining Med Univ, Med Res Ctr, Affiliated Hosp, Jining 272067, Shandong, Peoples R China. C3 Jining Medical University; Jining Medical University; Jining Medical University RP Xiong, HB; Zhang, H (corresponding author), Jining Med Univ, Inst Immunol & Mol Med, Jining, Shandong, Peoples R China.; Xiong, HB; Zhang, H (corresponding author), Jining Med Univ, Jining Key Lab Immunol, Jining, Shandong, Peoples R China.; Chen, S (corresponding author), Jining Med Univ, Med Res Ctr, Affiliated Hosp, Jining 272067, Shandong, Peoples R China. EM chenshang2010@163.com; xionghuabao@mail.jnmc.edu.cn; zhanghui1024@mail.jnmc.edu.cn RI Yan, Fenglian/KBP-8427-2024; ZHONG, ZHAOMING/AAN-3234-2020 FU Research Fund for Lin He's Academician Workstation of New Medicine and Clinical Translation at Jining Medical University FX We thank Editage (www.editage.com) for English language editing. CR Aratani Y, 2018, ARCH BIOCHEM BIOPHYS, V640, P47, DOI 10.1016/j.abb.2018.01.004 Banerjee P, 2023, AM J PATHOL, V193, P1400, DOI 10.1016/j.ajpath.2023.06.002 Hamosh A, 2005, NUCLEIC ACIDS RES, V33, pD514 Hao JH, 2022, INT IMMUNOPHARMACOL, V102, DOI 10.1016/j.intimp.2021.108411 Hatano M, 2008, CELL IMMUNOL, V251, P25, DOI 10.1016/j.cellimm.2008.02.003 Herkel J, 2005, J HEPATOL, V42, P920, DOI 10.1016/j.jhep.2005.02.009 Heymann F, 2016, NAT REV GASTRO HEPAT, V13, P88, DOI 10.1038/nrgastro.2015.200 Hu X, 2024, FOOD SCI HUM WELL, V13, P2102, DOI 10.26599/FSHW.2022.9250175 Lee S, 2015, INT IMMUNOPHARMACOL, V28, P328, DOI 10.1016/j.intimp.2015.06.015 Liu XSBJ, 2016, INT ARCH ALLERGY IMM, V170, P180, DOI 10.1159/000448331 Lu GM, 2015, NAT COMMUN, V6, DOI 10.1038/ncomms7676 Mantovani A, 2013, J PATHOL, V229, P176, DOI 10.1002/path.4133 Mussbacher M, 2023, FRONT IMMUNOL, V14, DOI 10.3389/fimmu.2023.1134661 Nakashima H, 2008, HEPATOLOGY, V48, P1979, DOI 10.1002/hep.22561 Park SJ, 2023, FRONT ENDOCRINOL, V14, DOI 10.3389/fendo.2023.1150118 Qi J, 2023, ANTIOXIDANTS-BASEL, V12, DOI 10.3390/antiox12091718 Safran M, 2010, DATABASE-OXFORD, DOI 10.1093/database/baq020 Schümann J, 2000, AM J PATHOL, V157, P1671, DOI 10.1016/S0002-9440(10)64804-3 Shi XJ, 2020, DRUG DES DEV THER, V14, P61, DOI 10.2147/DDDT.S230358 Tiegs G, 2007, Z GASTROENTEROL, V45, P63, DOI 10.1055/s-2006-927397 TIEGS G, 1992, J CLIN INVEST, V90, P196, DOI 10.1172/JCI115836 Toda G, 2021, STAR PROTOC, V2, DOI 10.1016/j.xpro.2020.100246 Velasco JAVR, 2024, REV GASTROENTEROL ME, V89, P106, DOI [10.1016/j.rgmxen.2023.12.001, 10.1016/j.rgmxen.2023.12.001, 10.1016/j.rgmx.2023.12.003] Wang HX, 2012, WORLD J GASTROENTERO, V18, P119, DOI 10.3748/wjg.v18.i2.119 Wang MH, 2021, INFLAMMATION, V44, P934, DOI 10.1007/s10753-020-01388-6 Wang X, 2017, NUCLEIC ACIDS RES, V45, pW356, DOI 10.1093/nar/gkx374 Wang YZ, 2023, J ETHNOPHARMACOL, V304, DOI 10.1016/j.jep.2022.116020 Wang Z, 2022, FRONT PHARMACOL, V13, DOI 10.3389/fphar.2022.953004 Xue JH, 2015, CELL PHYSIOL BIOCHEM, V35, P1557, DOI 10.1159/000373971 Yan FL, 2022, FRONT IMMUNOL, V12, DOI 10.3389/fimmu.2021.807509 Zhou ZX, 2022, TOXICOLOGY, V480, DOI 10.1016/j.tox.2022.153336 NR 31 TC 3 Z9 6 U1 0 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0360-3997 EI 1573-2576 J9 INFLAMMATION JI Inflammation PD AUG PY 2025 VL 48 IS 4 BP 2274 EP 2291 DI 10.1007/s10753-024-02189-x EA NOV 2024 PG 18 WC Cell Biology; Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology; Immunology GA 6FN3L UT WOS:001363264200001 PM 39589634 OA Green Submitted, hybrid DA 2026-03-26 ER PT J AU Ling, Y Yang, YZ Ren, NN Xu, H Cheng, CM Lu, DM Wang, QY Yao, XM Ma, WK AF Ling, Yi Yang, Yuzheng Ren, Nina Xu, Hui Cheng, Changming Lu, Daomin Wang, Qiuyi Yao, Xueming Ma, Wukai TI Jinwu Jiangu capsule attenuates rheumatoid arthritis via the SLC7A11/ GSH/GPX4 pathway in M1 macrophages SO PHYTOMEDICINE LA English DT Article DE Jinwu jiangu capsule; Rheumatoid arthritis; Reactive oxygen species; M1 macrophages; Ferroptosis AB Background: JinWu JianGu capsule (JWJGC) is a Chinese herbal medicine that alleviates the clinical manifestations of rheumatoid arthritis (RA). However, the mechanism of action requires further investigation.. Purpose: This study aimed to investigate the anti-inflammatory effects of JWJGC on RA via the regulation of reactive oxygen species (ROS) and ferroptosis. Materials and methods: JWJGC was administered to rats with collagen-induced arthritis (CIA) via oral gavage for 28 days. In vitro, M1 macrophages were pre-treated with JWJGC-containing serum. After assessing joint swelling and physiologic, the M1/M2 macrophage ratio was detected in CIA rats. The levels of ROS markers were assessed in the serum and cell supernatants. Liquid chromatography-tandem mass spectrometry analyses were employed to check lipid metabolism, and changes in mitochondrial morphology during ferroptosis were detected by transmission electron microscopy. Western blotting, immunofluorescence, immunohistochemistry, and qRT-PCR were performed to validate these results. Results: JWJGC ameliorated CIA by reducing ROS levels in rats. It also restored the balance of the M1/M2 macrophage ratio and reduced the levels of macrophage-related inflammatory markers. Additionally, JWJGC affected lipid metabolism to alleviate inflammation by downregulating lipids associated with ferroptosis. It attenuated ferroptosis by modulating glutathione (GSH)/ Glutathione peroxidase 4(GPX4) expression in CIA rats. In vitro, JWJGC targeted M1 macrophages via the solute carrier family 7a member 11 (SLC7A11)/GSH/GPX4 signaling pathway. Conclusions: This study showed that JWJGC improved RA, primarily through the integrated regulation of the SLC7A11/GSH/GPX4 pathway in M1 macrophages. These findings provide an innovative therapeutic basis for RA treatment and expanding the clinical applications of JWJGC. C1 [Ling, Yi; Yang, Yuzheng; Ren, Nina; Xu, Hui; Cheng, Changming; Lu, Daomin; Wang, Qiuyi; Yao, Xueming; Ma, Wukai] Guizhou Univ Tradit Chinese Med, 83 Feishan St,Yunyan, Guiyang 550000, Guizhou, Peoples R China. C3 Guizhou University of Traditional Chinese Medicine RP Yao, XM; Ma, WK (corresponding author), Guizhou Univ Tradit Chinese Med, 83 Feishan St,Yunyan, Guiyang 550000, Guizhou, Peoples R China. EM yxming19@foxmail.com; walker55@163.com RI Yao, Xue ming/HDM-5818-2022 FU Guizhou Provincial Health and Health Commission Science and Technology Fund Project [82274678, 82160869, 82405366, GZEYK-Y [2022] 37, QZYY-2023-020]; 2023 Postgraduate Education Innovation Plan Project of Guizhou Uni-versity of Traditional Chinese Medicine [gzwkj2024-354]; Innovation and Entrepreneurship Training Program for Guizhou University of Traditional Chinese Medicine Students [YCXKYB2023013]; Guizhou provincial basic research program (natural science) [(2023) 21]; Guizhou University of Traditional Chinese Medicine National and Pro-vincial Science and Technology Innovation Talent Team Cultivation Project (Guizhou University of Traditional Chinese Medicine TD) [ZK [2024]]; Guizhou University of Traditional Chinese Medicine [[2022] 004]; Guizhou Provincial Basic Research Program (Natural Science) [[2023-36]]; [412] FX The study was supported by the National Natural Science Foundation of China (82274678, 82160869, 82405366) , Youth Research Startup Fund of the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine (GZEYK-Y [2022] 37) , Scientific and Technological Research Topics of Traditional Chinese Medicine and Ethnic Medicine (QZYY-2023-020) , Guizhou Provincial Health and Health Commission Science and Technology Fund Project (gzwkj2024-354) , 2023 Postgraduate Education Innovation Plan Project of Guizhou University of Traditional Chinese Medicine (YCXKYB2023013) , Innovation and Entrepreneurship Training Program for Guizhou University of Traditional Chinese Medicine Students ( (2023) 21) , Guizhou provincial basic research program (natural science) (no. ZK [2024] General 416) , Guizhou University of Traditional Chinese Medicine National and Provincial Science and Technology Innovation Talent Team Cultivation Project (Guizhou University of Traditional Chinese Medicine TD NO. [2022] 004) , Guizhou University of Traditional Chinese Medicine (Guikehe Academic New Miao [2023-36] ) , Guizhou Provincial Basic Research Program (Natural Science) (no. Qiankehe Basics-ZK [2023] General 412) . 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We developed a pHtriggered colonic targeted delivery nano system utilizing natural polymers, including chitosan (CS), hyaluronic acid (HA), and calcium alginate (ALG), encapsulating the active component shikonin (SK) to structure SKloaded ALG/HA/CS delivery nano system (SK@LAS). The oral administration of SK@LAS specifically delivered SK in the colon via pH sensitivity and colonic targeting. SK@LAS was internalized by CD44 receptormediated endocytosis into macrophages. Furthermore, significant therapeutic effects of SK@LAS were observed in acute and chronic mouse colitis models, including reduced pro-inflammatory cytokines and mediators, increased expression of anti-inflammatory cytokines, and suppression of M1 polarization. Furthermore, SK@LAS upregulated the expression of tight junction proteins, thereby restoring intestinal barrier function. This colonic targeted delivery nano system exhibits promise as an oral drug delivery approach for the treatment of IBD. C1 [Yao, Min; Ren, Mengjiao; Ding, Wenxing; Li, Xiang; Chen, You; Chen, Yang; Fu, Xiuzhi; Zheng, Shulei; Ma, Ying; Zou, Jiafeng; Gao, Feng] East China Univ Sci & Technol, Shanghai Frontier Sci Ctr Optogenet Tech Cell Meta, Sch Pharm, 130 Meilong Rd, Shanghai 200237, Peoples R China. [Zou, Jiafeng; Gao, Feng] East China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China. [Zou, Jiafeng; Gao, Feng] East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China. [Gao, Feng] East China Univ Sci & Technol, Optogenet & Synthet Biol Interdisciplinary Res Ctr, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China. C3 East China University of Science & Technology; East China University of Science & Technology; East China University of Science & Technology; East China University of Science & Technology RP Gao, F (corresponding author), East China Univ Sci & Technol, Shanghai Frontier Sci Ctr Optogenet Tech Cell Meta, Sch Pharm, 130 Meilong Rd, Shanghai 200237, Peoples R China. EM fgao@ecust.edu.cn RI Zou, Jiafeng/PCR-7015-2025 OI Zou, Jiafeng/0000-0001-5703-1797 FU East China University of Science and Technology; Development Program of China [2019YFA0904800]; Nature Science Foundation of China [32030065, 31722033, 92049304]; Shanghai Sailing Program [21YF1410300]; Science and Technology Commission of Shanghai Municipality [10DZ2220500]; Shanghai Committee of Science and Technology [11DZ2260600]; Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism [03-28] FX We thank Prof. Yuzheng Zhao (East China University of Science and Technology) for the invaluable assistance of funding and equipment in this research. This work was supported by grants from the Development Program of China (Grant No. 2019YFA0904800 to Y.Z. and F.G.), National Nature Science Foundation of China (Grant Nos. 32030065, 31722033, and 92049304 to Y.Z. and F.G.), Shanghai Sailing Program (Grant No. 21YF1410300 to F.G.), Science and Technology Commission of Shanghai Municipality (Grant No. 10DZ2220500 to F.G.), the Shanghai Committee of Science and Technology (Grant No. 11DZ2260600 to F.G.), Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission, Grant 2021 Sci & Tech 03-28 to Y.Z. and F.G.) . 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PD DEC PY 2024 VL 102 AR 106336 DI 10.1016/j.jddst.2024.106336 EA NOV 2024 PN B PG 14 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA M7K9M UT WOS:001359295900001 OA hybrid DA 2026-03-26 ER PT J AU Chen, JY Zou, PJ Quan, L Gong, CC Fang, ZY Lin, B Lang, JY Chen, MH AF Chen, Junyang Zou, Pingjin Quan, Li Gong, Cuicui Fang, Zengyi Lin, Bing Lang, Jinyi Chen, Meihua TI Huaxian formula prevents the progression of radiation-induced pulmonary fibrosis by inhibiting the pro-fibrotic effects of macrophages SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Radiation induced pulmonary fibrosis; Huaxian formula; Macrophage; Fibroblast; Arginase1 ID LUNG INJURY; TGF-BETA; MECHANISMS; ACID AB Ethnopharmacological relevance: The Huaxian formula (HXF), a traditional Chinese medicine (TCM) remedy, specifically targets the pathological factors of "heat toxicity" and "phlegm stasis" induced by radiation in radiation-induced pulmonary fibrosis (RIPF). It works by clearing heat and invigorating the blood, addressing these key factors in the development of RIPF. Aim of the study: The HXF has demonstrated potential in preventing RIPF, although its underlying mechanisms remain unclear. This study aims to investigate the efficacy, molecular targets, and mechanisms of action of HXF. Materials and methods: The major constituents of the HXF were identified by ultra performance liquid chromatography and tandem mass spectrometry (UPLC-MS). C57BL/6j mice were divided into four groups: control (Ctrl), HXF alone (HXF), 17Gy-irradiation alone (IR), and irradiation plus HXF (IR + HXF). Lung damage and fibrosis were assessed by histopathological staining, and the flow cytometry and immunohistochemistry (IHC) were used to detect the macrophages phenotype of lung tissues in vivo at 16 weeks post-irradiation. Transcriptomic sequencing and bioinformatics analyses identified key genes modulated by HXF. In vitro assays included flow cytometry, western bolt, and quantitative PCR (qPCR) explored the impact of HXF on macrophage polarization and fibrotic activity, while co-culture experiments of the macrophage conditional medium and mouse embryo fibroblast NIH/3T3 investigated macrophage-fibroblast interactions. Results: 20 major constituents of HXF were identified. And the in vivo results revealed significant lung damage and fibrosis in the IR group, which were notably mitigated in the IR + HXF group. And HXF has been shown to significantly inhibit the infiltration of M2-type macrophages in lung tissues. Transcriptomic analysis identified differentially expressed genes (DEGs) such as Arg1, Mmp10, and Fgf23. Bioinformatics enrichment analysis indicated that these DEGs are involved in pathways related to the inhibition of extracellular matrix formation and inflammation. In vitro, HXF-containing serum reduced M2-type macrophage polarization and decreased the secretion of Arginase1 and TGF beta 1. Conditioned medium from HXF-treated macrophages suppressed fibroblast activation. Conclusion: HXF's preventive effects on RIPF involve multiple targets and mechanisms, including the modulation of Arg1, Mmp10, and Fgf23 expression. By inhibiting the pro-fibrotic capacity of macrophages, HXF suppresses fibroblast activation and collagen production, thereby alleviating lung fibrosis. These findings underscore the potential of HXF as a preventive strategy in managing RIPF. C1 [Chen, Junyang; Zou, Pingjin; Lang, Jinyi; Chen, Meihua] Univ Elect Sci & Technol China, Dept Radiat Oncol, Radiat Oncol Key Lab Sichuan Prov,Affiliated Canc, Sichuan Clin Res Ctr Canc,Sichuan Canc Hosp & Inst, Chengdu 610041, Peoples R China. [Quan, Li; Gong, Cuicui; Lin, Bing] Chengdu Univ Tradit Chinese Med, Chengdu 610032, Peoples R China. [Fang, Zengyi] Univ Elect Sci & Technol China, Sch Med, Chengdu 610054, Peoples R China. [Lang, Jinyi] Chengdu Univ Tradit Chinese Med, Inst Integrated Tradit Chinese & Western Med Canc, Chengdu 610032, Peoples R China. C3 University of Electronic Science & Technology of China; Chengdu University of Traditional Chinese Medicine; University of Electronic Science & Technology of China; Chengdu University of Traditional Chinese Medicine RP Lang, JY; Chen, MH (corresponding author), Univ Elect Sci & Technol China, Dept Radiat Oncol, Radiat Oncol Key Lab Sichuan Prov,Affiliated Canc, Sichuan Clin Res Ctr Canc,Sichuan Canc Hosp & Inst, Chengdu 610041, Peoples R China.; Lin, B (corresponding author), Chengdu Univ Tradit Chinese Med, Chengdu 610032, Peoples R China. EM linbingkeyan@gmail.com; langjy610@163.com; chenmeihua@scszlyy.org.cn RI Zou, Pingjin/KHV-2360-2024; Chen, Meihua/AAY-9585-2020 OI Chen, Meihua/0000-0003-2813-7423 FU Health Commission of Sichuan Province [ZH2023-801, 2024-803]; Chengdu Technology Bureau [2024-YF05-02230-SN]; Special Project of Clinical Medical Research Center of Affiliated Hospital of Chengdu University of Traditional Chinese Medicine [23LC05] FX This work was supported by the Health Commission of Sichuan Province (ZH2023-801, 2024-803) ; the Chengdu Technology Bureau (2024-YF05-02230-SN) ; and the Special Project of Clinical Medical Research Center of Affiliated Hospital of Chengdu University of Tradi-tional Chinese Medicine (23LC05) . 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Ethnopharmacol. PD FEB 10 PY 2025 VL 338 AR 119026 DI 10.1016/j.jep.2024.119026 EA NOV 2024 PN 2 PG 12 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA M7I1E UT WOS:001359222000001 PM 39515679 OA hybrid DA 2026-03-26 ER PT J AU Geng, XD Fu, ZN Geng, GR Chi, K Liu, C Hong, HJ Cai, GY Chen, XM Hong, Q AF Geng, Xiaodong Fu, Zhangning Geng, Guangrui Chi, Kun Liu, Chao Hong, Haijuan Cai, Guangyan Chen, Xiangmei Hong, Quan TI Astilbin improves the therapeutic effects of mesenchymal stem cells in AKI-CKD mice by regulating macrophage polarization through PTGS2-mediated pathway SO STEM CELL RESEARCH & THERAPY LA English DT Article DE Astilbin; Mesenchymal stem cells; Macrophage polarization; AKI-CKD; PGE2 ID INJURY; OPTIMIZATION AB BackgroundAlthough mesenchymal stem cells (MSCs) have been proven to be appropriate candidates for the treatment of AKI-CKD, their efficacy is limited and variable. Astilbin (AST) had a protective effect on MSCs from oxidative stress via ROS-scavenging, however, whether it can improve MSCs' renoprotection and the underlying mechanism need to be elucidated.MethodsAST-pretreated MSCs were administered intravenously into the ischemia-reperfusion injury mice models and the renal function, pathological changes and inflammation. Were evaluated. In addition, DARTS, molecular docking, surface plasma resonance(SPR), dual-luciferase reporter gene assay and the ChIP-PCR were utilized to explore the potential signaling pathways through which AST exert renal protective effects on MSCs.ResultsAST-pretreated MSCs markedly improved kidney function, reduced kidney pathological injury and inflammation in AKI and AKI-CKD mice. RNA-seq results showed that PTGS2 related pathway was significantly up-regulated in MSCs after AST pretreatment. DARTS assay, molecular docking and SPR assay revealed that AST could bind with the transcriptional factor of Kruppel-Like Factor 4(KLF4) protein. The promoter of PTGS2 had the binding and transcriptional activation by KLF4. Furthermore, AST pretreatment promoted the secretion of PGE2 in MSCs. And then the westren blot results showed that the protein levels of CD163 and CD206 were upregulated after coculture in AST-pretreated MSCs, indicating that the polarization of RAW264.7 cells towards M2-like macrophages was induced. Knockdown of PTGS2 reversed the ability of AST-pretreated MSCs in converting macrophages to M2 phenotype and reducing their therapeutic effects on AKI-CKD mice.ConclusionAST pretreatment enhances the efficacy of MSCs on AKI and AKI-CKD mice by inducing of M2-like phenotype polarization in macrophages through the PTGS2-mediated pathway. This approach not only provides a novel strategy to strengthen the capability of MSCs but also helps elucidate the beneficial effects of the Chinese herbal medicine AST. C1 [Geng, Xiaodong; Fu, Zhangning; Geng, Guangrui; Chi, Kun; Cai, Guangyan; Chen, Xiangmei; Hong, Quan] Chinese Peoples Liberat Army Gen Hosp, Nephrol Inst Chinese PLA, Natl Clin Res Ctr Kidney Dis,Beijing Key Lab Kidne, State Key Lab Kidney Dis,Dept Nephrol,Med Ctr 1, Beijing 100853, Peoples R China. [Fu, Zhangning; Geng, Guangrui; Chi, Kun; Cai, Guangyan; Chen, Xiangmei; Hong, Quan] Med Sch Chinese PLA, Beijing 100853, Peoples R China. [Geng, Xiaodong] Cent Mil Commiss, Hlth Care Off Serv Bur, Agcy Off Adm, Beijing 100034, Peoples R China. [Geng, Guangrui] 920th Hosp Joint Logist Support Force Chinese PLA, Dept Crit Care Med, Kunming 650032, Yunnan, Peoples R China. [Liu, Chao] Chinese Peoples Liberat Army Gen Hosp, Med Ctr 1, Dept Crit Care Med, Beijing 100853, Peoples R China. [Hong, Haijuan] Shanghai Songjiang Dist Cent Hosp, Dept Nephrol, Shanghai 201600, Peoples R China. C3 Chinese People's Liberation Army General Hospital; Chinese People's Liberation Army General Hospital; Chinese People's Liberation Army General Hospital RP Hong, Q (corresponding author), Chinese Peoples Liberat Army Gen Hosp, Nephrol Inst Chinese PLA, Natl Clin Res Ctr Kidney Dis,Beijing Key Lab Kidne, State Key Lab Kidney Dis,Dept Nephrol,Med Ctr 1, Beijing 100853, Peoples R China.; Hong, Q (corresponding author), Med Sch Chinese PLA, Beijing 100853, Peoples R China. EM hongquan@301hospital.com.cn RI cai, gy/OBN-9224-2025 FU National Natural Science Foundation of China FX The authors declare that they have not used Artificial Intelligence in this study. 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PD NOV 14 PY 2024 VL 15 IS 1 AR 427 DI 10.1186/s13287-024-04025-3 PG 14 WC Cell & Tissue Engineering; Cell Biology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology; Research & Experimental Medicine GA M2H5Z UT WOS:001355802500002 PM 39543734 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhu, YF Liu, C Wang, YD Xu, J Ma, J Zhang, H Zhang, PC Zhang, DW Xia, LM Song, H Huo, XX AF Zhu, Yong-fu Liu, Chang Wang, Ya-dong Xu, Jing Ma, Jia Zhang, Hao Zhang, Peng-cheng Zhang, Dong-wei Xia, Li-ming Song, Hang Huo, Xing-xing TI Mechanistic insights into traditional Chinese medicine for digestive tract cancers: implications for gastric, hepatic, esophageal, intestinal, and pancreatic tumors SO ONCOLOGIE LA English DT Review DE Chinese medicine; Chinese medicine compound; natural products; digestive tract; anti-tumor; mechanism ID COLON-CANCER; LIVER-CANCER; MACROPHAGE POLARIZATION; NETWORK PHARMACOLOGY; CELL PROLIFERATION; MOUSE MODEL; TGF-BETA; IN-VITRO; GROWTH; APOPTOSIS AB The increasing incidence of cancer-related deaths highlights the pressing need for effective treatment modalities, particularly in the context of digestive tract cancers, such as gastric, hepatic, esophageal, intestinal, and pancreatic tumors. While conventional drug therapies play a critical role in managing these malignancies, their associated side effects often pose significant challenges to patient quality of life. Thus, there is a growing focus on traditional Chinese medicine (TCM) and its compounds, which are safe, non-toxic, and reliable. During anti-tumor therapy, TCM compounds, based on their multi-target, multi-pathway, and multi-level regulatory effects, fully mobilize multiple mechanisms of the body, presenting significant advantages in inhibiting tumor development, boosting patient welfare, and increasing their lifespan. This article reviews the mechanisms by which TCM inhibits tumor cell proliferation, promotes tumor cell death, suppresses tumor cell invasion and metastasis, regulates the tumor microenvironment, inhibits angiogenesis, and enhances anti-tumor drug resistance. This knowledge might provide a theoretical and scientific basis for preventing and treating tumors using TCM. C1 [Zhu, Yong-fu; Zhang, Dong-wei; Xia, Li-ming] Anhui Univ Chinese Med, Affiliated Hosp 1, Dept Oncol, Hefei, Peoples R China. [Zhu, Yong-fu] Anhui Univ Chinese Med, Guo jun Hu Inheritance Talent Training Off, Affiliated Hosp 1, Hefei, Peoples R China. [Liu, Chang; Xu, Jing; Ma, Jia; Zhang, Hao] Anhui Univ Chinese Med, Clin Med Coll 1, Hefei, Peoples R China. [Wang, Ya-dong; Song, Hang] Anhui Univ Chinese Med, Sch Integrated Chinese & Western Med, Hefei, Peoples R China. [Zhang, Peng-cheng] Zhejiang Chinese Med Univ, Dept Oncol, Affiliated Hosp 1, Hangzhou, Peoples R China. [Huo, Xing-xing] Anhui Univ Chinese Med, Expt Ctr Clin Res, Sci Res Dept, Affiliated Hosp 1, Hefei, Peoples R China. C3 Anhui University of Chinese Medicine; Anhui University of Chinese Medicine; Anhui University of Chinese Medicine; Anhui University of Chinese Medicine; Zhejiang Chinese Medical University; Anhui University of Chinese Medicine RP Song, H (corresponding author), Anhui Univ Chinese Med, Sch Integrated Chinese & Western Med, Hefei, Peoples R China.; Huo, XX (corresponding author), Anhui Univ Chinese Med, Expt Ctr Clin Res, Sci Res Dept, Affiliated Hosp 1, Hefei, Peoples R China. EM zyf240@ahtcm.edu.cn; liuchang8073@163.com; wangyadong4925@sina.com; tojingxu@163.com; majia960222@163.com; zhanghao152534@163.com; zpc9503068131@163.com; 13866777039@163.com; limx123@sina.com; hangsong@ahtcm.edu.cn; hxx0520@ahtcm.edu.cn RI ; zhang, dongwei/GWU-7896-2022 OI Zhu, Yongfu/0000-0002-8158-4102; FU Horizontal scientific research Project FX We thank all authors who prepared, wrote, reviewed, and edited the entire manuscript. 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The advent of immune checkpoint inhibitors (ICIs) has marked a breakthrough in non-small cell lung cancer (NSCLC) treatment. However, a significant subset of patients exhibits primary or acquired resistance to anti-PD-1/PD-L1 therapies, necessitating the development of novel combination strategies to enhance therapeutic efficacy and overcome resistance. Purpose: This study aimed to explore the anti-tumor efficacy of liposomal honokiol (Lipo-HNK) and elucidate the synergistic effects of Lipo-HNK and ICIs on NSCLC. Methods: The effects of Lipo-HNK on cell proliferation and apoptosis were assessed in human lung cancer cell lines H460 and A549, and mouse Lewis lung cancer cell line (LL2). A murine lung cancer model was established by injecting LL2 cells via the tail vein to evaluate the therapeutic effects of Lipo-HNK and ICIs. Tumor microenvironment features were characterized using immunofluorescence and flow cytometry. Primary macrophages were extracted from mouse bone marrow for mechanistic studies. High-throughput sequencing and bioinformatics analyses of Lipo-HNK-treated macrophages were conducted to identify key signaling pathways, which were subsequently confirmed by Western blotting and inhibitor blockade. Results: Lipo-HNK, with enhanced solubility and bioavailability, demonstrated potent cytotoxicity against NSCLC cell lines. In the murine lung cancer model, Lipo-HNK exhibited synergistic anti-cancer effects when combined with anti-PD-1 therapy. Immunofluorescence and flow cytometry analyses revealed that Lipo-HNK significantly reduced the infiltration of myeloid-derived suppressor cells (MDSCs) and M2 macrophages (CD206+). Macrophage depletion experiment showed the anti-tumor effects of Lipo-HNK was macrophage-dependent. M2 macrophages induced by tumor-conditioned medium (TCM) or interleukin-4 (IL-4) released immunosuppressive cytokines such as IL-10, Arg-1, and TGF-beta. RNA sequencing analyses showed that Lipo-HNK effectively inhibited the PI3K/Akt signaling pathway, blocking macrophage polarization to the M2 type. Furthermore, the combination of Lipo-HNK and anti-PD-1 therapy led to increased CD8+ T-cell infiltration and activation, enhancing the overall anti-tumor immune response. Conclusion: This study validated the anti-tumor efficacy of Lipo-HNK against NSCLC. Lipo-HNK reduced the infiltration of MDSCs and M2 macrophages by inhibiting the PI3K/Akt pathway and enhanced the therapeutic effects of ICIs. These findings provide evidence and new insights into Lipo-HNK as a promising anti-cancer drug for NSCLC treatment, highlighting its potential to overcome resistance to current ICI therapies. C1 [Cheng, Yuan; Han, Xuejiao; Wei, Xiawei] Sichuan Univ, State Key Lab Biotherapy & Canc Ctr, Lab Aging Res & Canc Drug Target, Natl Clin Res Ctr Geriatr,West China Hosp,Dept Bio, 17,Block 3,Southern Renmin Rd, Chengdu 610041, Sichuan, Peoples R China. [Lai, Xintian] Chengdu Jinrui Fdn Biotech Co Ltd, Chengdu 610041, Sichuan, Peoples R China. C3 Sichuan University RP Wei, XW (corresponding author), Sichuan Univ, State Key Lab Biotherapy & Canc Ctr, Lab Aging Res & Canc Drug Target, Natl Clin Res Ctr Geriatr,West China Hosp,Dept Bio, 17,Block 3,Southern Renmin Rd, Chengdu 610041, Sichuan, Peoples R China. EM xiaweiwei@scu.edu.cn RI Hong, Weiqi/LKK-3400-2024 FU National Natural Science Foundation of China [82102896]; Natural Science Foundation of Sichuan Province [2024NSFSC1883]; Post-Doctor Research Project, West China Hospital, Sichuan University [2024SCU12022]; Post-doctor Research Fund of West China Hospital, Sichuan University [2024HXBH055] FX This work was supported by the National Natural Science Foundation of China (82102896), Natural Science Foundation of Sichuan Province (2024NSFSC1883), Post-Doctor Research Project, West China Hospital, Sichuan University (2024SCU12022), and Post-doctor Research Fund of West China Hospital, Sichuan University (2024HXBH055). 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Altalbawy, Farag M. A. Kumar, M. Ravi Chahar, Mamata Singh, Manmeet Kubaev, Aziz Alamir, Hassan Thoulfikar A. Mohammed, Faraj Kadhim, Abed J. Alhadrawi, Merwa TI Phytochemicals and Their Nanoformulations for Targeting Hepatocellular Carcinoma: Exploring Potential and Targeting Strategies SO CELL BIOCHEMISTRY AND FUNCTION LA English DT Review DE hepatocellular carcinoma (HCC); immune system; nanoparticles; phytochemicals; tumor stroma ID CANCER-ASSOCIATED FIBROBLASTS; T-CELL; EXTRACELLULAR-MATRIX; LIVER-CANCER; MACROPHAGE POLARIZATION; TUMOR MICROENVIRONMENT; ANTICANCER ACTIVITY; SUPPRESSOR-CELLS; IMMUNE-SYSTEM; NK CELLS AB Hepatocellular carcinoma (HCC) continues to pose a global health concern, necessitating the exploration of innovative therapeutic approaches. In the recent decade, targeting tumor stroma consisting of extracellular matrix (ECM), immune cells, vascular system, hypoxia, and also suppressive mechanisms in HCC has attracted interest in repressing tumor growth and metastasis. Phytochemicals have attained considerable attention because of their manifold biological effects and high capacity for anticancer activities. These chemical agents have shown the capability to modulate different cells and secretions within the stroma of malignancies. In recent years, the development of nanoformulations has further enhanced the therapeutic potential of phytochemicals by improving their solubility, bioavailability, and targeted delivery to tumor tissues. This review aims to provide an encyclopedic overview of the potential of phytochemicals and their nanoformulations as promising therapeutic strategies for targeting HCC. The review initially highlights the broad array of phytochemicals exhibiting potent anticancer properties, including flavonoids, alkaloids, terpenoids, and phenolic compounds, among others. Then, the nanoformulations and modification of these agents will be reviewed. Finally, we will review the latest experiments that have examined the modulation of HCC using adjuvant phytochemicals and their nanoformulations. C1 [Rab, Safia Obaidur] King Khalid Univ, Cent Labs, Abha, Al Quraa, Saudi Arabia. [Rab, Safia Obaidur] King Khalid Univ, Coll Appl Med Sci, Dept Clin Lab Sci, Abha, Saudi Arabia. [Roopashree, R.] JAIN Univ, Sch Sci, Dept Chem & Biochem, Bangalore, Karnataka, India. [Altalbawy, Farag M. A.] Univ Tabuk, Univ Coll Duba, Dept Chem, Tabuk, Saudi Arabia. [Kumar, M. Ravi] Raghu Engn Coll, Dept Chem, Visakhapatnam, Andhra Pradesh, India. [Chahar, Mamata] NIMS Univ Rajasthan, NIMS Inst Engn & Technol, Dept Chem, Jaipur, Rajasthan, India. [Singh, Manmeet] Chandigarh Engn Coll, Chandigarh Grp Coll Jhanjeri, Dept Appl Sci, Mohali, Punjab, India. [Kubaev, Aziz] Samarkand State Med Univ, Dept Maxillofacial Surg, Samarkand, Uzbekistan. [Alamir, Hassan Thoulfikar A.] Univ Al Ameed, Fac Pharm, Dept Pharmaceut, Karbala, Iraq. [Mohammed, Faraj] Al Manara Coll Med Sci, Dept Pharm, Amarah, Maysan, Iraq. [Kadhim, Abed J.] AL Nisour Univ Coll, Dept Med Engn, Baghdad, Iraq. [Alhadrawi, Merwa] Islamic Univ, Coll Tech Engn, Najaf, Iraq. [Alhadrawi, Merwa] Islamic Univ Al Diwaniyah, Coll Tech Engn, Al Diwaniyah, Iraq. [Alhadrawi, Merwa] Islamic Univ Babylon, Coll Tech Engn, Babylon, Iraq. C3 King Khalid University; King Khalid University; Jain University; University of Tabuk; Samarkand State Medical University; University of Al-Ameed; University of Manara; Al-Nisour University College; Islamic University College; Islamic University College; University of Babylon RP Altalbawy, FMA (corresponding author), Univ Tabuk, Univ Coll Duba, Dept Chem, Tabuk, Saudi Arabia. EM f_altalbawy@yahoo.com RI ; Altalbawy, Farag/GXA-0022-2022; Shree, Roopa/JRX-0730-2023; Rab, Safia/PKR-6143-2026; Alhadrawi, Merwa/NJR-2956-2025 OI Singh, Manmeet/0009-0006-2630-2199; Altalbawy, Farag/0000-0003-2708-9159; Kubaev, Aziz/0000-0001-5110-668X; FU This study was supported by King Khalid University.; University Higher Education Fund [CL/CO/B/5]; Central labs at King Khalid University FX The authors extend their appreciation to University Higher Education Fund for funding this research work under Research Support Program for Central labs at King Khalid University through the project number CL/CO/B/5. 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184 TC 6 Z9 7 U1 1 U2 4 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0263-6484 EI 1099-0844 J9 CELL BIOCHEM FUNCT JI Cell Biochem. Funct. PD NOV 9 PY 2024 VL 42 IS 8 AR e70013 DI 10.1002/cbf.70013 PG 17 WC Biochemistry & Molecular Biology; Cell Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Cell Biology GA O1G6Q UT WOS:001368700300001 PM 39521962 OA Bronze DA 2026-03-26 ER PT J AU Zhang, LN Li, JW Kou, YS Shen, LF Wang, H Wang, YY Ma, RL Wu, T Yang, X Gu, YH Yi, L AF Zhang, LingNa Li, JiaWei Kou, YuShun Shen, LuFan Wang, Hong Wang, YiYuan Ma, Ruiling Wu, Tao Yang, Xin Gu, YuanHui Yi, Lin TI Mechanisms and treatment of atherosclerosis: focus on macrophages SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE atherosclerosis; polarization of M1/M2 macrophages; targeted macrophage therapy; formation of atherosclerosis; source of macrophages ID ATTENUATES ATHEROSCLEROSIS; POLARIZATION; METABOLISM; INFLAMMATION AB Macrophages are the basic mediators and coordinators of various types of chronic inflammation and play a crucial role in the formation and development of atherosclerosis (AS). In the complex microenvironment of atherosclerotic plaques, macrophages of different sources are exposed to different signal stimuli and thus polarized into various subpopulations. Various types of macrophages with predominantly M1 and M2 phenotypes also play different regulatory roles in the initiation and progression of AS. Lipid-lowering drugs, mainly statins, are widely used in clinical practice, but the adverse reactions are obvious and there is a lack of personalized treatment. Emerging targeted macrophage and Traditional Chinese medicine (TCM)-related therapies can regulate the cellular microenvironment, inhibit the polarization of M1 macrophages, and promote the activation of M2 macrophages, providing new ideas for the prevention and treatment of AS. C1 [Zhang, LingNa; Li, JiaWei; Kou, YuShun; Shen, LuFan; Wang, Hong; Wang, YiYuan; Ma, Ruiling; Wu, Tao; Yi, Lin] Gansu Univ Chinese Med, Sch Tradit Chinese & Western Med, Lanzhou, Gansu, Peoples R China. [Wu, Tao; Gu, YuanHui] Gansu Prov Hosp, Dept Gen Surg, Lanzhou, Gansu, Peoples R China. [Yang, Xin] Gansu Univ Chinese Med, Sch Clin Med 1, Lanzhou, Gansu, Peoples R China. [Yi, Lin] Gansu Univ Tradit Chinese Med, Chron Dis Lab, Lanzhou, Gansu, Peoples R China. C3 Gansu University of Chinese Medicine; Gansu University of Chinese Medicine; Gansu University of Chinese Medicine RP Yi, L (corresponding author), Gansu Univ Chinese Med, Sch Tradit Chinese & Western Med, Lanzhou, Gansu, Peoples R China.; Gu, YH (corresponding author), Gansu Prov Hosp, Dept Gen Surg, Lanzhou, Gansu, Peoples R China.; Yi, L (corresponding author), Gansu Univ Tradit Chinese Med, Chron Dis Lab, Lanzhou, Gansu, Peoples R China. EM guyuanh@163.com; yilin@gszy.edu.cn FU National Natural Science Foundation of China [82160842]; Traditional Chinese Medicine scientific research Project in Gansu Province [GZKP-2022-40]; Open Subjects of Dunhuang Medicine in the Key Laboratory of Translation of the Ministry of Education [DHYX23-07]; General Program of the Joint Scientific Research Fund [23JRRA1521]; Youth Science and Technology Fund Program of Gansu Province [21JR7RA643]; Gansu Provincial People's Hospital youth training project [20GSSY4-22] FX The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the National Natural Science Foundation of China, No. 82160842; Traditional Chinese Medicine scientific research Project in Gansu Province in 2023, No. GZKP-2022-40; Open Subjects of Dunhuang Medicine in the Key Laboratory of Translation of the Ministry of Education, No. DHYX23-07; General Program of the Joint Scientific Research Fund, No. 23JRRA1521; Youth Science and Technology Fund Program of Gansu Province, NO. 21JR7RA643; Gansu Provincial People's Hospital youth training project, NO. 20GSSY4-22. 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Immunol. PD NOV 6 PY 2024 VL 15 AR 1490387 DI 10.3389/fimmu.2024.1490387 PG 16 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA M5P4L UT WOS:001358052600001 PM 39569201 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Tang, XJ He, M Ren, Y Ji, M Yan, XQ Zeng, W Lv, Y Li, YM He, YH AF Tang, Xiaojuan He, Min Ren, Yuan Ji, Meng Yan, Xiaoqi Zeng, Wen Lv, Yuan Li, Yongmin He, Yongheng TI Traditional Chinese Medicine formulas-based interventions on colorectal carcinoma prevention: The efficacies, mechanisms and advantages SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Intestinal precancerous lesions; Traditional Chinese medicine formulas; Herbal pairs; Herbal plant-derived nanoparticles; Mechanism ID INFLAMMATORY-BOWEL-DISEASE; INDUCED ULCERATIVE-COLITIS; INTESTINAL FLORA; GUT MICROBIOTA; DECOCTION; CANCER; CELLS; CHEMOPREVENTION; CARCINOGENESIS; TARGETS AB Ethnopharmacological relevance: The Traditional Chinese Medicine Formulas (TCMFs) represent a distinctive medical approach to disease treatment and have been utilized in clinical practice for treating intestinal diseases for thousands of years. Recently, TCMFs have received increasing attention due to their advantages of high efficiency, safety, as well as low toxicity, providing promising strategies for preventing colorectal carcinoma (CRC). Nonetheless, the potential mechanism of TCMFs in preventing CRC has not been fully elucidated. Aim of the study: The literature from the past three years was reviewed to highlight the therapeutic effects and underlying mechanisms of TCMFs in preventing CRC. Materials and methods: The keywords have been searched, including "traditional Chinese medicine formulas," "herb pairs," "Herbal plant-derived nanoparticles," et al. in "PubMed" and "China National Knowledge Infrastructure (CNKI)," and screened published articles related to the treatment of intestinal precancerous lesions. This review primarily examined the effectiveness and mechanisms of TCMFs in treating intestinal precancerous lesions, highlighting their significant potential in preventing CRC. Results: Gegen Qinlian decoction, Shaoyao decoction, Wu Wei Wan, etc., exert substantial therapeutic effects on intestinal precancerous lesions. These therapeutic effects are demonstrated by a reduction in disease activity index scores, suppression of intestinal inflammation, and preservation of body weight and intestinal function, all of which contribute to the effective prevention of CRC. Besides, the classic Chinese herbal pairs and the extra- cellular vesicle-like nanoparticles of herbaceous plants have demonstrated superior efficacy in the treatment of intestinal precancerous lesions. Mechanistically, protecting the epithelial barrier, regulating gut microbiota as well as related metabolism, modulating macrophage polarization, and maintaining immune balance contribute to the role of TCMFs in CRC prevention. Conclusions: This review demonstrates the great potential and mechanism of TCMFs in CRC prevention and provides a scientific basis for their utilization in CRC prevention. C1 [Tang, Xiaojuan] Hunan Univ, Sch Biomed Sci, Changsha 410012, Hunan, Peoples R China. [Tang, Xiaojuan; Yan, Xiaoqi; Lv, Yuan; Li, Yongmin; He, Yongheng] Hunan Acad Tradit Chinese Med, Affiliated Hosp, Hunan Prov Hosp Integrated Tradit Chinese & Wester, Changsha 410006, Hunan, Peoples R China. [Tang, Xiaojuan; Lv, Yuan; Li, Yongmin; He, Yongheng] Hunan Acad Chinese Med, Changsha 410006, Hunan, Peoples R China. [He, Min; Ren, Yuan; Ji, Meng; Zeng, Wen] Hunan Univ Chinese Med, Changsha 410208, Hunan, Peoples R China. C3 Hunan University; Hunan University of Chinese Medicine; Hunan University of Chinese Medicine RP Tang, XJ (corresponding author), Hunan Univ, Sch Biomed Sci, Changsha 410012, Hunan, Peoples R China.; Tang, XJ; He, YH (corresponding author), Hunan Acad Tradit Chinese Med, Affiliated Hosp, Hunan Prov Hosp Integrated Tradit Chinese & Wester, Changsha 410006, Hunan, Peoples R China. EM txj19920112@outlook.com; He13517401858@163.com FU Natural Science Foundation of Hunan province of China [2024JJ6286]; National Natural Science Foundation of China [82374462]; Research Project of Hunan Provincial Administration of Traditional Chinese Medicine [D2023014, B2024031] FX The current work funded by the Natural Science Foundation of Hunan province of China (2024JJ6286) , National Natural Science Foundation of China (82374462) , Research Project of Hunan Provincial Administration of Traditional Chinese Medicine (D2023014, B2024031) . 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ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-8741 EI 1872-7573 J9 J ETHNOPHARMACOL JI J. Ethnopharmacol. PD JAN 30 PY 2025 VL 337 AR 119008 DI 10.1016/j.jep.2024.119008 EA NOV 2024 PN 3 PG 25 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA L4I8L UT WOS:001350380400001 PM 39471879 OA hybrid DA 2026-03-26 ER PT J AU Yu, YM Mao, NN Yu, L Lin, FZ Shi, XF Lu, XQ Yang, Y Lu, Y Wang, DY AF Yu, Yaming Mao, Ningning Yu, Lin Lin, Fangzhu Shi, Xiaofeng Lu, Xuanqi Yang, Yang Lu, Yu Wang, Deyun TI YiMu-QingGong san alleviates lipopolysaccharide-induced endometritis in mice via inhibiting inflammation and oxidative stress through regulating macrophage polarization SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Macrophage polarization; Inflammation; Endometritis; NF-kappa B; Fibrosis; Uterine barrier ID PHYTOCHEMISTRY; INJURY AB Ethnopharmacological relevance: Endometritis is a common reproductive disease in dairy cattle after calving, characterized by persistent inflammation of the endometrium. YiMu-QingGong San (YMQGS), a patented Chinese medicine formulation, has demonstrated efficacy in the treatment of clinical endometritis in dairy cattle. However, the potential mechanisms by which YMQGS alleviates endometritis remain unclear. Aim of the study: The objective of this study is to elucidate the underlying therapeutic mechanisms of YMQGS in the context of endometritis. Materials and methods: The chemical components of YMQGS were analyzed using UHPLC/MS. The antiinflammatory capabilities of YMQGS were assessed by inducing an inflammatory response in RAW264.7 cells with lipopolysaccharide (LPS). Moreover, a clinical model of endometritis was simulated via vaginal injection of LPS into the uterine horns to investigate the therapeutic mechanisms of YMQGS. Results: YMQGS could downregulate the expression of inflammatory mediators (TNF-alpha, IL-6, IL-1 beta) by suppressing the activation of the TLRs/MyD88/TRAF6/NF-kappa B signaling pathway in RAW264.7 cells. Additionally, YMQGS facilitated the polarization of RAW264.7 cells towards M2-like macrophages (M phi s) while inhibiting M1like M phi s polarization, thereby exerting anti-inflammatory effects. Further investigation revealed that YMQGS could diminish ROS production, augment cellular antioxidant capacity, preserve mitochondrial membrane potential, and reduce intracellular [Ca2+]i accumulation, thereby minimizing cellular damage. In the mouse model of endometritis, YMQGS similarly inhibited the activation of the NF-kappa B signaling pathway in uterine tissues and modulated M phi polarization in the endometrium, leading to a decrease in the expression of inflammatory factors and subsidence of the inflammatory response in the endometrium. Histological staining results showed that YMQGS reduced endometrial fibrosis, increased the expression of endometrial ZO-1, Occludin and glycoprotein, protect the endometrial barrier function, and prevent the further development of endometritis. Conclusion: Collectively, the present study confirms that YMQGS possesses notable anti-inflammatory and antioxidant properties. The suppression of the NF-kappa B signaling pathway and the modulation of M phi polarization emerge as the pivotal mechanisms by which YMQGS alleviates endometritis. C1 [Yu, Yaming; Mao, Ningning; Yu, Lin; Lin, Fangzhu; Shi, Xiaofeng; Lu, Xuanqi; Yang, Yang; Wang, Deyun] Nanjing Agr Univ, Inst Tradit Chinese Vet Med, Coll Vet Med, Nanjing 210095, Peoples R China. [Yu, Yaming; Mao, Ningning; Yu, Lin; Lin, Fangzhu; Shi, Xiaofeng; Lu, Xuanqi; Yang, Yang; Wang, Deyun] Nanjing Agr Univ, Coll Vet Med, MOE Joint Int Res Lab Anim Hlth & Food Safety, Nanjing 210095, Peoples R China. [Lu, Yu] Jiangsu Acad Agr Sci, Inst Vet Immunol & Engn, Nanjing 210014, Peoples R China. C3 Nanjing Agricultural University; Nanjing Agricultural University; Jiangsu Academy of Agricultural Sciences RP Wang, DY (corresponding author), Nanjing Agr Univ, Inst Tradit Chinese Vet Med, Coll Vet Med, Nanjing 210095, Peoples R China. EM dywang@njau.edu.cn RI Shi, Xiao-Feng/G-8659-2014 FU National Key Research and Development Program [2022YFD1801103]; Fundamental Research Funds for the Central Universities [KYCXJC2023003]; National Natural Science Foundation of China [32373053]; China Postdoctoral Science Foundation [2022M721648]; Natural Science Foundation of Jiangsu Province [BK20221014]; Jiangsu Funding Program for Excellent Postdoctoral Talent [2022ZB320] FX Funding This work is funded by the National Key Research and Development Program (Grant No. 2022YFD1801103) , the Fundamental Research Funds for the Central Universities (Grant No. KYCXJC2023003) , the National Natural Science Foundation of China (Grant No. 32373053) , the China Postdoctoral Science Foundation (Grant No. 2022M721648) , the Natural Science Foundation of Jiangsu Province (Grant No. BK20221014) , the Jiangsu Funding Program for Excellent Postdoctoral Talent (Grant No. 2022ZB320) . 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Ethnopharmacol. PD JAN 30 PY 2025 VL 337 AR 118992 DI 10.1016/j.jep.2024.118992 EA OCT 2024 PN 3 PG 17 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA L1S3A UT WOS:001348584200001 PM 39454706 DA 2026-03-26 ER PT J AU Zhang, JX Hu, YX Liu, Y Chen, ZZ Zheng, JT Qu, XT Zhang, Y Tang, WY Huang, SC Liu, CS AF Zhang, Jia-Xuan Hu, Yin-Xia Liu, Yang Chen, Zi-Zhao Zheng, Jin-Ting Qu, Xuan-Tong Zhang, Yi Tang, Wen-Yin Huang, Si-Cong Liu, Chang-Shun TI Xianglian pill alleviates ulcerative colitis by inhibiting M1 macrophage polarization via modulation of energy metabolite itaconate SO PHYTOMEDICINE LA English DT Article DE Xianglian pill; Ulcerative colitis; M1 macrophage; Energy metabolism; Itaconate; Inflammatory response ID DEHYDROGENASE AB Background: Xianglian pill (XLP) is a traditional Chinese medicine (TCM) that is widely used to treat ulcerative colitis (UC). However, its mechanism of action in UC is unclear. Purpose: This study aimed to investigate the mechanism of action of XLP in treating UC and role of M1 macrophage polarization in this process. Study design: In vivo experiments were performed using UC mice while in vitro experiments were conducted using RAW264.7 cells. Methods: Mice were administered 3 % dextran sulfate to induce UC model and then treated with XLP. Changes in histopathology and pro-inflammatory cytokines were evaluated. The levels of M1 macrophages in mesenteric lymph nodes were detected by flow cytometry. Colon metabolite levels were analyzed using an energy metabolomic assay. To assess itaconate's impact, both in vivo (mice) and in vitro (RAW264.7 cells) models were employed. Immunofluorescence staining was used to measure the expression levels of TNF-alpha, IL-6, and iNOS, while qRT-PCR was utilized to quantify the mRNA levels of TET2, STAT1, and Nfkbiz. Results: XLP alleviated ulcerative damage and reduced TNF-alpha and IL-6 levels in colon, and also downregulated the levels of M1 macrophages and modulated the state of energy metabolism. Specifically, XLP significantly increased ITA level in colonic tissue and this increase was significantly associated with decreased levels of M1 macrophages and alleviation of UC following XLP treatment. Moreover, ITA directly suppressed the polarization of macrophage from M0 to M1 phenotype, accompanied by the decrease of TNF-alpha, IL-6, and iNOS levels. Further, ITA decreased inflammatory responses in M1 macrophage by inhibiting the TET2/STAT1 and TET2/NF-kappa B signaling pathways. Conclusion: XLP can treat UC by suppressing M1 macrophage polarization via increasing the level of energy metabolite ITA. C1 [Zhang, Jia-Xuan; Liu, Yang; Zheng, Jin-Ting; Qu, Xuan-Tong; Zhang, Yi; Tang, Wen-Yin; Liu, Chang-Shun] Southern Med Univ, Sch Tradit Chinese Med, Guangdong Prov Key Lab Chinese Med Pharmaceut, Guangzhou 510515, Peoples R China. [Zhang, Jia-Xuan; Liu, Yang; Liu, Chang-Shun] Guangdong Basic Res Ctr Excellence Integrated Trad, Guangzhou 510515, Peoples R China. [Hu, Yin-Xia] PLA Gen Hosp Southern Theater Command, Dept Gastroenterol, Guangzhou 510010, Peoples R China. [Chen, Zi-Zhao] Guangdong Pharmaceut Univ, Sch Clin Med, Guangzhou 510006, Peoples R China. [Huang, Si-Cong] Guangzhou Med Univ, Affiliated Hosp 2, Dept Clin Lab, Guangzhou 510260, Peoples R China. C3 Southern Medical University - China; Guangdong Pharmaceutical University; Guangzhou Medical University RP Liu, CS (corresponding author), 1023 South Shatai Rd, Guangzhou 510515, Guangdong, Peoples R China. EM lcshun1225@163.com RI ; Huang, Sicong/GQY-7544-2022 OI Liu, Yang/0000-0001-5079-8813; changshun, liu/0000-0003-2841-1795; FU National Natural Science Founda-tion of China [82104729]; Guangdong Medical Science and Tech-nology Research Fund Project [B2023049] FX The authors have no relevant interests to disclose. The authors have no conflicts of interest to declare that are relevant to the content of this article. This study was supported by the National Natural Science Founda-tion of China (82104729) and Guangdong Medical Science and Tech-nology Research Fund Project (B2023049) . 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However, the specific mechanism underlying the therapeutic effects of SYD on UC is not clear. Aim of study: In this study, we demonstrated the therapeutic effect of SYD on the polarization of M1 macrophages and elucidated the underlying mechanism. Materials and methods: UC mice were induced with 3% DSS for one week and subsequently treated with SYD for another week. The composition of SYD was determined by HPLC. To assess the therapeutic efficacy of SYD, key parameters, including body weight changes, DAI scores, colon length, and histological alterations in colonic tissues, were monitored. ELISA was performed to quantify inflammatory cytokines, while Western blotting and immunofluorescence analyses were performed to quantify tight junction protein expression and M1 macrophage infiltration, respectively. Functional assessments focused on lysosomal activity and glucose oxidation in primary macrophages and RAW 264.7 cells exposed to LPS, IL-17a, and SYD using dedicated kits. To elucidate the mechanisms underlying the action of SYD, the data derived from TMT-based proteomics were analyzed to screen and predict its potential targets and regulated pathways. Results: After treatment for seven days, SYD significantly mitigated colitis symptoms in mice, as determined by a decrease in body weight loss, an increase in colon length, and a decrease in disease activity index (DAI) score. The results of histopathological analysis showed substantial improvements in the integrity of colonic tissue. Additionally, SYD treatment significantly decreased the levels of proinflammatory cytokines, including IL-17a, IL-6, IL-1 beta, and TNF-alpha. This effect was accompanied by a reduction in the infiltration of CD86+ macrophages and restoration of occludin and ZO-1 levels, thus improving colonic mucosal permeability. SYD treatment also reversed the upregulation of cathepsin (CTS) E, CTSS, lysosomal-associated membrane protein (LAMP)-1, and LAMP-2 expression observed in CD86+ macrophages and RAW 264.7 cells treated with IL-17a. These changes were accompanied by an increase in lysosomal acidification and the enzymatic activities of CTSE and CTSS, suggesting that SYD can restore lysosomal function. SYD also corrected the metabolic alterations in M1 macrophages, characterized by an increase in the extracellular acidification rate (ECAR) and a decrease in oxygen consumption rate (OCR). This was confirmed by a decrease in the ADP/ATP ratio, downregulation of pyruvate dehydrogenase kinase 4 (PDK4) and lactate dehydrogenase (LDH) expression, and a decrease in the concentrations of intracellular pyruvate and lactate. These findings showed that SYD promotes glucose oxidation in macrophages. The data derived from TMT-based proteomics showed that the PPAR pathway was a key target in regulating the polarization of M1 macrophages. SYD was also found to regulate the expression of the PPAR-alpha, PPAR-gamma, and PPAR-S proteins. Conclusion: SYD inhibited the polarization of M1 macrophages induced by IL-17a. This effect occurred due to the restoration of lysosomal activity and glucose oxidation via activation of the PPAR/NF-kappa B pathway. Our findings provided novel insights into the mechanisms underlying the therapeutic effects of SYD in UC. C1 [Wang, Shiying; Cai, Linkun; Ma, Yanyan; Zhang, Haiyan] Guangzhou Univ Chinese Med, Affiliated Hosp 2, Dept Gastroenterol, 111 Dade Rd, Guangzhou 510120, Peoples R China. [Ma, Yanyan] Guangzhou Univ Chinese Med, Guangzhou 511400, Peoples R China. C3 Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine RP Zhang, HY (corresponding author), Guangzhou Univ Chinese Med, Affiliated Hosp 2, Dept Gastroenterol, 111 Dade Rd, Guangzhou 510120, Peoples R China. EM zhanghaiyan128@126.com FU National Natural Science Foundation of China [81904106, 82474402, U23A6012]; Natural Science Foundation Project in Guangdong province, China [2022KT1377]; Scientific special expenditure of Guangdong Provincial Hospital of Traditional Chinese Medicine [YN2020QN15] FX The authors thank all technical staff who provided help in the study. This study was supported by National Natural Science Foundation of China (81904106, 82474402, U23A6012) , the Natural Science Foundation Project in Guangdong province, China (2022KT1377) , scientific special expenditure of Guangdong Provincial Hospital of Traditional Chinese Medicine (YN2020QN15) . 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PD JAN 30 PY 2025 VL 337 AR 118941 DI 10.1016/j.jep.2024.118941 EA OCT 2024 PN 3 PG 13 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA K9A6I UT WOS:001346754200001 PM 39427735 OA hybrid DA 2026-03-26 ER PT J AU Gao, Y Wang, SX Gao, YH Yang, L AF Gao, Yan Wang, Sixiang Gao, Yuehong Yang, Li TI The active ingredient of Evodia rutaecarpa reduces inflammation in knee osteoarthritis rats through blocking calcium influx and NF-κB pathway SO BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY LA English DT Article DE anti-inflammatory; Evodiamine; NF-kappa B/calcium influx; osteoarthritis; polarization ID MATRIX METALLOPROTEINASES; ARTICULAR-CARTILAGE; ACTIVATION; EXPRESSION; DEGENERATION; CHONDROCYTES; PATHOGENESIS; TRANSECTION; APOPTOSIS; MODELS AB Chronic inflammation significantly contributes to the progression of osteoarthritis (OA), and an anti-inflammatory small molecule derived from medicinal herbs could be a potential drug candidate for OA. Herein, we investigated the function and mechanism of Evodiamine (EAE), the active ingredient from Evodia rutaecarpa, in chondrocytes and macrophages in vitro and in vivo. The cytotoxicity of EAE was determined using an MTT assay. And the anti-inflammatory and anti-extracellular matrix (ECM) degradation effects of EAE were investigated using qRT-PCR, western blot (WB), immunofluorescence (IF). Inductively Coupled Plasma Atomic Emission Spectrometry (ICP-AES), Fluo-4 AM, IF and AutoDock were used to elucidate the molecular mechanisms and signalling pathways of the reducing-inflammatory properties of EAE on chondrocytes in vitro. Moreover, the effect of EAE on macrophage polarization was detected by IF and flow cytometry (FC). Ultimately, we explored the in vivo therapeutic efficacy of EAE in an anterior cruciate ligament transection (ACLT)-induced OA model. The finding demonstrated that EAE blocked the phosphorylation of IKB alpha and Ca2+ influx, thereby curbing inflammation and ECM degradation. Additionally, EAE can prevent the polarization towards the M1 phenotype. Thus, our findings suggest that EAE has great potential as a therapeutic drug for the treatment of OA. C1 [Gao, Yan; Wang, Sixiang; Yang, Li] Chongqing Univ, Coll Bioengn, Natl Innovat & Attracting Talents Base 111, Key Lab Biorheol Sci & Technol,Minist Educ, Chongqing 400030, Peoples R China. [Gao, Yuehong] Jishou Univ, Coll Biol & Environm Sci, Jishou, Peoples R China. C3 Chongqing University; Jishou University RP Yang, L (corresponding author), Chongqing Univ, Coll Bioengn, Natl Innovat & Attracting Talents Base 111, Key Lab Biorheol Sci & Technol,Minist Educ, Chongqing 400030, Peoples R China. EM yanglicqu@126.com RI Gao, Yan/MSY-6363-2025 FU National Natural Science Foundation of China; Innovation and Attracting Talents Program for College and University ('111' Project) [B06023]; Home for Researchers editorial team; [11902058]; [11832008] FX We thank every member of the research group for their cooperation. We gratefully acknowledge the financial support from the National Natural Science Foundation of China (11902058, 11832008) and the Innovation and Attracting Talents Program for College and University ('111' Project) (B06023). We also thank the Home for Researchers editorial team () for the language editing service. 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Pharmacol. Toxicol. PD DEC PY 2024 VL 135 IS 6 BP 705 EP 719 DI 10.1111/bcpt.14096 EA OCT 2024 PG 15 WC Pharmacology & Pharmacy; Toxicology WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy; Toxicology GA O6A8K UT WOS:001337990800001 PM 39434543 OA Bronze DA 2026-03-26 ER PT J AU Shen, P Lin, WJ Huang, Y Ba, X Han, L Li, TT Qin, K Chen, Z Tu, SH AF Shen, Pan Lin, Weiji Huang, Yao Ba, Xin Han, Liang Li, Tingting Qin, Kai Chen, Zhe Tu, Shenghao TI Wutou decoction attenuates rheumatoid arthritis in rats through SIRT1-mediated deacetylation of the HMGB1/NF-κB pathway SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Rheumatoid arthritis; Wutou decoction; Silent information regulator 1; High-mobility group box 1; NF-kappa B ID COLLAGEN-INDUCED ARTHRITIS; HMGB1; METHOTREXATE; AUTOIMMUNE AB Ethnopharmacological relevance: In traditional Chinese medicine (TCM), Wutou Decoction (WTD) has long been used to alleviate arthritis. Emerging studies have reported that WTD could improve the symptoms of rheumatoid arthritis (RA). However, the mechanism by which WTD is involved in the treatment of RA remains elusive, posing a challenge to the worldwide acceptance of WTD as an efficient RA therapy. Aim of the study: This study investigated the antiarthritic efficacy of WTD in a collagen-induced arthritis (CIA) rat model and explored silent information regulator 1 (SIRT1)-mediated deacetylation of the high mobility group box 1 (HMGB1)/NF-kappa B pathway. Materials and methods: A rat CIA model was used to evaluate the antiarthritic activity of WTD. Clinical arthritis score assessment, left ankle thickness assessment, micro-CT, histopathological staining, immunofluorescence staining, and ELISA were conducted to elucidate the anti-inflammatory effects of WTD. The M1 macrophage polarization state, cell viability, and invasion were also determined to assess the effects of WTD on macrophage proliferation and invasion in vitro. Additionally, in vivo and in vitro HMGB1 nuclear translocation and NF-kappa B activation were analysed. Finally, deacetylase activity was assessed by Western blot, NAD+/NADH analysis, and co-immunoprecipitaion. Results: WTD significantly alleviated arthritis in CIA rats and inhibited pathological changes in joint lesions while concurrently suppressing TNF-alpha, IL-6, and IL-1 beta release. Mechanistically, WTD suppressed M1 infiltration in ankle tissues and their invasion in vitro. Furthermore, WTD downregulated HMGB1/p65 nuclear translocation and acetylation, which may be associated with SIRT1 upregulation. Conclusions: Overall, WTD potentially alleviates RA through SIRT1-mediated downregulation of HMGB1 and NF kappa B acetylation. C1 [Shen, Pan; Lin, Weiji; Huang, Yao; Ba, Xin; Han, Liang; Li, Tingting; Qin, Kai; Chen, Zhe; Tu, Shenghao] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Integrated Chinese Tradit & Western Med, Tongji Med Coll, Wuhan, Peoples R China. [Shen, Pan] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Dermatol, Wuhan, Peoples R China. C3 Huazhong University of Science & Technology; Huazhong University of Science & Technology RP Tu, SH (corresponding author), Huazhong Univ Sci & Technol, Tongji Hosp, Dept Integrated Chinese Tradit & Western Med, Tongji Med Coll, Wuhan, Peoples R China. EM 1550164963@qq.com; 308611815@qq.com; 1481276027@qq.com; 799641835@qq.com; 1105753788@qq.com; 1072624667@qq.com; gczxqk@163.com; zhepi2006@163.com; shtu@tjh.tjmu.edu.cn RI Huang, Yao/AAJ-3702-2020; Han, Liang/JZD-1497-2024; Li, Tingting/NSU-1563-2025; ba, xin/IUM-1649-2023 OI Tu, Shenghao/0000-0001-8530-270X; FU China Postdoctoral Science Foundation [2022M722483]; Program of Excellent Doctoral (Postdoctoral) of Zhongnan Hospital of Wuhan University [ZNYB2022021]; National Natural Science Foundation of China [81874383, 82405124, 82174185] FX This study received financial support from the China Postdoctoral Science Foundation (No. 2022M722483) , the Program of Excellent Doctoral (Postdoctoral) of Zhongnan Hospital of Wuhan University (No. ZNYB2022021) , and the National Natural Science Foundation of China (No. 81874383, 82405124 and 82174185) . The graphical abstract was created using BioRender.com . CR Ba X, 2021, FRONT PHARMACOL, V12, DOI 10.3389/fphar.2021.696802 Chen H, 2022, INT J HYPERTHER, V39, P977, DOI 10.1080/02656736.2022.2094476 Chen M, 2020, PULM PHARMACOL THER, V65, DOI 10.1016/j.pupt.2021.102000 Dong YJ, 2022, FRONT IMMUNOL, V13, DOI 10.3389/fimmu.2022.815257 Finckh A, 2022, NAT REV RHEUMATOL, V18, P591, DOI 10.1038/s41584-022-00827-y Goldstein RS, 2007, MOL MED, V13, P210, DOI 10.2119/2006-00108.Goldstein Harris HE, 2012, NAT REV RHEUMATOL, V8, P195, DOI 10.1038/nrrheum.2011.222 He LH, 2018, REJUV RES, V21, P442, DOI 10.1089/rej.2017.2011 Hu J, 2022, CELL BIOL INT, V46, P265, DOI 10.1002/cbin.11728 Hu M, 2023, FEBS J, V290, P1874, DOI 10.1111/febs.16678 Kaur I, 2020, LIFE SCI, V258, DOI 10.1016/j.lfs.2020.118164 Kokkola R, 2003, ARTHRITIS RHEUM, V48, P2052, DOI 10.1002/art.11161 Koyama A, 2017, J PHARM PHARMACOL, V69, P1145, DOI 10.1111/jphp.12752 Kurowska-Stolarska M, 2022, NAT REV RHEUMATOL, V18, P384, DOI 10.1038/s41584-022-00790-8 Lan W., 2019, Rheumatism and arthritis, V8 Lange F, 2005, ANN RHEUM DIS, V64, P599, DOI 10.1136/ard.2004.026120 Lee W, 2017, TOXICOL APPL PHARM, V329, P202, DOI 10.1016/j.taap.2017.06.006 Li G., 2018, Biosci Rep, V38 Li JM, 2023, ACTA PHARMACOL SIN, V44, P2504, DOI 10.1038/s41401-023-01124-4 Lin WJ, 2023, J ETHNOPHARMACOL, V301, DOI 10.1016/j.jep.2022.115802 Liu LM, 2022, J NEUROIMMUNOL, V362, DOI 10.1016/j.jneuroim.2021.577763 Luo S., 2008, New Chinese Medicine, V2008, P45 Miyoshi M, 2018, METHODS MOL BIOL, V1868, P3, DOI 10.1007/978-1-4939-8802-0_1 Park EJ, 2018, FEBS OPEN BIO, V8, P1119, DOI 10.1002/2211-5463.12456 Park JA, 2020, CURR MED RES OPIN, V36, P343, DOI 10.1080/03007995.2019.1688271 Shen P, 2021, J ETHNOPHARMACOL, V279, DOI 10.1016/j.jep.2021.114213 Steinle JJ, 2020, CELL SIGNAL, V73, DOI 10.1016/j.cellsig.2020.109687 Su XH, 2022, J ETHNOPHARMACOL, V298, DOI 10.1016/j.jep.2022.115611 Takeuchi O, 2010, CELL, V140, P805, DOI 10.1016/j.cell.2010.01.022 Tan LM, 2023, AUTOIMMUNITY, V56, DOI 10.1080/08916934.2023.2181234 Taniguchi N, 2018, HUM CELL, V31, P1, DOI 10.1007/s13577-017-0182-x Tu JJ, 2020, MEDIAT INFLAMM, V2020, DOI 10.1155/2020/1583647 Volchuk A, 2020, NAT COMMUN, V11, DOI 10.1038/s41467-020-18443-3 Wang QH, 2022, BIOMED PHARMACOTHER, V150, DOI 10.1016/j.biopha.2022.113067 Wang WJ, 2015, GENET MOL RES, V14, P17864, DOI 10.4238/2015.December.22.11 Wang Y., 2017, J. 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PD JAN 30 PY 2025 VL 337 AR 118921 DI 10.1016/j.jep.2024.118921 EA OCT 2024 PN 3 PG 10 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA J8C9X UT WOS:001339297400001 PM 39389393 DA 2026-03-26 ER PT J AU Wang, Y Peng, MH Yang, X Tu, LM Liu, JM Yang, YX Li, R Tang, X Hu, YQ Zhang, GW Zhao, Q Lu, QX AF Wang, Yu Peng, Meihao Yang, Xin Tu, Liming Liu, Jiamin Yang, Yixi Li, Rui Tang, Xue Hu, Yuqing Zhang, Guowu Zhao, Qi Lu, Qiuxia TI Total alkaloids in Fritillaria cirrhosa D. Don alleviate OVA-induced allergic asthma by inhibiting M2 macrophage polarization SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Fritillaria cirrhosa D. Don; Allergic asthma; M2 macrophages; JAK2/STAT3; Network pharmacological ID MURINE MODEL; AIRWAY; HYPERRESPONSIVENESS; MECHANISMS; DISEASE AB Ethnopharmacological relevance: Fritillaria cirrhosa D. Don (FCD) is a traditional Chinese medicine used to treat respiratory disorders, known for its effects in clearing heat, moistening the lungs, resolving phlegm, and relieving cough. Additionally, the total alkaloids extracted from FCD can alleviate asthma symptoms and reduce airway inflammation. However, no studies have investigated the effects of total alkaloids on lung macrophages. Aim of the study: This study explored whether the total alkaloids of FCD (TAs-FCD) reduce M2 macrophage polarization and, consequently, attenuate airway remodeling in asthmatic mice. This study further elucidated its mechanism of action in treating allergic asthma. Materials and methods: The extracted TAs-FCD was analyzed for its composition using UPLC-Q-TOF/MS. Network pharmacology was employed to identify the active ingredients and potential mechanisms of TAs-FCD in the treatment of allergic asthma. A mouse model of ovalbumin-induced allergic asthma was established, adopted, and validated through in vivo experiments. Hematoxylin-eosin staining (H&E), immunohistochemistry (IHC), immunofluorescence staining (IF), enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), and real-time fluorescence quantitative polymerase chain reaction (q-PCR) were used to investigate the role of TAsFCD in inhibiting M2 macrophage polarization in the context of allergic asthma. Results: A total of 66 active ingredients were screened from 116 compounds using SWISSADME. The targets of these 66 compounds were predicted by SwissTargetPrediction, resulting in 808 unique drug targets after excluding duplicates. Additionally, 1756 targets related to allergic asthma were identified from the DisGeNET, Genecard, and OMIM databases. This led to 267 cross-targets between the active ingredient targets and allergic asthma targets, including interleukin (IL)-1 beta, tumor necrosis factor (TNF), and STAT3. Animal experiments demonstrated that TAs-FCD improved histopathological injury in mouse lungs, reduced peri-airway collagen fiber accumulation, airway mucus secretion, and airway smooth muscle proliferation. TAs-FCD also lowered IL1 beta, TNF-alpha and IL-4 levels in lung tissues and alleviated airway inflammation. Furthermore, TAs-FCD significantly reduced levels of Arg1 and CD206, which are closely associated with M2 macrophages, and downregulated the expression of p-STAT3 and p-JAK2. Conclusion: TAs-FCD may inhibit M2 macrophage polarization by regulating the JAK2/STAT3 pathway, thereby alleviating airway remodeling and inflammation in allergic asthmatic mice. C1 [Wang, Yu; Peng, Meihao; Yang, Xin; Tu, Liming; Liu, Jiamin; Yang, Yixi; Li, Rui; Zhao, Qi; Lu, Qiuxia] Chengdu Univ, Engn Res Ctr Sichuan Tibet Tradit Med Plant, Chengdu 610106, Peoples R China. [Wang, Yu; Peng, Meihao; Liu, Jiamin; Yang, Yixi; Li, Rui; Zhao, Qi; Lu, Qiuxia] Chengdu Univ, Sch Pharm, Chengdu 610106, Peoples R China. [Yang, Xin; Tu, Liming; Yang, Yixi; Li, Rui; Zhao, Qi; Lu, Qiuxia] Chengdu Univ, Sch Food & Biol Engn, Chengdu 610106, Peoples R China. [Tang, Xue] Shimadzu China Co Ltd, Chengdu Analyt Applicat Ctr, Chengdu 610023, Peoples R China. [Hu, Yuqing; Zhang, Guowu] Shangri La Tianquan Chuanbei Technol Co Ltd, Yunnan 674401, Peoples R China. C3 Chengdu University; Chengdu University; Chengdu University RP Zhao, Q; Lu, QX (corresponding author), Chengdu Univ, Engn Res Ctr Sichuan Tibet Tradit Med Plant, Chengdu 610106, Peoples R China. EM zhaoqi@cdu.edu.cn; luqiuxia@cdu.edu.cn RI Li, Rui/LXU-3828-2024 FU National Natural Science Foundation of China [32100312, 32270407]; Sichuan Provincial Science Fund for Distinguished Young Scholars [2022JDJQ0053] FX This study was funded by the National Natural Science Foundation of China (grant no. 32100312 and 32270407) , the Sichuan Provincial Science Fund for Distinguished Young Scholars (grant no. 2022JDJQ0053) . 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PD JAN 30 PY 2025 VL 337 AR 118935 DI 10.1016/j.jep.2024.118935 EA OCT 2024 PN 3 PG 15 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA J5E7Y UT WOS:001337300600001 PM 39396718 DA 2026-03-26 ER PT J AU Liu, ZC Fu, HJ Li, NC Deng, FJ Gan, YK Ye, YJ Huang, BH Liu, C Chen, JH Li, XF AF Liu, Zhi-Chao Fu, Huan-Jie Li, Ning-Cen Deng, Fang-Jun Gan, Yong-Kang Ye, Yu-Jia Huang, Bing-Hui Liu, Chang Chen, Jin-Hong Li, Xiao-Feng TI Systematic pharmacology and experimental validation to elucidate the inflammation-associated mechanism of Huanglian Wendan (HLWD) decoction in the treatment of MAFLD associated with atherosclerosis SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Metabolic-associated fatty liver disease; Atherosclerosis; Huanglian wendan; Inflammation; Macrophage polarization; Network pharmacology ID FATTY LIVER-DISEASE; HIGH-DENSITY-LIPOPROTEIN; INSULIN-RESISTANCE; HEPATIC STEATOSIS; METABOLIC SYNDROME; RISK; PATHOGENESIS; CONTRIBUTES; PROGRESSION; ACTIVATION AB Ethnopharmacological relevance: Metabolic-associated fatty liver disease (MAFLD) and atherosclerosis are very common disorders that frequently coexist. The therapeutic efficacy of Huanglian Wendan (HLWD) decoction, a traditional Chinese medicine (TCM) prescription, is satisfactory in treating MAFLD associated with atherosclerosis. However, the underlying mechanisms through which HLWD exerts its effects need to be elucidated. Given the complex composition of HLWD and its multiple therapeutic targets, pharmacological investigation is challenging. Aim of this study: This study aimed to identify the effective compounds in HLWD and elucidate the mechanisms involved in its therapeutic effect on MAFLD associated with atherosclerosis. Materials and methods: We used a systematic pharmacology method to identify effective compounds present in HLWD and determine the mechanism by which it affects MAFLD associated with atherosclerosis. The effective components of HLWD were identified through ultrahigh-performance liquid chromatography-q exactive-orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). Next, a comprehensive in silico method was used to predict potential related targets and disease targets for these compounds to establish corresponding pathways. The accuracy of our assumed systemic pharmacology results was determined by conducting follow-up experiments. Results: By conducting UHPLC-Q-Orbitrap HRMS combined with network analysis, we identified 18 potentially active components of HLWD and assessed the inflammatory regulatory mechanism by which it affects MAFLD associated with atherosclerosis on the basis of 52 key targets. We used a high-fat, high-cholesterol (HFHC)-induced mice model of MAFLD associated with atherosclerosis to confirm our results. We found that administering HLWD significantly improved the appearance of their liver and reduced their body weight, liver weight, blood lipids, hepatic damage, and hepatic pathology. HLWD also decreased atherosclerotic lesion areas, foam cells, and inflammatory cells in the aorta. HLWD showed anti-inflammatory effects, suppressed M1 polarization, and promoted M2 polarization in the liver and aorta. HLWD might also regulate peroxisome proliferator-activated receptor-gamma (PPAR gamma)/nuclear factor kappa-B (NF-kappa B) signaling to influence macrophage polarization and inflammation. Conclusions: Our results showed that HLWD protected against HFHC diet-induced MAFLD associated with atherosclerosis by regulating PPAR gamma/NF-kappa B signaling, thus adjusting macrophage polarization and inflammation. Additionally, pharmacochemistry research, network pharmacology analysis, and experimental verification can be combined to form a comprehensive model used in studies on TCM. C1 [Liu, Zhi-Chao; Ye, Yu-Jia; Huang, Bing-Hui; Liu, Chang; Chen, Jin-Hong] Shandong Second Med Univ, Sch Rehabil Med, Weifang 261053, Shandong, Peoples R China. [Fu, Huan-Jie; Li, Xiao-Feng] Tianjin Univ Tradit Chinese Med, Teaching Hosp 2, Dept Cardiovasc, Tianjin 300150, Peoples R China. [Li, Ning-Cen] Tianjin Univ Tradit Chinese Med, Res Ctr Expt Acupuncture Sci, Tianjin 301617, Peoples R China. [Deng, Fang-Jun] Tianjin Acad Tradit Chinese Med, Affiliated Hosp, Dept Cardiovasc, Tianjin 300150, Peoples R China. [Gan, Yong-Kang] Tianjin Acad Tradit Chinese Med, Affiliated Hosp, Dept Vasc Surg, Tianjin 300150, Peoples R China. C3 Shandong Second Medical University; Tianjin University of Traditional Chinese Medicine; Tianjin University of Traditional Chinese Medicine RP Chen, JH (corresponding author), Shandong Second Med Univ, Sch Rehabil Med, Weifang 261053, Shandong, Peoples R China.; Li, XF (corresponding author), Tianjin Univ Tradit Chinese Med, Teaching Hosp 2, Dept Cardiovasc, Tianjin 300150, Peoples R China. EM liuzhichao93@126.com; huanjiefu1992@163.com; 517654179@qq.com; dfj2gl@163.com; channacat@163.com; 2922996048@qq.com; 1011834740@qq.com; 19707715068@139.com; chenjh2022@sdsmu.edu.cn; liuzhichao93@126.com RI Chen, Jinhong/LUY-4216-2024 OI 陈, 金红/0000-0003-0899-6431 FU Shandong Province Tradi-tional Chinese Medicine Technology Project [Q-2023006]; Shan-dong Province Medical and Health Technology Project [202303011361]; Weifang Science and Technology Development Plan Project [2022YX044, 2022YX045] FX This study was supported by grants from Shandong Province Tradi-tional Chinese Medicine Technology Project (No. Q-2023006) , Shan-dong Province Medical and Health Technology Project (No. 202303011361) , and Weifang Science and Technology Development Plan Project (No. 2022YX044 and No. 2022YX045) . 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Ethnopharmacol. PD JAN 30 PY 2025 VL 337 AR 118841 DI 10.1016/j.jep.2024.118841 EA SEP 2024 PN 1 PG 17 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA H1R9T UT WOS:001321292600001 PM 39299361 DA 2026-03-26 ER PT J AU Wang, SQ Xu, S Li, J Wang, N Zheng, YF Wang, ZY AF Wang, Shengqi Xu, Shang Li, Jing Wang, Neng Zheng, Yifeng Wang, Zhiyu TI XIAOPI formula inhibits chemoresistance and metastasis of triple-negative breast cancer by suppressing extracellular vesicle/CXCL1-induced TAM/ PD-L1 signaling SO PHYTOMEDICINE LA English DT Article DE Triple-negative breast cancer; Extracellular vesicle; CXCL1; Tumor-associated macrophage; PD-L1; XIAOPI formula ID TRADITIONAL CHINESE MEDICINE; CXCL1; CHEMOTHERAPY AB Background Triple-negative breast cancer (TNBC) is challenged by the low chemotherapy response and poor prognosis. Emerging evidence suggests that cytotoxic chemotherapy may lead to the pro-metastatic tumor microenvironment (TME) by eliciting pro-tumor extracellular vesicles (EVs) from cancer cells. However, the precise mechanisms and therapeutic approaches remain inadequately understood. Purpose This study aims to determine whether XIAOPI formula (Chinese name XIAOPI San, XPS), a nationally sanctioned medication for mammary hyperplasia, can chemosensitize TNBC by remodeling the TME via modulating EV signaling, and exploring its underlying mechanisms. Methods Multiple methodologies, such as EV isolation, transmission electron microscope, flow cytometry, dual-luciferase reporter assays, co-immunoprecipitation and in vivo breast cancer xenograft, were employed to elucidate the effect and molecular mechanisms of XPS on paclitaxel-induced EV signaling (EV-dead) of TNBC. Results XPS, at non-toxic concentrations, synergized with PTX to inhibit the invasion and chemoresistance of TNBC cells co-cultured with macrophages. Compared to EV-dead, XPS co-treatment-elicited EVs (EV-dead(XPS)) exhibited a decreased capacity to promote the invasion, chemoresistance and cancer stem cell subpopulation of the co-cultured TNBC cells. Mechanistically, XPS administration led to a reduction in CXCL1 cargo in EV-dead, and thereby attenuated its activation effect on macrophage polarization into M2 phenotype through the transcriptional downregulation of PD-L1 expression. Furthermore, XPS effectively reduced the number of EV-dead from TNBC cells by inhibiting CXCL1-mediated intraluminal vesicle (ILV) biogenesis in multivesicular bodies (MVBs). Moreover, molecular explorations revealed that XPS impaired ILV biogenesis by disrupting the RAB31/FLOT2 complex via suppressing the CXCL1/Myc signaling. Importantly, XPS significantly chemosensitized paclitaxel to inhibit TNBC growth and metastasis in vivo by suppressing EV-dead(CXCL1)-induced PD-L1 activation and M2 polarization of macrophages. Conclusion This pioneering study not only sheds novel light on EV-dead(CXCL1) as a potential therapeutic target to suppress TNBC chemoresistance and metastasis, but also provides XPS as a promising adjuvant formula to chemosensitize TNBC by remodeling EV-dead(CXCL1)-mediated immunosuppressive TME. C1 [Wang, Shengqi; Zheng, Yifeng; Wang, Zhiyu] Guangzhou Univ Chinese Med, Affiliated Hosp 2, State Key Lab Tradit Chinese Med Syndrome, State Key Lab Dampness Syndrome Chinese Med, Guangzhou, Peoples R China. [Wang, Shengqi; Xu, Shang; Li, Jing; Zheng, Yifeng; Wang, Zhiyu] Guangdong Prov Hosp Chinese Med, Breast Dis Specialist Hosp, Guangzhou, Guangdong, Peoples R China. [Wang, Shengqi; Xu, Shang; Li, Jing; Wang, Neng; Zheng, Yifeng; Wang, Zhiyu] Guangzhou Univ Chinese Med, Res Ctr Integrat Canc Med, Clin Coll 2, Discipline Integrated Chinese & Western Med, Guangzhou, Peoples R China. [Wang, Shengqi; Wang, Zhiyu] Guangdong Prov Hosp Chinese Med, Guangdong Prov Acad Chinese Med Sci, Guangdong Prov Key Lab Clin Res Tradit Chinese Med, Guangzhou, Peoples R China. [Wang, Shengqi; Wang, Neng; Zheng, Yifeng; Wang, Zhiyu] Guangzhou Univ Chinese Med, Guangdong Hong Kong Macau Joint Lab Chinese Med &, Guangzhou, Peoples R China. [Wang, Neng] Guangzhou Univ Chinese Med, Res Ctr Integrat Med, Sch Basic Med Sci, Guangzhou, Peoples R China. C3 Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine RP Wang, ZY (corresponding author), Guangzhou Univ Chinese Med, Affiliated Hosp 2, Guangzhou, Peoples R China. EM wangzhiyu@gzucm.edu.cn RI Zheng, Yifeng/H-2067-2017; Wang, Zhiyu/K-5255-2016 OI Zheng, Yifeng/0000-0002-7704-3557; Wang, Zhiyu/0000-0002-5299-8410 FU Hospital of Chinese Medicine [BJ2022KY12] FX This study was supported by the National Natural Science Foundation of China [82074165, 82174165, 82374446] ; the State Key Laboratory of Dampness Syndrome of Chinese Medicine [SZ2021ZZ19] ; the Science and Technology Planning Project of Guangdong Province [2022B1515230002, 2022A1515011412, 2023B1212060063] ; the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund (Guangdong-Hong Kong-Macau Joint Lab) [2020B1212030006] ; the Specific Research Fund for TCM Science and Technology of Guangdong Provincial Hospital of Chinese Medicine [YN2023MS31] ; Guangzhou Science and Technology Project [202201020357] ; the Young Elite Scientists Sponsorship Program by CACM [2021-QNRC2-B02] , the Research Fund for Qingmiao Talents of Guangdong Provincial Hospital of Chinese Medicine [SZ2022QN01] , and the Research Fund for Bajian Talents of Guangdong ProvincialHospital of Chinese Medicine [BJ2022KY12] .r Hospital of Chinese Medicine [BJ2022KY12] . 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Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA G9A2A UT WOS:001319473200001 PM 39303510 DA 2026-03-26 ER PT J AU Li, M Tang, HM Geng, XY Zhou, JH Mou, ST Li, C Chang, J Xu, MH Wang, CL Fu, RJ Wang, YH AF Li, Ming Tang, Huamin Geng, Xiaoyuan Zhou, Jiahua Mou, Sitong Li, Chang Chang, Jing Xu, Minhui Wang, Chuanlin Fu, Runjia Wang, Yanhua TI All-natural hydrogel composed of carboxymethyl chitosan and oxidized dextran for promoting wound healing by immune-microenvironment regulation SO CARBOHYDRATE POLYMERS LA English DT Article DE Bioactive herb hydrogels; Puerarin; Macrophage polarization; Wound healing ID ANTIBACTERIAL; DRESSINGS; PUERARIN AB Chronic wound treatment has always been a major clinical challenge owing to complex and dynamic wound microenvironment. The design and development of effective management with antimicrobial activity, ROSscavenging and regulation immune response is vital for tissue repair. Herein, we developed puerarin (PUE) loaded a double network hydrogel consisting of methacrylated carboxymethyl chitosan and oxidized dextran with Schiff base and photo-crosslinking reaction. The composite hydrogel presented fast self-healing and outstanding compressive performance to bear deformation. The hydrogel exhibits a cumulative drug release pattern with biphasic release, which offers great potential for accelerating tissue healing at all stages of wounding. In addition, the hydrogel has good biocompatibility, antimicrobial ability and tube-forming ability in vitro. The full-thickness skin wound model of Staphylococcus aureus infection showed that the hydrogel dressing can accelerate tissue repair. This study demonstrated that the design of combing natural biomacromolecules with traditional Chinese medicine could be severed as a promising candidate biomaterial for skin tissue recovery. C1 [Li, Ming; Geng, Xiaoyuan; Li, Chang; Chang, Jing; Xu, Minhui; Wang, Chuanlin] Peking Univ Peoples Hosp, Trauma Med Ctr, Beijing, Peoples R China. [Li, Ming; Geng, Xiaoyuan; Zhou, Jiahua; Li, Chang; Chang, Jing; Xu, Minhui; Wang, Chuanlin; Wang, Yanhua] Peking Univ, Key Lab Trauma & Neural Regenerat, Minist Educ, Beijing, Peoples R China. [Li, Ming; Geng, Xiaoyuan; Zhou, Jiahua; Li, Chang; Chang, Jing; Xu, Minhui; Wang, Chuanlin; Wang, Yanhua] Natl Ctr Trauma Med, Beijing, Peoples R China. [Tang, Huamin; Mou, Sitong] Guangxi Univ Chinese Med, Guangxi Int Zhuang Med Hosp, Nanning, Guangxi, Peoples R China. [Zhou, Jiahua; Wang, Yanhua] Peking Univ Peoples Hosp, Dept Orthoped & Trauma, Beijing, Peoples R China. [Fu, Runjia] Shandong Univ, Hosp 2, Cheeloo Coll Med, Dept Oncol, Jinan, Peoples R China. C3 Peking University; Guangxi University of Chinese Medicine; Peking University; Shandong University RP Wang, CL (corresponding author), Peking Univ Peoples Hosp, Trauma Med Ctr, Beijing, Peoples R China.; Fu, RJ (corresponding author), Shandong Univ, Hosp 2, Cheeloo Coll Med, Dept Oncol, Jinan, Peoples R China.; Wang, YH (corresponding author), Peking Univ Peoples Hosp, Trauma Orthoped Dept, Beijing, Peoples R China. EM wangchuanlinvip@163.com; furunjia@pku.edu.cn; 94719599@qq.com RI xu, minhui/PKR-4097-2026; wang, chuanlin/MGV-2377-2025; geng, xiaoyuan/HHC-4619-2022 FU National Key Research and Development Program of China [2022YFC3006200]; National Natural Science Foundation of China [82002471, 81901251, 82003992]; Beijing Natural Science Foundation [7232185]; Peking University People's Hospital Scientific Research Development Funds [RDX2023-10]; Cultivation fund of the Second Hospital of Shandong University [2023JX28]; Guangxi Science and Technology Base and Talent Project [AD22035052] FX This work was financially supported by the National Key Research and Development Program of China (2022YFC3006200) , the National Natural Science Foundation of China (82002471, 81901251, 82003992) , the Beijing Natural Science Foundation (7232185) , the Peking University People's Hospital Scientific Research Development Funds (RDX2023-10) , and the cultivation fund of the Second Hospital of Shandong University (2023JX28) and Guangxi Science and Technology Base and Talent Project (No. AD22035052) . 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PD JAN 1 PY 2025 VL 347 AR 122731 DI 10.1016/j.carbpol.2024.122731 EA SEP 2024 PG 11 WC Chemistry, Applied; Chemistry, Organic; Polymer Science WE Science Citation Index Expanded (SCI-EXPANDED) SC Chemistry; Polymer Science GA H0P2L UT WOS:001320545100001 PM 39486961 DA 2026-03-26 ER PT J AU Cheng, YF Li, JJ Feng, X Wu, YH Wu, XP Lau, BWM Ng, SSM Lee, SMY Seto, SW Leung, GPH Hu, YC Fu, CM Zhang, SY Zhang, JM AF Cheng, Yanfen Li, Jingjing Feng, Xi Wu, Yihan Wu, Xiaoping Lau, Benson Wui Man Ng, Shamay Sheung Mei Lee, Simon Ming-Yuen Seto, Sai-Wang Leung, George Pak-Heng Hu, Yichen Fu, Chaomei Zhang, Siyuan Zhang, Jinming TI Taohong Siwu decoction enhances the chemotherapeutic efficacy of doxorubicin by promoting tumor vascular normalization SO PHYTOMEDICINE LA English DT Article DE Taohong Siwu decoction; Doxorubicin; Breast cancer; Angiogenesis; Vascular normalization ID BREAST-CANCER; ENDOTHELIAL-CELLS; ANGIOGENESIS; LIMITATIONS; DELIVERY; THERAPY AB Background: Instead of completely suppressing blood vessels inside tumors, vascular normalization therapy is proposed to normalize and prune the abnormal vasculature in tumor microenvironment (TME) to acquire a normal and stable blood flow and perfusion. The theoretical basis for the use of "blood-activating and stasisresolving" formulas in Traditional Chinese Medicine to treat cancer is highly consistent with the principle of vascular normalization therapy, suggesting the potential application of these traditional formulas in vascular normalization therapy. Purpose: To study the underlying mechanisms of a classical "blood-activating and stasis-resolving" formula, Taohong Siwu decoction (TSD), in enhancing the efficacy of chemotherapy for breast cancer treatment. Study design: HUVECs and transgenic zebrafish embryos were used as the major model in vitro. A 4T1 mouse breast cancer model was applied to study tumor vasculature normalization of TSD and the combination effects with DOX. Results: Our data showed that TSD exhibited anti-angiogenic potential in HUVECs and transgenic zebrafish embryos. After 20 days treatment, TSD significantly normalized the tumor vasculature by remodeling vessel structure, reducing intratumoral hypoxia and vessel leakage, and promoting vessel maturation and blood perfusion in 4T1 breast tumor-bearing mice. Moreover, the anti-tumor efficacy of doxorubicin liposome in 4T1 breast tumors was significantly improved by TSD, including the suppression of tumor cell proliferation, angiogenesis, hypoxia, and the increase of cell apoptosis, which is likely through the vascular normalization induced by TSD. TSD also shifted the macrophage polarization from M2 to M1 phenotype in TME during the combination therapy, as evidenced by the reduced number of CD206(+) macrophages and increased number of CD86(+) macrophages. Additionally, TSD treatment protected against doxorubicin-induced cardiotoxicity in animals, as evidenced by the reduced cardiomyocytes apoptosis and improved heart function. Conclusion: This study demonstrated for the first time that TSD as a classical Chinese formula can enhance the drug efficacy and reduce the side effects of doxorubicin. These findings can support that TSD could be used as an adjuvant therapy in combination with conventional chemotherapy for the future breast cancer treatment. C1 [Cheng, Yanfen; Hu, Yichen] Chengdu Univ, Sch Food & Biol Engn, Key Lab Coarse Cereal Proc, Minist Agr & Rural Affairs, Chengdu, Peoples R China. [Cheng, Yanfen; Feng, Xi; Wu, Yihan; Fu, Chaomei; Zhang, Jinming] Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, 1166 Liutai Ave, Chengdu, Sichuan, Peoples R China. [Li, Jingjing; Lau, Benson Wui Man; Ng, Shamay Sheung Mei] Hong Kong Polytech Univ, Fac Hlth & Social Sci, Dept Rehabil Sci, Kowloon, Room ST527,11 Yuk Choi Rd, Hong Kong, Peoples R China. [Li, Jingjing; Ng, Shamay Sheung Mei; Lee, Simon Ming-Yuen; Seto, Sai-Wang] Hong Kong Polytech Univ, Res Ctr Chinese Med Innovat, Kowloon, Hong Kong, Peoples R China. [Wu, Xiaoping; Leung, George Pak-Heng] Univ Hong Kong, Li Ka Shing Fac Med, Dept Pharmacol & Pharm, Hong Kong, Peoples R China. [Lee, Simon Ming-Yuen; Seto, Sai-Wang] Hong Kong Polytech Univ, Fac Sci, Dept Food Sci & Nutr, Kowloon, Hong Kong, Peoples R China. [Zhang, Siyuan] Chengdu Med Coll, Sch Lab Med, Sichuan Prov Engn Lab Prevent & Control Technol Ve, Chengdu, Peoples R China. [Zhang, Siyuan] Chengdu Med Coll, China Natl Nucl Corp 416 Hosp, Affiliated Hosp 2, Chengdu, Peoples R China. [Zhang, Siyuan] Chengdu Med Coll, Sch Lab Med, 783 Xindu Ave, Chengdu city, Peoples R China. C3 Chengdu University; Chengdu University of Traditional Chinese Medicine; Hong Kong Polytechnic University; Hong Kong Polytechnic University; University of Hong Kong; Hong Kong Polytechnic University; Chengdu Medical College; China National Nuclear Corporation; Chengdu Medical College; Chengdu Medical College RP Zhang, JM (corresponding author), Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, 1166 Liutai Ave, Chengdu, Sichuan, Peoples R China.; Li, JJ (corresponding author), Hong Kong Polytech Univ, Fac Hlth & Social Sci, Dept Rehabil Sci, Kowloon, Room ST527,11 Yuk Choi Rd, Hong Kong, Peoples R China.; Zhang, SY (corresponding author), Chengdu Med Coll, Sch Lab Med, 783 Xindu Ave, Chengdu city, Peoples R China. EM kim07.li@polyu.edu.hk; siyuan92@163.com; cdutcmzjm@126.com RI Wu, Xiaoping/KVX-9826-2024; Leung, Gabriel/C-4336-2009; Ng, Shamay/E-2731-2016; Lau, Wui/C-4158-2009; lee, Simon Ming Yuen/NOE-8462-2025; Leung, George Pak Heng/B-4529-2009 OI Li, Jingjing/0000-0003-3636-0537; lee, Simon Ming Yuen/0000-0002-3966-6569; Leung, George Pak Heng/0000-0003-3529-9367 FU Shenzhen Science and Technology Program [JCYJ20230807140259002]; Guangdong Basic and Applied Basic Research Foundation [2023A1515011960]; Start-up Fund for research assistant professors under the Strategic Hiring Scheme [A0040914]; Life Science Research Start-up Fund 2023 of Hong Kong Polytechnic University Shenzhen Research Institute [I2023A006]; Seed Fund from Research Centre for Chinese Medicine Innovation [P0045264]; Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, P.R. China FX The present study was supported by Shenzhen Science and Technology Program (Grant no. JCYJ20230807140259002) , Guangdong Basic and Applied Basic Research Foundation (Grant no. 2023A1515011960) , Start-up Fund for research assistant professors under the Strategic Hiring Scheme (Grant no. A0040914) , Life Science Research Start-up Fund 2023 of Hong Kong Polytechnic University Shenzhen Research Institute (Grant no. I2023A006) , and Seed Fund from Research Centre for Chinese Medicine Innovation (Grant no. P0045264) , Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, P.R. China. 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Herein, in this study, alpha-tocopherol modified glycol chitosan (TG) nanoparticles encapsulated with phytochemical rhein (Rhein@TG NPs) were prepared for comprehensive anti-infection and promotion of MRSA infected wound healing. Rhein@TG NPs could not only specifically release rhein in the infection site in response to low pH and lipase of infectious microenvironment, but also up-regulated M1 macrophage polarization in the infection stage, thus achieving synergistically bacterial elimination with low possibility of developing resistance. Additionally, the NPs reduced the levels of proinflammatory factors in the post-infection stage, scavenged the ROS, promoted cell migration and angiogenesis, which significantly improved the microenvironment of infected wound healing. Therefore, this antibioticfree NPs enabling anti-infection and promotion of wound healing provides a new and long-term strategy for the treatment of MRSA infected wound. C1 [Li, Yanhua; Zhang, Zhiyun] Northeast Agr Univ, Coll Vet Med, Harbin 150030, Peoples R China. Heilongjiang Key Lab Anim Dis Control & Pharmaceut, Harbin 150030, Peoples R China. C3 Northeast Agricultural University - China RP Li, YH; Zhang, ZY (corresponding author), Northeast Agr Univ, Coll Vet Med, Harbin 150030, Peoples R China. EM liyanhua@neau.edu.cn; zhangzhiyun@neau.edu.cn RI Cui, Xilong/HHM-6692-2022; li, yanhua/AEW-6901-2022; Zou, Xinshu/KIK-1853-2024 FU Agriculture Research System of China of MOF [LBH-TZ2104]; MARA [CARS-35]; Foundation of Northeast Agricultural University FX This work was supported by the National Natural Science Foundation of China (No.3210190403), China Postdoctoral Science Foundation (2022T150104), the Natural Science Foundation of Heilongjiang Province (No. YQ2022C016), the Heilongjiang Postdoctoral Science Foundation (LBH-TZ2104), the Agriculture Research System of China of MOF and MARA (Grant No. CARS-35) and the Foundation of Northeast Agricultural University. 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PD NOV PY 2024 VL 279 AR 135360 DI 10.1016/j.ijbiomac.2024.135360 EA SEP 2024 PN 3 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA F8N7A UT WOS:001312323400001 PM 39242008 DA 2026-03-26 ER PT J AU Yang, XY Li, JL Xu, CC Zhang, GH Che, XZ Yang, JG AF Yang, Xinyu Li, Jinling Xu, Chengchao Zhang, Guangheng Che, Xinzhen Yang, Jiguo TI Potential mechanisms of rheumatoid arthritis therapy: Focus on macrophage polarization SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Review DE Macrophage polarization; Rheumatoid arthritis; Traditional Chinese medicine; Pharmacological mechanism; Disease-modifying antirheumatic drugs ID ER MIAO SAN; M2B MACROPHAGES; INSULIN-RESISTANCE; GLAUCOCALYXIN B; INFLAMMATION; PROMOTES; PATHWAY; NANOPARTICLES; ACTIVATION; EXPRESSION AB Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that affects multiple organs and systems in the human body, often leading to disability. Its pathogenesis is complex, and the long-term use of traditional antirheumatic drugs frequently results in severe toxic side effects. Therefore, the search for a safer and more effective antirheumatic drug is extremely important for the treatment of RA. As important immune cells in the body, macrophages are polarized. Under pathological conditions, macrophages undergo proliferation and are recruited to diseased tissues upon stimulation. In the local microenvironment, they polarize into different types of macrophages in response to specific factors and perform unique functions and roles. Previous studies have shown that there is a link between macrophage polarization and RA, indicating that certain active ingredients can ameliorate RA symptoms through macrophage polarization. Notably, Traditional Chinese medicine (TCM) monomer component and compounds demonstrate a particular advantage in this process. Building upon this insight, we reviewed and analyzed recent studies to offer valuable and meaningful insights and directions for the development and application of anti-rheumatic drugs. C1 [Yang, Xinyu; Li, Jinling; Yang, Jiguo] Shandong Univ Tradit Chinese Med, Coll Acupuncture & Massage, Jinan, Peoples R China. [Xu, Chengchao] Shandong Univ Tradit Chinese Med, Coll Rehabil Med, Jinan, Peoples R China. [Zhang, Guangheng; Che, Xinzhen] Shandong Univ Tradit Chinese Med, Dept Clin Med Coll 1, Jinan, Peoples R China. C3 Shandong University of Traditional Chinese Medicine; Shandong University of Traditional Chinese Medicine; Shandong University of Traditional Chinese Medicine RP Yang, JG (corresponding author), Shandong Univ Tradit Chinese Med, Coll Acupuncture & Massage, Jinan, Peoples R China. 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PD DEC 5 PY 2024 VL 142 AR 113058 DI 10.1016/j.intimp.2024.113058 EA SEP 2024 PN A PG 14 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA F6G3N UT WOS:001310778800001 PM 39236455 DA 2026-03-26 ER PT J AU Ding, XT Yang, CX Li, Y He, TT Xu, Y Cheng, XX Song, JY Xue, NN Min, W Feng, WM Zhao, HY Dong, J Liu, P Wang, YW Chen, J AF Ding, Xiaotong Yang, Chenxi Li, Yue He, Tangtang Xu, Yan Cheng, Xuxi Song, Jinyun Xue, Nannan Min, Wen Feng, Weimeng Zhao, Hongyu Dong, Jie Liu, Pei Wang, Yiwei Chen, Jun TI Reshaped commensal wound microbiome via topical application of Calvatia gigantea extract contributes to faster diabetic wound healing SO BURNS & TRAUMA LA English DT Article DE Calvatia gigantea extract; Diabetic wound healing; Commensal wound microbiome; Macrophage polarization, Inflammation ID FOOT ULCERS; PROLIFERATION; REGENERATION; MACROPHAGES; PHENOTYPE; RECOVERY AB Background Calvatia gigantea (CG) is widely used as a traditional Chinese medicine for wound treatment. In this study, we aimed to determine the effects of CG extract (CGE) on diabetic wound healing and the commensal wound microbiome.Method A wound model was established using leptin receptor-deficient db/db mice, with untreated mice as the control group and CGE-treated mice as the treatment group. The wound healing rate, inflammation and histology were analyzed. Additionally, wound microbiome was evaluated via 16S ribosomal RNA (rRNA) gene sequencing.Results CGE significantly accelerated the healing of diabetic ulcer wounds, facilitated re-epithelialization, and downregulated the transcription levels of the inflammatory cytokines, interleukin-1 beta and tumor necrosis factor-alpha. Furthermore, CGE treatment positively affected the wound microbiome, promoting diversity of the microbial community and enrichment of Escherichia-Shigella bacteria in the CGE-treated group.Conclusions Overall, CGE enhanced diabetic wound healing by modulating the wound microbiome and facilitating macrophage polarization during inflammation. These findings suggest modulation of the commensal wound microbiome using medicinal plants as a potential therapeutic strategy for diabetic wounds. Graphical Abstract C1 [Ding, Xiaotong; Yang, Chenxi; Li, Yue; He, Tangtang; Xu, Yan; Cheng, Xuxi; Xue, Nannan; Dong, Jie; Wang, Yiwei; Chen, Jun] Nanjing Univ Chinese Med, Jiangsu Prov Engn Res Ctr TCM External Medicat Dev, 138 Xianlin Rd, Nanjing 210023, Peoples R China. [Ding, Xiaotong; Li, Yue; He, Tangtang; Xu, Yan; Cheng, Xuxi; Xue, Nannan; Feng, Weimeng; Dong, Jie; Liu, Pei; Wang, Yiwei; Chen, Jun] Nanjing Univ Chinese Med, Sch Pharm, 138 Xianlin Rd, Nanjing 210023, Peoples R China. [Yang, Chenxi] Nanjing Univ Chinese Med, Sch Med, Dept Immunol, 138 Xianlin Rd, Nanjing 210023, Peoples R China. [He, Tangtang; Min, Wen] Nanjing Univ Chinese Med, Dept Bone Injury Tradit Chinese Med, Affiliated Hosp, 155 Hanzhong Rd, Nanjing 210029, Peoples R China. [Song, Jinyun; Feng, Weimeng; Zhao, Hongyu] Nanjing Univ Chinese Med, Hosp Nanjing 2, Clin Res Ctr, 1 Kangfu St, Nanjing 210003, Peoples R China. [Liu, Pei; Wang, Yiwei; Chen, Jun] Nanjing Univ Chinese Med, Jiangsu Collaborat Innovat Ctr Chinese Med Resourc, 138 Xianlin Rd, Nanjing 210023, Peoples R China. C3 Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine RP Wang, YW; Chen, J (corresponding author), Nanjing Univ Chinese Med, Jiangsu Prov Engn Res Ctr TCM External Medicat Dev, 138 Xianlin Rd, Nanjing 210023, Peoples R China.; Wang, YW; Chen, J (corresponding author), Nanjing Univ Chinese Med, Sch Pharm, 138 Xianlin Rd, Nanjing 210023, Peoples R China.; Wang, YW; Chen, J (corresponding author), Nanjing Univ Chinese Med, Jiangsu Collaborat Innovat Ctr Chinese Med Resourc, 138 Xianlin Rd, Nanjing 210023, Peoples R China. EM 20190462@njucm.edu.cn; yangchenxi@njucm.edu.cn; 20210827@njucm.edu.cn; 20233089@njucm.edu.cn; xuy.echo@foxmail.com; chengxuxi2021@163.com; fsyy01812@njucm.edu.cn; 20213108@njucm.edu.cn; wenge1977@126.com; fwm1101@163.com; njdie001@njucm.edu.cn; dongjie@njucm.edu.cn; liupei@njucm.edu.cn; yiweiwang@njucm.edu.cn; chenjun75@163.com RI Wang, Yiwei/AAE-9739-2021; Chenxi, Yang/JBJ-4554-2023; Feng, Weimeng/IZP-8620-2023 OI Wang, Yiwei/0000-0001-6585-6641; FU National Natural Science Foundation of China FX This work was financially supported by the National Natural Science Foundation of China(No.82372521;No.82172217;No.82003305), JiangsuProvinceTraditionalChinese Medicine Development Project(MS2022006),NaturalScienceResearchProjectoftheJiangsuHigherEducat ionInstitutionsofChina(No. 22KJA360002),theNaturalScienceFoundationofNanjingUniversityofChineseMedi cine(No.XZR2020048,No.XZR2020069),KeyScience and Technology Program Projects of Jinhua Science and TechnologyBureau (2022-3-147), the Graduate Student Scientific ResearchInnovation Projects in Jiangsu Province (No. SJCX23_0743) andtheCollegeStudentInnovationTrainingProgram(103152023164,202210315057Y ) CR Armstrong DG, 2023, JAMA-J AM MED ASSOC, V330, P62, DOI 10.1001/jama.2023.10578 Armstrong DG, 2017, NEW ENGL J MED, V376, P2367, DOI 10.1056/NEJMra1615439 Atri C, 2018, INT J MOL SCI, V19, DOI 10.3390/ijms19061801 Brancato SK, 2011, AM J PATHOL, V178, P19, DOI 10.1016/j.ajpath.2010.08.003 Brockway B., 2020, Introducing Escherichia coli (E. coli) part 1, The Secret Life of Skin Byrd AL, 2018, NAT REV MICROBIOL, V16, P143, DOI 10.1038/nrmicro.2017.157 Chen HJ, 2023, MATER TODAY BIO, V18, DOI 10.1016/j.mtbio.2023.100543 Chen SF, 2018, BIOINFORMATICS, V34, P884, DOI 10.1093/bioinformatics/bty560 Chen YE, 2018, NATURE, V553, P427, DOI 10.1038/nature25177 Dasari N, 2021, SEMIN PLAST SURG, V35, P153, DOI 10.1055/s-0041-1731460 Di Domizio J, 2020, NAT IMMUNOL, V21, P1034, DOI 10.1038/s41590-020-0721-6 Ding XT, 2022, BURNS TRAUMA, V10, DOI 10.1093/burnst/tkac014 Eming SA, 2014, SCI TRANSL MED, V6, DOI 10.1126/scitranslmed.3009337 Eroglu C, 2016, CYTOTECHNOLOGY, V68, P2075, DOI 10.1007/s10616-016-9947-4 Fu LM, 2012, BIOINFORMATICS, V28, P3150, DOI 10.1093/bioinformatics/bts565 Gardiner M, 2017, PEERJ, V5, DOI 10.7717/peerj.3543 Guillamón E, 2010, FITOTERAPIA, V81, P715, DOI 10.1016/j.fitote.2010.06.005 Hamidzadeh K, 2017, ANNU REV PHYSIOL, V79, P567, DOI 10.1146/annurev-physiol-022516-034348 He TT, 2022, FRONT ENDOCRINOL, V13, DOI 10.3389/fendo.2022.942549 Huang L, 2021, J PHARMACOL SCI, V147, P271, DOI 10.1016/j.jphs.2021.07.008 Kalan LR, 2019, CELL HOST MICROBE, V25, P641, DOI 10.1016/j.chom.2019.03.006 Kivrak I, 2016, INT J MED MUSHROOMS, V18, P97, DOI 10.1615/IntJMedMushrooms.v18.i2.10 Landén NX, 2016, CELL MOL LIFE SCI, V73, P3861, DOI 10.1007/s00018-016-2268-0 Li DH, 2015, BIOINFORMATICS, V31, P1674, DOI 10.1093/bioinformatics/btv033 Li GD, 2021, NAT COMMUN, V12, DOI 10.1038/s41467-021-23448-7 Li RQ, 2008, BIOINFORMATICS, V24, P713, DOI 10.1093/bioinformatics/btn025 Louiselle AE, 2021, TRANSL RES, V236, P109, DOI 10.1016/j.trsl.2021.05.006 Lu YF, 2021, ADV FUNCT MATER, V31, DOI 10.1002/adfm.202105749 Luo MJ, 2020, THERANOSTICS, V10, P3779, DOI 10.7150/thno.44115 Mallik SB, 2018, J DIABETES COMPLICAT, V32, P524, DOI 10.1016/j.jdiacomp.2018.01.015 McDermott K, 2023, DIABETES CARE, V46, P209, DOI 10.2337/dci22-0043 Mirza R, 2011, CYTOKINE, V56, P256, DOI 10.1016/j.cyto.2011.06.016 Mosser DM, 2008, NAT REV IMMUNOL, V8, P958, DOI 10.1038/nri2448 Noguchi H, 2006, NUCLEIC ACIDS RES, V34, P5623, DOI 10.1093/nar/gkl723 Ogbole OO, 2019, MYCOLOGY-UK, V10, P166, DOI 10.1080/21501203.2019.1595204 Patel BK, 2022, INT J MOL SCI, V23, DOI 10.3390/ijms23042375 Reid G, 2011, NAT REV MICROBIOL, V9, P27, DOI 10.1038/nrmicro2473 Rop O, 2009, NUTR REV, V67, P624, DOI 10.1111/j.1753-4887.2009.00230.x Sari M, 2017, FOOD CHEM, V216, P45, DOI 10.1016/j.foodchem.2016.08.010 Sawaya AP, 2020, NAT COMMUN, V11, DOI 10.1038/s41467-020-18276-0 Scharschmidt T.C., 2013, Drug Discovery Today Disease Mechanism, V10, pe83, DOI [DOI 10.1016/J.DDMEC.2012.12.003, 10.1016/j.ddmec.2012.12.003] Spragge F, 2023, SCIENCE, V382, DOI 10.1126/science.adj3502 Tang QH, 2023, ADV DRUG DELIVER REV, V192, DOI 10.1016/j.addr.2022.114671 Tomic-Canic M, 2020, AM J CLIN DERMATOL, V21, P36, DOI 10.1007/s40257-020-00536-w Wang GF, 2023, SCI ADV, V9, DOI 10.1126/sciadv.abo7555 Wang GF, 2021, CELL HOST MICROBE, V29, P777, DOI 10.1016/j.chom.2021.03.003 White EK, 2023, CSH PERSPECT BIOL, V15, DOI 10.1101/cshperspect.a041218 Witherel CE, 2019, ADV HEALTHC MATER, V8, DOI 10.1002/adhm.201801451 Wu XQ, 2022, BURNS TRAUMA, V10, DOI 10.1093/burnst/tkac051 Xu C, 2017, J DIABETES COMPLICAT, V31, P4, DOI 10.1016/j.jdiacomp.2016.10.010 Yang A., 2023, Chin. 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Diterpenes and triterpenes are the main bioactive components of E. kansui. Among them, ingenane-type diterpenes have multiple biological activities as a protein kinase C delta (PKC-delta) activator, which have previously been shown to promote anti-proliferative and pro-apoptotic effects in several human cancer cell lines. However, the activation of PKC subsequently promoted the survival of macrophages. Recently, we found that 13-hydroxyingenol-3-(2,3-dimethylbutanoate)-13-dodecanoate (compound A) from E. kansui showed dual bioactivity, including the inhibition of tumor-cell-line proliferation and regulation of macrophage polarization. This study identifies the possible mechanism of compound A in regulating the polarization state of macrophages, by regulating PKC-delta-extracellular signal regulated kinases (ERK) signaling pathways to exert anti-tumor immunity effects in vitro, which might provide a new treatment method from the perspective of immune cell regulation. C1 [Feng, Xiaoyi; Wang, Lizhong; Pu, Li; Li, Jianchun; Li, Hongmei; Liu, Dan; Li, Rongtao] Kunming Univ Sci & Technol, Fac Life Sci & Technol, Ctr Pharmaceut Sci & Engn, Kunming 650500, Peoples R China. [Feng, Xiaoyi] Yunnan Univ Chinese Med, Sch Basic Med Sci, Kunming 650500, Peoples R China. C3 Kunming University of Science & Technology; Yunnan University of Chinese Medicine RP Liu, D; Li, RT (corresponding author), Kunming Univ Sci & Technol, Fac Life Sci & Technol, Ctr Pharmaceut Sci & Engn, Kunming 650500, Peoples R China. EM liud@kust.edu.cn; lirt@kust.edu.cn RI ; Li, Hongmei/AAH-6365-2019 OI Feng, Xiaoyi/0000-0003-2333-0152; FU National Natural Science Foundation of China; Science and Technology Planning Project of Yunnan Province [202301AT070253, 202101AZ07001-030]; Key Laboratory of New drugs; Key Project of Research and Development of Yunnan Province [202103AC100005, 202302AG050004]; [82073737]; [22067012]; [82060737] FX This research was funded by the National Natural Science Foundation of China (No. 82073737, 22067012, 82060737), the Science and Technology Planning Project of Yunnan Province (No. 202301AT070253, 202101AZ07001-030), the Key Laboratory of New drugs (Traditional Chinese Medicine) for Respiratory Viral Diseases of Yunnan Province, and the Key Project of Research and Development of Yunnan Province (202103AC100005, 202302AG050004). 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J. Mol. Sci. PD SEP PY 2024 VL 25 IS 18 AR 10123 DI 10.3390/ijms251810123 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry GA H8T4N UT WOS:001326106100001 PM 39337608 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Chang, JW Tang, CH AF Chang, Jun-Way Tang, Chih-Hsin TI The role of macrophage polarization in rheumatoid arthritis and osteoarthritis: Pathogenesis and therapeutic strategies SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Review DE Macrophage; Rheumatoid arthritis; Osteoarthritis; Macrophage polarization; Macrophage polarization ID IN-VITRO; INFLAMMATION; MODULATION; ACTIVATION; SYSTEM; PROLIFERATION; MECHANISMS; BIOLOGY; M1; M2 AB Rheumatoid arthritis (RA) and osteoarthritis (OA) are common and debilitating joint disorders affecting millions of individuals worldwide. Despite their distinct pathological features, both conditions share a crucial role of macrophages in disease progression. Macrophages exhibit remarkable plasticity, polarizing into proinflammatory M1 or anti-inflammatory M2 phenotypes in response to environmental cues. An imbalance in macrophage polarization, particularly a shift towards the M1 phenotype, contributes to chronic inflammation and joint damage in RA and OA. This review explores the complex interplay between macrophages and various cell types, including T cells, B cells, synovial fibroblasts, osteoclasts, chondrocytes, and adipocytes, in the pathogenesis of these diseases. We discuss the current understanding of macrophage polarization in RA and OA, highlighting the molecular mechanisms involved. Furthermore, we provide an overview of potential therapeutic strategies targeting macrophage polarization, such as disease-modifying anti-rheumatic drugs, traditional Chinese medicine, nanomedicines, proteins, chemical compounds, and physical therapies. By elucidating the precise mechanisms governing macrophage polarization and its interactions with other cells in the joint microenvironment, researchers can identify novel therapeutic targets and develop targeted interventions to alleviate disease progression and improve patient outcomes in RA and OA. C1 [Chang, Jun-Way] China Med Univ, PhD Program Biotechnol & Biomed Ind, Taichung, Taiwan. [Tang, Chih-Hsin] China Med Univ, Sch Med, Dept Pharmacol, Taichung, Taiwan. [Tang, Chih-Hsin] China Med Univ, Grad Inst Biomed Sci, Taichung, Taiwan. [Tang, Chih-Hsin] China Med Univ, Chinese Med Res Ctr, Taichung, Taiwan. [Tang, Chih-Hsin] Asia Univ, Coll Med & Hlth Sci, Dept Med Lab Sci & Biotechnol, Taichung, Taiwan. 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We would like to thank BioRender for providing the tools to create the figures used in this study. 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PD DEC 5 PY 2024 VL 142 AR 113056 DI 10.1016/j.intimp.2024.113056 EA AUG 2024 PN A PG 12 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA F7H4T UT WOS:001311485300001 PM 39217882 DA 2026-03-26 ER PT J AU Zhang, Y Kang, QM He, LY Chan, KL Gu, H Xue, WJ Zhong, ZF Tan, W AF Zhang, Yang Kang, Qianming He, Luying Chan, Ka Long Gu, Hui Xue, Wenjing Zhong, Zhangfeng Tan, Wen TI Exploring the immunometabolic potential of Danggui Buxue Decoction for the treatment of IBD-related colorectal cancer SO CHINESE MEDICINE LA English DT Review DE Danggui Buxue Decoction; Astragali Radix; Angelicae Sinensis Radix; Immunometabolism; IBD-CRC ID INFLAMMATORY-BOWEL-DISEASE; CHINESE HERBAL DECOCTION; ANGELICA-SINENSIS; ASTRAGALOSIDE-IV; BREAST-CANCER; MACROPHAGE POLARIZATION; IMMUNOMODULATORY ACTIVITY; ANTIINFLAMMATORY ACTIVITY; INTESTINAL MICROBIOTA; ULCERATIVE-COLITIS AB Danggui Buxue (DGBX) decoction is a classical prescription composed of Astragali Radix (AR) and Angelicae Sinensis Radix (ASR), used to enrich blood, and nourish Qi in Chinese medicine, with the potential to recover energy and stimulate metabolism. Chronic inflammation is a risk factor in the development of inflammatory bowel disease (IBD)-related colorectal cancer (CRC). More importantly, AR and ASR have anti-inflammatory and anti-cancer activities, as well as prefiguring a potential effect on inflammation-cancer transformation. We, therefore, aimed to review the immunometabolism potential of DGBX decoction and its components in this malignant transformation, to provide a helpful complement to manage the risk of IBD-CRC. The present study investigates the multifaceted roles of DGBX decoction and its entire components AR and ASR, including anti-inflammation effects, anti-cancer properties, immune regulation, and metabolic regulation. This assessment is informed by a synthesis of scholarly literature, with more than two hundred articles retrieved from PubMed, Web of Science, and Scopus databases within the past two decades. The search strategy employed utilized keywords such as "Danggui Buxue", "Astragali Radix", "Angelicae Sinensis Radix", "Inflammation", and "Metabolism", alongside the related synonyms, with a particular emphasis on high-quality research and studies yielding significant findings. The potential of DGBX decoction in modulating immunometabolism holds promise for the treatment of IBD-related CRC. It is particularly relevant given the heterogeneity of CRC and the growing trend towards personalized medicine, but the precise and detailed mechanism necessitate further in vivo validation and extensive clinical studies to substantiate the immunometabolic modulation and delineate the pathways involved. Danggui Buxue decoction is a classical prescription consisting of Astragali Radix and Angelicae Sinensis Radix with the efficacy of tonifying blood and invigorating qi in traditional Chinese medicine.Astragali Radix and Angelicae Sinensis Radix, both have a variety of pharmacological activities, including anti-inflammation and anti-cancer effects.In view of inflammation and malignant transformation in inflammatory bowel disease-related colorectal cancer and the curative effects of Astragali Radix and Angelicae Sinensis Radix, immunometabolism modulation potential of DGBX were reviewed and discussed in the present study. C1 [Zhang, Yang; Kang, Qianming; He, Luying; Gu, Hui; Xue, Wenjing; Tan, Wen] Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China. [Chan, Ka Long; Zhong, Zhangfeng] Univ Macau, Inst Chinese Med Sci, Macao Ctr Res & Dev Chinese Med, Macau 999078, Peoples R China. C3 Lanzhou University; University of Macau RP Tan, W (corresponding author), Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China.; Zhong, ZF (corresponding author), Univ Macau, Inst Chinese Med Sci, Macao Ctr Res & Dev Chinese Med, Macau 999078, Peoples R China. EM zfzhong@um.edu.mo; tanwen@lzu.edu.cn RI Xue, Wenjing/R-4164-2016; Chan, Ka/AFL-5295-2022; He, Luying/OKR-7835-2025 FU Gansu Province Science Fund for Distinguished Young Scholars [20JR10RA650]; Outstanding Youth of the Fundamental Research Funds for the Central Universities [lzujbky-2021-ey21]; Macao Science and Technology Development Fund [FDCT 001/2023/ALC, 0123/2022/A, 0006/2020/AKP]; Natural Science Foundation of Guangdong Province, China [2020A1515010922]; Traditional Chinese Medicine Bureau of Guangdong Province, China [20201183]; Shenzhen-Hong Kong-Macau S&T Program (Category C) [SGDX2020110309420200]; Research Fund of the University of Macau [CPG2023-00028-ICMS] FX This research was funded by the Gansu Province Science Fund for Distinguished Young Scholars (20JR10RA650), and the Outstanding Youth of the Fundamental Research Funds for the Central Universities (lzujbky-2021-ey21). This study was also supported by the Macao Science and Technology Development Fund (FDCT 001/2023/ALC, 0123/2022/A and 0006/2020/AKP), Natural Science Foundation of Guangdong Province, China (2020A1515010922), Traditional Chinese Medicine Bureau of Guangdong Province, China (20201183), Shenzhen-Hong Kong-Macau S&T Program (Category C) (SGDX2020110309420200), and Research Fund of the University of Macau (CPG2023-00028-ICMS). 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Med. PD AUG 29 PY 2024 VL 19 IS 1 AR 117 DI 10.1186/s13020-024-00978-y PG 24 WC Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine; Pharmacology & Pharmacy GA E4B2U UT WOS:001302465700001 PM 39210410 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Wei, ZY Ni, X Cui, H Shu, C Peng, YX Liu, JY Li, YW AF Wei, Ziyun Ni, Xiao Cui, He Shu, Chang Peng, Yuxuan Liu, Jieyu Li, Yunwei TI Engeletin attenuates the inflammatory response via inhibiting TLR4-NFκB signaling pathway in Crohn's disease-like colitis SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Engeletin; CD-Like colitis; Macrophages; M1 polarization; NF-kappa B signaling ID FACTOR-KAPPA-B; MACROPHAGES; APOPTOSIS AB Ethnopharmacological relevance: Smilax glabra rhizome has a long history been used for clinical purposes in traditional Chinese medicinal for treating various inflammatory conditions. Engeletin1 (ENG) is one of the most abundant bioactive compounds found in Smilax glabra rhizome, with anti-inflammatory, antioxidant, and ulcerpreventing activities. Aim of the study: The purpose of this study was to investigate the ability of ENG to alleviate inflammatory symptoms and improve epithelial barrier integrity utilize a 2,4,6-trinitrobenzene sulfonic acid2 (TNBS)-induced murine model in Crohn's disease3 (CD)-like colitis, and to characterize the underlying anti-inflammatory mechanisms of action. Materials and methods: A colitis model was established in BALB/c mice and treated with ENG for 7 days. RAW264.7 macrophages were pre-treated with ENG and lipopolysaccharide4 (LPS) stimulation. The mice's weight and colon length were assessed. qPCR and Western blotting were used to analyze gene expression and TLR4-NF kappa B pathway. Flow cytometry was used to analyze the polarization states of the macrophages. Results: Treatment with ENG was sufficient to significantly alleviate symptoms of inflammation and colonic epithelial barrier integrity in treated mice. Significant inhibition of TNF-alpha, IL-1 beta, and IL-6 expression was observed following ENG treatment in vivo and in vitro. ENG was also determined to be capable of inhibiting the expression of iNOS and CD86, inhibited M1 macrophage polarization in vitro, as well as the TLR4-NF kappa B signaling pathway. Molecular docking showed a highly stable binding between ENG and TLR4. Conclusion: ENG has been proven to alleviate inflammation and ameliorate the damage of epithelial barrier in CD-like colitis. ENG also suppressed the M1 macrophages polarization and the inhibited inflammatory cytokines. TLR4-NF kappa B signaling pathway, especially TLR4, may be the target of ENG. These data offer a new insight into the therapeutic mechanisms of ENG. C1 [Li, Yunwei] China Med Univ, Hosp 1, Dept Anorectal Surg, Shenyang 110001, Liaoning, Peoples R China. [Wei, Ziyun; Ni, Xiao; Cui, He; Shu, Chang; Peng, Yuxuan; Liu, Jieyu; Li, Yunwei] China Med Univ, Sch Publ Hlth, Dept Hlth Lab Technol, Shenyang 110122, Liaoning, Peoples R China. [Liu, Jieyu] China Med Univ, Key Lab Environm Stress & Chron Dis Control & Prev, Minist Educ, Shenyang, Peoples R China. C3 China Medical University; China Medical University; China Medical University RP Li, YW (corresponding author), China Med Univ, Hosp 1, Dept Anorectal Surg, Shenyang 110001, Liaoning, Peoples R China.; Liu, JY; Li, YW (corresponding author), China Med Univ, Sch Publ Hlth, Dept Hlth Lab Technol, Shenyang 110122, Liaoning, Peoples R China. EM liujieyu@cmu.edu.cn; ywli@cmu.edu.cn FX The author would like to thank MJEditor for technical editing of the manuscript. 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PD JAN 10 PY 2025 VL 336 AR 118733 DI 10.1016/j.jep.2024.118733 EA AUG 2024 PG 11 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA E5F1S UT WOS:001303249800001 PM 39181281 OA hybrid DA 2026-03-26 ER PT J AU Wang, ZX Wang, X Fu, LH Xu, SY Wang, XJ Liao, Q Zhuang, TX Liu, LC Zhang, HY Li, W Xiong, AZ Gu, LH Wang, ZT Wang, RF Tao, F Yang, L Ding, LL AF Wang, Zixuan Wang, Xu Fu, Lihong Xu, Shuyang Wang, Xunjiang Liao, Qi Zhuang, Tongxi Liu, Longchan Zhang, Haoyue Li, Wei Xiong, Aizhen Gu, Lihua Wang, Zhengtao Wang, Rufeng Tao, Feng Yang, Li Ding, Lili TI Shengmai San formula alleviates high-fat diet-induced obesity in mice through gut microbiota-derived bile acid promotion of M2 macrophage polarization and thermogenesis SO PHYTOMEDICINE LA English DT Article DE Browning; Bile acids; M2 macrophages; Intestinal flora; Obesity; Shengmai San ID INSULIN-RESISTANCE; LIPOLYSIS; RECEPTOR; LIVER; RATS AB Background: Shengmai San Formula (SMS) is a traditional Chinese medicine (TCM) that has been used to treat wasting-thirst regarded as diabetes mellitus, which occurs disproportionately in obese patients. Therefore, we investigated whether SMS could be used to treat obesity, and explored possible mechanisms by which it might improve glucose and fat metabolism. Methods: To investigate the effects of SMS on a high-fat diet (HFD)-induced obesity (DIO) model, we studied glucose metabolism via glucose tolerance testing (GTT) and insulin tolerance testing (ITT). Browning of white adipose tissue (WAT) was evaluated using H&E staining, along with browning-related gene and protein expression. Changes in bile acid (BA) levels in serum, liver, ileum, and inguinal white adipose tissue were detected by Ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). In addition, antimicrobial mixture (ABX) and fecal microbial transplantation (FMT) experiments were used to verify the role of gut flora in the effects produced by SMS on HFD-induced obesity model. Results: SMS ameliorated diet-induced dyslipidemia in a dose-dependent manner and reduced glucose intolerance and insulin resistance in DIO mice, helping to restore energy metabolism homeostasis. SMS significantly altered the structure of intestinal microbiome composition, decreasing the abundance of Lactobacillus carrying bile salt hydrolase (BSH) enzymes and thereby increasing the level of conjugated BAs in the blood, ileum, and iWAT. Increased TCA content promoted the secretion of Slit3 from M2 macrophages in iWAT, which activates the protein kinase A/calmodulin-dependent protein kinase II (PKA/CaMKII) signaling pathway in sympathetic neurons via the roundabouts receptor 1(ROBO1). This pathway promotes the synthesis and release of norepinephrine (NE), inducing cyclic adenosine monophosphate (cAMP) release in adipose tissue that activates the cyclic adenosine monophosphate/protein kinase A/phosphorylated hormone-sensitive lipase (cAMP/PKA/pHSL) pathway and enhances WAT browning. ABX treatment eliminated SMS effects on glucose and lipid metabolism in DIO mice, whereas glucose and lipid metabolism in obese mice improved following SMS-FMT and increased the level of serum bile acids. Conclusion: SMS affects intestinal flora and bile acid composition in vivo and increased TCA promotes M2 macrophage polarization and Slit3 release in adipose tissue. This induces NE release and increases WAT browning in obese mice, which may be a mechanism by which SMS could be used to treat obesity. C1 [Wang, Zixuan; Wang, Xu; Xu, Shuyang; Wang, Xunjiang; Liao, Qi; Zhuang, Tongxi; Liu, Longchan; Zhang, Haoyue; Li, Wei; Xiong, Aizhen; Gu, Lihua; Wang, Zhengtao; Wang, Rufeng; Yang, Li; Ding, Lili] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, Shanghai Key Lab Complex Prescript, Shanghai 201203, Peoples R China. [Wang, Zixuan; Wang, Xu; Xu, Shuyang; Wang, Xunjiang; Liao, Qi; Zhuang, Tongxi; Liu, Longchan; Zhang, Haoyue; Li, Wei; Xiong, Aizhen; Gu, Lihua; Wang, Zhengtao; Wang, Rufeng; Yang, Li; Ding, Lili] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, Key Lab Standardizat Chinese Med, Minist Educ MOE, Shanghai 201203, Peoples R China. [Wang, Zixuan; Wang, Xu; Xu, Shuyang; Wang, Xunjiang; Liao, Qi; Zhuang, Tongxi; Liu, Longchan; Zhang, Haoyue; Li, Wei; Xiong, Aizhen; Gu, Lihua; Wang, Zhengtao; Wang, Rufeng; Yang, Li; Ding, Lili] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, Key Lab New Resources & Qual Evaluat Chinese Med, SATCM, Shanghai 201203, Peoples R China. [Wang, Zixuan; Wang, Xu; Xu, Shuyang; Wang, Xunjiang; Liao, Qi; Zhuang, Tongxi; Liu, Longchan; Zhang, Haoyue; Li, Wei; Xiong, Aizhen; Gu, Lihua; Wang, Zhengtao; Wang, Rufeng; Yang, Li; Ding, Lili] Shanghai R&D Ctr Standardizat Tradit Chinese Med, Shanghai 201203, Peoples R China. [Tao, Feng] Shanghai Univ Tradit Chinese Med, Shanghai Municipal Hosp Tradit Chinese Med, Endocrinol Dept, Shanghai 200071, Peoples R China. [Fu, Lihong] Shanghai Univ Tradit Chinese Med, Peoples Hosp 7, Dept Endocrinol, Shanghai 200137, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine RP Wang, RF; Tao, F; Yang, L; Ding, LL (corresponding author), Shanghai Univ Tradit Chinese Med, Inst Tradit Chinese Mat Med, Cai Lun Rd 1200, Shanghai 201203, Peoples R China. EM wrffrw0801@shutcm.edu.cn; taofeng@shutcm.edu.cn; yangli7951@hotmail.com; liliding@shutcm.edu.cn RI TAO, Feng/Q-7827-2016; Fu, Lihong/HLV-7902-2023; Xu, Shuyang/GQA-8488-2022; Wang, Zhengtao/AAH-7360-2019 OI TAO, Feng/0000-0003-1214-6800; Wang, Zhengtao/0000-0003-2797-4625 FU Natural Science Foundations of China [82122074, 82204406, 81920108033, 82130115, 82304992, 82274165, 82074011]; Program of Shanghai Municipal Natural Science Foundation [21ZR1482000]; Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine [2023YZZ01, 2023YZZ02]; NATCM's Project of High-level Construction of Key TCM Disciplines [zyyzdxk-2023058]; Pudong New Area Health Commission clinical characteristic discipline construction project [PWYts2021-13] FX This work is financially sponsored by Natural Science Foundations of China (82122074, 82204406, 81920108033, 82130115, 82304992, 82274165 and 82074011) and the Program of Shanghai Municipal Natural Science Foundation (Grant No. 21ZR1482000) . It is also supported by Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine (2023YZZ01, 2023YZZ02) , NATCM's Project of High-level Construction of Key TCM Disciplines (No: zyyzdxk-2023058) and Pudong New Area Health Commission clinical characteristic discipline construction project (PWYts2021-13) . 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In this study, a novel traditional Chinese medicine microneedle patch was designed based on the physiological characteristics of wounds, with properties including hemostasis, anti-inflammatory, antioxidant, antimicrobial, and induction of angiogenesis. Initially, white peony polysaccharide (BSP) with hemostatic properties and carboxymethyl chitosan (CMCS) with antimicrobial capabilities were used as materials for microneedle fabrication. To endow it with antimicrobial, procoagulant, and adhesive properties. Among them, loaded with ROS-sensitive nanoparticles of Astragalus polysaccharides (APS) based on effective components baicalein (Bai) and berberine (Ber) from Scutellaria baicalensis (SB) and Coptis chinensis (CC) drugs (APB@Ber). Together, they are constructed into multifunctional traditional Chinese medicine composite microneedles (C/B@APB@Ber). Bai and Ber synergistically exert anti-inflammatory and antimicrobial effects. Microneedle patches loaded with BSP and APS exhibited significant effects on cell proliferation and angiogenesis induction. The combination of composite polysaccharides enabled the microneedles to adhere stably to wounds and provide sufficient strength to penetrate the biofilm and induce dispersion. The combination of composite polysaccharides enabled the microneedles to adhere stably to wounds and provide sufficient strength to penetrate the biofilm and induce dispersion. Therefore, traditional Chinese medicine multifunctional microneedle patches offer potential medical value in promoting the healing of diabetic wounds. C1 [Liu, Xiaowei; Yang, Weili; Wang, Wenxin; Diao, Ningning; Cao, Min; Cao, Yuxin; Wang, Xuemei; Wang, Xinxin; Pei, Huijie; Jiang, Yifan; Chen, Daquan] Yantai Univ, Collaborat Innovat Ctr Adv Drug Delivery Syst & Bi, Sch Pharm, Yantai 264005, Peoples R China. [Guo, Chunjing; Kong, Ming] Ocean Univ China, Coll Marine Life Sci, 5 Yushan 10 Rd, Qingdao 266003, Peoples R China. C3 Yantai University; Ocean University of China RP Chen, DQ (corresponding author), Yantai Univ, Collaborat Innovat Ctr Adv Drug Delivery Syst & Bi, Sch Pharm, Yantai 264005, Peoples R China.; Kong, M (corresponding author), Ocean Univ China, Coll Marine Life Sci, 5 Yushan 10 Rd, Qingdao 266003, Peoples R China. EM kongming@ouc.edu.cn; cdq1981@126.com RI 刘, 小伟/AAI-5951-2021; chen, canxin/PGM-4677-2026; Jiang, Yifan/HCH-2365-2022 FU Taishan Scholar Foundation of Shandong Province [qnts20161035]; Natural Science Foundation of Shandong Province [ZR2019ZD24, ZR2019YQ30]; Graduate Innovation Foundation of Yantai University FX This funding was supported by the Taishan Scholar Foundation of Shandong Province (No. qnts20161035) ; Natural Science Foundation of Shandong Province (No. ZR2019ZD24, ZR2019YQ30) ; Graduate Innovation Foundation of Yantai University. 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PD DEC 1 PY 2024 VL 345 AR 122574 DI 10.1016/j.carbpol.2024.122574 EA AUG 2024 PG 16 WC Chemistry, Applied; Chemistry, Organic; Polymer Science WE Science Citation Index Expanded (SCI-EXPANDED) SC Chemistry; Polymer Science GA D1C1J UT WOS:001293625100001 PM 39227108 DA 2026-03-26 ER PT J AU Huang, Z Meng, FY Lu, LZ Guo, QQ Lv, CJ Tan, NH Deng, Z Chen, JY Zhang, ZS Zou, B Long, HP Zhou, Q Tian, S Mei, S Tian, XF AF Huang, Zhen Meng, Fan-Ying Lu, Lin-Zhu Guo, Qian-Qian Lv, Chang-Jun Tan, Nian-Hua Deng, Zhe Chen, Jun-Yi Zhang, Zi-Shu Zou, Bo Long, Hong-Ping Zhou, Qing Tian, Sha Mei, Si Tian, Xue-Fei TI Calculus bovis inhibits M2 tumor-associated macrophage polarization via Wnt/β-catenin pathway modulation to suppress liver cancer SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Calculus bovis; M2 tumor-associated macrophage polarization; Liver cancer; Wnt/beta-catenin pathway; Tumor microenvironment ID HEPATOCELLULAR-CARCINOMA; CELLS AB BACKGROUND Calculus bovis (CB), used in traditional Chinese medicine, exhibits anti-tumor effects in various cancer models. It also constitutes an integral component of a compound formulation known as Pien Tze Huang, which is indicated for the treatment of liver cancer. However, its impact on the liver cancer tumor microenvironment, particularly on tumor-associated macrophages (TAMs), is not well understood. AIM To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/beta-catenin pathway modulation. METHODS This study identified the active components of CB using UPLC-Q-TOF-MS, evaluated its anti-neoplastic effects in a nude mouse model, and elucidated the underlying mechanisms via network pharmacology, transcriptomics, and molecular docking. In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs, and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis. RESULTS This study identified 22 active components in CB, 11 of which were detected in the bloodstream. Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth. An integrated approach employing network pharmacology, transcriptomics, and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization. In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/beta-catenin pathway activation. The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001, confirming its pathway specificity. CONCLUSION This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/beta-catenin pathway, contributing to the suppression of liver cancer growth. C1 [Huang, Zhen; Lu, Lin-Zhu; Guo, Qian-Qian; Lv, Chang-Jun; Tan, Nian-Hua; Deng, Zhe; Chen, Jun-Yi; Tian, Sha; Tian, Xue-Fei] Hunan Univ Chinese Med, Coll Integrated Chinese & Western Med, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China. [Huang, Zhen; Lu, Lin-Zhu; Guo, Qian-Qian; Lv, Chang-Jun; Tan, Nian-Hua; Chen, Jun-Yi; Mei, Si; Tian, Xue-Fei] Hunan Univ Chinese Med, Hunan Key Lab Translat Res Formulas & Zheng Tradit, Changsha 410208, Hunan, Peoples R China. [Huang, Zhen; Lu, Lin-Zhu; Guo, Qian-Qian; Lv, Chang-Jun; Tan, Nian-Hua; Chen, Jun-Yi; Mei, Si; Tian, Xue-Fei] Hunan Univ Chinese Med, Key Lab Tradit Chinese Med Mech Tumor Prevent & Tr, Changsha 410208, Hunan, Peoples R China. [Meng, Fan-Ying; Zhang, Zi-Shu; Zou, Bo] Hunan Univ Tradit Chinese Med, Clin Coll Tradit Chinese Med 1, Changsha 410007, Hunan, Peoples R China. [Tan, Nian-Hua] Hunan Univ Chinese Med, Dept Hepatol, Changsha 410007, Hunan, Peoples R China. [Long, Hong-Ping; Zhou, Qing] Hunan Univ Chinese Med, Hosp 1, Changsha 410007, Hunan, Peoples R China. [Mei, Si] Hunan Univ Chinese Med, Fac Med, Changsha 410208, Hunan, Peoples R China. C3 Hunan University of Chinese Medicine; Hunan University of Chinese Medicine; Hunan University of Chinese Medicine; Hunan University of Chinese Medicine; Hunan University of Chinese Medicine; Hunan University of Chinese Medicine; Hunan University of Chinese Medicine RP Tian, XF (corresponding author), Hunan Univ Chinese Med, Coll Integrated Chinese & Western Med, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China. EM 003640@hnucm.edu.cn RI Chen, Jinyan/JJF-7875-2023; tian, xuefei/OJV-1564-2025 FU National Natural Science Foundation of China [82074450]; Education Department of Hunan Province [21A0243, 21B0374, 22B0397, 22B0392]; Research Project of "Academician Liu Liang Workstation" of Hunan University of Traditional Chinese Medicine [21YS003]; Hunan Administration of Traditional Chinese Medicine [B2023001, B2023009]; Hunan Provincial Natural Science Foundation of China [2023JJ40481] FX Supported by National Natural Science Foundation of China, No. 82074450; Education Department of Hunan Province, No. 21A0243, No. 21B0374, No. 22B0397, and No. 22B0392; Research Project of "Academician Liu Liang Workstation" of Hunan University of Traditional Chinese Medicine, No. 21YS003; Hunan Administration of Traditional Chinese Medicine, No. B2023001 and No. B2023009; and Hunan Provincial Natural Science Foundation of China, No. 2023JJ40481 CR Carvalho TGD, 2023, BIOMED PHARMACOTHER, V168, DOI 10.1016/j.biopha.2023.115663 Chen Y., 2024, J Cell Mol Med, V28, pe18072 Chen YN, 2020, EUR J PHARMACOL, V877, DOI 10.1016/j.ejphar.2020.173090 Cox N, 2021, ANNU REV IMMUNOL, V39, P313, DOI 10.1146/annurev-immunol-093019-111748 Cronan MR, 2016, IMMUNITY, V45, P861, DOI 10.1016/j.immuni.2016.09.014 Cutolo M, 2022, FRONT IMMUNOL, V13, DOI 10.3389/fimmu.2022.867260 Dall'Olio FG, 2021, IMMUNOTHERAPY-UK, V13, P257, DOI 10.2217/imt-2020-0179 Deng YL, 2020, FRONT PHARMACOL, V11, DOI 10.3389/fphar.2020.564131 Dimin N, 2022, Digital Chinese Medicine, V5, P83, DOI 10.1016/j.dcmed.2022.03.009 FIDLER IJ, 1988, BIOCHIM BIOPHYS ACTA, V948, P151, DOI 10.1016/0304-419X(88)90009-1 Gou HY, 2023, GASTROENTEROLOGY, V165, P1404, DOI 10.1053/j.gastro.2023.08.052 Guven DC, 2022, FRONT MOL BIOSCI, V9, DOI 10.3389/fmolb.2022.1039121 He S, 2024, BBA-MOL BASIS DIS, V1870, DOI 10.1016/j.bbadis.2023.166996 Laface C, 2022, CANCERS, V14, DOI 10.3390/cancers14164028 Li JJ, 2021, J INTEGR MED-JIM, V19, P469, DOI 10.1016/j.joim.2021.08.004 Li XY, 2018, EVID-BASED COMPL ALT, V2018, DOI 10.1155/2018/6714829 Li YH, 2016, CANCER RES, V76, P3364, DOI 10.1158/0008-5472.CAN-15-2302 Liu HX, 2022, BIOMED RES INT, V2022, DOI 10.1155/2022/3353464 Long G, 2024, FREE RADICAL BIO MED, V212, P162, DOI 10.1016/j.freeradbiomed.2023.11.030 Maki H, 2022, BIOSCI TRENDS, V16, P178, DOI 10.5582/bst.2022.01245 Mano Y, 2013, PATHOBIOLOGY, V80, P146, DOI 10.1159/000346196 Miao T G, 2022, Zhonghua Gan Zang Bing Za Zhi, V30, P923, DOI 10.3760/cma.j.cn501113-20220703-00365 Muñoz-Martínez S, 2021, CURR OPIN PHARMACOL, V60, P141, DOI 10.1016/j.coph.2021.07.009 Naramore Sara, 2015, Case Rep Gastroenterol, V9, P227, DOI [10.1159/000431217, 10.1159/000431217] Pai SG, 2017, J HEMATOL ONCOL, V10, DOI 10.1186/s13045-017-0471-6 Peng JY, 2023, J HEPATOL, V79, pe92, DOI 10.1016/j.jhep.2023.02.019 Rizzo A, 2023, CANCER IMMUNOL IMMUN, V72, P1381, DOI 10.1007/s00262-023-03366-x Rizzo A, 2022, J PERS MED, V12, DOI 10.3390/jpm12111788 Rizzo A, 2021, FUTURE ONCOL, V17, P755, DOI 10.2217/fon-2020-0986 Rizzo A, 2020, FUTURE ONCOL, V16, P2587, DOI 10.2217/fon-2020-0669 Rui R, 2023, FRONT IMMUNOL, V14, DOI 10.3389/fimmu.2023.1212476 Sen B, 2022, MED ONCOL, V39, DOI 10.1007/s12032-022-01732-w Sharma A, 2020, CELL, V183, P377, DOI 10.1016/j.cell.2020.08.040 Shi J, 2024, J NAT MED-TOKYO, V78, P633, DOI 10.1007/s11418-024-01812-3 Sica A, 2015, CELL MOL LIFE SCI, V72, P4111, DOI 10.1007/s00018-015-1995-y Wang C, 2023, CANCER MED-US, V12, P16295, DOI 10.1002/cam4.6242 Wang KL, 2021, BIOMED PHARMACOTHER, V133, DOI 10.1016/j.biopha.2020.111044 Wang WH, 2019, CANCERS, V11, DOI 10.3390/cancers11070926 Wu Y, 2012, CANCER MICROENVIRON, V5, P195, DOI 10.1007/s12307-012-0113-z Xiang D, 2023, J ETHNOPHARMACOL, V302, DOI 10.1016/j.jep.2022.115854 Xiang XN, 2021, SIGNAL TRANSDUCT TAR, V6, DOI 10.1038/s41392-021-00484-9 Xu B, 2022, EXPERT OPIN INV DRUG, V31, P337, DOI 10.1080/13543784.2022.2022121 Xu HB, 2023, J ETHNOPHARMACOL, V316, DOI 10.1016/j.jep.2023.116699 Yang Y, 2018, CELL DEATH DIS, V9, DOI 10.1038/s41419-018-0818-0 Yu ZJ, 2020, J ETHNOPHARMACOL, V254, DOI 10.1016/j.jep.2020.112649 Zhang Z, 2021, COMB CHEM HIGH T SCR, V24, P129, DOI 10.2174/1386207323666200808172051 NR 46 TC 28 Z9 30 U1 16 U2 61 PU BAISHIDENG PUBLISHING GROUP INC PI PLEASANTON PA 7041 Koll Center Parkway, Suite 160, PLEASANTON, CA, UNITED STATES SN 1007-9327 EI 2219-2840 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD AUG 7 PY 2024 VL 30 IS 29 DI 10.3748/wjg.v30.i29.3511 PG 24 WC Gastroenterology & Hepatology WE Science Citation Index Expanded (SCI-EXPANDED) SC Gastroenterology & Hepatology GA D1X5O UT WOS:001294185800006 PM 39156500 OA Green Submitted, hybrid DA 2026-03-26 ER PT J AU Lan, MY Lin, CL Zeng, LL Hu, SJ Shi, Y Zhao, Y Liu, X Sun, JF Liang, G Huang, MC AF Lan, Mengyao Lin, Cailu Zeng, Lulu Hu, Shijie Shi, Yuan Zhao, Yan Liu, Xin Sun, Jinfeng Liang, Guang Huang, Mincong TI Linderanine C regulates macrophage polarization by inhibiting the MAPK signaling pathway against ulcerative colitis SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE Linderanine C; Macrophage; M1 polarization; MAPK signaling pathway; Ulcerative colitis ID INFLAMMATORY-BOWEL-DISEASE; ACTIVATION; MECHANISMS; SYSTEM AB Ulcerative colitis (UC) is a chronic non-specific inflammatory disease involving the mucosa and submucosa of the rectum and colon. Lindera aggregate (Sims) Kosterm is a traditional Chinese herb used for thousands of years in the treatment of gastrointestinal diseases. Previously, we have demonstrated that the extracts of Lindera aggregate have good anti-UC effects, but their pharmacodynamic active components have not been fully clarified. Therefore, we explored the therapeutic effect of Linderanine C (LDC), a characteristic component of Lindera aggregata, on UC and its mechanism in this study. Firstly, we found that LDC could significantly reduce the disease activity index of UC and improve shortened colon and pathological changes in vivo. Colon tissue transcriptomics suggested that the anti-UC effect of LDC might be related to its anti-inflammatory activity. Cellular experiments revealed that LDC could inhibit the expression of the M1 cell marker CD86 in RAW264.7 cells, reduce the production of inflammatory mediators such as IL-6 and TNF-alpha, and have good anti-inflammatory activity in vitro. Cellular transcriptomics reveal the potential involvement of the MAPK signaling pathway in the antiinflammatory effect of LDC. The co-culture assay confirmed that LDC could significantly reduce inflammationmediated intestinal epithelial cell injury. In conclusion, LDC was able to inhibit macrophage M1 polarization and reduce inflammatory mediator production by inhibiting the MAPK signaling pathway, effectively improving UC. C1 [Lan, Mengyao; Lin, Cailu; Zeng, Lulu; Hu, Shijie; Shi, Yuan; Zhao, Yan; Liang, Guang; Huang, Mincong] Hangzhou Med Coll, Sch Pharmaceut Sci, Zhejiang TCM Key Lab Pharmacol & Translat Res Nat, Hangzhou 311399, Zhejiang, Peoples R China. [Sun, Jinfeng; Liang, Guang] Hangzhou Med Coll, Zhejiang Prov Peoples Hosp, Affiliated Peoples Hosp, Dept Pharm, Hangzhou 310014, Zhejiang, Peoples R China. [Sun, Jinfeng; Liang, Guang] Hangzhou Med Coll, Zhejiang Prov Peoples Hosp, Affiliated Peoples Hosp, Inst Inflammat, Hangzhou 310014, Zhejiang, Peoples R China. [Liu, Xin] Hangzhou Med Coll, Zhejiang Prov Peoples Hosp, Affiliated Peoples Hosp, Dept Colorectal Surg, Hangzhou 310014, Zhejiang, Peoples R China. [Sun, Jinfeng] Yanbian Univ, Coll Pharm, Key Lab Nat Med Changbai Mt, Minist Educ, Yanji 133002, Jilin, Peoples R China. C3 Hangzhou Medical College; Hangzhou Medical College; Zhejiang Provincial People's Hospital; Hangzhou Medical College; Zhejiang Provincial People's Hospital; Hangzhou Medical College; Zhejiang Provincial People's Hospital; Yanbian University RP Liang, G; Huang, MC (corresponding author), Hangzhou Med Coll, Sch Pharmaceut Sci, Zhejiang TCM Key Lab Pharmacol & Translat Res Nat, Hangzhou 311399, Zhejiang, Peoples R China. EM wzmcliangguang@163.com; hmc1218@163.com RI ; Lin, Cailu/E-5316-2011 OI lan, mengyao/0009-0003-9565-054X; FU National Natural Science Foundation of China [82004024, 82300589, 82360805]; Zhejiang Medical and Health Science and Technology Plan Project [2024KY917, 2021KY134]; Basic Scientific Research Funds of Department of Educa-tion of Zhejiang Province [KYYB2023002, KYYB2023017]; Natural Science Foundation of Zhejiang province [Q24H280064]; Administration of traditional Chinese Medicine of Zhejiang province [2024ZF056]; Key Discipline of Zhejiang Province in Public Health and Preventive Medicine (First Class, Category A), Hangzhou Medical College FX This work was financially supported by the National Natural Science Foundation of China (82004024, 82300589, 82360805) , Zhejiang Medical and Health Science and Technology Plan Project (2024KY917, 2021KY134) , Basic Scientific Research Funds of Department of Educa-tion of Zhejiang Province (KYYB2023002, KYYB2023017) , Natural Science Foundation of Zhejiang province (Q24H280064) , the administration of traditional Chinese Medicine of Zhejiang province (2024ZF056), Key Discipline of Zhejiang Province in Public Health and Preventive Medicine (First Class, Category A), Hangzhou Medical College. 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Pharmacother. PD SEP PY 2024 VL 178 AR 117239 DI 10.1016/j.biopha.2024.117239 EA AUG 2024 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA C3U2W UT WOS:001288639500001 PM 39098180 OA Green Submitted, gold DA 2026-03-26 ER PT J AU He, YB Xu, H Liu, Y Kempa, S Vechiatto, C Schmidt, R Yilmaz, EY Heidemann, L Schnorr, J Metzkow, S Schellenberger, E Häckel, A Patzak, A Müller, DN Savic, LJ AF He, Yubei Xu, Han Liu, Yu Kempa, Stefan Vechiatto, Carolina Schmidt, Robin Yilmaz, Emine Yaren Heidemann, Luisa Schnorr, Joerg Metzkow, Susanne Schellenberger, Eyk Haeckel, Akvile Patzak, Andreas Mueller, Dominik N. Savic, Lynn Jeanette TI The Effects of Hypoxia on the Immune-Metabolic Interplay in Liver Cancer SO BIOMOLECULES LA English DT Article DE hepatocellular carcinoma (HCC); hypoxia; M2-like polarization; GC-MS-based metabolic profiling; 2-amino-butanoic acid (2A-BA) ID MACROPHAGES; POLARIZATION; ARGINASE; CELLS; ACID AB M2-like macrophages promote tumor growth and cancer immune evasion. This study used an in vitro model to investigate how hypoxia and tumor metabolism affect macrophage polarization. Liver cancer cells (HepG2 and VX2) and macrophages (THP1) were cultured under hypoxic (0.1% O-2) and normoxic (21% O-2) conditions with varying glucose levels (2 g/L or 4.5 g/L). Viability assays and extracellular pH (pHe) measurements were conducted over 96 hours. Macrophages were exposed to the tumor-conditioned medium (TCM) from the cancer cells, and polarization was assessed using arginase and nitrite assays. GC-MS-based metabolic profiling quantified TCM meta-bolites and correlated them with M2 polarization. The results showed that pHe in TCMs decreased more under hypoxia than normoxia (p < 0.0001), independent of glucose levels. The arginase assay showed hypoxia significantly induced the M2 polarization of macrophages (control group: p = 0.0120,(0.1%)VX2-TCM group: p = 0.0149, (0.1%)HepG2-TCM group: p < 0.0001, (0.1%)VX2-TCMHG group: p = 0.0001, and (0.1%)HepG2-TCMHG group: p < 0.0001). TCMs also induced M2 polarization under normoxic conditions, but the strongest M2 polarization occurred when both tumor cells and macrophages were incubated under hypoxia with high glucose levels. Metabolomics revealed that several metabolites, particularly lactate, were correlated with hypoxia and M2 polarization. Under normoxia, elevated 2-amino-butanoic acid (2A-BA) strongly correlated with M2 polarization. These findings suggest that targeting tumor hypoxia could mitigate immune evasion in liver tumors. Lactate drives acidity in hypoxic tumors, while 2A-BA could be a therapeutic target for overcoming immunosuppression in normoxic conditions. C1 [He, Yubei; Xu, Han; Liu, Yu; Schmidt, Robin; Yilmaz, Emine Yaren; Heidemann, Luisa; Schnorr, Joerg; Metzkow, Susanne; Schellenberger, Eyk; Haeckel, Akvile; Savic, Lynn Jeanette] Charite Univ Med Berlin, Dept Radiol, Campus Virchow Klinikum, D-13353 Berlin, Germany. [He, Yubei; Xu, Han; Liu, Yu; Schmidt, Robin; Yilmaz, Emine Yaren; Heidemann, Luisa; Schnorr, Joerg; Metzkow, Susanne; Schellenberger, Eyk; Haeckel, Akvile; Savic, Lynn Jeanette] Free Univ Berlin, D-13353 Berlin, Germany. [He, Yubei; Xu, Han; Liu, Yu; Schmidt, Robin; Yilmaz, Emine Yaren; Heidemann, Luisa; Schnorr, Joerg; Metzkow, Susanne; Schellenberger, Eyk; Haeckel, Akvile; Savic, Lynn Jeanette] Humboldt Univ, D-13353 Berlin, Germany. [He, Yubei; Liu, Yu; Schmidt, Robin; Yilmaz, Emine Yaren; Heidemann, Luisa; Mueller, Dominik N.; Savic, Lynn Jeanette] Expt & Clin Res Ctr, D-13125 Berlin, Germany. [Kempa, Stefan; Vechiatto, Carolina; Mueller, Dominik N.] Max Delbruck Ctr Mol Med, Helmholtz Assoc, D-10115 Berlin, Germany. [Patzak, Andreas] Charite Univ Med Berlin, Inst Translat Physiol, D-10117 Berlin, Germany. [Savic, Lynn Jeanette] Charite Univ Med Berlin, Berlin Inst Hlth, D-10117 Berlin, Germany. C3 Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Free University of Berlin; Humboldt University of Berlin; Helmholtz Association; Max Delbruck Center for Molecular Medicine; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Humboldt University of Berlin; Free University of Berlin; Charite Universitatsmedizin Berlin; Berlin Institute of Health RP Savic, LJ (corresponding author), Charite Univ Med Berlin, Dept Radiol, Campus Virchow Klinikum, D-13353 Berlin, Germany.; Savic, LJ (corresponding author), Free Univ Berlin, D-13353 Berlin, Germany.; Savic, LJ (corresponding author), Humboldt Univ, D-13353 Berlin, Germany.; Savic, LJ (corresponding author), Expt & Clin Res Ctr, D-13125 Berlin, Germany.; Savic, LJ (corresponding author), Charite Univ Med Berlin, Berlin Inst Hlth, D-10117 Berlin, Germany. EM yubei.he@charite.de; han.xu@charite.de; yu.liu@charite.de; stefan.kempa@mdc-berlin.de; carolina.vechiatto@gmail.com; robin.schmidt@charite.de; emine-yaren.yilmaz@charite.de; luisa.heidemann@charite.de; joerg.schnorr@charite.de; susanne.metzkow@charite.de; eyk.schellenberger@charite.de; akvile.haeckel@charite.de; andreas.patzak@charite.de; dominik.mueller@mdc-berlin.de; lynn-jeanette.savic@charite.de RI Patzak, Aneas/MFZ-6965-2025; Kempa, Stefan/C-5213-2008 OI Patzak, Aneas/0000-0002-1088-6875; Kempa, Stefan/0000-0002-0696-9299; Schmidt, Robin/0000-0003-0012-2799; Schellenberger, Eyk/0000-0003-4096-6865; , Emine Yaren Yilmaz/0009-0004-1789-6488; Savic, Lynn Jeanette/0000-0003-2115-6728 FU Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [394046635-SFB 1365]; Berliner Krebsgesellschaft; Helmholtz Association; Charite-Universitatsmedizin Berlin; Berlin Institute of Health; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [394046635-SFB 1365, DFG-SFB1470/A06]; Deutsches Zentrum fur Herz-Kreislauf-Forschung (DZHK) [81Z0100106]; BMBF (The Federal Ministry of Education and Research) [Forderkennzeichen 01EJ2202D] FX This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)-Project-ID 372486779-SFB 1340. Outside the submitted work, L.J.S. received further funding from the DFG funded research unit FOR5628, and research grants and honoraria from Guerbet. R.S. and L.J.S. received a stipend and research grants from the Berliner Krebsgesellschaft, respectively. Y.H. and H.X. received stipends from the Chinese Scholar Council. E.Y.Y. received a stipend from the Fuldt Stiftung. C.V. was sponsored by the Helmholtz Association in the frame of the AMPRO project. L.J.S. is a fellow of the BIH Clinician Scientist Program funded by the Charite-Universitatsmedizin Berlin and the Berlin Institute of Health. D.N.M. was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Projektnummer 394046635-SFB 1365 and DFG-SFB1470/A06, by the Deutsches Zentrum fur Herz-Kreislauf-Forschung (DZHK, 81Z0100106) and by the BMBF (The Federal Ministry of Education and Research), Forderkennzeichen 01EJ2202D (TAhRget consortium). 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Babaodan capsule (BBD); Macrophage; CD8+T cell ID CANCER AB Ethnopharmacological relevance: Babaodan (BBD) is a unique Chinese medication utilized in traditional Chinese medicine. It can eliminate toxins, induce diuresis, and eliminate yellowish hue. In addition to treating acute and chronic viral hepatitis, cholecystitis, cholangitis, and urinary tract infections, BBD has garnered popularity as a substitution treatment for several malignant cancers, particularly hepatocellular carcinoma (HCC). Aim of the study: To elucidate the efficacy and mechanism of BBD alone and combined with camrelizumab (CLM) for treating HCC. Methods: We investigated the effects of BBD on the HCC tumor microenvironment in vivo. Furthermore, we evaluated its effects on tumor growth and metastasis induced by M2 macrophages in vitro. Results: In a mouse model of orthotopic HCC, BBD decreased tumor growth. Furthermore, it increased the M1/M2 macrophage ratio and CD8+ T-cell abundance in mice. In addition, BBD reversed HCC cell proliferation and metastasis induced by M2 macrophages, increased the anti-HCC effect of low-dose CLM, and attenuated organ damage induced by high-dose CLM. Lastly, BBD enhanced the efficacy of CLM via the PI3K/AKT/mTOR signaling pathway. Conclusion: BBD increases the antitumor effect of CLM by modulating the tumor immune microenvironment and attenuating its the toxic side effects of CLM. C1 [Liu, Caiyan; Zhang, Siqi; Pu, Weiling; Yang, Shenshen; Yu, Haiyang] Tianjin Univ Tradit Chinese Med, State Key Lab Component Based Chinese Med, Tianjin 301617, Peoples R China. [Lin, Xiaowei] Tianjin Univ Tradit Chinese Med, Sch Tradit Chinese Med, Tianjin 301617, Peoples R China. [Che, Li; Lai, Zhicheng; Chen, Xiyi] Xiamen Tradit Chinese Med Co Ltd, Xiamen 361100, Peoples R China. [Qiu, Yuling] Tianjin Med Univ, Sch Pharm, Tianjin 300070, Peoples R China. C3 Tianjin University of Traditional Chinese Medicine; Tianjin University of Traditional Chinese Medicine; Tianjin Medical University RP Yang, SS; Yu, HY (corresponding author), Tianjin Univ Tradit Chinese Med, State Key Lab Component Based Chinese Med, Tianjin 301617, Peoples R China.; Qiu, YL (corresponding author), Tianjin Med Univ, Sch Pharm, Tianjin 300070, Peoples R China.; Yu, HY (corresponding author), Tianjin Univ Tradit Chinese Med, State Key Lab Component Based Chinese 21 Med, Tianjin 301617, Peoples R China. EM shine2099@163.com; qiuyuling@tmu.edu.cn; hyyu@tjutcm.edu.cn RI Haiyang, Yu/ACP-8009-2022; zhang, siqi/KWU-0918-2024 FU Natural Science Foundation of Tianjin Municipality [23JCZXJC00150]; Shandong Provincial Key Research and Development Program [2021CXGC010508]; Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine [22HHZYSS00008] FX This research was supported by three fundings. Natural Science Foundation of Tianjin Municipality (23JCZXJC00150) and Shandong Provincial Key Research and Development Program (No.2021CXGC010508). In addition, our research was supported by Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine (22HHZYSS00008). 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Ethnopharmacol. PD NOV 15 PY 2024 VL 334 AR 118540 DI 10.1016/j.jep.2024.118540 EA JUL 2024 PG 15 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA A3F8O UT WOS:001281430100001 PM 38992397 DA 2026-03-26 ER PT J AU Shi, SQ Fu, ZY Wang, YJ Duan, CL Hu, SW Wu, HQ Zhang, BX Li, YM Song, QQ AF Shi, Shuqing Fu, Zhenyue Wang, Yajiao Duan, Chenglin Hu, Shaowei Wu, Huaqin Zhang, Bingxuan Li, Yumeng Song, Qingqiao TI Exploring the inflammation-related mechanisms of Lingguizhugan decoction on right ventricular remodeling secondary to pulmonary arterial hypertension based on integrated strategy using UPLC-HRMS, systems biology approach, and experimental validation SO PHYTOMEDICINE LA English DT Article DE Lingguizhugan decoction; Traditional Chinese medicine; Pulmonary arterial hypertension; Right ventricular dysfunction; Inflammation ID CHEMOKINE LIGAND 10; NF-KAPPA-B; DIASTOLIC DYSFUNCTION; MYOCARDIAL FIBROSIS; HEART-FAILURE; EXPRESSION; INJURY; CONTRIBUTES; ACTIVATION; LIQUIRITIN AB Background: Pulmonary arterial hypertension (PAH) and the consequent right heart dysfunction persist with high morbidity and mortality, and the mechanisms and pharmacologic interventions for chronic right-sided heart failure (RHF) have not been adequately investigated. Research has shown that prolonged inflammation is critical in precipitating the progression of PAH-associated right heart pathology. Some research demonstrated that Lingguizhugan decoction (LGZGD), as a classical Chinese medicine formula, had beneficial effects in alleviating PAH and RHF, while its underlying mechanisms involved are not fully elucidated. Purpose: Based on that, this study aims to investigate the effects and underlying mechanisms of LGZGD on PAHinduced RHF. Study Design: In this study, we identified the serum constituents and deciphered the potential anti-inflammatory mechanism and crucial components of LGZGD using combined approaches of UPLC-HRMS, transcriptomic analysis, and molecular docking techniques. Finally, we used in vivo experiments to verify the expression of key targets in the monocrotaline (MCT)-induced RHF model and the intervene effect of LGZGD. Results: Integrated strategies based on UPLC-HRMS and systems biology approach combined with in vivo experimental validation showed that LGZGD could improve right heart fibrosis and dysfunction via regulating diverse inflammatory signaling pathways and the activity of immune cells, including chemokine family CCL2, CXCR4, leukocyte integrins family ITGAL, ITGB2, and M2 macrophage infiltration, as well as lipid peroxidationassociated HMOX1, NOX4, and 4-HNE. Conclusion: The present research demonstrated for the first time that LGZGD might improve PAH-induced RHF through multiple anti-inflammatory signaling and inhibition of ferroptosis, which could provide certain directions for future research in related fields. C1 [Shi, Shuqing; Fu, Zhenyue; Wang, Yajiao; Zhang, Bingxuan; Li, Yumeng; Song, Qingqiao] China Acad Chinese Med Sci, Guanganmen Hosp, Dept Gen Internal Med, Beijing, Peoples R China. [Fu, Zhenyue] Beijing Univ Tradit Chinese Med, Coll Tradit Chinese Med, Beijing, Peoples R China. [Duan, Chenglin; Wu, Huaqin] China Acad Chinese Med Sci, Guanganmen Hosp, Dept Cardiol, Beijing, Peoples R China. [Hu, Shaowei] China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China. C3 China Academy of Chinese Medical Sciences; Guang'anmen Hospital, CACMS; Beijing University of Chinese Medicine; China Academy of Chinese Medical Sciences; Guang'anmen Hospital, CACMS; China Academy of Chinese Medical Sciences; Institute of Chinese Materia Medica, CACMS RP Li, YM; Song, QQ (corresponding author), China Acad Chinese Med Sci, Guanganmen Hosp, Dept Gen Internal Med, Beijing, Peoples R China. EM lym0707@163.com; Songqqbj@163.com RI ; Zhang, Bingxuan/IAM-9420-2023; Hu, Shaowei/C-7982-2017; shi, shuqing/GSO-0662-2022; Li, yumeng/LVR-8441-2024; Fu, Zhenyue/OGR-6722-2025 OI Duan, Chenglin/0009-0005-7576-8481; FU National Natural Science Foundation of China [82004348]; China Scholarship Council (CSC); Fundamental research funds for the central public welfare research institutes [ZZ16-YQ-017] FX This work was financially supported by a grant from the National Natural Science Foundation of China(Grant No: 82004348) and the China Scholarship Council (CSC) as well as the fundamental research funds for the central public welfare research institutes (No. ZZ16-YQ-017). 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Macrophages, a major cell population involved in cardiac immune response and inflammation, are highly heterogeneous and polarized into M1 and M2 types depending on the microenvironment. M1 macrophage releases inflammatory factors and chemokines to activate the immune response and remove harmful substances, while M2 macrophage releases anti-inflammatory factors to inhibit the overactive immune response and promote tissue repair. M1 and M2 restrict each other to maintain cardiac homeostasis. The dynamic balance of M1 and M2 is closely related to the Traditional Chinese Medicine (TCM) yin-yang theory, and the imbalance of yin and yang will result in a pathological state of the organism. Studies have confirmed that TCM produces positive effects on HF by regulating macrophage polarization. This review describes the critical role of macrophage polarization in inflammation, fibrosis, angiogenesis and electrophysiology in the course of HF, as well as the potential mechanism of TCM regulation of macrophage polarization in preventing and treating HF, thereby providing new ideas for clinical treatment and scientific research design of HF. C1 [Zhu, Zheqin; Wang, Min; Lu, Shenghua; Liu, Jianhe] Hunan Univ Chinese Med, Hosp, Changsha, Peoples R China. [Dai, Sisi] Hunan Univ Chinese Med, Changsha, Peoples R China. C3 Hunan University of Chinese Medicine; Hunan University of Chinese Medicine RP Liu, JH (corresponding author), Hunan Univ Chinese Med, Hosp, Changsha, Peoples R China. EM ljhtcm1@163.com OI Wang, Min/0009-0001-5317-2709; Liu, Jianhe/0000-0003-2473-858X FU Key Projects of Scientific Research Program of Hunan Provincial Administration of Traditional Chinese Medicine [D2023005, 2021011]; Key Projects of Scientific Research of Hunan Provincial Department of Education [21A0234]; The 2023 Double First-Class Discipline Construction-Research on Prevention and Treatment of Cardio-Cerebral Diseases by Traditional Chinese Medicine [6001001006] FX The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Key Projects of Scientific Research Program of Hunan Provincial Administration of Traditional Chinese Medicine (D2023005,2021011), the Key Projects of Scientific Research of Hunan Provincial Department of Education (21A0234), 2023 Double First-Class Discipline Construction-Research on Prevention and Treatment of Cardio-Cerebral Diseases by Traditional Chinese Medicine (6001001006). 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Pharmacol. PD JUL 18 PY 2024 VL 15 AR 1434654 DI 10.3389/fphar.2024.1434654 PG 18 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA A9T3G UT WOS:001285886100001 PM 39104386 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zong, YH Cao, JF Zhao, YH Gao, M Chen, WL Wu, M Xu, X Xu, ZY Zhang, XQ Tang, JZ Liu, YL Hu, XS Wang, SQ Zhang, X AF Zong, Yong-hua Cao, Jun-Feng Zhao, Yinghua Gao, Miao Chen, Wan-lin Wu, Mei Xu, Xiang Xu, Zhen-yan Zhang, Xue-qin Tang, Jia-zhi Liu, Yulin Hu, Xiao-song Wang, Shao-qing Zhang, Xiao TI Mechanism of Lian Hua Qing Wen capsules regulates the inflammatory response caused by M1 macrophage based on cellular experiments and computer simulations SO ACTA TROPICA LA English DT Article DE M 1 macrophage; Bioinformatics analysis; Inflammatory response; Molecular docking; Molecular dynamics ID ACUTE LUNG INJURY; FACTOR GM-CSF; NF-KAPPA-B; INTERFERON-GAMMA; LIANHUAQINGWEN CAPSULE; CYTOKINE STORM; ACTIVATION; CHEMOKINES; EXPRESSION; CELLS AB Purpose: The polarization of macrophages with the resulting inflammatory response play a crucial part in tissue and organ damage due to inflammatory. Study has proved Lian Hua Qing Wen capsules (LHQW) can reduce activation of inflammatory response and damage of tissue derived from the inflammatory reactions. However, the mechanism of LHQW regulates the macrophage-induced inflammatory response is unclear. Therefore, we investigated the mechanism of LHQW regulated the inflammatory response of M1 macrophages by cellular experiments and computer simulations. Methods: This study has analysed the targets and mechanisms of macrophage regulating inflammatory response at gene and protein levels through bioinformatics. The monomeric components of LHQW were analyzed by High Performance Liquid Chromatography (HPLC). We established the in vitro cell model by M1 macrophages (Induction of THP-1 cells into M1 macrophages). RT-qPCR and immunofluorescence were used to detect changes in gene and protein levels of key targets after LHQW treatment. Computer simulations were utilized to verify the binding stability of monomeric components and protein targets. Results: Macrophages had 140,690 gene targets, inflammatory response had 12,192 gene targets, intersection gene targets were 11,772. Key monomeric components (including: Pinocembrin, Fargesone-A, Nodakenin and Bowdichione) of LHQW were screened by HPLC. The results of cellular experiments indicated that LHQW could significantly reduce the mRNA expression of CCR5, CSF2, IFNG and TNF, thereby alleviating the inflammatory response caused by M1 macrophage. The computer simulations further validated the binding stability and conformation of key monomeric components and key protein targets, and IFNG/Nodakenin was able to form the most stable binding conformation for its action. Conclusion: In this study, the mechanism of LHQW inhibits the polarization of macrophages and the resulting inflammatory response was investigated by computer simulations and cellular experiments. We found that LHQW may not only reduce cell damage and death by acting on TNF and CCR5, but also inhibit the immune recognition process and inflammatory response by regulating CSF2 and IFNG to prevent polarization of macrophages. Therefore, these results suggested that LHQW may act through multiple targets to inhibit the polarization of macrophages and the resulting inflammatory response. C1 [Zhao, Yinghua; Gao, Miao; Chen, Wan-lin; Wu, Mei; Xu, Xiang; Xu, Zhen-yan; Tang, Jia-zhi; Liu, Yulin; Hu, Xiao-song; Wang, Shao-qing; Zhang, Xiao] Chengdu Med Coll, Chengdu, Peoples R China. [Cao, Jun-Feng] Southwest Jiaotong Univ, Coll Med, Chengdu, Peoples R China. [Zong, Yong-hua; Zhang, Xue-qin] Univ Tibetan Med, Lhasa, Peoples R China. C3 Chengdu Medical College; Southwest Jiaotong University; Xizang University of Tibetan Medicine RP Zhang, X (corresponding author), Chengdu Med Coll, Chengdu, Peoples R China. EM 954073462@qq.com RI ; Cao, Jun-Feng/AHH-0747-2022; liu, yulin/IQV-8714-2023 OI 高, 淼/0009-0005-4325-0784; FU Project of Scientific Research Support Program for Doctoral Cultivation of Traditional Chinese Medicine [BSDPY-21-05]; Science and Technology Project of Tibet Autonomous Region-Major Project [XZ201901-GA-02]; Sichuan Innovation and Entrepreneurship Training Program for College Students [S202313705067] FX Project of Scientific Research Support Program for Doctoral Cultivation of Traditional Chinese Medicine (Tibetan Medicine) (BSDPY-21-05) . This research was supported by grants from the Science and Technology Project of Tibet Autonomous Region-Major Project (No. XZ201901-GA-02) . Sichuan Innovation and Entrepreneurship Training Program for College Students (S202313705067). 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PD SEP PY 2024 VL 257 AR 107320 DI 10.1016/j.actatropica.2024.107320 EA JUL 2024 PG 14 WC Parasitology; Tropical Medicine WE Science Citation Index Expanded (SCI-EXPANDED) SC Parasitology; Tropical Medicine GA ZJ6Z6 UT WOS:001274981300001 PM 39002739 DA 2026-03-26 ER PT J AU Wang, H Wang, XF Zhang, QK Liang, YC Wu, H AF Wang, Hui Wang, Xiaofei Zhang, Qingkun Liang, Yanchen Wu, Hong TI Matrine reduces traumatic heterotopic ossification in mice by inhibiting M2 macrophage polarization through the MAPK pathway SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE Matrine; Heterotopic osssification; M2 macrophages; Phenotype; MAPK ID MOUSE MODEL; INFLAMMATION AB In this study, the role of matrine, a component derived from traditional Chinese medicine, in modulating macrophage polarization and its effects on traumatic heterotopic ossification (HO) in mice was investigated. Traumatic HO is a pathological condition characterized by abnormal bone formation in nonskeletal tissues, often following severe trauma or surgery. The mechanisms underlying HO involve an enhanced inflammatory response and abnormal bone formation, with macrophages playing a crucial role. Our study demonstrated that matrine effectively inhibits the polarization of bone marrow-derived macrophages (BMDMs) toward the M2 phenotype, a subtype associated with anti-inflammatory processes and implicated in the progression of HO. Using in vitro assays, we showed that matrine suppresses key M2 markers and inhibits the MAPK signaling pathway in BMDMs. Furthermore, in vivo experiments revealed that matrine treatment significantly reduced HO formation in the Achilles tendons of mice and downregulated the expression of markers associated with M2 macrophages and the MAPK pathway. Our findings suggest that the ability of matrine to modulate macrophage polarization and inhibit the MAPK pathway has therapeutic potential for treating traumatic HO, providing a novel approach to managing this complex condition. C1 [Wang, Hui; Zhang, Qingkun; Liang, Yanchen] Shandong Univ Tradit Chinese Med, Affiliated Hosp, Orthoped Dis Ctr, Jinan 250000, Shandong, Peoples R China. [Wang, Xiaofei] Shandong First Med Univ, Peoples Hosp, Pediat Surg Dept, Jinan 271100, Shandong, Peoples R China. [Wu, Hong] Shandong Univ Tradit Chinese Med, Affiliated Hosp, Dept Radiat Oncol, Jinan 250000, Shandong, Peoples R China. C3 Shandong University of Traditional Chinese Medicine; Shandong First Medical University & Shandong Academy of Medical Sciences; Shandong University of Traditional Chinese Medicine RP Liang, YC (corresponding author), Shandong Univ Tradit Chinese Med, Affiliated Hosp, Orthoped Dis Ctr, Jinan 250000, Shandong, Peoples R China.; Wu, H (corresponding author), Shandong Univ Tradit Chinese Med, Affiliated Hosp, Dept Radiat Oncol, Jinan 250000, Shandong, Peoples R China. EM 185492453@qq.com; banbu.duo@163.com OI Wang, Hui/0000-0001-5055-5491 FU Natural science Foundation of Shandong Province [ZR2022MH171] FX The present study was funded by the Natural science Foundation of Shandong Province (ZR2022MH171). CR Arabpour M, 2021, INT IMMUNOPHARMACOL, V97, DOI 10.1016/j.intimp.2021.107823 Cao GR, 2023, BONE, V168, DOI 10.1016/j.bone.2022.116655 Chen XS, 2022, PHARMACOL RES, V185, DOI 10.1016/j.phrs.2022.106473 Chen YN, 2020, EUR J PHARMACOL, V877, DOI 10.1016/j.ejphar.2020.173090 Convente MR, 2018, J BONE MINER RES, V33, P269, DOI 10.1002/jbmr.3304 Franken L, 2016, CELL MICROBIOL, V18, P475, DOI 10.1111/cmi.12580 Gao ZR, 2022, CHIN MED-UK, V17, DOI 10.1186/s13020-022-00640-5 Genêt F, 2015, J PATHOL, V236, P229, DOI 10.1002/path.4519 Guo J, 2018, MOL IMMUNOL, V97, P20, DOI 10.1016/j.molimm.2018.03.005 Herman ZJ, 2021, ORTHOPEDICS, V44, P10, DOI 10.3928/01477447-20201119-03 Huang YF, 2021, NPJ REGEN MED, V6, DOI 10.1038/s41536-021-00178-4 Hwang C, 2019, BONE RES, V7, DOI 10.1038/s41413-019-0075-6 Kang J, 2021, SCI REP-UK, V11, DOI 10.1038/s41598-021-89086-7 Lawand J, 2023, ORTHOP CLIN N AM, V54, P37, DOI 10.1016/j.ocl.2022.08.007 Li MR, 2021, FRONT IMMUNOL, V12, DOI 10.3389/fimmu.2021.681710 Li ZY, 2022, STEM CELL RES THER, V13, DOI 10.1186/s13287-022-02975-0 Lu JS, 2021, ARTHRITIS RES THER, V23, DOI 10.1186/s13075-021-02512-z Martina JA, 2023, EMBO REP, V24, DOI 10.15252/embr.202255472 Olmsted-Davis E, 2021, FRONT IMMUNOL, V12, DOI 10.3389/fimmu.2021.686769 Patel NK, 2022, JCI INSIGHT, V7, DOI 10.1172/jci.insight.144925 Pulik L, 2020, CELLS-BASEL, V9, DOI 10.3390/cells9061324 Ramesh A, 2020, BIOMATERIALS, V227, DOI 10.1016/j.biomaterials.2019.119559 Song YF, 2022, FRONT PHARMACOL, V13, DOI 10.3389/fphar.2022.936632 Sorkin M, 2020, NAT COMMUN, V11, DOI 10.1038/s41467-019-14172-4 Sun XY, 2022, FRONT CHEM, V10, DOI 10.3389/fchem.2022.867318 Torossian F, 2017, JCI INSIGHT, V2, DOI 10.1172/jci.insight.96034 Tu B, 2023, INFLAMMATION, V46, P202, DOI 10.1007/s10753-022-01723-z Wang H, 2023, BIOMED PHARMACOTHER, V161, DOI 10.1016/j.biopha.2023.114508 Wang Z, 2023, MATER TODAY BIO, V23, DOI 10.1016/j.mtbio.2023.100822 Wang Z, 2023, J ORTHOP TRANSL, V42, P31, DOI 10.1016/j.jot.2023.06.004 Wang Z, 2023, FRONT IMMUNOL, V13, DOI 10.3389/fimmu.2022.1090529 Xuan XY, 2023, MEDICINE, V102, DOI 10.1097/MD.0000000000033748 Yang L, 2023, J SURG RES, V281, P264, DOI 10.1016/j.jss.2022.08.003 Yu XH, 2019, CLIN SCI, V133, P551, DOI 10.1042/CS20180912 Zhang J, 2020, LAB INVEST, V100, P762, DOI 10.1038/s41374-019-0367-x Zhao B, 2021, AM J CANCER RES, V11, P4308 Zhou JL, 2019, MED SCI MONITOR, V25, P4130, DOI 10.12659/MSM.917151 Zhou YY, 2022, COMMUN BIOL, V5, DOI 10.1038/s42003-022-03369-x NR 38 TC 10 Z9 10 U1 2 U2 13 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI ISSY-LES-MOULINEAUX PA 65 RUE CAMILLE DESMOULINS, CS50083, 92442 ISSY-LES-MOULINEAUX, FRANCE SN 0753-3322 EI 1950-6007 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PD AUG PY 2024 VL 177 AR 117130 DI 10.1016/j.biopha.2024.117130 EA JUL 2024 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA ZF9O4 UT WOS:001274000200001 PM 39018873 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Guo, KE Yin, YT Zheng, LX Wu, ZN Rao, XY Zhu, WF Zhou, BG Liu, LJ Liu, DY AF Guo, Kaien Yin, Yuting Zheng, Linxin Wu, Zenan Rao, Xiaoyong Zhu, Weifeng Zhou, Bugao Liu, Liangji Liu, Duanyong TI Integration of microbiomics, metabolomics, and transcriptomics reveals the therapeutic mechanism underlying Fuzheng-Qushi decoction for the treatment of lipopolysaccharide-induced lung injury in mice SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Fuzheng-Qushi decoction; Lung injury; Transcriptomics; Gut microbiota; Metabolomics ID GUT MICROBIOTA; INFLAMMATORY RESPONSES; CELLS; POLARIZATION; CYTOKINES; MEDICINE; PATHWAY; DAMAGE AB Ethnopharmacological relevance: Fuzheng-Qushi decoction (FZQS) is a practical Chinese herbal formula for relieving cough and fever. Therefore, the action and specific molecular mechanism of FZQS in the treatment of lung injury with cough and fever as the main symptoms need to be further investigated. Aims of the study: To elucidate the protective effects of FZQS against lung injury in mice and reveal its potential targets and key biological pathways for the treatment of lung injury based on transcriptomics, microbiomics, and untargeted metabolomics analyses. Materials and methods: Lipopolysaccharide (LPS) was used to induce a mouse model of lung injury, followed by the administration of FZQS. ELISA was used to detect IL-1 beta, IL-6, IL-17A, IL-4, IL-10, and TNF-alpha, in mouse lung tissues. Macrophage polarization and neutrophil activation were measured by flow cytometry. RNA sequencing (RNA-seq) was applied to screen for differentially expressed genes (DEGs) in lung tissues. RT-qPCR and Western blot assays were utilized to validate key DEGs and target proteins in lung tissues. 16S rRNA sequencing was employed to characterize the gut microbiota of mice. Metabolites in the gut were analyzed using untargeted metabolomics. Results: FZQS treatment significantly ameliorated lung histopathological damage, decreased pro-inflammatory cytokine levels, and increased anti-inflammatory cytokine levels. M1 macrophage levels in the peripheral blood decreased, M2 macrophage levels increased, and activated neutrophils were inhibited in mice with LPSinduced lung injury. Importantly, transcriptomic analysis showed that FZQS downregulated macrophage and neutrophil activation and migration and adhesion pathways by reversing 51 DEGs, which was further confirmed by RT-qPCR and Western blot analysis. In addition, FZQS modulated the dysbiosis of the gut microbiota by reversing the abundance of Corynebacterium, Facklamia, Staphylococcus, Paenalcaligenes, Lachnoclostridium, norank_f_Muribaculaceae, and unclassified_f_Lachnospiraceae. Meanwhile, metabolomics analysis revealed that FZQS significantly regulated tryptophan metabolism by reducing the levels of 3-Indoleacetonitrile and 5Hydroxykynurenine. Conclusion: FZQS effectively ameliorated LPS-induced lung injury by inhibiting the activation, migration, and adhesion of macrophages and neutrophils and modulating gut microbiota and its metabolites. C1 [Guo, Kaien; Zheng, Linxin; Wu, Zenan] Jiangxi Univ Chinese Med, Dept Postgrad, Nanchang 330004, Jiangxi, Peoples R China. [Yin, Yuting] Jiangxi Univ Chinese Med, Coll Pharm, Nanchang 330004, Jiangxi, Peoples R China. [Rao, Xiaoyong] Natl Engn Ctr Mfg Technol Solid Preparat Tradit Ch, Nanchang 330004, Jiangxi, Peoples R China. [Zhu, Weifeng; Liu, Duanyong] JiangXi Univ Chinese Med, 1688 Meiling Rd, Nanchang 330004, Jiangxi, Peoples R China. [Zhou, Bugao] Jiangxi Univ Tradit Chinese Med, Res Dept, Jiangxi Nanchang 330004, Peoples R China. [Liu, Liangji] Jiangxi Univ Chinese Med, Affiliated Hosp, Nanchang 330004, Jiangxi, Peoples R China. [Liu, Duanyong] Jiangxi Univ Chinese Med, Formula Pattern Res Ctr, Nanchang 330004, Jiangxi, Peoples R China. [Liu, Duanyong] Jiangxi Univ Chinese Med, Sch Nursing, Nanchang 330004, Jiangxi, Peoples R China. C3 Jiangxi University of Traditional Chinese Medicine; Jiangxi University of Traditional Chinese Medicine; Jiangxi University of Traditional Chinese Medicine; Jiangxi University of Traditional Chinese Medicine; Jiangxi University of Traditional Chinese Medicine; Jiangxi University of Traditional Chinese Medicine; Jiangxi University of Traditional Chinese Medicine RP Liu, DY (corresponding author), JiangXi Univ Chinese Med, 1688 Meiling Rd, Nanchang 330004, Jiangxi, Peoples R China.; Zhou, BG (corresponding author), Jiangxi Univ Tradit Chinese Med, Res Dept, Jiangxi Nanchang 330004, Peoples R China.; Liu, LJ (corresponding author), Jiangxi Univ Chinese Med, Affiliated Hosp, Nanchang 330004, Jiangxi, Peoples R China. EM zhoubugao@163.com; llj6505@163.com; liuduanyong@163.com RI YIN, YUTING/AGW-9086-2022; Duanyong, Liu/GRS-6297-2022 FU Jiangxi Province annual centralized guidance of local science and technology development funds project [20222ZDH01096]; National Natural Science Foundation of China [82060798, 81860791]; Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program [CXTD22008]; Young and Middle-aged Backbone Talent Project of Jiangxi Administration of Traditional Chinese Medicine [[2020]05]; Young Qihuang Scholars support Project of National Administration of Traditional Chinese Medicine [[2022]256] FX This study is supported by the Jiangxi Province annual centralized guidance of local science and technology development funds project (the second batch), No. 20222ZDH01096; the National Natural Science Foundation of China, No. 82060798 and 81860791; Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program, No. CXTD22008; the Young and Middle-aged Backbone Talent Project of Jiangxi Administration of Traditional Chinese Medicine, No. [2020]05; and Young Qihuang Scholars support Project of National Administration of Traditional Chinese Medicine, No. [2022]256. 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PD NOV 15 PY 2024 VL 334 AR 118584 DI 10.1016/j.jep.2024.118584 EA JUL 2024 PG 22 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA ZH4F7 UT WOS:001274385700001 PM 39019418 DA 2026-03-26 ER PT J AU Oumeddour, DZ Al-Dalali, S Zhao, L Zhao, L Wang, CT AF Oumeddour, Dounya Zad Al-Dalali, Sam Zhao, Liang Zhao, Lei Wang, Chengtao TI Recent advances on cyanidin-3-O-glucoside in preventing obesity-related metabolic disorders: A comprehensive review SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Review DE Anthocyanin; C3G bioavailability; Lipid metabolism; Energy homeostasis; Insulin resistance; Inflammatory bowel disease; Liver steatosis; Gut microbiota dysbiosis; Cancer; Alzheimer disease; C3G anti-oxidant activity; C3G anti-inflammatory activity ID INTESTINAL EPITHELIAL-CELLS; INDUCED INFLAMMATION; INSULIN-RESISTANCE; BLACK-RASPBERRY; HIGH-FAT; ANTHOCYANIN ABSORPTION; CYANIDIN 3-O-GLUCOSIDE; PHENOLIC-COMPOUNDS; WINE ANTHOCYANINS; GINSENOSIDE F2 AB Anthocyanins, found in various pigmented plants as secondary metabolites, represent a class of dietary polyphenols known for their bioactive properties, demonstrating health-promoting effects against several chronic diseases. Among these, cyanidin-3-O-glucoside (C3G) is one of the most prevalent types of anthocyanins. Upon consumption, C3G undergoes phases I and II metabolism by oral epithelial cells, absorption in the gastric epithelium, and gut transformation (phase II & microbial metabolism), with limited amounts reaching the bloodstream. Obesity, characterized by excessive body fat accumulation, is a global health concern associated with heightened risks of disability, illness, and mortality. This comprehensive review delves into the biodegradation and absorption dynamics of C3G within the gastrointestinal tract. It meticulously examines the latest research findings, drawn from in vitro and in vivo models, presenting evidence underlining C3G's bioactivity. Notably, C3G has demonstrated significant efficacy in combating obesity, by regulating lipid metabolism, specifically decreasing lipid synthesis, increasing fatty acid oxidation, and reducing lipid accumulation. Additionally, C3G enhances energy homeostasis by boosting energy expenditure, promoting the activity of brown adipose tissue, and stimulating mitochondrial biogenesis. Furthermore, C3G shows potential in managing various prevalent obesity-related conditions. These include cardiovascular diseases (CVD) and hypertension through the suppression of reactive oxygen species (ROS) production, enhancement of endogenous antioxidant enzyme levels, and inhibition of the nuclear factor-kappa B (NF-kappa B) signaling pathway and by exercising its cardioprotective and vascular effects by decreasing pulmonary artery thickness and systolic pressure which enhances vascular relaxation and angiogenesis. Type 2 diabetes mellitus (T2DM) and insulin resistance (IR) are also managed by reducing gluconeogenesis via AMPK pathway activation, promoting autophagy, protecting pancreatic beta-cells from oxidative stress and enhancing glucose-stimulated insulin secretion. Additionally, C3G improves insulin sensitivity by upregulating GLUT-1 and GLUT-4 expression and regulating the PI3K/Akt pathway. C3G exhibits anti-inflammatory properties by inhibiting the NF-kappa B pathway, reducing proinflammatory cytokines, and shifting macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. C3G demonstrates antioxidative effects by enhancing the expression of antioxidant enzymes, reducing ROS production, and activating the Nrf2/AMPK signaling pathway. Moreover, these mechanisms also contribute to attenuating inflammatory bowel disease and regulating gut microbiota by decreasing Firmicutes and increasing Bacteroidetes abundance, restoring colon length, and reducing levels of inflammatory cytokines. The therapeutic potential of C3G extends beyond metabolic disorders; it has also been found effective in managing specific cancer types and neurodegenerative disorders. The findings of this research can provide an important reference for future investigations that seek to improve human health through the use of naturally occurring bioactive compounds. C1 [Oumeddour, Dounya Zad; Zhao, Liang; Zhao, Lei; Wang, Chengtao] Beijing Technol & Business Univ, Key Lab Geriatr Nutr & Hlth, Minist Educ, Beijing 100048, Peoples R China. [Oumeddour, Dounya Zad; Zhao, Liang; Zhao, Lei; Wang, Chengtao] Beijing Technol & Business Univ, Beijing Engn & Technol Res Ctr Food Addit, Beijing 100048, Peoples R China. [Al-Dalali, Sam] Guilin Tourism Univ, Sch Food & Hlth, Guilin 541006, Peoples R China. [Al-Dalali, Sam] Ibb Univ, Fac Agr & Food Sci, Dept Food Sci & Technol, Ibb 70270, Yemen. C3 Beijing Technology & Business University; Beijing Technology & Business University; Guilin Tourism University RP Zhao, L; Zhao, L; Wang, CT (corresponding author), Beijing Technol & Business Univ, Key Lab Geriatr Nutr & Hlth, Minist Educ, Beijing 100048, Peoples R China. EM douniazed.oumeddour@gmail.com; salihsam4@gmail.com; liangzhao@btbu.edu.cn; zhaolei@th.btbu.edu.cn; wct5566@163.com RI Al-Dalali, Sam/ABC-6689-2021; Zhao, Lei/AAS-2428-2021 OI Zhao, Lei/0000-0003-0813-6140 FU Cultivation Project of the Double First-Class Disciplines of Food Science and Engineering, Beijing Technology and Business University [BTBUYXTD202207]; Discipline Construction-Food Science and Engineering [SPKX-202204]; Research Foundation for Youth Scholars of Beijing Technology and Business University [QNJJ2022-06]; Xinjiang 'Two Zones' Science and Technology Development Plan Project [2022LQ02003] FX This work was supported by the fund of the Cultivation Project of the Double First-Class Disciplines of Food Science and Engineering, Beijing Technology and Business University (No. BTBUYXTD202207) , Discipline Construction-Food Science and Engineering (No. SPKX-202204) , the Research Foundation for Youth Scholars of Beijing Technology and Business University (No. QNJJ2022-06) , and Xinjiang 'Two Zones' Science and Technology Development Plan Project (No. 2022LQ02003) . 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Biophys. Res. Commun. PD OCT 15 PY 2024 VL 729 AR 150344 DI 10.1016/j.bbrc.2024.150344 EA JUL 2024 PG 22 WC Biochemistry & Molecular Biology; Biophysics WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Biophysics GA YH7J3 UT WOS:001267660700001 PM 38976946 DA 2026-03-26 ER PT J AU Rahman, MA Rakib-Uz-Zaman, SM Chakraborti, S Bhajan, SK Gupta, RD Jalouli, M Parvez, MAK Shaikh, MH Apu, EH Harrath, AH Moon, S Kim, B AF Rahman, Md Ataur Rakib-Uz-Zaman, S. M. Chakraborti, Somdeepa Bhajan, Sujay Kumar Gupta, Rajat Das Jalouli, Maroua Parvez, Md. Anowar Khasru Shaikh, Mushfiq H. Apu, Ehsanul Hoque Harrath, Abdel Halim Moon, Seungjoon Kim, Bonglee TI Advancements in Utilizing Natural Compounds for Modulating Autophagy in Liver Cancer: Molecular Mechanisms and Therapeutic Targets SO CELLS LA English DT Review DE autophagy; homeostasis; natural compound; hepatocellular carcinoma; cancer therapy ID HUMAN HEPATOCELLULAR-CARCINOMA; IN-VITRO; SIGNALING PATHWAY; BETULINIC ACID; MACROPHAGE POLARIZATION; MEDIATED APOPTOSIS; RESVERATROL EXERTS; CELL-DEATH; EMODIN; INDUCTION AB Autophagy, an intrinsic catabolic mechanism that eliminates misfolded proteins, dysfunctional organelles, and lipid droplets, plays a vital function in energy balance and cytoplasmic quality control, in addition to maintaining cellular homeostasis. Liver cancer such as hepatocellular carcinoma (HCC) is one of the most common causes of cancer deaths globally and shows resistance to several anticancer drugs. Despite the rising incidence and poor prognosis of malignant HCC, the underlying molecular mechanisms driving this aggressive cancer remain unclear. Several natural compounds, such as phytochemicals of dietary and non-dietary origin, affect hepatocarcinogenesis signaling pathways in vitro and in vivo, which may help prevent and treat HCC cells. Current HCC cells treatments include chemotherapy, radiation, and surgery. However, these standard therapies have substantial side effects, and combination therapy enhances side effects for an acceptable therapeutic benefit. Therefore, there is a need to develop treatment strategies for HCC cells that are more efficacious and have fewer adverse effects. Multiple genetic and epigenetic factors are responsible for the HCC cells to become resistant to standard treatment. Autophagy contributes to maintain cellular homeostasis, which activates autophagy for biosynthesis and mitochondrial regulation and recycling. Therefore, modifying autophagic signaling would present a promising opportunity to identify novel therapies to treat HCC cells resistant to current standard treatments. This comprehensive review illustrates how natural compounds demonstrate their anti-hepatocellular carcinoma function through autophagy. C1 [Rahman, Md Ataur] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. [Rakib-Uz-Zaman, S. M.; Chakraborti, Somdeepa] Univ Delaware, Dept Biol Sci, Newark, DE 19716 USA. [Rakib-Uz-Zaman, S. M.] BRAC Univ, Sch Data & Sci, Dept Math & Nat Sci, Biotechnol Program, Dhaka 1212, Bangladesh. [Bhajan, Sujay Kumar] Bangabandhu Sheikh Mujibur Rahman Sci & Technol Un, Dept Biotechnol & Genet Engn, Gopalganj 8100, Bangladesh. [Gupta, Rajat Das] Univ South Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. [Jalouli, Maroua] Imam Mohammad Ibn Saud Islamic Univ IMSIU, Coll Sci, Dept Biol, Riyadh 11623, Saudi Arabia. [Parvez, Md. Anowar Khasru] Jahangirnagar Univ, Dept Microbiol, Savar 1342, Bangladesh. [Shaikh, Mushfiq H.] Western Univ, Dept Otolaryngol Head & Neck Surg, London, ON N6A 4V2, Canada. [Apu, Ehsanul Hoque] Lincoln Mem Univ, Coll Dent Med, Dept Biomed Sci, Knoxville, TN 37923 USA. [Apu, Ehsanul Hoque] Lincoln Mem Univ, DeBusk Coll Osteopath Med, Harrogate, TN 37752 USA. [Apu, Ehsanul Hoque] Univ Michigan, Dept Internal Med, Div Hematol & Oncol, Michigan Med, Ann Arbor, MI 48109 USA. [Harrath, Abdel Halim] King Saud Univ, Coll Sci, Zool Dept, Riyadh 11451, Saudi Arabia. [Moon, Seungjoon; Kim, Bonglee] Kyung Hee Univ, Coll Korean Med, Dept Pathol, 1-5 Hoegidong, Seoul 02447, South Korea. [Kim, Bonglee] Kyung Hee Univ, Coll Korean Med, Korean Med Based Drug Repositioning Canc Res Ctr, Seoul 02447, South Korea. C3 University of Michigan System; University of Michigan; University of Delaware; Bangladesh Rural Advancement Committee BRAC; BRAC University; Gopalganj Science & Technology University (GSTU); University of South Carolina System; University of South Carolina Columbia; Imam Mohammad Ibn Saud Islamic University (IMSIU); Jahangirnagar University; Western University (University of Western Ontario); Lincoln Memorial University; Lincoln Memorial University; University of Michigan System; University of Michigan; King Saud University; Kyung Hee University; Kyung Hee University RP Kim, B (corresponding author), Kyung Hee Univ, Coll Korean Med, Dept Pathol, 1-5 Hoegidong, Seoul 02447, South Korea.; Kim, B (corresponding author), Kyung Hee Univ, Coll Korean Med, Korean Med Based Drug Repositioning Canc Res Ctr, Seoul 02447, South Korea. EM ataur1981rahman@hotmail.com; rakibsust07@gmail.com; somdeepa7@gmail.com; sujaybge@gmail.com; rajatdas@email.sc.edu; maroua.jalouli@gmail.com; khasru73@juniv.edu; mushfiq.shaikh@lhsc.on.ca; ehsanul.hoqueapu@lmunet.edu; hharrath@ksu.edu.sa; capre@naver.com; bongleekim@khu.ac.kr RI ; Hoque Apu, Ehsanul/AAA-9569-2020; Kim, Bonglee/AAH-9077-2020; Rakib-Uz-Zaman, S M/AAC-5378-2020; Shaikh, Mushfiq H/AAO-9358-2020; Harrath, Abdel Halim/K-2166-2014; Rahman, Ataur/AAE-1071-2019; Das Gupta, Rajat/E-5545-2018 OI , Sujay Kumar Bhajan/0009-0002-7564-2078; Hoque Apu, Ehsanul/0000-0001-6840-3787; Kim, Bonglee/0000-0002-8678-156X; Rakib-Uz-Zaman, S M/0000-0003-4126-8751; Jalouli, Maroua/0000-0003-4726-0507; Shaikh, Mushfiq H/0000-0001-9953-3939; Harrath, Abdel Halim/0000-0002-2170-1303; Chakraborti, Soeepa/0009-0000-9553-7246; Parvez, Anowar Khasru/0000-0002-0246-3872; Rahman, Ataur/0000-0001-6649-3694; Das Gupta, Rajat/0000-0002-7680-676X FU Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [NRF-2020R1I1A2066868]; National Research Foundation of Korea (NRF) - Korea government (MSIT) [2020R1A5A2019413, RS-2024-00350362]; Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [RS-2020-KH087790] FX This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2020R1I1A2066868),the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No.2020R1A5A2019413), a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: RS-2020-KH087790) and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (RS-2024-00350362). 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PHARMACOL, V155, P252, DOI 10.1016/j.bcp.2018.07.006 Zhu MY, 2023, FRONT PHARMACOL, V14, DOI 10.3389/fphar.2023.1238841 NR 158 TC 5 Z9 7 U1 2 U2 10 PU MDPI PI BASEL PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND EI 2073-4409 J9 CELLS-BASEL JI Cells PD JUL PY 2024 VL 13 IS 14 AR 1186 DI 10.3390/cells13141186 PG 24 WC Cell Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology GA ZQ4P6 UT WOS:001276750900001 PM 39056768 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Li, JT Liu, DL Zhao, HX Zhang, PX Cai, FY Li, HL Chu, SF AF Li, Juntong Liu, Deliang Zhao, Hengxia Zhang, Pengxiang Cai, Fangying Li, Huilin Chu, Shufang TI Chinese medicine compound prescription HeQi San ameliorates chronic inflammatory states and modulates gut flora in dehydroepiandrosterone-induced polycystic ovary syndrome mouse model SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Polycystic ovary syndrome; HeQi San; Macrophage; Apoptosis; Gut flora ID MARKERS; CELLS AB Background: Polycystic ovary syndrome (PCOS) is a common and complex endocrine disease in women, with a prevalence of 5% to 18% worldwide. HeQi San (HQS) is a Chinese medicine compound prescription, which has been applied to treat various endocrine and metabolic diseases. Objective: The study was intended to investigate the effect of HQS on PCOS, and clarify the potential mechanism via in vivo and in vitro experiments. Methods: The PCOS mouse model was established by injecting the dehydroepiandrosterone (DHEA) subcutaneously and fading high-fat diet for 3 weeks. After making model, PCOS mice were treated with HQS (8.75 g/kg and 17.5 g/kg, ig.) for 4 weeks. Firstly, we assessed the histopathological changes in ovary tissues and detected the hormone level. Subsequently, the study evaluated the capability of anti-inflammatory and regulating macrophage polarization of HQS in vivo and in vitro. The secretion of inflammation indicators was measured with Elisa kits, and the expression level of phosphorylated nuclear factor kappa-B (P-NF kappa B) and B-lymphocyte activation antigen B7 (CD80) was measured by immunofluorescence and Western blot. Meanwhile, the apoptosis of ovarian granulosa cells was detected via tunel staining and Western blot. The co-culture model in vitro was utilized to assess the effect between macrophage polarization and human ovarian granulosa cells (KGN cells) apoptosis. Furthermore, 16S rDNA sequencing was utilized to elevate gut microbiota change in PCOS mice. Results: HQS reversed the abnormal hormone increase, ameliorated insulin resistance, and improved histopathological changes of the ovary tissue to exert the therapeutic effect. HQS inhibited the expression of P-NF-kappa B and decreased the production of interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) to further prohibit the macrophage M1 polarization in ovary tissues and macrophages. The apoptosis-positive cells, Bcl-2 Assaciated X protein (BAX), and cleaved-caspase 3 expression were also decreased in the treatment group. The B-cell lymphoma-2 (Bcl2) expression was enhanced after HQS treatment in vivo. The co-culture experiments also verified that HQS could prevent the apoptosis of KGN cells. Furthermore, HQS mediated the abundance of gut flora. The abundance of bifldobacterium and parasutterella was increased and the abundance of lachnoclostridium was decreased. . Conclusion: The study verified that HQS has the effect of anti-inflammation and inhibits macrophage M1 polarization. Besides, HQS could mediate the abundance of gut microbiota in mice with PCOS. Thus, this study would provide more reasonable basis of HQS for clinical use. In conclusion, HQS might be a potential candidate for PCOS treatment. C1 [Li, Juntong; Liu, Deliang; Zhao, Hengxia; Zhang, Pengxiang; Cai, Fangying; Li, Huilin; Chu, Shufang] Shenzhen Tradit Chinese Med Hosp, Dept Endocrinol, Shenzhen 518033, Guangdong, Peoples R China. [Liu, Deliang; Zhao, Hengxia; Zhang, Pengxiang; Cai, Fangying; Li, Huilin; Chu, Shufang] Guangzhou Univ Chinese Med, Guangzhou 510405, Peoples R China. C3 Shenzhen Traditional Chinese Medicine Hospital; Guangzhou University of Chinese Medicine RP Li, HL; Chu, SF (corresponding author), Shenzhen Tradit Chinese Med Hosp, Dept Endocrinol, Shenzhen 518033, Guangdong, Peoples R China.; Li, HL; Chu, SF (corresponding author), Guangzhou Univ Chinese Med, Guangzhou 510405, Peoples R China. EM sztcmlhl@163.com; chushufanggzhtcm@163.com OI chu, shu fang/0000-0002-7134-8173; , Li/0000-0002-6284-3797 FU Shenzhen Science and Technology foundation [JCYJ20230807094504008]; Project of Administration of Traditional Chinese Medicine of Guangdong Province of China [20231287]; Shenzhen Longgang District Science and Technology Innovation Special Foundation [LGWJ2023-099] FX The study was supported by Shenzhen Science and Technology foundation (JCYJ20230807094504008) , Project of Administration of Traditional Chinese Medicine of Guangdong Province of China (20231287) and Shenzhen Longgang District Science and Technology Innovation Special Foundation (LGWJ2023-099) . 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Immunopharmacol. PD AUG 20 PY 2024 VL 137 AR 112491 DI 10.1016/j.intimp.2024.112491 EA JUN 2024 PG 13 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA J0F4Q UT WOS:001333916600001 PM 38909499 DA 2026-03-26 ER PT J AU He, Q Tian, D Wang, ZY Zheng, D Zhi, LQ Ma, JB An, J Zhang, R AF He, Qi Tian, Ding Wang, Zhiyuan Zheng, Dan Zhi, Liqiang Ma, Jianbing An, Jing Zhang, Rui TI Modified Si Miao Powder granules alleviates osteoarthritis progression by regulating M1/M2 polarization of macrophage through NF-κB signaling pathway SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE osteoarthritis; inflammation; modified Si Miao Powder; macrophage polarization; NF-kappa B signaling pathway ID CONSTITUENTS; INFLAMMATION; EXPRESSION; SYNOVITIS; FIBROSIS; RHIZOMA AB Background Osteoarthritis (OA) is a chronic degenerative disease mainly characterized by cartilage damage and synovial inflammation. Si Miao Powder, an herbal formula, was recorded in ancient Chinese medicine prescription with excellent anti-inflammatory properties. Based on the classical formula, the modified Si Miao Powder (MSMP) was developed with the addition of two commonly Chinese orthopedic herbs, which had the efficacy of strengthening the therapeutic effect for OA.Methods In the in vivo experiments, thirty-six 8-week-old male C57BL/6 mice were randomly divided into six groups: sham group, OA group, celecoxib group, low-MSMP group, middle-MSMP group, and high-MSMP group. OA mice were constructed by destabilization of medial meniscus (DMM) and treated with MSMP granules or celecoxib by gavage. The effects of MSMP on cartilage, synovitis and inflammatory factor of serum were tested. For in vitro experiments, control serum and MSMP-containing serum were prepared from twenty-five C57BL/6 mice. Macrophages (RAW264.7 cells) were induced by lipopolysaccharide (LPS) and then treated with MSMP-containing serum. The expression of inflammatory factors and the change of the NF-kappa B pathway were tested.Results In vivo, celecoxib and MSMP alleviated OA progression in the treated groups compared with OA group. The damage was partly recovered in cartilage, the synovial inflammatory were reduced in synovium, and the concentrations of IL-6 and TNF-alpha were reduced and the expression of IL-10 was increased in serum. The function of the middle MSMP was most effective for OA treatment. The results of in vitro experiments showed that compared with the LPS group, the MSMP-containing serum significantly reduced the expression levels of pro-inflammatory (M1-type) factors, such as CD86, iNOS, TNF-alpha and IL-6, and promoted the expression levels of anti-inflammatory (M2-type) factors, such as Arg1 and IL-10. The MSMP-containing serum further inhibited NF-kappa B signaling pathway after LPS induction.Conclusion The study demonstrated that MSMP alleviated OA progression in mice and MSMP-containing serum modulated macrophage M1/M2 phenotype by inhibiting the NF-kappa B signaling pathway. Our study provided experimental evidence and therapeutic targets of MSMP for OA treatment. C1 [He, Qi; Tian, Ding; Wang, Zhiyuan; Zhi, Liqiang; Ma, Jianbing; An, Jing; Zhang, Rui] Xi An Jiao Tong Univ, Honghui Hosp, Translat Med Ctr, Dept Joint Surg, Xian, Shaanxi, Peoples R China. [Zheng, Dan; Zhang, Rui] Guiyang Healthcare Vocat Univ, Dept Med Technol, Guiyang, Guizhou, Peoples R China. C3 Xi'an Jiaotong University; Guiyang Healthcare Vocational University RP An, J; Zhang, R (corresponding author), Xi An Jiao Tong Univ, Honghui Hosp, Translat Med Ctr, Dept Joint Surg, Xian, Shaanxi, Peoples R China.; Zhang, R (corresponding author), Guiyang Healthcare Vocat Univ, Dept Med Technol, Guiyang, Guizhou, Peoples R China. EM anjing198812@126.com; zhangruity12@163.com FU Natural Science Foundation of Guizhou Province [Qiankehejichu-ZK[2024]yiban588]; Natural Science Foundation of Shaanxi Province [2021JM-569]; Capacity Building Program of the Shaanxi Administration of Traditional Chinese Medicine [SZY-NLTL-2022-003]; National Natural Science Foundation of China [82002268] FX The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Natural Science Foundation of Guizhou Province (No. Qiankehejichu-ZK[2024]yiban588), the Natural Science Foundation of Shaanxi Province (No. 2021JM-569), the Capacity Building Program of the Shaanxi Administration of Traditional Chinese Medicine (No. SZY-NLTL-2022-003), the National Natural Science Foundation of China (No. 82002268). 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PD JUN 21 PY 2024 VL 15 AR 1361561 DI 10.3389/fphar.2024.1361561 PG 13 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA XN7B7 UT WOS:001262419100001 PM 38974041 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Liu, H Huang, MR Xin, DD Wang, H Yu, HY Pu, WL AF Liu, Hao Huang, Manru Xin, Dandan Wang, Hong Yu, Haiyang Pu, Weiling TI Natural products with anti-tumorigenesis potential targeting macrophage SO PHYTOMEDICINE LA English DT Article DE Herbal medicine; Macrophage; Tumorigenesis; Natural products; Mechanism ID COLITIS-ASSOCIATED TUMORIGENESIS; TUMOR-ASSOCIATED MACROPHAGES; BREAST-CANCER; ONCOSTATIN-M; CYCLOOXYGENASE-2 EXPRESSION; SCUTELLARIA-BAICALENSIS; PANCREATIC-CANCER; CELL; POLARIZATION; INFLAMMATION AB Background: Inflammation is a risk factor for tumorigenesis. Macrophage, a subset of immune cells with high plasticity, plays a multifaceted role in this process. Natural products, which are bioactive compounds derived from traditional herbs or foods, have exhibited diverse effects on macrophages and tumorigenesis making them a valuable resource of drug discovery or optimization in tumor prevention. Purpose: Provide a comprehensive overview of the various roles of macrophages in tumorigenesis, as well as the effects of natural products on tumorigenesis by modulating macrophage function. Methods: A thorough literature search spanning the past two decades was carried out using PubMed, Web of Science, Elsevier, and CNKI following the PRISMA guidelines. The search terms employed included "macrophage and tumorigenesis", "natural products, macrophages and tumorigenesis", "traditional Chinese medicine and tumorigenesis", "natural products and macrophage polarization", "macrophage and tumor related microenvironment", "macrophage and tumor signal pathway", "toxicity of natural products" and combinations thereof. Furthermore, certain articles are identified through the tracking of citations from other publications or by accessing the websites of relevant journals. Studies that meet the following criteria are excluded: (1) Articles not written in English or Chinese; (2) Full texts were not available; (3) Duplicate articles and irrelevant studies. The data collected was organized and summarized based on molecular mechanisms or compound structure. Results: This review elucidates the multifaceted effect of macrophages on tumorigenesis, encompassing process such as inflammation, angiogenesis, and tumor cell invasion by regulating metabolism, non -coding RNA, signal transduction and intercellular crosstalk. Natural products, including vitexin, ovatodiolide, ligustilide, and emodin, as well as herbal remedies, have demonstrated efficacy in modulating macrophage function, thereby attenuating tumorigenesis. These interventions mainly focus on mitigating the initial inflammatory response or modifying the inflammatory environment within the precancerous niche. C1 [Liu, Hao; Huang, Manru; Xin, Dandan; Wang, Hong; Pu, Weiling] Tianjin Univ Tradit Chinese Med, State Key Lab Component based Chinese Med, Tianjin 301617, Peoples R China. [Liu, Hao; Huang, Manru; Xin, Dandan; Wang, Hong; Pu, Weiling] Tianjin Univ Tradit Chinese Med, Inst Tradit Chinese Med, Tianjin 301617, Peoples R China. [Yu, Haiyang] Haihe Lab Modern Chinese Med, Tianjin 301617, Peoples R China. [Wang, Hong] Tianjin Univ Tradit Chinese Med, Sch Med Technol, Tianjin 301617, Peoples R China. C3 Tianjin University of Traditional Chinese Medicine; Tianjin University of Traditional Chinese Medicine; Tianjin University of Traditional Chinese Medicine RP Wang, H; Yu, HY; Pu, WL (corresponding author), Poyanghu Rd, Tianjin 301617, Peoples R China. EM wanghongsys@tjutcm.edu.cn; HYYU@tjutcm.edu.cn; puweiling1988@tjutcm.edu.cn RI Haiyang, Yu/ACP-8009-2022 FU National Natural Science Foundation of China [82204793, 82274154]; National Key Research and Devel-opment Program of China [2021YFE0203100] FX This study was funded by National Natural Science Foundation of China (NO. 82204793, 82274154) , National Key Research and Devel-opment Program of China (No: 2021YFE0203100) . 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Integrative & Complementary Medicine GA WM0N0 UT WOS:001255169100001 PM 38875811 DA 2026-03-26 ER PT J AU Gui, H Fan, XH AF Gui, Hua Fan, Xiaohong TI Anti-tumor effect of dandelion flavone on multiple myeloma cells and its mechanism SO DISCOVER ONCOLOGY LA English DT Article DE Dandelion flavone; Traditional Chinese medicine; Multiple myeloma; Macrophages; PI3K/AKT pathway ID TUMOR-ASSOCIATED MACROPHAGES; PROLIFERATION; APOPTOSIS; DRUG AB Background Multiple myeloma (MM) is a prevalent hematologic malignancy characterized by the uncontrolled proliferation of monoclonal plasma cells in the bone marrow and excessive monoclonal immunoglobulin production, leading to organ damage. Despite therapeutic advancements, recurrence and drug resistance remain significant challenges.Objective This study investigates the effects of dandelion flavone (DF) on MM cell proliferation, migration, and invasion, aiming to elucidate the mechanisms involved in MM metastasis and to explore the potential of traditional Chinese medicine in MM therapy.Methods DF's impact on myeloma cell viability was evaluated using the CCK-8 and colony formation assays. Cell mobility and invasiveness were assessed through wound healing and transwell assays, respectively. RT-PCR was employed to quantify mRNA levels of MMP-2, MMP-9, TIMP-1, and TIMP-2. Apoptotic rates and molecular markers were analyzed via flow cytometry and RT-PCR. The PI3K/AKT signaling pathway was studied using Western blot and ELISA, with IGF-1 and the PI3K inhibitor LY294002 used to validate the findings.Results DF demonstrated dose-dependent inhibitory effects on MM cell proliferation, migration, and invasion. It reduced mRNA levels of MMP-2 and MMP-9 while increasing those of TIMP-1 and TIMP-2. Furthermore, DF enhanced the expression of pro-apoptotic proteins and inhibited M2 macrophage polarization by targeting key molecules and enzymes. The anti-myeloma activity of DF was mediated through the inhibition of the PI3K/AKT pathway, as evidenced by diminished phosphorylation and differential effects in the presence of IGF-1 and LY294002.Conclusion By modulating the PI3K/AKT pathway, DF effectively inhibits MM cell proliferation, migration, and invasion, and induces apoptosis, establishing a novel therapeutic strategy for MM based on traditional Chinese medicine. C1 [Gui, Hua; Fan, Xiaohong] Fudan Univ, Hematol Dept, ZhongShan Hosp, QingPu Branch, 1158 Pk Rd E, Shanghai, Peoples R China. C3 Fudan University RP Fan, XH (corresponding author), Fudan Univ, Hematol Dept, ZhongShan Hosp, QingPu Branch, 1158 Pk Rd E, Shanghai, Peoples R China. EM guihua9293@163.com; fangxiaohong2020@126.com RI Fan, Xiaohong/NSN-3484-2025 FU Hospital-level scientific research project of Zhongshan Hospital Affiliated to Fudan University FX No Statement Available CR Bao TH, 2018, J MOL MED, V96, P661, DOI 10.1007/s00109-018-1652-7 Cencini E, 2023, CURR ONCOL, V30, P6111, DOI 10.3390/curroncol30070455 Cong YH, 2023, FRONT IMMUNOL, V14, DOI 10.3389/fimmu.2023.1122057 Cowan AJ, 2022, JAMA-J AM MED ASSOC, V327, P464, DOI 10.1001/jama.2022.0003 De Beule N, 2017, J PATHOL, V241, P534, DOI 10.1002/path.4860 Feng N, 2016, MOL MED REP, V13, P3243, DOI 10.3892/mmr.2016.4887 Gutiérrez-González A, 2016, BLOOD, V128, P2241, DOI 10.1182/blood-2016-01-695395 Hao P, 2020, SAUDI J BIOL SCI, V27, P1674, DOI 10.1016/j.sjbs.2020.04.031 Heider M, 2021, ONCOL RES TREAT, V44, P672, DOI 10.1159/000520312 Ignat MV, 2021, PLANTS-BASEL, V10, DOI 10.3390/plants10020216 Jackaman C, 2017, AGEING RES REV, V36, P105, DOI 10.1016/j.arr.2017.03.008 Jackson HW, 2017, NAT REV CANCER, V17, P38, DOI 10.1038/nrc.2016.115 Kuang CM, 2023, NAT COMMUN, V14, DOI 10.1038/s41467-023-37699-z Kumar SK, 2017, NAT REV DIS PRIMERS, V3, DOI 10.1038/nrdp.2017.46 Lee YT, 2018, EUR J PHARMACOL, V834, P188, DOI 10.1016/j.ejphar.2018.07.034 Li Y, 2023, HEPATOLOGY, V78, P1352, DOI 10.1097/HEP.0000000000000028 Li YX, 2022, FRONT PHARMACOL, V13, DOI 10.3389/fphar.2022.897465 Locati M, 2020, ANNU REV PATHOL-MECH, V15, P123, DOI 10.1146/annurev-pathmechdis-012418-012718 Mantovani A, 2013, ARTERIOSCL THROM VAS, V33, P1478, DOI 10.1161/ATVBAHA.113.300168 Ntanasis-Stathopoulos I, 2019, CANCER J, V25, P2, DOI 10.1097/PPO.0000000000000348 Oh SM, 2015, CHIN J NAT MEDICINES, V13, P808, DOI 10.1016/S1875-5364(15)30084-4 Ovadje P, 2016, ONCOTARGET, V7, P73080, DOI 10.18632/oncotarget.11485 Pan DR, 2022, FRONT ONCOL, V11, DOI 10.3389/fonc.2021.819127 Panchabhai S, 2016, LEUKEMIA, V30, P951, DOI 10.1038/leu.2015.191 Petty AJ, 2019, CELLS-BASEL, V8, DOI 10.3390/cells8121526 Shapouri-Moghaddam A, 2018, J CELL PHYSIOL, V233, P6425, DOI 10.1002/jcp.26429 Shay G, 2016, J MOL MED, V94, P21, DOI 10.1007/s00109-015-1345-4 Slika H, 2022, BIOMED PHARMACOTHER, V146, DOI 10.1016/j.biopha.2021.112442 Wang YS, 2020, BIOMED PHARMACOTHER, V121, DOI 10.1016/j.biopha.2019.109570 Xiang YN, 2019, CANCER MED-US, V8, P1958, DOI 10.1002/cam4.2108 Yang BJ, 2017, ONCOTARGETS THER, V10, P935, DOI 10.2147/OTT.S123398 Zhang XY, 2021, BIOSCI TRENDS, V15, P283, DOI 10.5582/bst.2021.01318 Zhang Y, 2021, FRONT IMMUNOL, V11, DOI 10.3389/fimmu.2020.609705 Zheng Y, 2013, LEUKEMIA, V27, P702, DOI 10.1038/leu.2012.272 NR 34 TC 8 Z9 8 U1 5 U2 12 PU SPRINGER PI NEW YORK PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES EI 2730-6011 J9 DISCOV ONCOL JI Discov. 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PD JUN 8 PY 2024 VL 15 IS 1 AR 215 DI 10.1007/s12672-024-01076-z PG 11 WC Oncology; Endocrinology & Metabolism WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Endocrinology & Metabolism GA TT9C1 UT WOS:001243616600001 PM 38850433 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Tian, LL Chen, J Yang, MQ Chen, L Qiu, JN Jiang, YW Tan, XL Qian, QY Liang, X Dou, XB AF Tian, Lulu Chen, Jing Yang, Meiqi Chen, Lin Qiu, Jiannan Jiang, Yuwei Tan, Xiaolong Qian, Qianyu Liang, Xiao Dou, Xiaobing TI Xiezhuo Tiaozhi formula inhibits macrophage pyroptosis in the non-alcoholic fatty liver disease by targeting the SIRT1 pathway SO PHYTOMEDICINE LA English DT Article DE Xiezhuo Tiaozhi formula; Non-alcoholic fatty liver disease; Macrophage pyroptosis; Macrophage polarization; SIRT1 pathway ID GASDERMIN-D; IN-VITRO; POLARIZATION; NAFLD; INFLAMMATION AB Background: Non-alcoholic fatty liver disease (NAFLD) is a challenging disease to interfere with and represents a potential long -term risk factor for hepatic fibrosis and liver cancer. The Xiezhuo Tiaozhi (XZTZ) formula, a water extract from crude herbs, has been widely used as an anti-NAFLD agent through clinical observation. However, the underlying pharmacological mechanisms of the XZTZ formula and its impact on the potential pathways against NAFLD have not been elucidated. Purpose: Our study aims to investigate the pharmacological effects and underlying regulatory mechanisms of the XZTZ formula to treat NAFLD. Methods: The possible active components and pharmacological mechanisms of the XZTZ formula against NAFLD were identified using ultra -performance liquid chromatography-quadrupole time -of -flight mass spectrometry (UPLC-Q-TOF/MS) and molecular docking. To further explore the potential mechanisms, forty-eight 6-week-old male C57BL/6 J mice were given individual attention with high -fat and high-sugar diet (HFHSD) or relevant control (Ctrl) diets for 16 weeks to successfully construct a NAFLD mouse model. Subsequently, the levels of serum biochemicals, pathological changes in the liver, and pyroptosis levels were assessed in mice to investigate the therapeutic effects of the XZTZ formula. Further, LPS-induced RAW264.7 cells and Immortalized Mouse Kupffer cells (ImKC) were used to verify the potential mechanisms of the XZTZ formula against NAFLD in vitro . Results: We identified 7 chemical compounds and 2 potential therapeutic targets as plausible therapeutic points for the treatment of NAFLD using the XZTZ formula. Subsequent histopathological analysis revealed marked hepatic steatosis and lipid accumulation in the HFHSD mice liver, while conditions were effectively ameliorated by administration of the XZTZ formula. Additionally, our work demonstrated that the XZTZ formula could attenuate M1 polarization, promote M2 polarization, and suppress pyroptosis via the SIRT1 pathway in tissue samples. Moreover, validation performed through LPS-induced RAW264.7 and ImKC cells by showing that silencing SIRT1 weaken the effects of the XZTZ formula on relative pyroptosis affirmed that its role was associated with the SIRT1 pathway in macrophage. Conclusion: These findings suggest that the XZTZ formula alleviated hepatic steatosis and lipid accumulation in NAFLD mice. These ameliorations are associated with mechanisms involving the attenuation of M1 polarization, promotion of M2 polarization, and anti-pyroptosis effects through the SIRT1 pathway. C1 [Tian, Lulu; Chen, Jing; Chen, Lin; Qiu, Jiannan; Jiang, Yuwei; Tan, Xiaolong; Qian, Qianyu; Dou, Xiaobing] Zhejiang Chinese Med Univ, Sch Life Sci, Hangzhou, Zhejiang, Peoples R China. [Yang, Meiqi] Liaoning Univ Tradit Chinese Med, Xinglin Coll, Shenyang, Liaoning, Peoples R China. [Liang, Xiao] Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Gen Surg, Hangzhou, Zhejiang, Peoples R China. [Liang, Xiao] 453 Stadium Rd, Hangzhou 310053, Zhejiang, Peoples R China. [Dou, Xiaobing] 548 Binwen Rd, Hangzhou 310053, Zhejiang, Peoples R China. C3 Zhejiang Chinese Medical University; Liaoning University of Traditional Chinese Medicine; Zhejiang University RP Liang, X (corresponding author), 453 Stadium Rd, Hangzhou 310053, Zhejiang, Peoples R China.; Dou, XB (corresponding author), 548 Binwen Rd, Hangzhou 310053, Zhejiang, Peoples R China. EM srrshlx@zju.edu.cn; xbdou77@163.com RI jiang, yuwei/MZS-0693-2025 OI Chen, Lin/0000-0003-4509-0823 FU Natural Science Foundation of China [82374102]; Research Project of Zhejiang Chinese Medical University [2022RCZXZK32] FX This project was supported by grants from the Natural Science Foundation of China [82374102] and supported by the Research Project of Zhejiang Chinese Medical University [2022RCZXZK32] . 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Tanshinol (TAN) is an active ingredient of Salvia miltiorrhiza, which possesses pharmacological effects such as anti-inflammatory and antioxidant properties. However, the effects of TAN on psoriasis have not been widely reported. Therefore, the aim of this study was to investigate the therapeutic effects and mechanisms of TAN in psoriasis.Methods An imiquimod (IMQ)-induced psoriasis mouse model was constructed and treated with different doses of TAN to observe the changes in skin lesion phenotype, macrophage polarization, inflammation and Notch signaling pathway in mice. Further removal of macrophages or inhibition or activation of Notch signaling pathway was performed to examine the changes in skin lesion phenotype, macrophage polarization, inflammation and Notch signaling pathway in mice. In addition, in vitro experiments verified that TAN regulates RAW264.7 macrophage polarization and cytokine secretion through the Notch pathway.Results The results showed that TAN alleviated IMQ-induced skin lesions and pathological phenotypes in psoriasis mice and inhibited Notch signaling pathway and M1-type macrophage polarization. Moreover, macrophage clearance and Notch signaling pathway activation inhibited the effect of TAN on psoriasis. Further in vitro experiments showed that Notch agonists reversed the effects of TAN on macrophage polarization and inflammatory cytokines.Conclusions Collectively, these findings suggest that TAN may exert a therapeutic effect on psoriasis by inhibiting the Notch signaling pathway and thus M1-type macrophage polarization. C1 [Liu, Junhao] peoples Hosp dazhou, Dept Dermatol, Dazhou, Peoples R China. [Yong, Shuangshuang] peoples Hosp dazhou, Dept Dermatol, Dazhou, Peoples R China. [Yin, Sisi; Feng, Jinhong] Chengdu Univ Tradit Chinese Med, Dept Med Aesthet, Affiliated Hosp, Chengdu, Peoples R China. [Lian, Caihua] Chengdu Seventh Peoples Hosp, Chengdu Med Coll, Dept Dermatol, Affiliated Canc Hosp, Chengdu, Peoples R China. [Chen, Jie] Gulin Tradit Chinese Med Hosp, Dept Dermatol, Luzhou, Peoples R China. [Chen, Jie] Gulin Tradit Chinese Med Hosp, Dept Dermatol, 56 Luhong Rd,Jinlan St, Luzhou, Sichuan, Peoples R China. C3 Chengdu University of Traditional Chinese Medicine; Chengdu Medical College RP Chen, J (corresponding author), Gulin Tradit Chinese Med Hosp, Dept Dermatol, Luzhou, Peoples R China.; Chen, J (corresponding author), Gulin Tradit Chinese Med Hosp, Dept Dermatol, 56 Luhong Rd,Jinlan St, Luzhou, Sichuan, Peoples R China. EM junhaoliu2016@126.com; 1476030660@qq.com; sisiyin2020@126.com; 819342057@qq.com; smu3120010207@163.com; cj208208@163.com RI Liu, Junhao/GNH-4246-2022 FX Not applicable. 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Pharmacol. PD NOV PY 2024 VL 397 IS 11 BP 8745 EP 8758 DI 10.1007/s00210-024-03166-9 EA JUN 2024 PG 14 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA K6J3Z UT WOS:001239300100004 PM 38832986 OA Green Submitted, hybrid DA 2026-03-26 ER PT J AU Song, HY Zhang, JB Lou, N Jiang, XY Cui, YY Liu, JM Hu, FL Jiao, JY Pan, C Liu, JJ Wang, ZZ Shang, D AF Song, Huiyi Zhang, Jianbin Lou, Ni Jiang, Xinyue Cui, Yuying Liu, Jinming Hu, Fenglin Jiao, Juying Pan, Chen Liu, Jianjun Wang, Zhizhou Shang, Dong TI Emodin nanocapsules inhibit acute pancreatitis by regulating lipid metabolic reprogramming in macrophage polarization SO PHYTOMEDICINE LA English DT Article DE Mannosylated chitosan lipid nanocapsules; SAP; Macrophage polarization; Lipid metabolism reprogramming ID ALTERNATIVE ACTIVATION; NANOPARTICLES; CHAIN AB Background: Emodin is a chemical compound found in traditional Chinese herbs. It possesses anti-inflammatory and many other pharmacological effects. Our previous study showed that emodin significantly alleviates the inflammation effect of severe acute pancreatitis (SAP). However, its poor solubility, high toxicity and limited pancreas retention time hinder its clinical application. Purpose: We aimed to prepare emodin nanocapsules with improved bioavailability to achieve the controlled release of emodin by targeting macrophages. Further, the mechanism of mannose-conjugated chitosan-coated lipid nanocapsules loaded with emodin (M-CS-E-LNC) in the treatment of SAP was explored. Methods: M-CS-E-LNC were prepared by the phase inversion method with slight modification. The expression of inflammation mediators and the anti-inflammation efficacy of M-CS-E-LNC were examined by ELISA, IHC and IF in macrophage cells and LPS-induced SAP mice. IVIS spectrum imaging and HPLC were applied to explore the controlled release of M-CS-E-LNC in the pancreas. LC-MS/MS was performed for lipidomics analysis of macrophages. Moreover, a vector-based short hairpin RNA (shRNA) method was used to silence CTP1 gene expression in macrophage cells. Results: The levels of inflammatory mediators in macrophages were markedly decreased after treatment with MCS-E-LNC. The same anti-inflammation effects were detected in SAP mouse through the analysis of serum levels of amylase, TNF-alpha and IL-6. Importantly, M-CS-E-LNC allowed the emodin to selectively accumulate at pancreas and gastrointestinal tissues, thus exhibiting a targeted release. Mechanistically, the M-CS-E-LNC treatment group showed up-regulated expression of the carnitine palmitoyltransferase 1 (CPT1) protein which promoted intracellular long-chain fatty acid transport, thereby promoting the M2 phenotype polarization of macrophages. Conclusion: M-CS-E-LNC exhibited significantly improved bioavailability and water solubility, which translated to greater therapeutic effects on macrophage polarization. Our findings also demonstrate, for the first time, that CPT1 may be a new therapeutic target for SAP treatment. C1 [Song, Huiyi; Lou, Ni; Jiang, Xinyue; Cui, Yuying; Hu, Fenglin; Jiao, Juying; Pan, Chen; Liu, Jianjun; Wang, Zhizhou; Shang, Dong] Dalian Med Univ, Affiliated Hosp 1, Clin Lab Integrat Med, 222 Zhongshan Rd, Dalian 116023, Liaoning, Peoples R China. [Zhang, Jianbin] Dalian Med Univ, Coll Pharm, Dalian, Liaoning, Peoples R China. [Liu, Jinming; Shang, Dong] Dalian Med Univ, Affiliated Hosp 1, Dept Gen Surg 3, Dalian, Liaoning, Peoples R China. C3 Dalian Medical University; Dalian Medical University; Dalian Medical University RP Wang, ZZ; Shang, D (corresponding author), Dalian Med Univ, Affiliated Hosp 1, Clin Lab Integrat Med, 222 Zhongshan Rd, Dalian 116023, Liaoning, Peoples R China. EM shangdong@dmu.edu.cn RI Cui, Yuying/NJS-4430-2025; Zhang, Jianbin/P-9165-2016; hu, fenglin/ORI-7452-2025; Jiao, Juying/HCI-3778-2022 OI Pan, Chen/0000-0001-7392-8262 FU Foundation of Liaoning Education Committee [LJKZZ20220098] FX Funding This work was supported by the Foundation of Liaoning Education Committee (LJKZZ20220098) CR Deng Z, 2019, TOXICOL APPL PHARM, V366, P83, DOI 10.1016/j.taap.2019.01.022 Gordon S, 2003, NAT REV IMMUNOL, V3, P23, DOI 10.1038/nri978 Granger J, 2005, SHOCK, V24, P45, DOI 10.1097/01.shk.0000191413.94461.b0 Hu Q, 2022, ACTA PHARM SIN B, V12, P3986, DOI 10.1016/j.apsb.2021.10.008 Jadhav SH, 2007, ARCH ENVIRON CON TOX, V53, P667, DOI 10.1007/s00244-007-0031-0 Jain SK, 2008, NANOMED-NANOTECHNOL, V4, P41, DOI 10.1016/j.nano.2007.11.004 Jiang Chang-gui, 2010, Zhongguo Wei Zhong Bing Ji Jiu Yi Xue, V22, P249 Jiang NA, 2022, NAT COMMUN, V13, DOI 10.1038/s41467-022-29137-3 Leppkes M, 2016, NAT COMMUN, V7, DOI 10.1038/ncomms10973 Lin LC, 2024, TRENDS ENDOCRIN MET, V35, P164, DOI 10.1016/j.tem.2023.10.004 Liu X, 2021, SCI TRANSL MED, V13, DOI 10.1126/scitranslmed.aaz6314 Liu XX, 2016, INFLAMMATION, V39, P1421, DOI 10.1007/s10753-016-0374-7 Liu Y, 2013, COLLOID SURFACE B, V103, P345, DOI 10.1016/j.colsurfb.2012.11.012 Mehnert W, 2001, ADV DRUG DELIVER REV, V47, P165, DOI 10.1016/S0169-409X(01)00105-3 Miguel V, 2021, J CLIN INVEST, V131, DOI 10.1172/JCI140695 Mikami Y, 2003, PANCREAS, V27, P253, DOI 10.1097/00006676-200310000-00011 NEWSHOLME P, 1986, BIOCHEM J, V239, P121, DOI 10.1042/bj2390121 Qiao XH, 2023, LIPIDS HEALTH DIS, V22, DOI 10.1186/s12944-023-01807-1 Ranjan A, 2020, DRUG DELIV TRANSL RE, V10, P515, DOI 10.1007/s13346-019-00696-1 Rodrigues HG, 2012, J INVEST DERMATOL, V132, P208, DOI 10.1038/jid.2011.265 Roszer T, 2015, MEDIAT INFLAMM, V2015, DOI 10.1155/2015/816460 Saikia S, 2023, CURR PHARM BIOTECHNO, V24, P1847, DOI 10.2174/1389201024666230413084603 Sendler M, 2013, GUT, V62, P430, DOI 10.1136/gutjnl-2011-300771 Sheng LP, 2023, J BIOCHEM MOL TOXIC, V37, DOI 10.1002/jbt.23242 Sica A, 2012, J CLIN INVEST, V122, P787, DOI 10.1172/JCI59643 Van Ginderachter JA, 2006, IMMUNOBIOLOGY, V211, P487, DOI 10.1016/j.imbio.2006.06.002 Vazquez A, 2010, BMC SYST BIOL, V4, DOI 10.1186/1752-0509-4-58 WADHWA MS, 1995, J DRUG TARGET, V3, P111, DOI 10.3109/10611869509059211 Wang G, 2007, MEDIAT INFLAMM, V2007, DOI 10.1155/2007/29638 Wang SP, 2012, INT J PHARMACEUT, V430, P238, DOI 10.1016/j.ijpharm.2012.03.027 Wijagkanalan W, 2008, J CONTROL RELEASE, V125, P121, DOI 10.1016/j.jconrel.2007.10.011 Xia SL, 2019, INFLAMMATION, V42, P2129, DOI 10.1007/s10753-019-01077-z Xiang H, 2017, FRONT IMMUNOL, V8, DOI 10.3389/fimmu.2017.01488 YALPANI M, 1984, MACROMOLECULES, V17, P272, DOI 10.1021/ma00133a003 Yang CB, 2014, CHIN MED-UK, V9, DOI 10.1186/1749-8546-9-23 Yu T, 2016, J PERIODONTOL, V87, P1092, DOI 10.1902/jop.2016.160081 Zhang QK, 2019, ONCOL REP, V42, P1589, DOI 10.3892/or.2019.7270 Zhao J, 2017, MOL NEUROBIOL, V54, P2801, DOI 10.1007/s12035-016-9870-x Zhou ZG, 2003, PANCREAS, V27, pE46, DOI 10.1097/00006676-200310000-00019 NR 39 TC 17 Z9 17 U1 8 U2 39 PU ELSEVIER GMBH PI MUNICH PA HACKERBRUCKE 6, 80335 MUNICH, GERMANY SN 0944-7113 EI 1618-095X J9 PHYTOMEDICINE JI Phytomedicine PD JUL 25 PY 2024 VL 130 AR 155763 DI 10.1016/j.phymed.2024.155763 EA MAY 2024 PG 13 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA UR3P4 UT WOS:001249748900003 PM 38820661 DA 2026-03-26 ER PT J AU Li, JN Wang, MY Tan, YR Wang, LL AF Li, Jia-Ni Wang, Meng-Yu Tan, Yu-Rong Wang, Li-Li TI Multidirectional Intervention of Chinese Herbal Medicine in the Prevention and Treatment of Atherosclerosis: From Endothelial Protection to Immunomodulation SO AMERICAN JOURNAL OF CHINESE MEDICINE LA English DT Article DE Atherosclerosis; Atherosclerotic Cardiovascular Disease; Traditional Chinese Medicine; Herbal Medicine; Chinese Medicine Therapeutics; Review ID INDUCED APOE(-/-) MICE; FOAM CELL-FORMATION; OXIDATIVE STRESS; MACROPHAGE POLARIZATION; NITRIC-OXIDE; ATTENUATES ATHEROSCLEROSIS; BIOACTIVE COMPOUNDS; SIGNALING PATHWAYS; PATENT MEDICINE; APOPTOSIS AB Atherosclerosis is a significant risk factor for developing cardiovascular disease and a leading cause of death worldwide. The occurrence of atherosclerosis is closely related to factors such as endothelial injury, lipid deposition, immunity, and inflammation. Conventional statins, currently used in atherosclerosis treatment, have numerous adverse side effects that limit their clinical utility, prompting the urgent need to identify safer and more effective therapeutic alternatives. Growing evidence indicates the significant potential of Chinese herbs in atherosclerosis treatment. Herbal monomer components, such as natural flavonoid compounds extracted from herbs like Coptis chinensis and Panax notoginseng, have been utilized for their lipid-lowering and inflammation-inhibiting effects in atherosclerosis treatment. These herbs can be used as single components in treating diseases and with other Chinese medicines to form herbal combinations. This approach targets the disease mechanism in multiple ways, enhancing the therapeutic effects. Thus, this review examines the roles of Chinese herbal medicine monomers and Chinese herbal compounds in inhibiting atherosclerosis, including regulating lipids, improving endothelial function, reducing oxidative stress, regulating inflammation and the immune response, and apoptosis. By highlighting these roles, our study offers new perspectives on atherosclerosis treatment with Chinese herbs and is anticipated to contribute to advancements in related research fields. C1 [Li, Jia-Ni; Wang, Meng-Yu; Tan, Yu-Rong; Wang, Li-Li] Cent South Univ, Xiangya Sch Med, Dept Med Microbiol, Xiangya Rd 88, Changsha 410078, Hunan, Peoples R China. C3 Central South University RP Tan, YR; Wang, LL (corresponding author), Cent South Univ, Xiangya Sch Med, Dept Med Microbiol, Xiangya Rd 88, Changsha 410078, Hunan, Peoples R China. 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PY 2024 VL 52 IS 04 BP 925 EP 947 DI 10.1142/S0192415X24500381 EA MAY 2024 PG 23 WC Integrative & Complementary Medicine; Medicine, General & Internal WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine; General & Internal Medicine GA XQ4N8 UT WOS:001231114500001 PM 38798151 DA 2026-03-26 ER PT J AU Zhang, SJ Hou, B Xu, AJ Wen, YY Zhu, XX Cai, WW Han, ZJ Chen, J Nhamdriel, T Mi, M Qiu, LY Sun, HJ AF Zhang, Shijie Hou, Bao Xu, Anjing Wen, Yuanyuan Zhu, Xuexue Cai, Weiwei Han, Zhijun Chen, Jing Nhamdriel, Tsedien Mi, Ma Qiu, Liying Sun, Haijian TI Ganlu formula ethyl acetate extract (GLEE) blocked the development of experimental arthritis by inhibiting NLRP3 activation and reducing M1 type macrophage polarization SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Ganlu; Rheumatoid arthritis; NLRP3; M1 macrophages; UPLC-Q-TOF-MS AB Ethnopharmacological relevance: The Tibetan medicine Ganlu Formula, as a classic prescription, is widely used across the Qinghai-Tibet Plateau area of China, which has a significant effect on relieving the course of rheumatoid arthritis (RA). However, the active compounds and underlying mechanisms of Ganlu Formula in RA treatment remain largely unexplored. Aim of the study: This study aimed to elucidate the active substances and potential mechanisms of the ethyl acetate extract of Ganlu Formula ethyl acetate extract (GLEE) in the treatment of RA. Materials and methods: Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was utilized to analyze and identify the chemical constituents within GLEE. Discovery Studio molecular virtual docking technology was utilized to dock the interaction of GLEE with inflammation-related pathway proteins. The GLEE gene library was obtained by transcriptome sequencing. Collagen-induced arthritic(CIA) rats were utilized to assess the antiarthritic efficacy of GLEE. Micro-CT imaging was employed to visualize the rat paw, and ultrasound imaging revealed knee joint effusion. Evaluation of synovial tissue pathological changes was conducted through hematoxylin-eosin staining and saffranine solid green staining, while immunohistochemical staining was employed to assess NLRP3 expression along with inflammatory markers. Immunofluorescence staining was utilized to identify M1 macrophages. Results: Metabolomic analysis via UPLC-Q-TOF-MS identified 28 potentially bioactive compounds in GLEE, which interacted with the active sites of key proteins such as NLRP3, NF-kappa B, and STAT3 through hydrogen bonds, C-H bonds, and electrostatic attractions. In vitro analyses demonstrated that GLEE significantly attenuated NLRP3 inflammasome activation and inhibited the polarization of bone marrow-derived macrophages (BMDMs) towards the M1 phenotype. In vivo, GLEE not only prevented bone mineral density (BMD) loss but also reduced ankle swelling in CIA rats. Furthermore, it decreased the expression of the NLRP3 inflammasome and curtailed the release of inflammatory mediators within the knee joint. Conclusion: GLEE effectively mitigated inflammatory responses in both blood and knee synovial membranes of CIA rats, potentially through the down-regulation of the NLRP3/Caspase-1/IL-1 beta signaling pathway and reduction in M1 macrophage polarization. C1 [Zhang, Shijie; Hou, Bao; Xu, Anjing; Wen, Yuanyuan; Zhu, Xuexue; Cai, Weiwei; Qiu, Liying; Sun, Haijian] Jiangnan Univ, Wuxi Sch Med, Dept Basic Med, Wuxi 214122, Peoples R China. [Han, Zhijun] Jiangnan Univ, Dept Clin Res Ctr, Med Ctr, Wuxi 214001, Jiangsu, Peoples R China. [Chen, Jing; Nhamdriel, Tsedien; Mi, Ma] Tibet Univ Med, Dept Basic Med, Lhasa 850000, Peoples R China. [Sun, Haijian] China Pharmaceut Univ, State Key Lab Nat Med, 24 Tongjia Lane, Nanjing 210009, Peoples R China. C3 Jiangnan University; Jiangnan University; China Pharmaceutical University RP Qiu, LY; Sun, HJ (corresponding author), Jiangnan Univ, Wuxi Sch Med, Dept Basic Med, Wuxi 214122, Peoples R China.; Mi, M (corresponding author), Tibet Univ Med, Dept Basic Med, Lhasa 850000, Peoples R China.; Sun, HJ (corresponding author), China Pharmaceut Univ, State Key Lab Nat Med, 24 Tongjia Lane, Nanjing 210009, Peoples R China. EM rbmm2626@163.com; qiulydoc@sina.com; sunhaijian927@163.com RI Cai, Weiwei/AAQ-3840-2021; Sun, Hai-Jian/JJC-4020-2023 OI Sun, Hai-Jian/0000-0002-7791-5335; Zhu, Xuexue/0000-0002-4735-5648 FU Natural Science Foundation of China, China [82370364, 82300414, 82170424]; High-level introduction of talents and scientific research start-up funds of JNU, China [1286010241222100]; Tibetan medicine 14th Five -Year Plan connotation construction project [2023ZYYGH04, 2021ZYYGH002] FX This work was supported by the Natural Science Foundation of China, China (82370364, 82300414, 82170424) . High-level introduction of talents and scientific research start-up funds of JNU, China (1286010241222100) , Tibetan medicine 14th Five-Year Plan connotation construction project (2023ZYYGH04, 2021ZYYGH002) . 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Ethnopharmacol. PD OCT 5 PY 2024 VL 332 AR 118377 DI 10.1016/j.jep.2024.118377 EA MAY 2024 PG 16 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA UD3P5 UT WOS:001246087700001 PM 38782307 DA 2026-03-26 ER PT J AU Zhao, M Chen, YQ Bao, XJ Wang, ZD Yuan, NN Jin, ZX Huang, YQ Yang, LL Yang, YS Zeng, L AF Zhao, Min Chen, Yanqi Bao, Xiaojiang Wang, Zhongda Yuan, Ningning Jin, Zixiang Huang, Yuqiu Yang, Lili Yang, Yousheng Zeng, Li TI HuoXueTongFu formula induces M2c macrophages via the MerTK/PI3K/ AKT pathway to eliminate NETs in intraperitoneal adhesion in mice SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Intraperitoneal adhesion; HuoXueTongFu formula; Neutrophil extracellular traps (NETs); Macrophage; MerTK ID RHEUMATOID-ARTHRITIS; ATHEROSCLEROSIS; NEUTROPHILS AB Ethnopharmacological relevance: HuoXueTongFu Formula (HXTF) is a traditional Chinese herbal formula that has been used as a supplement and alternative therapy for intraperitoneal adhesion (IA). However, its specific mechanism of action has not been fully understood. Aim of the study: In surgery, IA presents an inevitable challenge, significantly impacting patients' physical and mental well-being and increasing the financial burden. Our previous research has confirmed the preventive effects of HXTF on IA formation. However, the precise mechanism of its action still needs to be understood. Methods: In this study, the IA model was successfully established by using the Ischemic buttons and treated with HXTF for one week with or without Mer Tyrosine Kinase (MerTK) inhibitor. We evaluated the pharmacodynamic effect of HXTF on IA mice. The MerTK/phosphoinositol 3-kinase (PI3K)/protein kinase B (AKT) pathwayassociated proteins were detected by Western blotting. Neutrophil extracellular traps (NETs) were detected by immunofluorescence. Macrophage phenotype was assessed by immunohistochemistry and flow cytometry. Inflammatory cytokines were detected by Real Time Quantitative PCR and Western blotting. Results: HXTF reduced inflammatory response and alleviated IA. HXTF significantly enhanced MerTK expression, increased the number of M2c macrophages, and decreased the formation of NETs. In addition, the MerTK/PI3K/ AKT pathway was significantly activated by HXTF. However, after using MerTK inhibitors, the role of HXTF in inducing M2c macrophage through activation of the PI3K/AKT pathway was suppressed and there was no inhibitory effect on NETs formation and inflammatory responses, resulting in diminished inhibition of adhesion. Conclusion: HXTF may improve IA by activating the MerTK/PI3K/AKT pathway to induce M2c polarization, which removes excess NETs and attenuates the inflammatory response. C1 [Zhao, Min; Chen, Yanqi; Bao, Xiaojiang; Wang, Zhongda; Yuan, Ningning; Jin, Zixiang; Huang, Yuqiu] Nanjing Univ Chinese Med, Sch Integrat Med, Nanjing 210023, Peoples R China. [Zeng, Li] Macau Univ Sci & Technol, Fac Chinese Med, Taipa, Macau, Peoples R China. [Yang, Yousheng] Suzhou Integrated Tradit Chinese & Western Med Ho, Dept Gen Surg, Suzhou 215101, Peoples R China. [Chen, Yanqi; Zeng, Li] Nanjing Univ Chinese Med, Sch Clin Med 1, Nanjing 210023, Peoples R China. [Yang, Lili] Nanjing Univ Chinese Med, Lib, Nanjing 210023, Peoples R China. [Zhao, Min; Zeng, Li] Jiangsu Prov Engn Res Ctr TCM External Medicat De, Nanjing 210023, Peoples R China. C3 Nanjing University of Chinese Medicine; Macau University of Science & Technology; Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine RP Zeng, L (corresponding author), Macau Univ Sci & Technol, Fac Chinese Med, Taipa, Macau, Peoples R China.; Yang, YS (corresponding author), Suzhou Integrated Tradit Chinese & Western Med Ho, Dept Gen Surg, Suzhou 215101, Peoples R China. EM yangyousheng1991@163.com; zengbingli@njucm.edu.cn OI Huang, Yuqiu/0000-0002-9082-5115; Yang, Lili/0000-0001-5220-3094 FU National Natural Science Foundation of China [82174394, 82374466, 82104857]; Jiangsu Chinese Medicine Science and Technology Development Project [QN202002]; Natural Science Foundation of Jiangsu Province [BK20201401, BK20210690]; Science and Technology Development Fund, Macau SAR [0121/2022/A3, 0127/2023/RIA2]; Faculty Research Grants of Macau University of Science and Technology [FRG-22-110-FC]; Jiangsu Provincial Center for T.C.M. Innovations FX This work was supported by Grants from the National Natural Science Foundation of China (No.82174394; No. 82374466; No.82104857) , Jiangsu Chinese Medicine Science and Technology Development Project (No. QN202002) , the Natural Science Foundation of Jiangsu Province (No. BK20201401; No. BK20210690) , the Science and Technology Development Fund, Macau SAR (No. 0121/2022/A3; No. 0127/2023/RIA2) and the Faculty Research Grants of Macau University of Science and Technology (FRG-22-110-FC) . This work was also supported by Jiangsu Provincial Center for T.C.M. Innovations. 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Ethnopharmacol. PD SEP 15 PY 2024 VL 331 AR 118290 DI 10.1016/j.jep.2024.118290 EA MAY 2024 PG 11 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA TN2Z0 UT WOS:001241889900001 PM 38703872 DA 2026-03-26 ER PT J AU Wang, Y Wang, WH Liu, KL Liu, YZ Shen, XY Li, QL Deng, FY Hao, XL Wang, YL AF Wang, Yan Wang, Wenhui Liu, Kaili Liu, Yanzhi Shen, Xiaoyu Li, Qiule Deng, Fanying Hao, Xuliang Wang, Yingli TI The mechanism of Xihuang pills' intervention in the tumour immune microenvironment for the treatment of liver cancer based on the STAT3-PDL1 pathway SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Liver cancer; Xihuang pills; Immune microenvironment; PD-1/PD-L1 AB Ethnopharmacological relevance: Xihuang pills, a time-honored Chinese compound formula with a history spanning thousands of years, have demonstrated remarkable efficacy in treating various cancers, such as breast cancer, colon cancer, and liver cancer. Clinical applications over the years have established their effectiveness. Several scholars conducting experimental studies have elucidated the potent tumor -suppressing effects of Xihuang pills. While the inhibition of tumor vascular development and prevention of tumor cell invasion and metastasis have been well -explored mechanisms, the impact on the tumor immune microenvironment has received less attention. This study focuses on investigating the immune microenvironment adjustments induced by Xihuang pills in hepatocellular carcinoma. Aim of the study: Tumour cells will find an escape phenomenon during tumour immunotherapy, which will affect immunotherapy results. We will research the regulation of the tumour immune microenvironment, to provide a more complete and precise basis for the elucidation of the mechanism of Xihuang pills in treating cancers. It provides new research ideas for people to treat liver cancer. Materials and methods: Through in vivo and in vitro assessments confirming the intervention effects of Xihuang pills, we observed alterations in T cell typing, macrophage polarization, and tumor -associated cytokine levels. The primary active ingredients of Xihuang pills were identified using UPLC-MS/GC-MS, and relevant pathways in the treatment of hepatocellular carcinoma were predicted through network pharmacology. Combining the network pharmacology approach, we predicted the pathways relevant to Xihuang pills in treating hepatocellular carcinoma and experimentally validated the involvement of PD-1/PD-L1, a key immunity -related axis. Results: Xihuang Pill has a regulatory effect on the tumor immune microenvironment. Conclusions: The results indicated that Xihuang pills could impact splenic lymphocyte phenotyping, macrophage polarization, and IL -6 cytokine expression in liver cancer mice. The mechanism of action was associated with the regulation of the PD-1/PD-L1 signaling pathway by the STAT3 protein. C1 [Wang, Yan; Wang, Wenhui; Liu, Kaili; Shen, Xiaoyu; Li, Qiule; Deng, Fanying; Wang, Yingli] Shanxi Univ Chinese Med, Inst Pharmaceut & Food Engn, 121 Daxue Rd, Jinzhong 030619, Peoples R China. [Liu, Yanzhi] Shanxi Zhendong Anxin Biopharmaceut Co, Jinzhong 030619, Peoples R China. [Hao, Xuliang] Shanxi Univ Tradit Chinese Med, Affiliated Hosp, 75,Sect 1,Jinci Rd, Taiyuan 030024, Peoples R China. C3 Shanxi University of Chinese Medicine RP Wang, YL (corresponding author), Shanxi Univ Chinese Med, Inst Pharmaceut & Food Engn, 121 Daxue Rd, Jinzhong 030619, Peoples R China. EM wyl@sxtcm.edu.cn FU Shanxi Provincial Science and Technology Department, China [202203021221205]; Shanxi Provincial Education Department, China [2021L362]; Shanxi Zhendong Anxin Biopharmaceutical Co FX This study was funded by a project of the Shanxi Provincial Science and Technology Department, China (Grant No. 202203021221205) , a project of the Shanxi Provincial Education Department, China (Grant No. 2021L362) , and funds from Shanxi Zhendong Anxin Biopharmaceutical Co. CR Anwanwan D, 2020, BBA-REV CANCER, V1873, DOI 10.1016/j.bbcan.2019.188314 [程志强 CHENG Zhi-qiang], 2010, [中华中医药杂志, China Journal of Traditional Chinese Medicine and Pharmacy], V25, P52 Du Jun, 2023, China Pract. Med., V18, P159 Gan Linwang, 2023, Chin. J. Comp. Med., V1-11, P10 Ganesan P, 2023, CLIN LIVER DIS, V27, P85, DOI 10.1016/j.cld.2022.08.004 Gou Q, 2023, ADV SCI, V10, DOI 10.1002/advs.202304068 Guo Jingjing, 2023, Int. J. Obstetr. 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PD SEP 15 PY 2024 VL 331 AR 118278 DI 10.1016/j.jep.2024.118278 EA MAY 2024 PG 13 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA TI9R4 UT WOS:001240758100001 PM 38710457 DA 2026-03-26 ER PT J AU Yan, FL Wang, L Zhang, JF Liu, ZH Yu, B Li, WB Guo, ZR Shi, DM Zhang, H Xiong, HB AF Yan, Fenglian Wang, Lin Zhang, Junfeng Liu, Zhihong Yu, Bin Li, Wenbo Guo, Zhengran Shi, Dongmei Zhang, Hui Xiong, Huabao TI Cornuside alleviates psoriasis-like skin lesions in mice by relieving inflammatory effects SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Psoriasis; Macrophages; Cornuside; Traditional Chinese medicine ID MACROPHAGE POLARIZATION; CELLS; MAPK; PATHOGENESIS; ACTIVATION; DISEASE AB Psoriasis is a chronic inflammatory skin disease substantially affecting the quality of life, with no complete cure owing to its complex pathogenesis. Cornuside, a major bioactive compound present in Cornus officinalis Sieb. et Zucc., which is a well-known traditional Chinese medicine with a variety of biological and pharmacological activities, such as anti-apoptotic, antioxidant, and anti-inflammatory properties. However, its effects on psoriasis remain unclear. Our preliminary analysis of network pharmacology showed that cornuside may be involved in psoriasis by regulating the inflammatory response and IL-17 signaling pathway. Thus, we investigated the protective role and mechanism of cornuside in the pathogenesis of psoriasis in an imiquimod (IMQ)-induced psoriasis mouse model. In-vivo experiments demonstrated that cornuside-treated mice had reduced skin erythema, scales, thickness, and inflammatory infiltration. The Psoriasis Area Severity Index score was significantly lower than that of the IMQ group. Flow cytometry analysis indicated that cornuside effectively inhibited Th1and Th17-cell infiltration and promoted aggregation of Th2 cells in skin tissues. Cornuside also inhibited the infiltration of macrophages to the skin. Furthermore, in-vitro experiments indicated that cornuside also decreased the polarization of M1 macrophages and reduced the levels of associated cytokines. Western blotting demonstrated that cornuside suppressed the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular receptor kinase (ERK) in bone marrow-derived macrophages. Our findings indicate that cornuside has a protective effect against IMQ-induced psoriasis by inhibiting M1 macrophage polarization through the ERK and JNK signaling pathways and modulating the infiltration of immune cells as well as the expression of inflammatory factors. C1 [Yan, Fenglian; Wang, Lin; Zhang, Junfeng; Li, Wenbo; Guo, Zhengran; Zhang, Hui; Xiong, Huabao] Jining Med Univ, Inst Immunol & Mol Med, Jining, Peoples R China. [Yan, Fenglian; Zhang, Junfeng; Zhang, Hui; Xiong, Huabao] Jining Med Univ, Jining Key Lab Immunol, Jining, Peoples R China. [Liu, Zhihong] Shandong First Med Univ, Sch Basic Med, Jinan, Peoples R China. [Yu, Bin] Jining Med Univ, Coll Integrated Chinese & Western Med, Jining, Peoples R China. [Shi, Dongmei] Jining First Peoples Hosp, Dept Dermatol, Lab Med Mycol, Jining, Peoples R China. C3 Jining Medical University; Jining Medical University; Shandong First Medical University & Shandong Academy of Medical Sciences; Jining Medical University RP Zhang, H; Xiong, HB (corresponding author), Jining Med Univ, Inst Immunol & Mol Med, Jining, Peoples R China.; Zhang, H; Xiong, HB (corresponding author), Jining Med Univ, Jining Key Lab Immunol, Jining, Peoples R China.; Shi, DM (corresponding author), Jining First Peoples Hosp, Dept Dermatol, Lab Med Mycol, Jining, Peoples R China. EM shidongmei28@163.com; zhanghuitjwh@hotmail.com; xionghbl@yahoo.com RI Yan, Fenglian/KBP-8427-2024; Li, Wenbo/AAP-2905-2021 FU National Natural Science Foundation of China [JYHL2021ZD01, JYHL2022MS21]; Natural Science Foundation of Shandong Province [82171810]; Projects of Medical and Health Technology Development Program in Shandong Province [ZR2021MH287]; [202202070388] FX This study was supported by Research Fund for Academician Lin He New Medicine (JYHL2021ZD01 , JYHL2022MS21) , National Natural Science Foundation of China (82171810) , Natural Science Foundation of Shandong Province (ZR2021MH287) , Projects of Medical and Health Technology Development Program in Shandong Province (202202070388) . 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PD JUN 15 PY 2024 VL 134 AR 112183 DI 10.1016/j.intimp.2024.112183 EA MAY 2024 PG 13 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA TB1G1 UT WOS:001238699700001 PM 38705031 DA 2026-03-26 ER PT J AU Zhang, XY Wu, Y Gong, H Xiong, Y Chen, Y Li, L Zhi, B Lv, SQ Peng, T Zhang, H AF Zhang, Xinyi Wu, Ye Gong, Heng Xiong, Yan Chen, Yu Li, Lin Zhi, Biao Lv, Saiqun Peng, Tao Zhang, Hui TI A Multifunctional Herb-Derived Glycopeptide Hydrogel for Chronic Wound Healing SO SMALL LA English DT Article DE Chinese herb-derived; chronic wound; drug deliveries; glycopeptide hydrogel; immunoregulation ID PAEONIFLORIN; NANOPARTICLES AB Chronic wounds constitute an increasingly prevalent global healthcare issue, characterized by recurring bacterial infections, pronounced oxidative stress, compromised functionality of immune cells, unrelenting inflammatory reactions, and deficits in angiogenesis. In response to these multifaceted challenges, the study introduced a stimulus-responsive glycopeptide hydrogel constructed by oxidized Bletilla striata polysaccharide (OBSP), gallic acid-grafted epsilon-Polylysine (PLY-GA), and paeoniflorin-loaded micelles (MIC@Pae), called OBPG&MP. The hydrogel emulates the structure of glycoprotein fibers of the extracellular matrix (ECM), exhibiting exceptional injectability, self-healing, and biocompatibility. It adapts responsively to the inflammatory microenvironment of chronic wounds, sequentially releasing therapeutic agents to eradicate bacterial infection, neutralize reactive oxygen species (ROS), modulate macrophage polarization, suppress inflammation, and encourage vascular regeneration and ECM remodeling, playing a critical role across the inflammatory, proliferative, and remodeling phases of wound healing. Both in vitro and in vivo studies confirmed the efficacy of OBPG&MP hydrogel in regulating the wound microenvironment and enhancing the regeneration and remodeling of chronic wound skin tissue. This research supports the vast potential for herb-derived multifunctional hydrogels in tissue engineering and regenerative medicine. This research aimed to build a herb-derived versatile glycopeptide hydrogel as a promising dressing to promote chronic wound repair. image C1 [Zhang, Xinyi; Xiong, Yan; Chen, Yu; Li, Lin; Zhi, Biao; Lv, Saiqun; Peng, Tao] Chengdu Univ, Affiliated Hosp, Dept Radiol, Chengdu 610081, Sichuan, Peoples R China. [Wu, Ye; Gong, Heng; Zhang, Hui] Sichuan Univ, West China Hosp, Dept Orthoped Surg, Chengdu 610041, Sichuan, Peoples R China. [Wu, Ye; Gong, Heng; Zhang, Hui] Sichuan Univ, West China Hosp, Orthoped Res Inst, Chengdu 610041, Sichuan, Peoples R China. [Zhang, Hui] Sichuan Univ, MedX Ctr Mfg, Chengdu 610041, Sichuan, Peoples R China. C3 Chengdu University; Sichuan University; Sichuan University; Sichuan University RP Peng, T (corresponding author), Chengdu Univ, Affiliated Hosp, Dept Radiol, Chengdu 610081, Sichuan, Peoples R China.; Zhang, H (corresponding author), Sichuan Univ, West China Hosp, Dept Orthoped Surg, Chengdu 610041, Sichuan, Peoples R China.; Zhang, H (corresponding author), Sichuan Univ, West China Hosp, Orthoped Res Inst, Chengdu 610041, Sichuan, Peoples R China.; Zhang, H (corresponding author), Sichuan Univ, MedX Ctr Mfg, Chengdu 610041, Sichuan, Peoples R China. EM pengtao919@cdu.edu.cn; zhanghui1437@wchscu.cn RI Wu, Ye/JQX-0640-2023; Zhang, Hui/OTH-2486-2025; Peng, Tao/IWM-5792-2023 FU National Natural Science Foundation of China; China Postdoctoral Science Foundation [2023M732459, GZC20231805]; Sichuan Science and Technology Program [2023NSFSC1746, 2023YFS0014]; West China Hospital, Sichuan University [2023HXBH082]; Med-X Center for Manufacturing Project, Sichuan University [00402053A29VQ]; [82202747] FX X.Z. and Y.W. contributed equally to this work. This work was supported by The National Natural Science Foundation of China (82202747), China Postdoctoral Science Foundation (2023M732459, GZC20231805), Sichuan Science and Technology Program (2023NSFSC1746, 2023YFS0014), Post-Doctor Research Project, West China Hospital, Sichuan University (2023HXBH082). Med-X Center for Manufacturing Project, Sichuan University (00402053A29VQ). 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PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 1613-6810 EI 1613-6829 J9 SMALL JI Small PD SEP PY 2024 VL 20 IS 36 DI 10.1002/smll.202400516 EA APR 2024 PG 17 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter WE Science Citation Index Expanded (SCI-EXPANDED) SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA L1H0U UT WOS:001209588100001 PM 38686688 DA 2026-03-26 ER PT J AU Liu, FG Yang, YF Dong, HR Zhu, YH Feng, WS Wu, HZ AF Liu, Fugang Yang, Yanfang Dong, Haoran Zhu, Yanhui Feng, Weisheng Wu, Hezhen TI Essential oil from Cinnamomum cassia Presl bark regulates macrophage polarization and ameliorates lipopolysaccharide-induced acute lung injury through TLR4/MyD88/NF-κB pathway SO PHYTOMEDICINE LA English DT Article DE Essential oil extracted from the bark of; Cinnamomum cassia Presl; Gas chromatography -mass spectrometry; Acute lung injury; Toll -like receptor 4; M1 macrophage polarization; M2 macrophage polarization ID TRANS-CINNAMALDEHYDE; INFLAMMATION AB Background: Cinnamomum cassia Presl, a traditional Chinese medicine recorded in "Shennong's Herbal Classic," has been historically used to treat respiratory diseases and is employed to address inflammation. The essential oil derived from Cinnamomum cassia bark is a primary anti-inflammatory agent. However, there remains ambiguity regarding the chemical composition of cinnamon bark essential oil (BCEO), its principal anti-inflammatory components, and their potential efficacy in typical inflammatory respiratory conditions, such as acute lung injury (ALI). Purpose: This study aimed to unveil the chemical composition of BCEO. In addition, the mechanism of action of BCEO in ameliorating ALI and regulating macrophage polarization through the TLR4/MyD88/NF-kappa B pathway was elucidated. Methods: BCEO was extracted using supercritical fluid extraction (SFE) and characterized through gas chromatography-mass spectrometry (GC-MS) analysis. Acute oral toxicity was observed in C57BL/6 J mice. The pharmacological effects and underlying mechanisms of BCEO were evaluated in a mouse model of ALI, which was induced by administering 5 mg/kg of lipopolysaccharide (LPS) through intratracheal instillation. Results: GC-MS analysis revealed 99.08% of the constituents of BCEO. The primary components of BCEO were trans-cinnamaldehyde, o-methoxycinnamaldehyde, (+)-alpha-muurolene, delta-cadinene, and copaene. Oral acute toxicity tests indicated that the maximum tolerated dose of BCEO was 12 g/kg/day. BCEO treatment significantly reduced lung W/D ratio, total protein concentration in BALF, levels of TNF-alpha, IL-6, and IL-1 beta in BALF, WBC count and NEU% in peripheral blood, and lung histological damage. Pulmonary function, IL-10 levels, and LYM% in peripheral blood also showed improvement. BCEO effectively decreased the proportion of M1 phenotype macrophages in BALF, M1/M2 ratio, and apoptotic cells in the lung tissue while increasing the proportion of M2 phenotype macrophages in BALF. Furthermore, BCEO treatment led to reduced protein and mRNA levels of TLR4, MyD88, and p-p65, alongside increased p65 expression, suggesting its potential to impede the TLR4/ MyD88/NF-kappa B signaling pathway. Conclusion: SFE-extracted BCEO or its major constituents could serve as a viable treatment for ALI by reducing lung inflammation, improving pulmonary function, and protecting against LPS-induced ALI in mice. This therapeutic effect is achieved by inhibiting M1 macrophage polarization, promoting M2 macrophage polarization, and suppressing the TLR4/MyD88/NF-kappa B signaling pathway. C1 [Liu, Fugang; Yang, Yanfang; Wu, Hezhen] Hubei Univ Chinese Med, Fac Pharm, Wuhan 430065, Peoples R China. [Liu, Fugang; Zhu, Yanhui; Feng, Weisheng] Henan Univ Chinese Med, Sch Pharm, Zhengzhou 450046, Peoples R China. [Yang, Yanfang; Wu, Hezhen] Modern Engn Res Ctr Tradit Chinese Med & Ethn Med, Wuhan 430065, Peoples R China. [Dong, Haoran] Henan Univ Chinese Med, Acad Chinese Med Sci, Zhengzhou 450046, Peoples R China. [Feng, Weisheng] Engn & Technol Ctr Chinese Med Dev Henan Prov Chin, Zhengzhou 450046, Peoples R China. C3 Hubei University of Chinese Medicine; Henan University of Traditional Chinese Medicine; Henan University of Traditional Chinese Medicine RP Wu, HZ (corresponding author), Hubei Univ Chinese Med, Fac Pharm, Wuhan 430065, Peoples R China.; Feng, WS (corresponding author), Henan Univ Chinese Med, Sch Pharm, Zhengzhou 450046, Peoples R China. EM fwsh@hactcm.edu.cn; hezh_wu@163.com RI liu, fugang/NBX-7954-2025; Dong, Haoran/OHY-7393-2025; Zhu, Yanhui/GVU-5794-2022 FU Key Research Projects of Henan Higher Education Institutions [23A360015]; National Natural Science Foundation of China [82204736] FX This research was supported by the Key Research Projects of Henan Higher Education Institutions (23A360015) and the National Natural Science Foundation of China (No. 82204736) . We would like to thank MogoEdit (https:// www.mogoedit.com ) for its English editing during the preparation of this manuscript. 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However, only a few studies have addressed the mechanisms of ZL in treating AIS. Aim of the study: To explore the underlying mechanism of macrophage polarization and inflammation mediated by ZL, and to provide a reference for AIS treatment. Materials and methods: Sixteen SD rats were fed with different dose of ZL (0, 0.4, 0.8, and 1.6 g/kg/d) for 4 days to prepare ZL serum. After 500 ng/mL lipopolysaccharide (LPS) stimulation, RAW264.7 cells were administrated with ZL serum. Then, experiments including ELISA, flow cytometry, real-time quantitative PCR and Western blot were performed to verify the effects of ZL on macrophage polarization and inflammation. Next, let -7i inhibitor was transfected in RAW264.7 cells when treated with LPS and ZL serum to verify the regulation of ZL on the let7i/TLR9/MyD88 signaling pathway. Moreover, the interaction between let -7i and TLR9 was confirmed by the dual-luciferase assay. Results: ZL serum significantly decreased the expression of interleukin (IL) -6 and tumor necrosis factor- alpha (TNF- alpha), and increased the expression of IL -10 and transforming growth factor 81 (TGF-81) of LPS stimulatedmacrophages. Furthermore, ZL serum polarized macrophages toward M2, decreased the expressions of TLR9, MyD88, and iNOS, as well as increased the expressions of let -7i, CHIL3, and Arginase-1. It is worth mentioning that the effect of ZL serum is dose -dependent. However, let -7i inhibitor restored all the above effects in LPS stimulated -macrophages. In addition, TLR9 was the target of let -7i. Conclusions: ZL targeted let -7i to inhibit TLR9 expression, thereby inhibiting the activation of the TLR9/MyD88 pathway, promoting the M2 polarization, and inhibiting the development of inflammation in AIS. C1 [Kang, Ya-Fei; Bai, Xue; Wang, Tao; Pan, Chuan-Ling; Xie, Cheng; Liao, Hui-Ling] Southwest Med Univ, Affiliated Tradit Chinese Med Hosp, Dept Neurol, Luzhou, Peoples R China. [Kang, Ya-Fei] Bazhong Hosp Tradit Chinese Med, Dept Neurol, Bazhong, Peoples R China. [Wang, Kong -Yu] Bazhong Hosp Tradit Chinese Med, Dept Intens Care Med, Bazhong, Peoples R China. [Liang, Bo] Third Mil Med Univ, Army Med Univ, Xinqiao Hosp, Chongqing Clin Res Ctr Kidney & Urol Dis,Dept Neph, Chongqing, Peoples R China. C3 Southwest Medical University; Army Medical University RP Liao, HL (corresponding author), Southwest Med Univ, Affiliated Tradit Chinese Med Hosp, Dept Neurol, Luzhou, Peoples R China.; Liang, B (corresponding author), Third Mil Med Univ, Army Med Univ, Xinqiao Hosp, Chongqing Clin Res Ctr Kidney & Urol Dis,Dept Neph, Chongqing, Peoples R China. EM liangbo1993@tmmu.edu.cn; liaohl@swmu.edu.cn RI Liang, Bo/AAZ-2834-2020 OI Liang, Bo/0000-0002-1749-6976 FU Innovation Team of The Affiliated Traditional Chinese Medicine Hospital [2022-CXTD-05]; Southwest Medical University [2022-CXTD-05] FX This study was partly supported by Innovation Team of The Affili- ated Traditional Chinese Medicine Hospital, Southwest Medical Uni- versity (2022-CXTD-05) . We are grateful to The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University for providing the components of ZL. 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PD AUG 10 PY 2024 VL 330 AR 118208 DI 10.1016/j.jep.2024.118208 EA APR 2024 PG 8 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA SC2M8 UT WOS:001232195000002 PM 38636581 DA 2026-03-26 ER PT J AU Yan, ZP Ji, FP Yan, RJ Jiao, JZ Wang, WB Zhang, MM Li, FH Zhao, YY Chang, ZJ Yan, SG Li, JT AF Yan, Zhipeng Ji, Fanpu Yan, Ruijuan Jiao, Junzhe Wang, Wenba Zhang, Miaomiao Li, Fenhong Zhao, Yunyu Chang, Zhanjie Yan, Shuguang Li, Jingtao TI Reyanning mixture inhibits M1 macrophage polarization through the glycogen synthesis pathway to improve lipopolysaccharide-induced acute lung injury SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Reyanning (RYN) mixture; Acute lung injury; Glycogen synthesis ID INFLAMMATION; PNEUMONIA; MEDICINE; TARGET AB Ethnopharmacological relevance: Reyanning (RYN) mixture is a traditional Chinese medicine composed of Taraxacum, Polygonum cuspidatum, Scutellariae Barbatae and Patrinia villosa and is used for the treatment of acute respiratory system diseases with significant clinical efficacy. Aim of the study: Acute lung injury (ALI) is a common clinical disease characterized by acute respiratory failure. This study was conducted to evaluate the therapeutic effects of RYN on ALI and to explore its mechanism of action. Materials and methods: Ultra -high -performance liquid chromatography-tandem mass spectrometry (UPLC-MS/ MS) was used to analyze the chemical components of RYN. 7.5 mg/kg LPS was administered to induce ALI in rats. RYN was administered by gavage at doses of 2 ml/kg, 4 ml/kg or 8 ml/kg every 8 h for a total of 6 doses. Observations included lung histomorphology, lung wet/dry (W/D) weight ratio, lung permeability index (LPI), HE staining, Wright-Giemsa staining. ELISA was performed to detect the levels of TNF-alpha, IL-6, IL-10, Arg-1, UDPG. Immunohistochemical staining detected IL-6, F4/80 expression. ROS, MDA, SOD, GSH/GSSG were detected in liver tissues. Multiple omics techniques were used to predict the potential mechanism of action of RYN, which was verified by in vivo closure experiments. Immunofluorescence staining detected the coexpression of CD86 and CD206, CD86 and P2Y14, CD86 and UGP2 in liver tissues. qRT-PCR detected the mRNA levels of UGP2, P2Y14 and STAT1, and immunoblotting detected the protein expression of UGP2, P2Y14, STAT1, p-STAT1. Results: RYN was detected to contain 1366 metabolites, some of the metabolites with high levels have antiinflammatory, antibacterial, antiviral and antioxidant properties. RYN (2, 4, and 8 ml/kg) exerted dosedependent therapeutic effects on the ALI rats, by reducing inflammatory cell infiltration and oxidative stress damage, inhibiting CD86 expression, decreasing TNF-alpha and IL-6 levels, and increasing IL-10 and Arg-1 levels. Transcriptomics and proteomics showed that glucose metabolism provided the pathway for the anti-ALI properties of RYN and that RYN inhibited lung glycogen production and distribution. Immunofluorescence costaining showed that RYN inhibited CD86 and UGP2 expressions. In vivo blocking experiments revealed that blocking glycogen synthesis reduced UDPG content, inhibited P2Y14 and CD86 expressions, decreased P2Y14 and STAT1 mRNA and protein expressions, reduced STAT1 protein phosphorylation expression, and had the same therapeutic effect as RYN. Conclusion: RYN inhibits M1 macrophage polarization to alleviate ALI. Blocking glycogen synthesis and inhibiting the UDPG/P2Y14/STAT1 signaling pathway may be its molecular mechanism. C1 [Yan, Zhipeng; Yan, Ruijuan; Jiao, Junzhe; Zhang, Miaomiao; Li, Fenhong; Chang, Zhanjie; Li, Jingtao] Shaanxi Univ Chinese Med, Affiliated Hosp, Dept Infect Dis, Xianyang 712000, Peoples R China. [Ji, Fanpu; Zhao, Yunyu] Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Infect Dis, Xian 710004, Peoples R China. [Wang, Wenba; Yan, Shuguang] Shaanxi Univ Chinese Med, Coll Basic Med, Xianyang 712046, Peoples R China. [Yan, Ruijuan; Jiao, Junzhe; Chang, Zhanjie; Yan, Shuguang; Li, Jingtao] Shaanxi Univ Chinese Med, Key Lab Gastrointestinal Dis & Prescript Shaanxi P, Xianyang 712046, Peoples R China. C3 Shaanxi University of Chinese Medicine; Xi'an Jiaotong University; Shaanxi University of Chinese Medicine; Shaanxi University of Chinese Medicine RP Li, JT (corresponding author), Shaanxi Univ Chinese Med, Affiliated Hosp, Dept Infect Dis, Xianyang 712000, Peoples R China.; Yan, SG (corresponding author), Shaanxi Univ Chinese Med, Coll Basic Med, Xianyang 712046, Peoples R China. EM ysg2002.student@sina.com; dr_lijingtao@163.com RI Li(李), Jitao(继涛)/J-6677-2019 FU National Natural Science Foundation of China (NSFC) [82374418]; Fund of Science and Technology Department of Shaanxi Province [2022TD-55, 2023-JC-YB-779]; Fund of Central Administration Bureau of Shaanxi Province [2021-02-ZZ-004, 2022-SLRH-LJ- 002]; Fundamental Research Funds for the Central Universities for COVID-19 [xzy032020040]; Discipline innovation team construction project of Shaanxi University of Chinese Medicine [2023-CXTD-01] FX This research was supported by the National Natural Science Foundation of China (NSFC) (Grant No. 82374418) ; Fund of Science and Technology Department of Shaanxi Province (Grant No. 2022TD-55 and No. 2023-JC-YB-779) ; Fund of Central Administration Bureau of Shaanxi Province (Grant No. 2021-02-ZZ-004 and No. 2022-SLRH-LJ- 002) ; Fundamental Research Funds for the Central Universities for COVID-19 (Grant No. xzy032020040) ; Discipline innovation team construction project of Shaanxi University of Chinese Medicine (Grant No. 2023-CXTD-01) . 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PD JUN 28 PY 2024 VL 328 AR 118005 DI 10.1016/j.jep.2024.118005 EA APR 2024 PG 14 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA PT6S9 UT WOS:001216381400001 PM 38508433 DA 2026-03-26 ER PT J AU Shi, J Yang, MM Yang, S Fan, FY Zheng, GB Miao, YD Hua, YQ Zhang, J Cheng, YF Liu, SJ Guo, YY Guo, LP Yang, XX Fan, GW Ma, CR AF Shi, Jia Yang, Ming Ming Yang, Shu Fan, Fangyang Zheng, Guobin Miao, Yaodong Hua, Yunqing Zhang, Jing Cheng, Yanfei Liu, Shangjing Guo, Yuying Guo, Liping Yang, Xiaoxiao Fan, Guanwei Ma, Chuanrui TI MaiJiTong granule attenuates atherosclerosis by reducing ferroptosis via activating STAT6-mediated inhibition of DMT1 and SOCS1/p53 pathways in LDLR- /- mice SO PHYTOMEDICINE LA English DT Article DE MJT; Atherosclerosis; Ferroptosis; STAT6; DMT1; SOCS1/p53 ID FOAM CELL-FORMATION; MACROPHAGE POLARIZATION; MYOCARDIAL-INFARCTION; LIPID-PEROXIDATION; PLAQUE; STAT6; DYSFUNCTION; MONOCYTES; INFLAMMATION; CHOLESTEROL AB Background and Purpose: Atherosclerosis is the primary pathological basis of cardiovascular disease. Ferroptosis is a regulated form of cell death, a process of lipid peroxidation driven by iron, which can initiate and promote atherosclerosis. STAT6 is a signal transducer that shows a potential role in regulating ferroptosis, but, the exact role in ferroptosis during atherogenesis remains unclear. The Traditional Chinese Medicine Maijitong granule (MJT) is used for treating cardiovascular disease and shows a potential inhibitory effect on ferroptosis. However, the antiatherogenic effect and the underlying mechanism remain unclear. In this study, we determined the role of STAT6 in ferroptosis during atherogenesis, investigated the antiatherogenic effect of MJT, and determined whether its antiatherogenic effect was dependent on the inhibition of ferroptosis. Methods: 8-week-old male LDLR -/- mice were fed a high-fat diet (HFD) at 1st and 10th week, respectively, to assess the preventive and therapeutic effects of MJT on atherosclerosis and ferroptosis. Simultaneously, the antiferroptotic effects and mechanism of MJT were determined by evaluating the expression of genes responsible for lipid peroxidation and iron metabolism. Subsequently, we reanalyzed microarray data in the GSE28117 obtained from cells after STAT6 knockdown or overexpression and analyzed the correlation between STAT6 and ferroptosis. Finally, the STAT6 -/- mice were fed HFD and injected with AAV-PCSK9 to validate the role of STAT6 in ferroptosis during atherogenesis and revealed the antiatherogenic and anti-ferroptotic effect of MJT. Results: MJT attenuated atherosclerosis by reducing plaque lesion area and enhancing plaque stability in both preventive and therapeutic groups. MJT reduced inflammation via suppressing inflammatory cytokines and inhibited foam cell formation by lowering the LDL level and promoting ABCA1/G1-mediated lipid efflux. MJT ameliorated the ferroptosis by reducing lipid peroxidation and iron dysregulation during atherogenesis. Mechanistically, STAT6 negatively regulated ferroptosis by transcriptionally suppressing SOCS1/p53 and DMT1 pathways. MJT suppressed the DMT1 and SOCS1/p53 via stimulating STAT6 phosphorylation. In addition, STAT6 knockout exacerbated atherosclerosis and ferroptosis, which abolished the antiatherogenic and antiferroptotic effects of MJT. Conclusion: STAT6 acts as a negative regulator of ferroptosis and atherosclerosis via transcriptionally suppressing DMT1 and SOCS1 expression and MJT attenuates atherosclerosis and ferroptosis by activating the STAT6mediated inhibition of DMT1 and SOCS1/p53 pathways, which indicated that STAT6 acts a novel promising therapeutic target to ameliorate atherosclerosis by inhibiting ferroptosis and MJT can serve as a new therapy for atherosclerosis treatment. C1 [Shi, Jia; Fan, Fangyang; Hua, Yunqing; Zhang, Jing; Cheng, Yanfei; Liu, Shangjing; Guo, Yuying; Fan, Guanwei; Ma, Chuanrui] Tianjin Univ Tradit Chinese Med, Teaching Hosp 1, Natl Clin Res Ctr Chinese Med Acupuncture & Moxibu, 88Chang Ling Rd, Tianjin, Peoples R China. [Zheng, Guobin] Tianjin Med Univ, Chu Hsien I Mem Hosp, NHC Key Lab Hormones & Dev, Tianjin Key Lab Metab Dis, Tianjin 300134, Peoples R China. [Zheng, Guobin] Tianjin Med Univ, Tianjin Inst Endocrinol, Tianjin 300134, Peoples R China. [Yang, Shu] Southern Univ Sci & Technol, Affiliated Hosp 1, Jinan Univ,Shenzhen Clin Res Ctr Geriatr, Shenzhen Peoples Hosp,Clin Med Coll 2,Guangdong Pr, Shenzhen 518020, Guangdong, Peoples R China. [Yang, Xiaoxiao] Hefei Univ Technol, Sch Food & Biol Engn, Dept Educ, Key Lab Major Metab Dis & Nutr Regulat Anhui, Hefei, Peoples R China. [Yang, Ming Ming] Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Ophthalmol, Shenzhen 518020, Peoples R China. [Yang, Ming Ming] Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518020, Peoples R China. [Shi, Jia; Guo, Liping] Tianjin Acad Tradit Chinese Med, Affiliated Hosp, Tianjin, Peoples R China. [Miao, Yaodong] Tianjin Univ Tradit Chinese Med, Affiliated Hosp 2, Tianjin, Peoples R China. C3 Tianjin University of Traditional Chinese Medicine; Tianjin Medical University; Tianjin Medical University; Jinan University; Southern University of Science & Technology; Hefei University of Technology; Jinan University; Southern University of Science & Technology; Tianjin University of Traditional Chinese Medicine RP Fan, GW; Ma, CR (corresponding author), Tianjin Univ Tradit Chinese Med, Teaching Hosp 1, Natl Clin Res Ctr Chinese Med Acupuncture & Moxibu, 88Chang Ling Rd, Tianjin, Peoples R China.; Yang, XX (corresponding author), Hefei Univ Technol, Sch Food & Biol Engn, Dept Educ, Key Lab Major Metab Dis & Nutr Regulat Anhui, Hefei, Peoples R China. EM yangxiaoxiao@hfut.edu.cn; guanwei.fan@tjutcm.edu.cn; chuanruima2013@mail.nankai.edu.cn RI guanwei, fan/M-8193-2019; guo, yuying/GSD-3092-2022; HUA, yun/ADD-1143-2022; Fan, Fangyang/JLL-7693-2023; yang, shu/GLN-3976-2022 OI Fan, Fangyang/0000-0002-4043-0801; yang, shu/0000-0002-4912-777X; Y, Ming-Ming/0000-0002-5550-7293 FU Program of National Administration of Traditional Chinese Medicine [ZYYCXTD-D-202207, ZYYCXTD-C-202203]; Tianjin College Students Innovation and Entrepreneurship Training Program [202210063008] FX This work was supported by grants from the National Natural Science Foundation of China (82003747, 82373867, 82370876, 82000824) ; the second batch of high-level talents in the health industry selection and training project (TJSQNYXXR-D2-064) ; Natural Science Foundation of Tianjin (20JCZXJC00150) ; Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202207; ZYYCXTD-C-202203) ; Tianjin College Students Innovation and Entrepreneurship Training Program (202210063008, Effect and mechanism of Panax notoginseng saponins on improving hepatotoxicity during statin treatment of atherosclerosis) .r Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202207; ZYYCXTD-C-202203) ; Tianjin College Students Innovation and Entrepreneurship Training Program (202210063008, Effect and mechanism of Panax notoginseng saponins on improving hepatotoxicity during statin treatment of atherosclerosis) . 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Yang, WL AF Tang, Chao Jiang, Shi-Ting Li, Cheng-Xia Jia, Xiao-Fang Yang, Wen-Li TI The Effect of Salvianolic Acid A on Tumor-Associated Macrophage Polarization and Its Mechanisms in the Tumor Microenvironment of Triple-Negative Breast Cancer SO MOLECULES LA English DT Article DE salvianolic acid A; tumor-associated macrophage; triple-negative breast cancer; macrophage polarization ID ALTERNATIVE ACTIVATION; GASTRIC-CANCER; CELLS; INFILTRATION; DIFFERENTIATION; EXPRESSION; CARCINOMA; SURVIVAL; M1 AB Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with a high degree of malignancy and poor prognosis. Tumor-associated macrophages (TAMs) have been identified as significant contributors to the growth and metastasis of TNBC through the secretion of various growth factors and chemokines. Salvianolic acid A (SAA) has been shown to have anti-cancer activities. However, the potential activity of SAA on re-polarized TAMs remains unclear. As there is a correlation between the TAMs and TNBC, this study investigates the effect of SAA on TAMs in the TNBC microenvironment. For that purpose, M2 TAM polarization was induced by two kinds of TNBC-conditioned medium (TNBC-TCM) in the absence or presence of SAA. The gene and protein expression of TAM markers were analyzed by qPCR, FCM, IF, ELISA, and Western blot. The protein expression levels of ERK and p-ERK in M2-like TAMs were analyzed by Western blot. The migration and invasion properties of M2-like TAMs were analyzed by Transwell assays. Here, we demonstrated that SAA increased the expression levels of CD86, IL-1 beta, and iNOS in M2-like TAMs and, conversely, decreased the expression levels of Arg-1 and CD206. Moreover, SAA inhibited the migration and invasion properties of M2-like TAMs effectively and decreased the protein expression of TGF-beta 1 and p-ERK in a concentration-dependent manner, as well as TGF-beta 1 gene expression and secretion. Our current findings for the first time demonstrated that SAA inhibits macrophage polarization to M2-like TAMs by inhibiting the ERK pathway and promotes M2-like TAM re-polarization to the M1 TAMs, which may exert its anti-tumor effect by regulating M1/M2 TAM polarization. These findings highlight SAA as a potential regulator of M2 TAMs and the possibility of utilizing SAA to reprogram M2 TAMs offers promising insights for the clinical management of TNBC. C1 [Tang, Chao; Jiang, Shi-Ting; Li, Cheng-Xia; Jia, Xiao-Fang; Yang, Wen-Li] Southwest Med Univ, Inst Canc Med, Sch Basic Med Sci, Luzhou 646000, Peoples R China. [Yang, Wen-Li] Southwest Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Luzhou 646000, Peoples R China. C3 Southwest Medical University; Southwest Medical University RP Yang, WL (corresponding author), Southwest Med Univ, Inst Canc Med, Sch Basic Med Sci, Luzhou 646000, Peoples R China.; Yang, WL (corresponding author), Southwest Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Luzhou 646000, Peoples R China. EM tc920803@163.com; jiangshiting2023@163.com; lcx2512987955@163.com; jxf0416@163.com; ywl0621@swmu.edu.cn RI Jia, Xiaofang/E-8009-2019; Chao, Tang/AEX-2250-2022 FU Sichuan Science and Technology Program FX We gratefully acknowledge the support of T.H. (Tao He), X.L. (Xuesen, Li), Y.L. (Yan Lin), M.Y. (Mao Yang), X.Z. (Xianyu, Zhu) and W.W. (Wenjun, Wang). 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Chemistry, Multidisciplinary WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry GA NN4A2 UT WOS:001201104700001 PM 38611749 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Fan, ZP Cui, YR Chen, LY Liu, P Duan, WB AF Fan, Zeping Cui, Yaru Chen, Lanying Liu, Peng Duan, Wenbin TI 23-Hydroxybetulinic acid attenuates 5-fluorouracil resistance of colorectal cancer by modulating M2 macrophage polarization via STAT6 signaling SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE 23-Hydroxybetulinic acid; Macrophage polarization; STAT6; Colorectal cancer; 5-fluorouracil; Chemoresistance ID NATURAL COMPOUNDS; THERAPY AB Macrophage polarization is closely associated with the inflammatory processes involved in the development and chemoresistance of colorectal cancer (CRC). M2 macrophages, the predominant subtype of tumor-associated macrophages (TAMs) in a wide variety of malignancies, have been demonstrated to promote the resistance of CRC to multiple chemotherapeutic drugs, such as 5-fluorouracil (5-FU). In our study, we investigated the potential of 23-Hydroxybetulinic Acid (23-HBA), a significant active component of Pulsatilla chinensis (P. chinensis), to inhibit the polarization of M2 macrophages induced by IL-4. Our results showed that 23-HBA reduced the expression of M2 specific marker CD206, while downregulating the mRNA levels of M2 related genes (CD206, Arg1, IL-10, and CCL2). Additionally, 23-HBA effectively attenuated the inhibitory effects of the conditioned medium from M2 macrophages on apoptosis in colorectal cancer SW480 cells. Mechanistically, 23-HBA prevented the phosphorylation and nuclear translocation of the STAT6 protein, resulting in the inhibition of IL-10 release in M2 macrophages. Moreover, it interfered with the activation of the IL-10/STAT3/Bcl-2 signaling pathway in SW480 cells, ultimately reducing M2 macrophage-induced resistance to 5-FU. Importantly, depleting STAT6 expression in macrophages abolished the suppressive effect of 23-HBA on M2 macrophage polarization, while also eliminating its ability to decrease M2 macrophage-induced 5-FU resistance in cancer cells. Furthermore, 23-HBA significantly diminished the proportion of M2 macrophages in the tumor tissues of colorectal cancer mice, simultaneously enhancing the anti-cancer efficacy of 5-FU. The findings presented in this study highlight the capacity of 23-HBA to inhibit M2 macrophage polarization, a process that contributes to reduced 5-FU resistance in colorectal cancer. C1 [Fan, Zeping; Cui, Yaru; Chen, Lanying; Liu, Peng; Duan, Wenbin] Jiangxi Univ Chinese Med, Sch Pharm, Nanchang 330006, Jiangxi, Peoples R China. [Fan, Zeping; Cui, Yaru; Chen, Lanying; Liu, Peng; Duan, Wenbin] Jiangxi Univ Chinese Med, Natl Pharmaceut Engn Ctr Solid Preparat Chinese He, Nanchang 330006, Jiangxi, Peoples R China. [Cui, Yaru; Chen, Lanying; Duan, Wenbin] Key Lab Evaluat Antitumor Effect Chinese Med Stren, Nanchang 330006, Jiangxi, Peoples R China. C3 Jiangxi University of Traditional Chinese Medicine; Jiangxi University of Traditional Chinese Medicine RP Chen, LY (corresponding author), Jiangxi Univ Chinese Med, Sch Pharm, Nanchang 330006, Jiangxi, Peoples R China.; Chen, LY (corresponding author), Jiangxi Univ Chinese Med, Natl Pharmaceut Engn Ctr Solid Preparat Chinese He, Nanchang 330006, Jiangxi, Peoples R China.; Chen, LY (corresponding author), Key Lab Evaluat Antitumor Effect Chinese Med Stren, Nanchang 330006, Jiangxi, Peoples R China. EM cly5831@163.com FU National Natural Science Foundation of China FX We sincerely thank all the people who have provided helpful support. 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Immunother. PD MAR 30 PY 2024 VL 73 IS 5 AR 83 DI 10.1007/s00262-024-03662-0 PG 14 WC Oncology; Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Immunology GA MR9T8 UT WOS:001195485600015 PM 38554148 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Wang, TT Wang, S Jia, XH Li, CL Ma, XR Tong, HM Liu, M Li, L AF Wang, Tiantian Wang, Shuang Jia, Xihui Li, Chenglin Ma, Xiaoran Tong, Huimin Liu, Meng Li, Ling TI Baicalein alleviates cardiomyocyte death in EAM mice by inhibiting the JAK-STAT1/4 signalling pathway SO PHYTOMEDICINE LA English DT Article DE BAI; EAM; M1-type macrophages; Th1 cells; Myocyte death ID CARDIAC INJURY; MYOCARDITIS; MECHANISMS; CELLS; HEART AB Background: The experimental autoimmune myocarditis (EAM) model is valuable for investigating myocarditis pathogenesis. M1-type macrophages and CD4+T cells exert key pathogenic effects on EAM initiation and progression. Baicalein (5,6,7-trihydroxyflavone, C15H10O5, BAI), which is derived from the Scutellaria baicalensis root, is a primary bioactive compound with potent anti-inflammatory and antioxidant properties. BAI exerts good therapeutic effects against various autoimmune diseases; however, its effect in EAM has not been thoroughly researched. Purpose: This study aimed to explore the possible inhibitory effect of BAI on M1 macrophage polarisation and CD4+T cell differentiation into Th1 cells via modulation of the JAK-STAT1/4 signalling pathway, which reduces the secretion of pro-inflammatory factors, namely, TNF-alpha and IFN-gamma, and consequently inhibits TNF-alpha- and IFN gamma-triggered apoptosis in cardiomyocytes of the EAM model mice. Study design and methods: Flow cytometry, immunofluorescence, real-time quantitative polymerase chain reaction (q-PCR), and western blotting were performed to determine whether BAI alleviated M1/Th1-secreted TNF-alpha and IFN-gamma-induced myocyte death in the EAM model mice through the inhibition of the JAK-STAT1/4 signalling pathway. Results: These results indicate that BAI intervention in mice resulted in mild inflammatory infiltrates. BAI inhibited JAK-STAT1 signalling in macrophages both in vivo and in vitro, which attenuated macrophage polarisation to the M1 type and reduced TNF-alpha secretion. Additionally, BAI significantly inhibited the differentiation of CD4+ T cells to Th1 cells and IFN-gamma secretion both in vivo and in vitro by modulating the JAKSTAT1/4 signalling pathway. This ultimately led to decreased TNF-alpha and IFN-gamma levels in cardiac tissues and reduced myocardial cell apoptosis. Conclusion: This study demonstrates that BAI alleviates M1/Th1-secreted TNF-alpha- and IFN-gamma-induced cardiomyocyte death in EAM mice by inhibiting the JAK-STAT1/4 signalling pathway. C1 [Wang, Tiantian; Li, Chenglin; Tong, Huimin; Li, Ling] Qingdao Univ, Sch Basic Med, Dept Human Anat Histol & Embryol, 308 Ningxia Rd, Qingdao 266071, Shandong, Peoples R China. [Wang, Shuang; Jia, Xihui; Liu, Meng] Qingdao Univ, Sch Basic Med, Dept Biochem & Mol Biol, Qingdao, Peoples R China. [Ma, Xiaoran] Qing dao Binhai Univ, Sch Med, Qingdao, Peoples R China. C3 Qingdao University; Qingdao University; Qingdao Binhai University RP Li, L (corresponding author), Qingdao Univ, Sch Basic Med, Dept Human Anat Histol & Embryol, 308 Ningxia Rd, Qingdao 266071, Shandong, Peoples R China. EM liling1@qdu.edu.cn RI Ma, Xiaoran/PMR-0269-2026; Li, Chenglin/W-3567-2019 OI Li, Ling/0000-0001-5358-4968 FU Natural Science Foundation of Shandong Province [ZR2020MH416]; National natural Science Foundation of China [82001754] FX Natural Science Foundation of Shandong Province (ZR2020MH416) , The National natural Science Foundation of China (82001754) sup-ported this work. 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PANoptosis, an avant-garde conceptualization of cell deaths, is closely associated with mitochondrial damage and linked to multiple liver disorders. SiWu-Tang (SWT), a traditional Chinese herbal prescription renowned for regulating blood-related disorders and ameliorating gynecological and hepatic diseases, has been demonstrated to alleviate liver fibrosis by regulating bile acid metabolism and immune responses. Aim of the study: However, the mechanisms by which mtDNA is released from PANoptotic hepatocytes, triggering macrophage activation and hepatitis and whether this process can be reversed by SWT remain unclear. Materials and methods: Here, sophisticated RNA-sequencing complemented by molecular approaches were applied to explore the underlying mechanism of SWT against NAFLD in methionine/choline-deficient diet (MCD)-induced mice and relative in vitro models. Results: We revealed that SWT profoundly repaired mitochondrial dysfunction, blocked mitochondrial permeability transition and mtDNA released to the cytoplasm, subsequently reversing hepatocyte PANoptosis and macrophage polarization both in MCD-stimulated mice and in vitro. Mechanically, loaded lipids dramatically promoted the opening of mPTP and oligomerization of VDAC2 to orchestrate mtDNA release, which was combined with ZBP1 to promote hepatocyte PANoptosis and also taken by macrophages to trigger M1 polarization via the FSTL1 and PKM2 combination. SWT effectively blocked NOXA signaling and reversed all these detrimental outcomes. Conclusion: Our findings show that SWT protects against hepatitis-mediated hepatocyte PANoptosis and macrophage M1 polarization by influencing intrahepatic synthesis, release and intercellular transfer of mtDNA, suggesting a potential therapeutic strategy for ameliorating NAFLD. C1 [Ma, Zhi; Xie, Kaihong; Xue, Xiaoyong; Li, Jianan; Wu, Jianzhi; Li, Xiaojiaoyang] Beijing Univ Chinese Med, Sch Life Sci, Beijing 100029, Peoples R China. [Yang, Yang; Li, Yufei] Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing 100029, Peoples R China. C3 Beijing University of Chinese Medicine; Beijing University of Chinese Medicine RP Li, XJY (corresponding author), Beijing Univ Chinese Med, Sch Life Sci, Beijing 100029, Peoples R China. EM xiaojiaoyang.li@bucm.edu.cn RI Li, Xiaojiaoyang/CAG-6603-2022; xue, XIAOYONG/GSE-3369-2022 OI Li, Xiaojiaoyang/0000-0003-0291-5856; FU National Natural Science Foundation of China [82274186, 82004045]; National Key Research and Development Program on Modernization of Traditional Chinese Medicine [2022YFC3502100]; Fundamental Research Funds for the Central Universities [2023- JYB-JBZD-046]; National High -Level Talents Special Support Program; Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine [ZYYCXTD-C-202006] FX This work was supported by National Natural Science Foundation of China (Grant NO. 82274186 and Grant NO. 82004045 to XL) ; National Key Research and Development Program on Modernization of Traditional Chinese Medicine (Grant NO. 2022YFC3502100 to XL) ; Fundamental Research Funds for the Central Universities (Grant NO. 2023- JYB-JBZD-046 to XL) ; National High -Level Talents Special Support Program to XL; Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (Grant NO. ZYYCXTD-C-202006 to XL) . 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Ethnopharmacol. PD JUN 28 PY 2024 VL 328 AR 118057 DI 10.1016/j.jep.2024.118057 EA MAR 2024 PG 17 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA QG5O8 UT WOS:001219741700001 PM 38518965 DA 2026-03-26 ER PT J AU Tan, NH Jian, GH Peng, J Tian, XF Chen, B AF Tan, Nianhua Jian, Gonghui Peng, Jie Tian, Xuefei Chen, Bin TI Chishao - Fuzi herbal pair restore the macrophage M1/M2 balance in acute-on-chronic liver failure SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE ACLF; Immune reconstitution; Macrophage polarization; Chishao-Fuzi herbal pair AB Ethnopharmacological relevance: Traditional herbal pair Paeoniae Radix Rubra (roots of Paeonia lactiflora Pall., Chishao in Chinese) and Aconiti Lateralis Radix Praeparata (lateral roots of Aconitum carmichaelii Debeaux, Fuzi in Chinese) are widely used for the treatment of liver diseases, demonstrating clinical efficacy against acute-onchronic liver failure (ACLF). As the core drug pair representing the "clearing method" and "warming method" in traditional Chinese medicine (TCM), they align with the TCM syndromic characteristics of ACLF, characterized by a mixture of deficiencies and realities. However, the molecular mechanisms underlying the anti-ACLF effects of Chishao - Fuzi herbal pair remain unclear. Aim of the study: To reveal the immunoinflammatory status of patients with hepatitis B virus-related ACLF (HBVACLF) based on macrophage polarization and to explore the mechanism of action of Chishao - Fuzi herbal pair in regulating macrophage polarization against ACLF. Materials and methods: Peripheral blood samples were prospectively obtained from patients with HBV-ACLF, patients with chronic hepatitis B (CHB) in the immunoactive phase and healthy individuals. Flow cytometry, qRT-qPCR, and ELISA were used to reveal the activation status of monocyte-macrophages and the expression differences in related cytokines in the peripheral blood of patients with HBV-ACLF. Then, an ACLF rat model and a macrophage inflammation model in vitro were established. Hematoxylin-eosin staining, immunohistochemical staining, transmission electron microscopy, flow cytometry, western blotting, RT-qPCR, and ELISA were used to observe changes in the expression of M1/M2 macrophage markers and related inflammatory factors after Chishao - Fuzi herbal pair intervention, both in vivo and in vitro. Results: Patients with HBV-ACLF exhibited an imbalance in M1/M2 macrophage polarization, showing a tendency to activate M1 macrophages with high expression of CD86 and iNOS. This imbalance led to an increase in relevant pro-inflammatory factors (IL-1 beta, IL-6, TNF-alpha) and a decrease in anti-inflammatory factors (IL-10, TGF-beta, VEGF), exacerbating the uncontrolled immune-inflammatory response. Chishao - Fuzi herbal pair intervention improved liver function, coagulation function, and histopathological injury in ACLF rats. It also partially ameliorated endotoxemia and inflammatory injury in ACLF. The mechanism was to restore the immuneinflammatory imbalance and prevent the exacerbation of inflammatory response to liver failure by promoting macrophage polarization toward M2 anti-inflammatory direction, inhibiting M1 macrophage activation, and increasing the levels of anti-inflammatory factors and decreasing pro-inflammatory factors. Conclusion: Chishao - Fuzi herbal pair can reduce the systemic inflammatory burden of liver failure by modulating macrophage polarization and restoring ACLF immune-inflammatory imbalance. This study provides new perspectives and strategies for studying HBV-ACLF immune reconstitution and inflammatory response control. C1 [Tan, Nianhua; Jian, Gonghui; Tian, Xuefei] Hunan Univ Chinese Med, Coll Integrated Chinese & Western Med, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China. [Tan, Nianhua; Peng, Jie; Chen, Bin] Hunan Univ Chinese Med, Hosp 1, Dept Hepatol, 95 Shaoshan Rd, Changsha 410007, Hunan, Peoples R China. [Tian, Xuefei] Hunan Prov Univ Key Lab Oncol Tradit Chinese Med, Hunan Univ Chinese Med, Changsha 410208, Hunan, Peoples R China. [Tian, Xuefei] Hunan Univ Chinese Med, Key Lab Tradit Chinese Med Mech Tumor Prevent &Tre, Changsha 410208, Hunan, Peoples R China. C3 Hunan University of Chinese Medicine; Hunan University of Chinese Medicine; Hunan University of Chinese Medicine; Hunan University of Chinese Medicine RP Tian, XF (corresponding author), Hunan Univ Chinese Med, Coll Integrated Chinese & Western Med, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.; Chen, B (corresponding author), Hunan Univ Chinese Med, Hosp 1, Dept Hepatol, 95 Shaoshan Rd, Changsha 410007, Hunan, Peoples R China. EM l00342@hnucm.edu.cn; 003640@hnucm.edu.cn; chenbin0410@126.com RI tian, xuefei/OJV-1564-2025 OI Tan, Nianhua/0000-0003-0240-2903 FU Hunan Provincial Natural Science Foundation of China [2023JJ40487, 2020JJ4475]; China Postdoctoral Science Foundation [2022M721127]; Hunan Administration of Traditional Chinese Medicine [B2023009, C2022005]; Scientific Research Project of Education Department of Hunan Province [22B0392]; Hunan University of Chinese Medicine School Level Scientific Research Project [2022XJZKC009] FX Supported by the Hunan Provincial Natural Science Foundation of China, No. 2023JJ40487 and 2020JJ4475; China Postdoctoral Science Foundation, NO. 2022M721127; the Hunan Administration of Traditional Chinese Medicine, NO. B2023009 and C2022005. Scientific Research Project of Education Department of Hunan Province, No. 22B0392. Hunan University of Chinese Medicine School Level Scientific Research Project, No. 2022XJZKC009. 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PD JUN 28 PY 2024 VL 328 AR 118010 DI 10.1016/j.jep.2024.118010 EA MAR 2024 PG 13 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA QC7W5 UT WOS:001218755300001 PM 38499260 DA 2026-03-26 ER PT J AU Yang, SJ Li, YX Zheng, XM Zheng, XR Lin, YS Guo, SN Liu, C AF Yang, Shijing Li, Yaoxing Zheng, Xiaoman Zheng, Xirui Lin, Yongshi Guo, Shining Liu, Cui TI Effects of folate-chicory acid liposome on macrophage polarization and TLR4/NF- κB signaling pathway in ulcerative colitis mouse SO PHYTOMEDICINE LA English DT Article DE Folate-chicory acid liposome; Macrophage polarization; Ulcerative colitis ID ENCAPSULATION EFFICIENCY AB Background: Chichoric acid (CA) is a major active ingredient found in chicory and Echinacea. As a derivative of caffeic acid, it has various pharmacological effects. Purpose: Due to the unclear etiology and disease mechanisms, effective treatment methods for ulcerative colitis (UC) are currently lacking. The study investigated the therapeutic effects of the folate-chicory acid liposome on both LPS-induced macrophage inflammation models and dextran sulfate sodium (DSS)-induced mouse UC models. Methods: Folate-chicory acid liposome was prepared using the double emulsion ultrasonic method with the aim of targeting folate receptors specifically expressed on macrophages. The study investigated the therapeutic effects of the folate-chicory acid liposome on both LPS-induced macrophage inflammation models and DSS -induced mouse UC models. Furthermore, the effects of the liposomes on macrophage polarization and their underlying mechanisms in UC were explored. Results: The average particle size of folate-chicory acid liposome was 120.4 +/- 0.46 nm, with an encapsulation efficiency of 77.32 +/- 3.19 %. The folate-chicory acid liposome could alleviate macrophage apoptosis induced by LPS, decrease the expression of inflammatory factors in macrophages, enhance the expression of antiinflammatory factors, inhibit macrophage polarization towards the M1 phenotype, and mitigate cellular inflammation in vetro. In vivo test, folate-chicory acid liposome could attenuate clinical symptoms, increased colon length, reduced DAI scores, CMDI scores, and alleviated the severity of colonic histopathological damage in UC mice. Furthermore, it inhibited the polarization of macrophages towards the M1 phenotype in the colon and downregulated the TLR4/NF- kappa B signaling pathway, thereby ameliorating UC in mice. Conclusion: Folate-chicory acid liposome exhibited a uniform particle size distribution and high encapsulation efficiency. It effectively treated UC mice by inhibiting the polarization of macrophages towards the M1 phenotype in the colon and downregulating the TLR4/NF- kappa B signaling pathway. C1 [Yang, Shijing; Guo, Shining; Liu, Cui] South China Agr Univ, Coll Vet Med, Guangzhou 510642, Peoples R China. [Guo, Shining; Liu, Cui] Guangdong Lab Lingnan Modern Agr, Guangzhou 510642, Peoples R China. [Guo, Shining; Liu, Cui] Guangdong Technol Res Ctr Tradit Chinese Vet Med &, Guangzhou 510642, Peoples R China. C3 South China Agricultural University; Guangdong Laboratory for Lingnan Modern Agriculture RP Liu, C (corresponding author), South China Agr Univ, Coll Vet Med, Guangzhou 510642, Peoples R China.; Liu, C (corresponding author), Guangdong Lab Lingnan Modern Agr, Guangzhou 510642, Peoples R China.; Liu, C (corresponding author), Guangdong Technol Res Ctr Tradit Chinese Vet Med &, Guangzhou 510642, Peoples R China. EM liuc@scau.edu.cn OI Liu, Cui/0000-0002-0609-0073 FU National Natural Science Foundation of China [32273046]; Guangdong Basic and Applied Basic Research Foundation [2022A1515011692] FX Acknowledgments Thank you for the funding from National Natural Science Foundation of China (32273046) , and the Guangdong Basic and Applied Basic Research Foundation (2022A1515011692) . 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Arenobufagin (ARBU) was extracted and isolated from toad venom (purity >= 98 %), which is the main active ingredient of the traditional Chinese medicine Chan'su with good antitumor effects. Purpose: To investigate the regulatory effect of ARBU on lipid metabolism in tumor microenvironment, interfere with macrophage polarization, and determine its mechanism of action on liver cancer progression. Methods: In this study, the inhibitory effect of ARBU on the proliferation of Hepa1-6 in C57 mice and the safety of administration were evaluated by establishing a transplanted tumor model of Hepa1-6 hepatocellular carcinoma mice and using 5-FU as a positive control drug. In addition, we constructed a co-culture system of Hepa1-6 cells and primary mouse macrophages to study the effects of ARBU on the polarization phenotypic transformation of macrophages and the proliferation and migration of hepatoma cells. The influence of ARBU on the metabolism of lipids in the hepatocellular carcinoma mouse model was investigated by combining it with lipidomics technology. The influence of ARBU on the PCSK9/LDL-R signaling pathway and macrophage polarization, which regulate cholesterol metabolism, was tested by using qRT-PCR, gene editing, IF, and WB. Conclusion: ARBU significantly inhibited the proliferation of Hepa1-6 in vivo and in vitro, regulated cholesterol metabolism, and promoted the M1-type polarization of macrophages in the tumor microenvironment. ARBU inhibits cholesterol synthesis in the TME through the PCSK9/LDL-R signaling pathway, thereby blocking macrophage M2 polarization, promoting apoptosis of the tumor cells, and inhibiting their proliferation and migration. C1 [Li, Yueyue; Yang, Yuting; Cheng, Hui; Li, Qinglin; Wang, Meng] Anhui Univ Tradit Chinese Med, Minist Educ, Anhui Prov Key Lab R&D Chinese Med, Key Lab Xinan Med, 103 Meishan Rd, Hefei 230038, Anhui, Peoples R China. [Chen, Yang; Zhang, Mei] Anhui Med Univ, Affiliated Hosp 1, Oncol Dept Integrated Tradit Chinese & Western Med, Hefei 230022, Anhui, Peoples R China. [Zhao, Cheng] Anqing Petrochem Hosp, Med Oncol, Nanjing Gulou Hosp Grp, Anqing 264000, Anhui, Peoples R China. C3 Anhui University of Chinese Medicine; Anhui Medical University RP Li, QL; Wang, M (corresponding author), Anhui Univ Tradit Chinese Med, Minist Educ, Anhui Prov Key Lab R&D Chinese Med, Key Lab Xinan Med, 103 Meishan Rd, Hefei 230038, Anhui, Peoples R China. EM liqinglin@ahtcm.edu.cn; wangmeng@ahtcm.edu.cn RI Yang, Yuting/MEO-9352-2025 FU National Natural Science Foundation of China [82305023]; Key projects of natural science research in Anhui Universities [2022AH050529]; Key Natural Science Project of Anhui University of Chinese Medicine [2021zrzd08]; First batch of talent support plan projects of Anhui University of Chinese medicine in 2022 [2022rcyb016] FX This work was supported by the National Natural Science Foundation of China [Grant No. 82305023 to Meng Wang], Key projects of natural science research in Anhui Universities [Grant No. 2022AH050529 to Meng Wang], the Key Natural Science Project of Anhui University of Chinese Medicine [Grant No. 2021zrzd08 to Meng Wang] and The first batch of talent support plan projects of Anhui University of Chinese medicine in 2022 [Grant No. 2022rcyb016 to Meng Wang]. 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Acetyl-11-keto-beta-boswellic acid (AKBA) is the active component of the natural drug boswellia, which has anti-inflammatory and antioxidant effects and offers a possible therapeutic option for spinal cord injury.MethodsIn this study, a spinal cord injury model was established by crushing spinal cord, respectively, to detect the M1 macrophage inflammatory markers: iNOS, TNF-alpha, IL-1 beta, and the M2 macrophage markers CD206, ARG-1, IL-10, and the detection of antioxidant enzymes and MDA. In vitro, macrophages were cultured to verify the main mechanism of the macrophage switch from Nrf2/HO-1 to M2 type by flow cytometry, immunofluorescence, and other techniques. Macrophage and Schwann cell co-culture validated the migration mechanism of Schwann cells promoted by AKBA.ResultsAKBA significantly enhanced the antioxidant enzyme activities of CAT, GSH-Px, T-AOC, and SOD, reduced MDA content, and reduced oxidative damage caused by spinal cord injury via the Nrf2/HO-1 signaling pathway; AKBA mediates Nrf2/HO-1/IL-10, converts macrophages from M1 to M2 type, reduces inflammation, and promotes Schwann cell migration, thereby accelerating the repair of spinal cord injury in rats.ConclusionsOur work demonstrates that AKBA can attenuate oxidative stress as well as the secondary inflammatory injury caused by macrophages after SCI, promote Schwann cell migration to the injury site, and thus accelerate the repair of the injured spinal cord. Acetyl-11-keto-beta-boswellic acid (AKBA) can protect against spinal cord injury by regulating the redox system Nrf2/HO-1 signaling pathway, reducing the ROS generation, and promoting the migration of macrophages to M2 polarization and Schwann cells.image C1 [Wang, Yao; Xiong, Zongliang; Zhang, Qiyuan; Zhou, Guanghu; Zhou, Chong; Ma, Xianglin; Jiang, Xiaowen; Yu, Wenhui] Northeast Agr Univ, Dept Vet Med, Harbin, Heilongjiang, Peoples R China. [Qiao, Yuncong] Northeast Agr Univ, Sch Life Sci, Harbin, Heilongjiang, Peoples R China. [Yu, Wenhui] Northeast Agr Univ, Dept Common Anim Dis Prevent & Treatment, Key Lab Heilongjiang Educ, Harbin, Heilongjiang, Peoples R China. [Yu, Wenhui] Northeast Agr Univ, Inst Chinese Vet Med, Harbin, Heilongjiang, Peoples R China. C3 Northeast Agricultural University - China; Northeast Agricultural University - China; Northeast Agricultural University - China; Northeast Agricultural University - China RP Jiang, XW; Yu, WH (corresponding author), Northeast Agr Univ, Dept Vet Med, Harbin, Heilongjiang, Peoples R China. EM jiangxiaowen@neau.edu.cn; yuwenhui@neau.edu.cn RI ; zhou, chong/IQT-4490-2023 OI Yu, Wenhui/0000-0002-3744-4575; Xiong, Zong-Liang/0000-0001-5529-6951; FU National Natural Science Foundation of China FX No Statement Available CR Banji D, 2022, J ETHNOPHARMACOL, V292, DOI 10.1016/j.jep.2022.115200 Beattie MS, 1997, EXP NEUROL, V148, P453, DOI 10.1006/exnr.1997.6695 Börner F, 2023, ADV SCI, V10, DOI 10.1002/advs.202205604 Buss A, 2007, BRAIN, V130, P940, DOI 10.1093/brain/awl374 Buss A, 2009, BMC NEUROL, V9, DOI 10.1186/1471-2377-9-32 Chen YN, 2020, EUR J PHARMACOL, V877, DOI 10.1016/j.ejphar.2020.173090 Chi QR, 2022, J HAZARD MATER, V439, DOI 10.1016/j.jhazmat.2022.129502 Chi QR, 2021, REDOX BIOL, V44, DOI 10.1016/j.redox.2021.102003 Deng LX, 2021, NEURAL REGEN RES, V16, P186, DOI 10.4103/1673-5374.289436 Díaz-Bulnes P, 2020, FRONT IMMUNOL, V10, DOI 10.3389/fimmu.2019.02951 Ding Y, 2016, MOL NEUROBIOL, V53, P3842, DOI 10.1007/s12035-015-9333-9 Dong XH, 2021, BIOMATERIALS, V272, DOI 10.1016/j.biomaterials.2021.120767 Early JO, 2018, P NATL ACAD SCI USA, V115, pE8460, DOI 10.1073/pnas.1800431115 Fan BY, 2018, CELL TRANSPLANT, V27, P853, DOI 10.1177/0963689718755778 Fu HT, 2022, FRONT NEUROSCI-SWITZ, V16, DOI 10.3389/fnins.2022.800513 Funes SC, 2018, IMMUNOLOGY, V154, P186, DOI 10.1111/imm.12910 Gensel JC, 2015, BRAIN RES, V1619, P1, DOI 10.1016/j.brainres.2014.12.045 Griess B, 2020, FREE RADICAL BIO MED, V147, P48, DOI 10.1016/j.freeradbiomed.2019.12.018 Harusato A, 2013, INFLAMM BOWEL DIS, V19, P740, DOI 10.1097/MIB.0b013e3182802968 Hellenbrand DJ, 2021, J NEUROINFLAMM, V18, DOI 10.1186/s12974-021-02337-2 Jiang XW, 2020, LIFE SCI, V254, DOI 10.1016/j.lfs.2019.116887 Kanno H, 2015, REV NEUROSCIENCE, V26, P121, DOI 10.1515/revneuro-2014-0068 Kjell J, 2016, DIS MODEL MECH, V9, P1125, DOI 10.1242/dmm.025833 Kroner A, 2014, NEURON, V83, P1098, DOI 10.1016/j.neuron.2014.07.027 Lanza M, 2019, MOL NEUROBIOL, V56, P3937, DOI 10.1007/s12035-018-1347-7 Lin S, 2021, FREE RADICAL BIO MED, V172, P622, DOI 10.1016/j.freeradbiomed.2021.07.014 Liu JZ, 2022, J NANOBIOTECHNOL, V20, DOI 10.1186/s12951-022-01435-4 Liu W, 2022, REDOX BIOL, V53, DOI 10.1016/j.redox.2022.102344 Liu W, 2021, J PINEAL RES, V71, DOI 10.1111/jpi.12769 Luo X, 2022, REDOX BIOL, V57, DOI 10.1016/j.redox.2022.102511 Lv JC, 2022, JAMA-J AM MED ASSOC, V327, P1888, DOI 10.1001/jama.2022.5368 Mahon OR, 2020, BIOMATERIALS, V239, DOI 10.1016/j.biomaterials.2020.119833 Nadeem A, 2022, INT IMMUNOPHARMACOL, V107, DOI 10.1016/j.intimp.2022.108703 Ricchetti GA, 2004, J LEUKOCYTE BIOL, V76, P719, DOI 10.1189/jlb.0104046 Rodríguez-Barrera R, 2021, CELLS-BASEL, V10, DOI 10.3390/cells10061499 Sailer ER, 1996, BRIT J PHARMACOL, V117, P615, DOI 10.1111/j.1476-5381.1996.tb15235.x Shapouri-Moghaddam A, 2018, J CELL PHYSIOL, V233, P6425, DOI 10.1002/jcp.26429 Stewart AN, 2021, J NEUROINFLAMM, V18, DOI 10.1186/s12974-021-02161-8 Torretta S, 2020, NAT COMMUN, V11, DOI 10.1038/s41467-020-20164-6 Wang X, 2015, GLIA, V63, P635, DOI 10.1002/glia.22774 Wang Y, 2022, INT J MOL SCI, V23, DOI 10.3390/ijms232415903 Wang Y, 2022, NEURAL REGEN RES, V17, P2778, DOI 10.4103/1673-5374.339494 Wang Y, 2022, REDOX BIOL, V57, DOI 10.1016/j.redox.2022.102494 Wang Y, 2021, SMALL, V17, DOI 10.1002/smll.202101505 Wu HJ, 2021, J NEUROINFLAMM, V18, DOI 10.1186/s12974-020-02041-7 Yang TK, 2022, FRONT PHARMACOL, V13, DOI 10.3389/fphar.2022.927871 Zeng H, 2019, J NEUROINFLAMM, V16, DOI 10.1186/s12974-019-1658-2 Zhang AP, 2021, STEM CELL RES THER, V12, DOI 10.1186/s13287-021-02407-5 Zhang J, 2020, CELL METAB, V31, P1136, DOI 10.1016/j.cmet.2020.05.004 Zhang SX, 2013, NEURAL REGEN RES, V8, P177, DOI 10.3969/j.issn.1673-5374.2013.02.011 NR 50 TC 11 Z9 11 U1 4 U2 16 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-5930 EI 1755-5949 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PD MAR 2 PY 2024 VL 30 IS 3 AR e14642 DI 10.1111/cns.14642 PG 18 WC Neurosciences; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Neurosciences & Neurology; Pharmacology & Pharmacy GA JY0G2 UT WOS:001176596400001 PM 38430464 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Deng, TT Xu, JH Wang, Q Wang, X Jiao, Y Cao, XX Geng, QS Zhang, MX Zhao, L Xiao, C AF Deng, Tingting Xu, Jiahe Wang, Qiong Wang, Xing Jiao, Yi Cao, Xiaoxue Geng, Qishun Zhang, Mengxiao Zhao, Lu Xiao, Cheng TI Immunomodulatory effects of curcumin on macrophage polarization in rheumatoid arthritis SO FRONTIERS IN PHARMACOLOGY LA English DT Review DE macrophage polarization; epigenetic regulation; curcumin; rheumatoid arthritis; autoimmune diseases ID COLLAGEN-INDUCED ARTHRITIS; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; DIAGNOSTIC INDICATORS; IMPROVES SYMPTOMS; M2 POLARIZATION; DOUBLE-BLIND; MONOCYTES; CELLS; INFLAMMATION AB Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovial inflammation, cartilage destruction, pannus formation and bone erosion. Various immune cells, including macrophages, are involved in RA pathogenesis. The heterogeneity and plasticity of macrophages render them pivotal regulators of both the induction and resolution of the inflammatory response. Predominantly, two different phenotypes of macrophages have been identified: classically activated M1 macrophages exacerbate inflammation via the production of cytokines, chemokines and other inflammatory mediators, while alternatively activated M2 macrophages inhibit inflammation and facilitate tissue repair. An imbalance in the M1/M2 macrophage ratio is critical during the initiation and progression of RA. Macrophage polarization is modulated by various transcription factors, epigenetic elements and metabolic reprogramming. Curcumin, an active component of turmeric, exhibits potent immunomodulatory effects and is administered in the treatment of multiple autoimmune diseases, including RA. The regulation of macrophage polarization and subsequent cytokine production as well as macrophage migration is involved in the mechanisms underlying the therapeutic effect of curcumin on RA. In this review, we summarize the underlying mechanisms by which curcumin modulates macrophage function and polarization in the context of RA to provide evidence for the clinical application of curcumin in RA treatment. C1 [Deng, Tingting; Xu, Jiahe; Wang, Qiong; Wang, Xing; Jiao, Yi; Cao, Xiaoxue; Geng, Qishun; Zhang, Mengxiao; Zhao, Lu; Xiao, Cheng] China Japan Friendship Hosp, Inst Clin Med, Beijing, Peoples R China. [Xu, Jiahe] Peking Univ, China Japan Friendship Sch Clin Med, Beijing, Peoples R China. [Wang, Qiong; Wang, Xing; Jiao, Yi] Beijing Univ Chinese Med, China Japan Friendship Clin Med Coll, Beijing, Peoples R China. [Xu, Jiahe; Cao, Xiaoxue; Geng, Qishun] Chinese Acad Med Sci, Grad Sch Peking Union Med Coll, Peking Union Med Coll, Beijing, Peoples R China. [Zhao, Lu] Capital Med Univ, China Japan Friendship Hosp, Beijing, Peoples R China. [Xiao, Cheng] China Japan Friendship Hosp, Dept Emergency, Beijing, Peoples R China. C3 China-Japan Friendship Hospital; Peking University; Beijing University of Chinese Medicine; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Capital Medical University; China-Japan Friendship Hospital; China-Japan Friendship Hospital RP Xiao, C (corresponding author), China Japan Friendship Hosp, Inst Clin Med, Beijing, Peoples R China.; Xiao, C (corresponding author), China Japan Friendship Hosp, Dept Emergency, Beijing, Peoples R China. EM xc2002812@126.com RI xiao, Cheng/AAM-7764-2020 OI xiao, Cheng/0000-0002-5601-9670 FU National High Level Hospital Clinical Research Funding of China-Japan Friendship Hospital [2023-NHLHCRF-DJZD-02] FX The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by National High Level Hospital Clinical Research Funding of China-Japan Friendship Hospital (No. 2023-NHLHCRF-DJZD-02). 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Pharmacol. PD FEB 28 PY 2024 VL 15 AR 1369337 DI 10.3389/fphar.2024.1369337 PG 13 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA KT1Q5 UT WOS:001182128500001 PM 38487171 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Quan, YZ Ma, A Ren, CQ An, YP Qiao, PS Gao, C Zhang, YK Li, XW Lin, SM Li, NN Chen, DL Pan, Y Zhou, H Lin, DM Lin, SQ Li, M Yang, BX AF Quan, Ya-zhu Ma, Ang Ren, Chao-qun An, Yong-pan Qiao, Pan-shuang Gao, Cai Zhang, Yu-kun Li, Xiao-wei Lin, Si -mei Li, Nan-nan Chen, Di-long Pan, Yan Zhou, Hong Lin, Dong-mei Lin, Shu-qian Li, Min Yang, Bao-xue TI Ganoderic acids alleviate atherosclerosis by inhibiting macrophage M1 polarization via TLR4/MyD88/NF-κB signaling pathway SO ATHEROSCLEROSIS LA English DT Article DE Ganoderma lucidum; Ganoderic acid; Atherosclerosis; Macrophage polarization; Inflammation; Nuclear factor-kappa B ID ACTIVATION; PHARMACOLOGY; METABOLISM AB Background and aims: Atherosclerosis (AS) is a chronic inflammatory disease characterized by lipid infiltration and plaque formation in blood vessel walls. Ganoderic acids (GA), a class of major bioactive compounds isolated from the Chinese traditional medicine Ganoderma lucidum, have multiple pharmacological activities. This study aimed to determine the anti-atherosclerotic effect of GA and reveal the pharmacological mechanism. Methods: ApoE-/- mice were fed a high -cholesterol diet and treated with GA for 16 weeks to induce AS and identify the effect of GA. Network pharmacological analysis was performed to predict the anti-atherosclerotic mechanisms. An in vitro cell model was used to explore the effect of GA on macrophage polarization and the possible mechanism involved in bone marrow dereived macrophages (BMDMs) and RAW264.7 cells stimulated with lipopolysaccharide or oxidized low-density lipoprotein. Results: It was found that GA at 5 and 25 mg/kg/d significantly inhibited the development of AS and increased plaque stability, as evidenced by decreased plaque in the aorta, reduced necrotic core size and increased collagen/lipid ratio in lesions. GA reduced the proportion of M1 macrophages in plaques, but had no effect on M2 macrophages. In vitro experiments showed that GA (1, 5, 25 mu g/mL) significantly decreased the proportion of CD86+ macrophages and the mRNA levels of IL -6, IL-1 beta, and MCP-1 in macrophages. Experimental results showed that GA inhibited M1 macrophage polarization by regulating TLR4/MyD88/NF-kappa B signaling pathway. Conclusions: This study demonstrated that GA play an important role in plaque stability and macrophage polarization. GA exert the anti-atherosclerotic effect partly by regulating TLR4/MyD88/NF-kappa B signaling pathways to inhibit M1 polarization of macrophages. Our study provides theoretical basis and experimental data for the pharmacological activity and mechanisms of GA against AS. C1 [Quan, Ya-zhu; Ma, Ang; Ren, Chao-qun; An, Yong-pan; Qiao, Pan-shuang; Gao, Cai; Zhang, Yu-kun; Li, Xiao-wei; Lin, Si -mei; Li, Nan-nan; Pan, Yan; Zhou, Hong; Li, Min; Yang, Bao-xue] Peking Univ, Sch Basic Med Sci, Dept Pharmacol, State Key Lab Vasc Homeostasis & Remodeling, Beijing 100191, Peoples R China. [Ma, Ang] China Acad Chinese Med Sci, Inst Chinese Materia Med, Artemisinin Res Ctr, Beijing 100007, Peoples R China. [Zhang, Yu-kun; Chen, Di-long] Chongqing Three Gorges Med Coll, Chongqing Key Lab Dev & Utilizat Genuine Med Mat T, Chongqing 404020, Peoples R China. [Li, Xiao-wei] China Resources Pharmaceut Grp Ltd, Beijing 100000, Peoples R China. [Lin, Dong-mei; Lin, Shu-qian] Fujian Agr & Forestry Univ, China Natl Engn Res Ctr JUNCAO Technol, Fuzhou 350002, Peoples R China. [Yang, Bao-xue] Peking Univ, Sch Basic Med Sci, Dept Pharmacol, 38 Xueyuan Rd, Beijing 100191, Peoples R China. C3 Peking University; China Academy of Chinese Medical Sciences; Fujian Agriculture & Forestry University; Peking University RP Yang, BX (corresponding author), Peking Univ, Sch Basic Med Sci, Dept Pharmacol, 38 Xueyuan Rd, Beijing 100191, Peoples R China. EM baoxue@bjmu.edu.cn RI ma, ang/MTA-5572-2025; 安, 永盼/JFL-0137-2023; Lin, Dongmei/JVE-1152-2024 FU National Natural Science Foundation of China [82273999, 81974083, 81800388]; Beijing Natural Science Foundation [7212151]; Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2022-JKCS-15]; Fundamental Research Funds for the Central Public Welfare Research Institutes [ZZ15-YQ-062, ZZ16-ND-10-07] FX This work was supported by National Natural Science Foundation of China grants 82273999, 81974083 and 81800388, the Beijing Natural Science Foundation grant 7212151, and the grant from the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences 2022-JKCS-15 and the Fundamental Research Funds for the Central Public Welfare Research Institutes ZZ15-YQ-062 and ZZ16-ND-10-07. 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In addition, the effects of phytochemical ingredients and different natural plants, mainly traditional Chinese medicines, on the regulation of different cardiovascular diseases via the JAK2/ STAT3 pathway are discussed. Surprisingly, the JAK2 pathway has dual roles in different cardiovascular diseases. Future research should focus on the dual regulatory effects of different phytochemical ingredients and natural plants on JAK2 to pave the way for their use in clinical trials. C1 [Guo, Bing; He, Xuan; Tang, Siqin; Mao, Yilin] Hunan Univ Chinese Med, Affiliated Hosp 2, Changsha 410005, Peoples R China. [Yu, Yunfeng; Wang, Min; Liu, Qili] Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha 410007, Peoples R China. [Li, Ronghui] Hunan Univ Chinese Med, Coll Chinese Med, Changsha 410208, Peoples R China. C3 Hunan University of Chinese Medicine; Hunan University of Chinese Medicine; Hunan University of Chinese Medicine RP Mao, YL (corresponding author), Hunan Univ Chinese Med, Affiliated Hosp 2, Geriatr Dept, Changsha 410005, Hunan, Peoples R China. EM maoyilin8518@126.com RI ; Guo, Bing/PGL-9509-2026; Yu, Yunfeng/NVL-9814-2025 OI Wang, Min/0009-0001-5317-2709; He, Xuan/0000-0003-3031-314X; FU Science AMP; Research Project of Hunan Provincial Administration of Traditional Chinese Medicine [C2022004] FX Funding sources This work was supported by the Science & Research Project of Hunan Provincial Administration of Traditional Chinese Medicine (grant number C2022004) . 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Pharmacother. PD MAR PY 2024 VL 172 AR 116313 DI 10.1016/j.biopha.2024.116313 EA FEB 2024 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA MA5G2 UT WOS:001190907700001 PM 38377736 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Yang, MJ Zhang, YN Qiao, Z Xu, RY Chen, SM Hu, P Yu, HL Pan, Y Cao, J AF Yang, Meng-juan Zhang, Yi-nuo Qiao, Zhi Xu, Rui-ying Chen, Si-min Hu, Po Yu, Hong-li Pan, Yang Cao, Jing TI An investigation into the HIF-dependent intestinal barrier protective mechanism of Qingchang Wenzhong decoction in ulcerative colitis management SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Ulcerative colitis; Traditional Chinese medicine; HIF; Network pharmacology; Intestinal barrier ID HEME OXYGENASE-1 GENE; INDUCIBLE FACTOR-I; NF-KAPPA-B; MACROPHAGE POLARIZATION; OXIDATIVE STRESS; ACTIVATION; INFLAMMATION; CROSSTALK; BERBERINE; APOPTOSIS AB Ethnopharmacological relevance: Ulcerative colitis (UC) is a chronic, non-specific inflammatory disease affecting the colon and rectum with an etiology that remains elusive. Traditional Chinese medicine (TCM) has been widely used on long-term UC treatment to better maintain the efficacy than traditional aminosalicylic acid or glucocorticosteroids and to ease financial burden of patients. Qingchang Wenzhong Decoction (QCWZD) is a modern TCM decoction with established clinical efficacy but the mechanism of its protection on intestinal barrier function remains unclear. Aim of the study: Current findings highlight that the activation of the hypoxia inducible factor (HIF) pathway can facilitate the repair of intestinal epithelium barrier. This study is to investigate the protective effects of QCWZD and its HIF-targeted ingredients on hypoxia-dependent intestinal barrier. Methods: The mice model of UC was induced by dextran sulfate sodium (DSS). Disease activity index (DAI) and histopathology scores and colon length were used to measure the severity of colitis. The DAO activity in serum and protein expression of tight junction (TJ) proteins were detected to explore the function of intestinal barrier. The protein levels of HIF-1 alpha and its downstream gene heme oxygenase-1 (HO-1) were measured as well. HIFtargeted active ingredients in QCWZD were selected by network pharmacology and molecular docking. Protective effects of six constituents on HIF-related anti-oxidative and barrier protective pathway were evaluated by lipopolysaccharide (LPS)-induced HT29 and RAW264.7 cells, through the measurement of the production of ROS and mRNA level of pro-inflammatory cytokines. HIF-1 alpha knockdown was carried out to explore the correlation of protection effects with HIF-related pathway of the active ingredients. Results: QCWZD effectively alleviated colitis induced by DSS and demonstrated a protective effect on intestinal barrier function by upregulating HIF-related pathways. Six specific ingredients in QCWZD, targeting HIF, successfully reduced the production of cellular ROS and proinflammatory cytokines in LPS-induced cells. It is noteworthy that the barrier protection provided by these molecules is intricately linked with the HIF-related pathway. Conclusions: This study elucidates the HIF-related molecular mechanism of QCWZD in protecting the function of the epithelial barrier. Six compounds targeting the activation of the HIF-dependent pathway were demonstrated to unveil a novel therapeutic approach for managing UC. C1 [Yang, Meng-juan; Zhang, Yi-nuo; Qiao, Zhi; Xu, Rui-ying; Chen, Si-min; Hu, Po; Yu, Hong-li; Pan, Yang; Cao, Jing] Nanjing Univ Chinese Med, Sch Pharm, 138 Xianlin Rd, Nanjing 210023, Peoples R China. C3 Nanjing University of Chinese Medicine RP Pan, Y; Cao, J (corresponding author), Nanjing Univ Chinese Med, Sch Pharm, 138 Xianlin Rd, Nanjing 210023, Peoples R China. EM ypan@njucm.edu.cn; caojing@njucm.edu.cn OI Cao, Jing/0000-0002-1089-3653 FU National Natural Science Foundation of China, China [82004039, 82204420]; Natural Science Foundation of Jiangsu province, China [BK20220474]; Major Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutions , China [23KJA360004]; Natural Science Foundation for Young Scholars of Nanjing University of Chinese Medicine, China [NZY82004039] FX We gratefully acknowledge Dr. Meng-yuan Li for her help in processing MINT dataset. This work was supported by National Natural Science Foundation of China, China (82004039 and 82204420) ; Natural Science Foundation of Jiangsu province, China (BK20220474) ; Major Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutions , China (23KJA360004) ; Natural Science Foundation for Young Scholars of Nanjing University of Chinese Medicine, China (NZY82004039) . 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Ethnopharmacol. PD MAY 10 PY 2024 VL 325 AR 117807 DI 10.1016/j.jep.2024.117807 EA FEB 2024 PG 17 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA LQ2Z6 UT WOS:001188215900001 PM 38280661 DA 2026-03-26 ER PT J AU Chen, SY Zeng, JS Li, R Zhang, YR Tao, YW Hou, Y Yang, L Zhang, YT Wu, JS Meng, XL AF Chen, Shiyu Zeng, Jiuseng Li, Rui Zhang, Yingrui Tao, Yiwen Hou, Ya Yang, Lu Zhang, Yating Wu, Jiasi Meng, Xianli TI Traditional Chinese medicine in regulating macrophage polarization in immune response of inflammatory diseases SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Traditional Chinese medicine; Macrophage polarization; Metabolic reprogramming; Inflammtion; Immune response ID NF-KAPPA-B; PPAR-GAMMA; SIGNALING PATHWAY; NITRIC-OXIDE; M1 POLARIZATION; GENE-EXPRESSION; CELLS; METABOLISM; ACTIVATION; RATS AB Ethnopharmacological relevance: Numerous studies have demonstrated that various traditional Chinese medicines (TCMs) exhibit potent anti-inflammatory effects against inflammatory diseases mediated through macrophage polarization and metabolic reprogramming. Aim of the study: The objective of this review was to assess and consolidate the current understanding regarding the pathogenic mechanisms governing macrophage polarization in the context of regulating inflammatory diseases. We also summarize the mechanism action of various TCMs on the regulation of macrophage polarization, which may contribute to facilitate the development of natural anti-inflammatory drugs based on reshaping macrophage polarization. Materials and methods: We conducted a comprehensive review of recently published articles, utilizing keywords such as "macrophage polarization" and "traditional Chinese medicines" in combination with "inflammation," as well as "macrophage polarization" and "inflammation" in conjunction with "natural products," and similar combinations, to search within PubMed and Google Scholar databases. Results: A total of 113 kinds of TCMs (including 62 components of TCMs, 27 TCMs as well as various types of extracts of TCMs and 24 Chinese prescriptions) was reported to exert anti-inflammatory effects through the regulation of key pathways of macrophage polarization and metabolic reprogramming. Conclusions: In this review, we have analyzed studies concerning the involvement of macrophage polarization and metabolic reprogramming in inflammation therapy. TCMs has great advantages in regulating macrophage polarization in treating inflammatory diseases due to its multi-pathway and multi-target pharmacological action. This review may contribute to facilitate the development of natural anti-inflammatory drugs based on reshaping macrophage polarization. C1 [Chen, Shiyu; Zeng, Jiuseng; Zhang, Yingrui; Tao, Yiwen; Hou, Ya; Yang, Lu; Zhang, Yating; Meng, Xianli] Chengdu Univ Tradit Chinese Med, Innovat Inst Chinese Med & Pharm, State Key Lab Southwestern Chinese Med Resources, Chengdu 611137, Peoples R China. [Li, Rui] Chengdu Univ Tradit Chinese Med, Affiliated Meishan Hosp, Meishan 620010, Peoples R China. [Wu, Jiasi] Chengdu Univ Tradit Chinese Med, Acupuncture & Tuina Sch, Chengdu 611137, Peoples R China. C3 Chengdu University of Traditional Chinese Medicine; Chengdu University of Traditional Chinese Medicine; Chengdu University of Traditional Chinese Medicine RP Meng, XL (corresponding author), Chengdu Univ Tradit Chinese Med, Innovat Inst Chinese Med & Pharm, State Key Lab Southwestern Chinese Med Resources, Chengdu 611137, Peoples R China.; Wu, JS (corresponding author), Chengdu Univ Tradit Chinese Med, Acupuncture & Tuina Sch, Chengdu 611137, Peoples R China. EM wujiasi@cdutcm.edu.cn; xlm999@cdutcm.edu.cn OI Chen, Shiyu/0009-0006-9659-6807 FU National Natural Science Foundation of China [82274207]; Science & Technology Department of Sichuan Province [2020YFQ0032, 2023NSFSC1782]; Xinglin Scholar Research Promotion Project of Chengdu University of TCM [XKTD2022013] FX This work was supported by the National Natural Science Foundation of China (Grant No. 82274207) , the Science & Technology Department of Sichuan Province (2020YFQ0032, 2023NSFSC1782) , Xinglin Scholar Research Promotion Project of Chengdu University of TCM (XKTD2022013) . 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Ethnopharmacol. PD MAY 10 PY 2024 VL 325 AR 117838 DI 10.1016/j.jep.2024.117838 EA FEB 2024 PG 27 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA LC0U7 UT WOS:001184470900001 PM 38310986 DA 2026-03-26 ER PT J AU Han, X Bao, JP Ni, JB Li, B Song, PL Wan, R Wang, XP Hu, GY Chen, CY AF Han, Xiao Bao, Jingpiao Ni, Jianbo Li, Bin Song, Pengli Wan, Rong Wang, Xingpeng Hu, Guoyong Chen, Congying TI Qing Xia Jie Yi Formula granules alleviated acute pancreatitis through inhibition of M1 macrophage polarization by suppressing glycolysis SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Acute pancreatitis; Macrophage polarization; Qing Xia Jie Yi Formula granules; Glycolysis; Lung injury ID ACTIVATION AB Ethnopharmacological relevance: Herbal formulas from Traditional Chinese Medicine are common and wellestablished practice for treating acute pancreatitis (AP) patients. However, little is known about their bioactive ingredients and mechanisms, such as their targets and pathways to inhibit inflammation. Aim of the study: This study aimed to evaluate the effect of Qing Xia Jie Yi Formula (QXJYF) granules on AP and discuss the molecular mechanisms involved. Materials and methods: Major compounds in QXJYF granules were identified using UPLC-quadrupole-Orbitrap mass spectrometry (UPLC-Q-Orbitrap MS). The effect of QXJYF granules on experimental AP models both in vitro and in vivo, and detailed mechanisms were clarified. Two AP models were induced in mice by intraperitoneally injections of caerulein or L-arginine, and QXJYF granules were used to treat AP mice in vivo. Histological evaluation of pancreas and lung, serum amylase and lipase levels, serum inflammatory cytokines, inflammatory cell infiltration and macrophage phenotype were assessed. Bone marrow derived macrophages (BMDMs) were cultured and treated with QXJYF granules in vitro. BMDM phenotype and glycolysis levels were measured. Lastly, clinical effect of QXJYF granules on AP patients was verified. Predicted severe AP (pSAP) patients eligible for inclusion were assessed for enrollment. Results: Nine major compounds were identified in QXJYF granules. Data showed that QXJYF granules significantly alleviated AP severity both in caerulein and L-arginine-induced AP models in vivo, pancreatic injury and inflammatory cell infiltration, systematic inflammation, lung injury and inflammatory cell infiltration were all improved after QXJYF treatment. QXJYF granules significantly reduced M1 macrophages during AP both in vivo and in vitro; besides, the mRNA expression levels of M1 genes such as inos, Tnf alpha, Il1 beta and Il6 were significantly lower after QXJYF treatment in M1 macrophages. Mechanistically, we found that HK2, PFKFB3, PKM, LDH alpha levels were increased in M1 macrophages, but significantly decreased after QXJYF treatment. Clinical data indicated that QXJYF granules could significantly reduce CRP levels and shorten the duration of organ failure, thereby reducing the incidence of SAP and preventing pSAP patients from progressing to SAP. Conclusion: QXJYF granules alleviated AP through the inhibition of M1 macrophage polarization by suppressing glycolysis. C1 [Han, Xiao; Bao, Jingpiao; Ni, Jianbo; Li, Bin; Song, Pengli; Wan, Rong; Wang, Xingpeng; Hu, Guoyong; Chen, Congying] Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Gastroenterol, Shanghai, Peoples R China. [Han, Xiao; Bao, Jingpiao; Ni, Jianbo; Li, Bin; Song, Pengli; Wan, Rong; Wang, Xingpeng; Hu, Guoyong; Chen, Congying] Shanghai Jiao Tong Univ, Sch Med, Inst Pancreat Dis, Shanghai Key Lab Pancreat Dis, Shanghai, Peoples R China. [Hu, Guoyong; Chen, Congying] Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Gastroenterol, 100 Haining Rd, Shanghai 200080, Peoples R China. C3 Shanghai Jiao Tong University; Shanghai Jiao Tong University; Shanghai Jiao Tong University RP Hu, GY; Chen, CY (corresponding author), Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Gastroenterol, 100 Haining Rd, Shanghai 200080, Peoples R China. EM guoyong.hu@shgh.cn; congyin.chen@shgh.cn RI Wan, Ronghao/KXQ-5617-2024; Bao, Jingpiao/MFJ-6818-2025; Han, Xiao/JNS-3098-2023 FU National Natural Science Foundation of China [81900584]; Shanghai Traditional Chinese Medicine and Western Clinical Cooperation Pilot Project [FWTX-1004]; Clinical Research Plan of SHDC [SHDC2020CR5013] FX The study was supported by National Natural Science Foundation of China (No.81900584, XH) , Shanghai Traditional Chinese Medicine and Western Clinical Cooperation Pilot Project (No. ZY (2018-2020) -FWTX-1004, XPW) and Clinical Research Plan of SHDC (No.SHDC2020CR5013, HGY). 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Ethnopharmacol. PD MAY 10 PY 2024 VL 325 AR 117750 DI 10.1016/j.jep.2024.117750 EA FEB 2024 PG 14 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA LC7G7 UT WOS:001184640400001 PM 38216100 DA 2026-03-26 ER PT J AU Zhang, XM Lu, XA Shi, J Li, YY Li, Y Tao, R Huang, LY Tang, YF Zhu, XJ Li, M Gao, YQ Feng, H Yu, Z AF Zhang, Xuemei Lu, Xiaona Shi, Jia Li, Yuyao Li, Yue Tao, Ru Huang, Lingying Tang, Yifei Zhu, Xiaojun Li, Man Gao, Yueqiu Feng, Hai Yu, Zhuo TI Bufalin suppresses hepatocellular carcinogenesis by targeting M2 macrophage-governed Wnt1/β-catenin signaling SO PHYTOMEDICINE LA English DT Article DE Bufalin; M2 macrophage; Wnt1; beta-catenin signaling; Hepatocellular carcinoma ID WNT; INVASION; GENE; EXPRESSION; GROWTH; CELLS; LIVER AB Background: The interplay of tumor-associated macrophages (TAMs) and tumor cells plays a key role in the development of hepatocellular carcinoma (HCC) and provides an important target for HCC therapy. The communication between them is still on the investigation. Bufalin, the active component derived from the traditional Chinese medicine (TCM) Chansu, has been evidenced to possess anti-HCC activity by directly suppressing tumor cells, while its immunomodulatory effect on the tumor microenvironment (TME) is unclear. Purpose: To explore the mechanism of M2 TAM-governed tumor cell proliferation and the inhibitory effect of bufalin on HCC growth by targeting M2 macrophages. Methods: Morphology and marker proteins were detected to evaluate macrophage polarization via microscopy and flow cytometry. Cellular proliferation and malignant transformation of HCC cells cultured with macrophage conditioned medium (CM) or bufalin-primed M2-CM, were assessed by cell viability, colony formation and soft agar assays. Regulations of gene transcription and protein expression and release were determined by RT-qPCR, immunoblotting, immunoprecipitation, ELISA and immunofluorescence. Tumorigenicity upon bufalin treatment was verified in orthotopic and diethylnitrosamine-induced HCC mouse model. Results: In this study, we first verified that M2 macrophages secreted Wnt1, which acted as a mediator to trigger beta-catenin activation in HCC cells, leading to cellular proliferation. Bufalin suppressed HCC cell proliferation and malignant transformation by inhibiting Wnt1 release in M2 macrophages, and dose-dependently inhibited HCC progression in mice. Mechanistically, bufalin specially targeted to block Wnt1 transcription, thus inactivating beta-catenin signaling cascade in HCC cells and leading to tumor regression in HCC mouse model. Conclusion: These results clearly reveal a novel potential of bufalin to suppress HCC through immunomodulation, and shed light on a new M2 macrophage-based modality of HCC immunotherapy, which additively enhances direct tumor-inhibitory efficacy of bufalin. C1 [Zhang, Xuemei; Lu, Xiaona; Shi, Jia; Li, Yuyao; Li, Yue; Huang, Lingying; Tang, Yifei; Zhu, Xiaojun; Gao, Yueqiu; Yu, Zhuo] Shanghai Univ Tradit Chinese Med, Dept Hepatopathy, Shuguang Hosp, Shanghai 201203, Peoples R China. [Gao, Yueqiu; Feng, Hai] Shanghai Univ Tradit Chinese Med, Inst Infect Dis, Shuguang Hosp, Shanghai 201203, Peoples R China. [Li, Man] Shanghai Univ Tradit Chinese Med, Laboratoy Cellular Immun, Shuguang Hosp, Shanghai 201203, Peoples R China. [Tao, Ru] Shanghai Univ Tradit Chinese Med, Dept Nursing, Shuguang Hosp, Shanghai 201203, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine RP Gao, YQ; Yu, Z (corresponding author), Shanghai Univ Tradit Chinese Med, Dept Hepatopathy, Shuguang Hosp, Shanghai 201203, Peoples R China.; Gao, YQ; Feng, H (corresponding author), Shanghai Univ Tradit Chinese Med, Inst Infect Dis, Shuguang Hosp, Shanghai 201203, Peoples R China. EM gaoyueqiu@shutcm.edu.cn; fogsea@163.com; zhuoyu@shutcm.edu.cn RI ; Yu, Zhuo/AAQ-6164-2020 OI Lu, Xiaona/0000-0003-2964-681X; Feng, Hai/0000-0001-9820-7111; Yu, Zhuo/0000-0003-4100-8415; Tang, Yifei/0009-0006-5262-6410 FU National Natural Science Foundation of China [82222074, 82074154, 81774240]; Siming Scholar from Shanghai Shuguang Hospital [SGXZ-201904]; Shuguang Program of Shanghai Education Development Foundation; Shanghai Municipal Education Commission; Youth Tip-top Talent program in Shanghai; Constant-eminent program in Shanghai; Xinglin Youth Scholar from Shanghai University of Traditional Chinese Medicine FX This work was supported by National Natural Science Foundation of China (No's.82222074, 82074154, 81774240) , The Siming Scholar from Shanghai Shuguang Hospital (SGXZ-201904) , Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission, Youth Tip-top Talent program in Shanghai, Constant-eminent program in Shanghai, Xinglin Youth Scholar from Shanghai University of Traditional Chinese Medicine. 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Wolf in the treatment of diabetic ulcers via regulating the PI3K-AKT signaling pathway SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Poria cocos (Schw.) Wolf; Bioactive compounds; UHPLC-Q-TOF-MS; Systemic pharmacology; Diabetic ulcer ID NETWORK PHARMACOLOGY; ACTIVATION; DRUG AB Ethnopharmacological relevance: Diabetic ulcers represent a chronic condition characterized by prolonged hyperglycemia and delayed wound healing, accompanied by endocrine disorders, inflammatory responses, and microvascular damage in the epidermal tissue, demanding effective clinical treatment approaches. For thousands of years, ancient Chinese ethnopharmacological studies have documented the use of Poria cocos (Schw.) Wolf in treating diabetic ulcers. Recent research has substantiated the diverse pharmacological effects of Poria cocos (Schw.) Wolf, including its potential to alleviate hyperglycemia and exhibit anti-inflammatory, antioxidant, and immune regulatory properties, which could effectively mitigate diabetic ulcer symptoms. Furthermore, being a natural medicine, Poria cocos (Schw.) Wolf has demonstrated promising therapeutic effects and safety in the management of diabetic ulcers, holding significant clinical value. Despite its potential clinical efficacy and applications in diabetic ulcer treatment, the primary active components and underlying pharmacological mechanisms of Poria cocos (Schw.) Wolf remains unclear. Further investigations are imperative to establish a solid foundation for drug development in this domain. Aim of the study and Materials and methods: In this study, we aimed to identify the active compounds and potential targets of Poria cocos (Schw.) Wolf using UHPLC-Q-TOF-MS and TCMSP databases. Additionally, we attempt to identify targets related to diabetic ulcers. Following enrichment analysis, a network of protein-protein interactions was constructed to identify hub genes based on the common elements between the two datasets. To gain insights into the binding activities of the hub genes and active ingredients, molecular docking analysis was employed. Furthermore, to further validate the therapeutic effect of Poria cocos (Schw.) Wolf, we exerted in vitro experiments using human umbilical vein vascular endothelial cells and human myeloid leukemia monocytes (THP-1). The active ingredient of Poria cocos (Schw.) Wolf was applied in these experiments. Our investigations included various assays, such as CCK-8, scratch test, immunofluorescence, western blotting, RT-PCR, and flow cytometry, to explore the potential of Poria cocos (Schw.) Wolf triterpenoid extract (PTE) in treating diabetic ulcers. Results: The findings here highlighted PTE as the primary active ingredient in Poria cocos (Schw.) Wolf. Utilizing network pharmacology, we identified 74 potential targets associated with diabetic ulcer treatment for Poria cocos (Schw.) Wolf, with five hub genes (JUN, MAPK1, STAT3, AKT1, and CTNNB1). Enrichment analysis revealed the involvement of multiple pathways in the therapeutic process, with the PI3K-AKT signaling pathway showing significant enrichment. Through molecular docking, we discovered that relevant targets within this pathway exhibited strong binding with the active components of Poria cocos (Schw.) Wolf. In vitro experiments unveiled that PTE (10 mg/L) facilitated the migration of human umbilical vein vascular endothelial cells (P < 0.05). PTE also increased the expression of CD31 and VEGF mRNA (P < 0.05) while activating the expressions of p-PI3K and p-AKT (P < 0.05). Moreover, PTE demonstrated its potential by reducing the expression of IL-1 beta, IL-6, TNF-alpha, and NF-kappa B mRNA in THP-1 (P < 0.05) and fostering M2 macrophage polarization. These results signify the potential therapeutic effects of PTE in treating diabetic ulcers, with its beneficial actions mediated through the PI3K-AKT signaling pathway. Conclusions: PTE is the main active ingredient in Poria cocos (Schw.) Wolf that exerts therapeutic effects. Through PI3K-AKT signaling pathway activation and inflammatory response reduction, PTE promotes angiogenesis, thereby healing diabetic ulcers. C1 [Ding, Xiaofeng; Lai, Yongxian] Tongji Univ, Shanghai Skin Dis Hosp, Sch Med, Shanghai 200443, Peoples R China. [Chen, Bin] Nanjing Res Inst Comprehens Utilizat Wild Plants, Inst Plant Resources & Chem, Nanjing 210042, Peoples R China. [Li, Shiyan; Ding, Youjun] Nanjing Univ, Nanjing Drum Tower Hosp, Affiliated Hosp, Dept Burns & Plast Surg,Med Sch, 321 Zhongshan Rd, Nanjing, Jiangsu, Peoples R China. [Shen, Jiayun] China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China. [Chen, Timson; Ma, Ling] Guangzhou Degu Personal Care Prod Co Ltd, Adolph Innovat Lab, Guangzhou 510000, Peoples R China. [Wang, Yiwei] Nanjing Univ Chinese Med, Jiangsu Prov Engn Res Ctr TCM External Medicat Dev, Nanjing, Peoples R China. [Liu, Jinfang] Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Dept Plast & Reconstruct Surg, Shanghai 200072, Peoples R China. [Huang, Heyan; Tan, Qian] Nanjing Univ Chinese Med, Dept Burns & Plast Surg, Clin Coll, Nanjing Drum Tower Hosp, Nanjing 210008, Peoples R China. C3 Tongji University; Nanjing University; China Academy of Chinese Medical Sciences; Institute of Chinese Materia Medica, CACMS; Nanjing University of Chinese Medicine; Tongji University; Nanjing University of Chinese Medicine; Nanjing University RP Chen, B (corresponding author), Nanjing Res Inst Comprehens Utilizat Wild Plants, Inst Plant Resources & Chem, Nanjing 210042, Peoples R China.; Wang, YW (corresponding author), Nanjing Univ Chinese Med, Jiangsu Prov Engn Res Ctr TCM External Medicat Dev, Nanjing, Peoples R China.; Tan, Q (corresponding author), Nanjing Univ Chinese Med, Dept Burns & Plast Surg, Clin Coll, Nanjing Drum Tower Hosp, Nanjing 210008, Peoples R China. EM chen_bin_nj@163.com; yiweiwang@njucm.edu.cn; peterding1993@163.com RI Chen, Bin/AAA-5877-2021; Chen, Tim/KVV-8381-2024; lai, yongxian/MCK-1190-2025; Wang, Yiwei/AAE-9739-2021; 丁, 丁友军/HSH-1839-2023 OI shen, jiayun/0000-0001-5011-4303; Wang, Yiwei/0000-0001-6585-6641; FU National Natural Science Foundation of China [82172217] FX Funding statement National Natural Science Foundation of China (82172217) . 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PD MAY 10 PY 2024 VL 325 AR 117812 DI 10.1016/j.jep.2024.117812 EA FEB 2024 PG 17 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA KY6Y8 UT WOS:001183581200001 PM 38301984 DA 2026-03-26 ER PT J AU Lu, JH Zhao, HQ Wang, ZJ Lin, XY Pi, WM Zhang, X Yang, LP Yao, SC Zhang, YZ Huang, XM Lei, HM Wang, PL AF Lu, Jihui Zhao, Haoqiang Wang, Zhijia Lin, Xiaoyu Pi, Wenmin Zhang, Xiang Yang, Luping Yao, Shuchang Zhang, Yaozhi Huang, Xuemei Lei, Haimin Wang, Penglong TI Glucose Epimerization-Modulated Phytochemicals Constructing Carrier-Free Hydrogel for Regulation of Macrophage Phenotype to Promote Wound Healing SO ADVANCED FUNCTIONAL MATERIALS LA English DT Article DE carrier-free hydrogel; glucose epimerization; macrophage polarization; phytochemicals; wound healing ID SUPRAMOLECULAR CHIRALITY; POLARIZATION AB The self-assembly of phytochemicals with multiple chiral centers is receiving significant attention for its potential in biomedical applications. However, the impact of single chiral center epimerization on molecular self-assembly remains unexplored. Herein, the self-assembly behavior and bioactivities of 1,2,3,4,6-penta-O-galloyl-alpha-D-glucose (alpha-D-PGG) and 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (beta-D-PGG) is examined, a pair of natural ellagitannins abundant in plants. Interestingly, beta-D-PGG formed a hydrogel without modification, while alpha-D-PGG does not. This occurred due to the balanced distribution of aromatic rings and phenolic hydroxyl groups in beta-D-PGG, facilitating self-assembly via hydrogen bonding and pi-pi stacking into nanofibers. In contrast, alpha-D-PGG's self-assembly is inhibited by steric hindrance. Notably, beta-D-PGG hydrogel demonstrated exceptional antibacterial activity and by regulating macrophage polarization toward the M2 phenotype, thereby reducing inflammation. This study not only reveals the distinct self-assembly behaviors of glucose derivatives but also offers new insights into their potential in biomedical applications, such as wound healing. beta-D-PGG can self-assemble into hydrogels in deionized water without any chemical modification or pretreatment, whereas its epimer alpha-D-PGG does not self-assemble. beta-D-PGG hydrogel not only exhibits great antibacterial activity, anti-inflammatory activity, and promotes wound healing by reducing M1 macrophage expression and increasing M2 macrophage expression, but also exhibits stability, injectability, self-healing, and thermosensitivity, making it potentially an ideal wound dressing. image C1 [Lu, Jihui; Zhao, Haoqiang; Wang, Zhijia; Lin, Xiaoyu; Pi, Wenmin; Zhang, Xiang; Yang, Luping; Yao, Shuchang; Zhang, Yaozhi; Huang, Xuemei; Lei, Haimin; Wang, Penglong] Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing 102488, Peoples R China. C3 Beijing University of Chinese Medicine RP Wang, PL (corresponding author), Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing 102488, Peoples R China. EM wpl581@126.com RI Wang, Zhijia/ADM-7962-2022 FU Fundamental Research Funds for the Central Universities; National Natural Science Foundation of China [82073974, 82274072]; Beijing Key Laboratory for Basic and Development Research on Chinese Medicine [100102]; [2023-JYB-JBZD-049]; [2022-XJ-KYQD-008]; [2023-JYB-JBQN-052] FX J.L. and H.Z. contributed equally to this work. Financial support from the Fundamental Research Funds for the Central Universities (2023-JYB-JBZD-049, 2022-XJ-KYQD-008, 2023-JYB-JBQN-052, China), the National Natural Science Foundation of China (No. 82073974, 82274072), the Beijing Key Laboratory for Basic and Development Research on Chinese Medicine (Beijing, 100102) are gratefully acknowledged. 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PD MAY PY 2024 VL 34 IS 22 DI 10.1002/adfm.202314089 EA FEB 2024 PG 16 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter WE Science Citation Index Expanded (SCI-EXPANDED) SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 1KV8U UT WOS:001157860400001 DA 2026-03-26 ER PT J AU Lv, WJ Jin, WX Lin, J Wang, ZH Ma, YM Zhang, WB Zhu, YQ Hu, YF Qu, Q Guo, SN AF Lv, Weijie Jin, Wenxin Lin, Jin Wang, Zhihua Ma, Yimu Zhang, Wenbo Zhu, Yongqi Hu, Yifan Qu, Qian Guo, Shining TI Forsythia suspensa polyphenols regulate macrophage M1 polarization to alleviate intestinal inflammation in mice SO PHYTOMEDICINE LA English DT Article DE Inflammatory bowel diseases; Forsythia suspensa polyphenols; Macrophage polarization ID COLITIS; PERMEABILITY; PATHWAYS AB Background: Inflammatory bowel disease (IBD) was a chronic intestinal disease related to autoimmunity, and its pathogenesis was complex. Forsythia suspensa (F. suspensa) had good anti-inflammatory and antioxidant effects. The active component polyphenols had significant effects in the treatment of intestinal inflammation. Researches had found that polarization, pyroptosis and apoptosis of macrophages can drive the occurrence and development of colitis. Purpose: In this study, we examined whether F. suspensa polyphenols (FPP) mitigated DSS-induced colitis, and explored its potential mechanisms. Methods: The potential targets of F. suspensa in intestinal inflammation were predicted through network pharmacology. Using LPS and IFN-gamma induced macrophage M1 polarization in J774A.1 cells. Macrophage polarization was detected through RT-qPCR, flow cytometry and ELISA. Ulcerative colitis (UC) in mice was induced by 2.5% DSS for 7 days, and then oral administrated different doses of FPP for another 7 days. Then we assessed the body weight, diarrhea, bleeding in stool, colon length, cytokines of serum and pathology of colon. The effects of FPP on the gut microbiota in mice also tested and evaluated. Results: Our results showed that the main active ingredient of F. suspensa in protecting intestinal inflammation were polyphenols and F. suspensa was multi-targeted in the treatment of intestinal inflammation. FPP inhibited M1 polarization and polarizes towards M2 in J774A.1 cells. FPP inhibited pyroptosis and apoptosis to exert antiinflammatory effects. FPP had a good protective effect on DSS induced UC in mice. In unison, FPP inhibited M1 polarization, apoptosis, and pyroptosis in UC mice. FPP regulated intestinal homeostasis in mice with UC by improving the gut microbiota and enhancing the intestinal metabolites short-chain fatty acid (SCFAs). Conclusions: These data indicated that FPP may alleviate UC by inhibiting M1 polarization in mice. Collectively, these findings suggest that the reduction of colitis by FPP may related to macrophage polarization, pyroptosis and apoptosis. C1 [Lv, Weijie; Jin, Wenxin; Lin, Jin; Wang, Zhihua; Ma, Yimu; Zhang, Wenbo; Zhu, Yongqi; Hu, Yifan; Qu, Qian; Guo, Shining] South China Agr Univ, Coll Vet Med, Guangzhou, Peoples R China. [Guo, Shining] Guangdong Res Ctr Vet Tradit Chinese Med & Nat Med, Guangzhou 510642, Guangdong, Peoples R China. C3 South China Agricultural University RP Qu, Q; Guo, SN (corresponding author), South China Agr Univ, Coll Vet Med, Guangzhou, Peoples R China. EM qianqu@scau.edu.cn; shining@scau.edu.cn RI ; jin, wenxin/GRE-8267-2022; Qu, Qian/KIK-8611-2024 OI Lv, Weijie/0000-0002-1176-6664; FU Basic and Applied Basic Research Projects of Guangzhou [2023A04J0119]; National Key Research and Development Program [2022YFD1801103] FX Funding This work was supported by the Basic and Applied Basic Research Projects of Guangzhou (2023A04J0119) and National Key Research and Development Program (2022YFD1801103) . 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In the joint, macrophages have an immune defense role where the presence of urate crystals results in the inflammatory mediators secretion, inflammatory cells recruitment to the joint, and shift macrophage population toward M1 pro-inflammatory phenotypes. Current treatment modalities of gout arthritis have side effects that limit their use in the elderly. A novel treatment that targets macrophage polarization to reestablish homeostasis may initiate a drug discovery program of novel disease-modifying agents for gout. Zerumbone (Zer) is a sesquiterpenoid bioactive compound found in the rhizome of Zingiberaceae family and possesses anti-inflammatory, antioxidant, and anti-proliferative activity. Our study hypothesized that soluble uric acid (sUA) and Pam3CSK4 (TLR2 agonist) reduce the anti-inflammatory function of murine M2 bone marrowderived macrophages and change the expression of M2 genetic markers toward M1 phenotypes. We observed that priming of M2 macrophages with sUA and Pam3CSK4 significantly decreased M2 specific markers expression, e.g., Arg-1, Ym-1, and Fizz-1, enhanced mRNA expression of IL-1 beta, TNF-alpha, CXCL2, and iNOS and increased oxidative stress in M2 macrophages, as exhibited by a reduction in Nrf2 expression. We also aimed to study the impact of Zer on reducing the pro-inflammatory effect of sUA in TLR2-stimulated M2 macrophages. We noticed that Zer treatment significantly reduced L-1 beta and TNF-alpha production following Pam3CSK4 + sUA treatment on M2 macrophages. Furthermore, Zer reduced the caspase-1 activity without altering cytosolic NLRP3 content in challenged M2 BMDMs. We also observed that Zer significantly enhanced M2-associated marker's expression, e.g., Arg-1, Ym-1, and Fizz-1, and augmented Nrf-2 and other antioxidant proteins, including HMOX1 and srxn1expression following Pam3CSK4 + sUA treatment. We draw the conclusion that Zer is a potentially effective anti-inflammatory treatment for gout arthritis linked to hyperuricemia. C1 [Qadri, Marwa; Ahmed, Rayan; Hakami, Walaa] Jazan Univ, Coll Pharm, Dept Pharmacol & Toxicol, Jizan 45142, Saudi Arabia. [Qadri, Marwa; Alaqi, Reem] Jazan Univ, Hlth Sci Res Ctr HSRC, Inflammat Pharmacol & Drug Discovery Unit, Jizan 45142, Saudi Arabia. [Khired, Zenat] Jazan Univ, Fac Med, Surg Dept, Jizan 45142, Saudi Arabia. [Elsayed, Sandy] October Univ Modern Sci & Arts MSA, Fac Pharm, Dept Pharmacol & Toxicol, Giza 12451, Egypt. [Alarifi, Abdulaziz] King Saud bin Abdulaziz Univ Hlth Sci, Coll Sci & Hlth Profess, Dept Basic Sci, Riyadh, Saudi Arabia. [Alarifi, Abdulaziz] King Abdullah Int Med Res Ctr, Riyadh, Saudi Arabia. [Alhamami, Hussain] King Saud Univ, Coll Pharm, Dept Pharmacol & Toxicol, Riyadh 11451, Saudi Arabia. [Khardali, Amani] Jazan Univ, Coll Pharm, Dept Clin Pharm, Jizan 45142, Saudi Arabia. [Khardali, Amani] Jazan Univ, Coll Pharm, Pharm Practice Res Unit, Jizan 45142, Saudi Arabia. [Qadri, Marwa] Jazan Univ, Coll Pharm, Hlth Sci Res Ctr HSRC, Dept Pharmacol & Toxicol,Inflammat Pharmacol & Dru, Al Maarefah Rd, Jazan 45142, Saudi Arabia. C3 Jazan University; Jazan University; Jazan University; Egyptian Knowledge Bank (EKB); Modern Sciences & Arts University (MSA); King Saud Bin Abdulaziz University for Health Sciences; King Saud Bin Abdulaziz University for Health Sciences; King Abdullah International Medical Research Center (KAIMRC); King Saud University; Jazan University; Jazan University; Jazan University RP Qadri, M (corresponding author), Jazan Univ, Coll Pharm, Hlth Sci Res Ctr HSRC, Dept Pharmacol & Toxicol,Inflammat Pharmacol & Dru, Al Maarefah Rd, Jazan 45142, Saudi Arabia. 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J. PD MAR PY 2024 VL 32 IS 3 AR 101956 DI 10.1016/j.jsps.2024.101956 EA JAN 2024 PG 10 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA JD1D8 UT WOS:001171119600001 PM 38318316 OA Green Submitted, hybrid DA 2026-03-26 ER PT J AU Shao, XQ Zeng, WR Wang, Q Liu, SP Guo, QL Luo, DS Luo, QM Wang, DW Wang, LX Zhang, Y Diao, HT Piao, SH Yan, ML Guo, J AF Shao, Xiaoqi Zeng, Wenru Wang, Qing Liu, Suping Guo, Qiaoling Luo, Duosheng Luo, Qingmao Wang, Dongwei Wang, Lexun Zhang, Yue Diao, Hongtao Piao, Shenghua Yan, Meiling Guo, Jiao TI Fufang Zhenzhu Tiaozhi (FTZ) suppression of macrophage pyroptosis: Key to stabilizing rupture-prone plaques SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Fufang Zhenzhu Tiaozhi; Atherosclerosis; Pyroptosis; Macrophage polarization; NLRP3 inflammasome ID OXIDATIVE STRESS; ATHEROSCLEROSIS; INFLAMMATION; EXPRESSION; CHINESE; M1 AB Background: Research on the Chinese herbal formula Fufang Zhenzhu Tiaozhi (FTZ) has demonstrated its effectiveness in treating hyperlipidemia and glycolipid metabolic disorders. Additionally, FTZ has shown inhibitory effects on oxidative stress, regulation of lipid metabolism, and reduction of inflammation in these conditions. However, the precise mechanisms through which FTZ modulates macrophage function in atherosclerosis remain incompletely understood. Therefore, this study aims to investigate whether FTZ can effectively stabilize rupture-prone plaques by suppressing macrophage pyroptosis and impeding the development of M1 macrophage polarization in ApoE-/- mice. Methods: To assess the impact of FTZ on macrophage function and atherosclerosis in ApoE-/- mice, we orally administered FTZ at a dosage of 1.2 g/kg body weight daily for 14 weeks. Levels of interleukin-18 and interleukin-1 beta were quantified using ELISA kits to gauge FTZ's influence on inflammation. Total cholesterol content was measured with a Cholesterol Assay Kit to evaluate FTZ's effect on lipid metabolism. Aortic tissues were stained with Oil Red O, and immunohistochemistry techniques were applied to assess atherosclerotic lesions and plaque stability. To evaluate the effects of FTZ on macrophage pyroptosis and oxidative damage, immunofluorescence staining was utilized. Additionally, we conducted an analysis of protein and mRNA expression levels of NLRP3 inflammasome-related genes and macrophage polarization-related genes using RT-PCR and western blotting techniques. Results: This study illustrates the potential therapeutic effectiveness of FTZ in mitigating the severity of atherosclerosis and improving serum lipid profiles by inhibiting inflammation. The observed enhancements in atherosclerosis severity and inflammation can be attributed to the suppression of NLRP3 inflammasome activity and M1 polarization by FTZ. Conclusion: The current findings indicate that FTZ provides protection against atherosclerosis, positioning it as a promising candidate for novel therapies targeting atherosclerosis and related cardiovascular diseases. C1 [Shao, Xiaoqi; Zeng, Wenru; Wang, Qing; Liu, Suping; Guo, Qiaoling; Luo, Duosheng; Luo, Qingmao; Wang, Dongwei; Wang, Lexun; Zhang, Yue; Diao, Hongtao; Piao, Shenghua; Yan, Meiling; Guo, Jiao] Guangdong Pharmaceut Univ, Inst Chinese Med, Guangdong Metab Dis Res Ctr Integrated Chinese & W, Guangzhou 510006, Peoples R China. [Guo, Jiao] Guangdong Pharmaceut Univ, Minist Educ China, Key Lab Glucolipid Metab Disorder, Guangzhou 510006, Peoples R China. [Guo, Jiao] Guangdong Key Lab Metab Dis Prevent & Treatment Tr, Guangzhou 510006, Peoples R China. [Yan, Meiling; Guo, Jiao] Guangdong Pharmaceut Univ, Guangzhou Higher Educ Mega Ctr, 280 Wai Huan Dong Rd, Guangzhou 510006, Peoples R China. C3 Guangdong Pharmaceutical University; Guangdong Pharmaceutical University; Guangdong Pharmaceutical University RP Yan, ML; Guo, J (corresponding author), Guangdong Pharmaceut Univ, Guangzhou Higher Educ Mega Ctr, 280 Wai Huan Dong Rd, Guangzhou 510006, Peoples R China. EM shaoxiaoqi@gdpu.edu.cn; 1577926375@qq.com; 1798764346@qq.com; 278412778@qq.com; 1690412538@qq.com; lds0901@163.com; 228653479@qq.com; 1179399063@qq.com; wanglexun@gdpu.edu.cn; zhangyuegpu@163.com; diaohongtao94@163.com; piaow@163.com; yanmeiling0122@163.com; gyguoyz@163.com RI ; Guo, Jiao/PFK-0669-2025; shao, xiaoqi/AFZ-7753-2022; Diao, Dht/HCG-9725-2022; Wang, lexun/GSE-0692-2022 OI Guo, Jiao/0000-0002-0050-5055; FU Key Project of National Natural Science Foundation of China [81,830,113]; National key R & D plan of China "Research on modernization of traditional Chinese medicine" [2018YFC1704200]; Major basic and applied basic research projects of Guangdong Province of China [2019B030302005]; Project of Administration of Traditional Chinese Medicine of Guangdong Province of China [20222114]; Youth Innovative Talents Project of Guangdong Provincial Department Education [2020KQNCX037]; Guangzhou Basic and Applied Basic Research Project [202201010113]; Health Commission of Guangdong Province [A2023256] FX This work was supported by Key Project of National Natural Science Foundation of China (81,830,113); National key R & D plan of China "Research on modernization of traditional Chinese medicine" (2018YFC1704200) ; Major basic and applied basic research projects of Guangdong Province of China (2019B030302005) ; Project of Administration of Traditional Chinese Medicine of Guangdong Province of China (20222114) , and the Youth Innovative Talents Project of Guangdong Provincial Department Education (2020KQNCX037) . Guangzhou Basic and Applied Basic Research Project (202201010113) . The Health Commission of Guangdong Province (A2023256). 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Ethnopharmacol. PD APR 24 PY 2024 VL 324 AR 117705 DI 10.1016/j.jep.2024.117705 EA JAN 2024 PG 12 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA JU5A8 UT WOS:001175677300001 PM 38219878 OA hybrid DA 2026-03-26 ER PT J AU Deng, JW Yuan, S Shi, LP Chen, X Liu, J Chen, ZW Tan, KY Yang, Q Cao, WF AF Deng, Jing-Wei Yuan, Su Shi, Li-Peng Chen, Xin Liu, Jun Chen, Zhi-Wei Tan, Kai-Yue Yang, Qian Cao, Wen-Fu TI Integration of network pharmacology and serum medicinal chemistry to investigate the pharmacological mechanisms of QiZhuYangGan Decoction in the treatment of hepatic fibrosis SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Hepatic fibrosis; Network pharmacology; Traditional Chinese medicine; Molecular docking; Molecular dynamics simulation ID TRADITIONAL CHINESE MEDICINE; MOLECULAR-MECHANISMS; SIGNALING PATHWAY; LIVER AB Ethnopharmacological relevance: Qizhuyanggan Decoction (QZD), a traditional Chinese medicine formula, is frequently utilized in clinical practice for managing hepatic fibrosis. However, the specific target and mechanism of action of QZD for hepatic fibrosis treatment remain unknown. Aim of the study: By combining network pharmacology, serum medicinal chemistry, and experimental validation methods, our study aimed to investigate the therapeutic effects of QZD on hepatic fibrosis, the anti-hepatic fibrosis active ingredients, and the possible mechanism of anti-hepatic fibrosis action. Materials and methods: The study aimed to investigate the therapeutic effect of QZD on hepatic fibrosis induced by CCl4 in SD rats, as well as its mechanism of action. The rats were anesthetized intraperitoneally using 3% pentobarbital and were executed after asphyxiation with high concentrations of carbon dioxide. Several techniques were employed to evaluate the efficacy of QZD, including ELISA, Western blot, HYP reagent assay, and various pathological examinations such as HE, Masson, Sirius Red staining, and immunohistochemistry (IHC). Additionally, serum biochemical assays were conducted to assess the effect of QZD on liver injury. Network pharmacology, UPLC, molecular docking, and molecular dynamics simulation were utilized to explore the mechanism of QZD in treating hepatic fibrosis. Finally, experimental validation was performed through ELISA, IHC, RT-qPCR, and Western blot analysis. Result: Liver histopathology showed that QZD reduced inflammation and inhibited collagen production, and QZD significantly reduced HA and LN content to treat hepatic fibrosis. Serum biochemical analysis showed that QZD improved liver injury. Network pharmacology combined with UPLC screened six active ingredients and obtained 87 targets for the intersection of active ingredients and diseases. The enrichment analysis results indicated that the PI3K/AKT pathway might be the mechanism of action of QZD in the treatment of hepatic fibrosis, and counteracting the inflammatory response might be one of the pathways of action of QZD. Molecular docking and molecular dynamics simulations showed that the active ingredient had good binding properties with PI3K, AKT, and mTOR proteins. Western blot, ELISA, PCR, and IHC results indicated that QZD may treat hepatic fibrosis by inhibiting the PI3K/AKT/mTOR pathway and suppressing M1 macrophage polarization, while also promoting M2 macrophage polarization. Conclusions: QZD may be effective in the treatment of hepatic fibrosis by inhibiting the PI3K/AKT/mTOR signaling pathway and M1 macrophage polarization, while promoting M2 macrophage polarization. This provides a strong basis for the clinical application of QZD. C1 [Yuan, Su; Shi, Li-Peng; Chen, Xin; Liu, Jun; Tan, Kai-Yue; Yang, Qian; Cao, Wen-Fu] Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing, Peoples R China. [Deng, Jing-Wei; Yuan, Su; Shi, Li-Peng; Chen, Xin; Liu, Jun; Chen, Zhi-Wei; Tan, Kai-Yue; Yang, Qian; Cao, Wen-Fu] Chongqing Key Lab Tradit Chinese Med Prevent & Cu, Chongqing, Peoples R China. [Yuan, Su; Liu, Jun; Cao, Wen-Fu] Chongqing Med Univ, Affiliated Hosp 1, Dept Combinat Chinese & Western Med, Chongqing, Peoples R China. [Cao, Wen-Fu] Chongqing Med Univ, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China. C3 Chongqing Medical University; Chongqing Medical University; Chongqing Medical University RP Cao, WF (corresponding author), Chongqing Med Univ, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China. EM caowenfu20220401@163.com RI liu, jun/LMP-4753-2024; Chen, Xin/KDO-5560-2024 FU National Natural Science Foundation of China [81573860, 82004168]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJQN202215101, KJZD-K202315101] FX This work was supported by the National Natural Science Foundation of China (No. 81573860, No. 82004168) , Science and Technology Research Program of Chongqing Municipal Education Commission (Grant No.: KJQN202215101, KJZD-K202315101) . We thank the au- thors for the development of the database and software used in this paper, we also thank Figdraw ( www.figdraw.com ) for the assistance in creating flow chart. 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Ethnopharmacol. PD APR 6 PY 2024 VL 323 AR 117730 DI 10.1016/j.jep.2024.117730 EA JAN 2024 PG 12 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA IB8O0 UT WOS:001163955900001 PM 38190954 DA 2026-03-26 ER PT J AU Gong, ZY Guo, J Liu, B Guo, Y Cheng, CC Jiang, Y Liang, N Hu, MZ Song, T Yang, L Li, HZ Zhang, HL Zong, XY Che, QZ Shi, NN AF Gong, Zhaoyuan Guo, Jing Liu, Bin Guo, Yang Cheng, Cuicui Jiang, Yin Liang, Ning Hu, Mingzhi Song, Tian Yang, Lu Li, Huizhen Zhang, Haili Zong, Xingyu Che, Qianzi Shi, Nannan TI Mechanisms of immune response and cell death in ischemic stroke and their regulation by natural compounds SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE ischemic stroke; inflammatory; immune cells; cell death; natural compounds ID NF-KAPPA-B; FOCAL CEREBRAL-ISCHEMIA; MICROGLIA/MACROPHAGE POLARIZATION DYNAMICS; T-CELLS; BRAIN-INJURY; REACTIVE ASTROCYTES; SIGNALING PATHWAY; RECEPTOR 4; RAT MODEL; INFLAMMASOMES MECHANISM AB Ischemic stroke (IS), which is the third foremost cause of disability and death worldwide, has inflammation and cell death as its main pathological features. IS can lead to neuronal cell death and release factors such as damage-related molecular patterns, stimulating the immune system to release inflammatory mediators, thereby resulting in inflammation and exacerbating brain damage. Currently, there are a limited number of treatment methods for IS, which is a fact necessitating the discovery of new treatment targets. For this review, current research on inflammation and cell death in ischemic stroke was summarized. The complex roles and pathways of the principal immune cells (microglia, astrocyte, neutrophils, T lymphocytes, and monocytes/macrophage) in the immune system after IS in inflammation are discussed. The mechanisms of immune cell interactions and the cytokines involved in these interactions are summarized. Moreover, the cell death mechanisms (pyroptosis, apoptosis, necroptosis, PANoptosis, and ferroptosis) and pathways after IS are explored. Finally, a summary is provided of the mechanism of action of natural pharmacological active ingredients in the treatment of IS. Despite significant recent progress in research on IS, there remain many challenges that need to be overcome. C1 [Gong, Zhaoyuan; Guo, Jing; Liu, Bin; Guo, Yang; Cheng, Cuicui; Jiang, Yin; Liang, Ning; Hu, Mingzhi; Song, Tian; Yang, Lu; Li, Huizhen; Zhang, Haili; Zong, Xingyu; Che, Qianzi; Shi, Nannan] China Acad Chinese Med Sci, Inst Basic Res Clin Med, Beijing, Peoples R China. C3 China Academy of Chinese Medical Sciences; Institute of Basic Research In Clinical Medicine, CACMS RP Che, QZ; Shi, NN (corresponding author), China Acad Chinese Med Sci, Inst Basic Res Clin Med, Beijing, Peoples R China. EM cheqianzi123@126.com; 13811839164@vip.126.com RI Zhang, Haili/JTT-7717-2023; liang, ning/AAH-3307-2020; Song, Tian/PFZ-3251-2026; Gong, zhaoyuan/KRQ-3077-2024; liu, Bin/AAP-1252-2020; Che, Qianzi/JCN-7084-2023 OI Liu, Bin/0000-0003-1162-5930; Song, Tian/0000-0003-4215-6591; FU National Natural Science Foundation of China10.13039/501100001809 FX We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript. 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Immunol. PD JAN 11 PY 2024 VL 14 AR 1287857 DI 10.3389/fimmu.2023.1287857 PG 23 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA FU1O4 UT WOS:001148279500001 PM 38274789 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhang, Y Qi, YF Jia, ZJ Li, YM Wu, LQ Zhou, QB Xu, FQ AF Zhang, Yan Qi, Yifei Jia, Zijun Li, Yiming Wu, Liqi Zhou, Qingbing Xu, Fengqin TI Effects and mechanisms of Zhizi Chuanxiong herb pair against atherosclerosis: an integration of network pharmacology, molecular docking, and experimental validation SO CHINESE MEDICINE LA English DT Article DE Atherosclerosis; Macrophage polarization; Zhizi Chuanxiong herb pair; TNF/NF-kappa B axis; Network pharmacology; Molecular docking ID ADHESION AB Background The Zhizi Chuanxiong herb pair (ZCHP) can delay pathological progression of atherosclerosis (AS); however, its pharmacological mechanism remains unclear because of its complex components. The purpose of current study is to systematically investigate the anti-AS mechanism of ZCHP.Methods The databases of TCMSP, STITCH, SwissTargetPrediction, BATMAN-TCM, and ETCM were searched to predict the potential targets of ZCHP components. Disease targets associated with AS was retrieved from the GEO database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analyses were executed using DAVID 6.8. Molecular docking method was employed to evaluate the core target binding to blood components, and animal experiments were performed to test action mechanism.Results A ZCHP-components-targets-AS network was constructed by using Cytoscape, included 11 main components and 52 candidate targets. Crucial genes were shown in the protein-protein interaction network, including TNF, IL-1 beta, IGF1, MMP9, COL1A1, CCR5, HMOX1, PTGS1, SELE, and SYK. KEGG enrichment illustrated that the NF-kappa B, Fc epsilon RI, and TNF signaling pathways were important for AS treatment. These results were validated by molecular docking. In ApoE(-/-) mice, ZCHP significantly reduced intima-media thickness, pulse wave velocity, plaque area, and serum lipid levels while increasing the difference between the end-diastolic and end-systolic diameters. Furthermore, ZCHP significantly decreased the mRNA and protein levels of TNF-alpha and IL-1 beta, suppressed NF-kappa B activation, and inhibited the M1 macrophage polarization marker CD86 in ApoE(-/-) mice.Conclusion This study combining network pharmacology, molecular biology, and animal experiments showed that ZCHP can alleviate AS by suppressing the TNF/NF-kappa B axis and M1 macrophage polarization. C1 [Zhang, Yan; Qi, Yifei; Li, Yiming; Wu, Liqi; Zhou, Qingbing; Xu, Fengqin] China Acad Chinese Med Sci, Xiyuan Hosp, Inst Geriatr, Beijing, Peoples R China. [Jia, Zijun] Comprehens Care China Japan Friendship Hosp, Beijing, Peoples R China. [Li, Yiming] Peking Univ, Dept Integrated Tradit & Western Med, Beijing, Peoples R China. C3 China Academy of Chinese Medical Sciences; Xiyuan Hospital, CACMS; Peking University RP Zhou, QB; Xu, FQ (corresponding author), China Acad Chinese Med Sci, Xiyuan Hosp, Inst Geriatr, Beijing, Peoples R China. EM zhouqingbing0910@163.com; Dr.xufengqin@outlook.com RI zhou, qingbing/C-7518-2012 FU National Natural Science Foundation of China FX Not applicable. 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Med. PD JAN 11 PY 2024 VL 19 IS 1 AR 8 DI 10.1186/s13020-023-00874-x PG 12 WC Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine; Pharmacology & Pharmacy GA EV8M2 UT WOS:001141798700001 PM 38212797 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhang, JL Li, N Hu, XY AF Zhang, Junli Li, Na Hu, Xiaoyu TI Metabolic Reprograming of Macrophages: A New Direction in Traditional Chinese Medicine for Treating Liver Failure SO JOURNAL OF IMMUNOLOGY RESEARCH LA English DT Review DE acute liver failure; Chinese medicine; glucose metabolism; macrophage polarization; signal transduction ID NF-KAPPA-B; ENERGY HOMEOSTASIS; GLUCOSE-METABOLISM; SIGNALING PATHWAY; PROTEIN-KINASE; ACTIVATION; AMPK; TRANSPLANTATION; INFLAMMATION; INNATE AB Acute liver failure (ALF) is a fulminant clinical syndrome that usually leads to multiple organ failure and high mortality. Macrophages play a crucial role in the initiation, development, and recovery of ALF. Targeting macrophages through immunotherapy holds significant promise as a therapeutic strategy. These cells exhibit remarkable plasticity, enabling them to differentiate into various subtypes based on changes in their surrounding microenvironment. M1-type macrophages are associated with a pro-inflammatory phenotype and primarily rely predominantly on glycolysis. In contrast, M2-type macrophages, which are characterized by anti-inflammatory phenotype, predominantly obtain their energy from oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO). Shifting macrophage metabolism from glycolysis to OXPHOS inhibits M1 macrophage activation and promotes M2 macrophage activation, thereby exerting anti-inflammatory and reparative effects. This study elucidates the relationship between macrophage activation and glucose metabolism reprograming from an immunometabolism perspective. A comprehensive literature review revealed that several signaling pathways may regulate macrophage polarization through energy metabolism, including phosphatidyl-inositol 3-kinase/protein kinase B (PI3K/AKT), mammalian target of rapamycin (mTOR)/hypoxia-inducible factor 1 alpha (HIF-1 alpha), nuclear factor-kappa B (NF-kappa B), and AMP-activated protein kinase (AMPK), which exhibit crosstalk with one another. Additionally, we systematically reviewed several traditional Chinese medicine (TCM) monomers that can modulate glucose metabolism reprograming and influence the polarization states of M1 and M2 macrophages. This review aimed to provide valuable insights that could contribute to the development of new therapies or drugs for ALF. C1 [Zhang, Junli; Li, Na; Hu, Xiaoyu] Hosp Chengdu Univ Tradit Chinese Med, Dept Infect Dis, Chengdu, Peoples R China. [Zhang, Junli; Li, Na] Chengdu Univ Tradit Chinese Med, Dept Clin Med, Chengdu, Peoples R China. C3 Chengdu University of Traditional Chinese Medicine; Chengdu University of Traditional Chinese Medicine RP Hu, XY (corresponding author), Hosp Chengdu Univ Tradit Chinese Med, Dept Infect Dis, Chengdu, Peoples R China. EM tcmxiaoyuhu@aliyun.com OI Zhang, JunLi/0000-0003-1851-4512 FU National Natural Science Foundation of China FX Thanks to Professor Xiaoyu Hu for his valuable suggestions on revising this article. 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Res. PY 2024 VL 2024 IS 1 AR 5891381 DI 10.1155/jimr/5891381 PG 15 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA R3K4E UT WOS:001390476600001 PM 39741958 OA Green Submitted, gold DA 2026-03-26 ER PT J AU He, WF Zhao, HY Xue, WQ Luo, Y Yan, MY Li, JL Qing, LJ Wu, W Jin, Z AF He, Weifeng Zhao, Huanyi Xue, Weiqi Luo, Yuan Yan, Mengyuan Li, Junlong Qing, Lijin Wu, Wei Jin, Zheng TI Qingre Huoxue Decoction Alleviates Atherosclerosis by Regulating Macrophage Polarization Through Exosomal miR-26a-5p SO DRUG DESIGN DEVELOPMENT AND THERAPY LA English DT Article DE Qingre Huoxue decoction; atherosclerosis; exosomes; miR-26a-5p; macrophage polarization ID NF-KAPPA-B; MYOCARDIAL-INFARCTION; UP-REGULATION; BAICALIN; INJURY; CYCLOOXYGENASE-2; M2; CARDIOMYOCYTES; PHARMACOLOGY; EXPRESSION AB Background: Qingre Huoxue Decoction (QRHX) is a classical Chinese herbal prescription widely used in clinical practice for the treatment of atherosclerosis (AS). Our previous study demonstrated its efficacy in stabilizing plaque and improving prognosis, as well as its ability to regulate macrophage polarization. This study aimed to further investigate the effects of QRHX on AS and explore the underlying mechanisms. Methods: ApoE-/- mice were fed a high-fat diet (HFD) for 8 weeks in order to establish an AS model. Oil Red O, H&E, Masson, and IHC staining were employed to assess lipid accumulation, plaque development, collagen loss and target of the aortas tissue. ELISA was employed to measure the levels of TNF-alpha and IL-10 in serum. Dual luciferase reporter assay was conducted to ascertain the connection between miR-26a-5p and PTGS2 in vitro. Western blot and RT-qPCR assay were conducted to assess the NF-xB signaling pathway and macrophage polarization. The effects of miR-26a-5p were tested after transfecting miR-26a-5p over-expressive lentivirus. Results: QRHX attenuated HFD-induced plaque progression and inflammation of AS model mice. BMDM-derived exosomes (BMDM-exo) increased miR-26a-5p and decreased PTGS2 expressions, inhibited the NF-xB signaling pathway and regulated macrophage polarization in vivo. These effects of BMDM-exo were further enhanced after QRHX intervention. Dual luciferase reporter assay results showed that miR-26a-5p directly binds to the 3'-UTR of PTGS2 mRNA and regulates the expression of PTGS2. The miR-26a-5p of BMDM-exo played a key role in macrophage polarization. After overexpression of miR-26a-5p, the NF-xB signaling pathway was inhibited and macrophages were converted from M1 to M2 in vitro. Conclusion: QRHX can exert anti-inflammatory and plaque-stabilizing effects through exosomal miR-26a-5p via inhibiting the PTGS2/NF-xB signaling pathway and regulating macrophage phenotype from M1 to M2 polarization in AS. C1 [He, Weifeng; Xue, Weiqi; Luo, Yuan; Yan, Mengyuan] Guangzhou Univ Chinese Med, Guangzhou 510405, Guangdong, Peoples R China. [Zhao, Huanyi; Li, Junlong; Qing, Lijin; Wu, Wei; Jin, Zheng] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangzhou 510405, Guangdong, Peoples R China. C3 Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine RP Wu, W; Jin, Z (corresponding author), Guangzhou Univ Chinese Med, Affiliated Hosp 1, Dept Cardiovasc, 16 Ji Chang Rd, Guangzhou 510405, Peoples R China. EM wwhrlz@163.com; zyjinzheng@163.com OI Xue, Weiqi/0000-0002-7579-3928; Wu, Wei/0000-0001-8911-6920 FU National Natural Science Foundation of China [82204984, 82204987]; Youth Project of Guangdong Natural Science Foundation [2021A1515110287] FX Funding This study was supported by grants from the National Natural Science Foundation of China (82204984, 82204987) and the Youth Project of Guangdong Natural Science Foundation (No. 2021A1515110287) . 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Dev. Ther. PY 2024 VL 18 BP 6389 EP 6411 DI 10.2147/DDDT.S487476 PG 23 WC Chemistry, Medicinal; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA Q5V1P UT WOS:001385343500001 PM 39749190 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhang, YQ Chen, LT Fei, YC Chen, PF Pan, L AF Zhang, Yiqiong Chen, Luting Fei, Yuchang Chen, Peifeng Pan, Lei TI Qingrexiaoji Recipe Regulates the Differentiation of M2 TAM via miR-29 in GC SO COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING LA English DT Article DE Qingrexiaoji recipe; M2; tumor-associated macrophages (TAMs); gastric cancer; HDAC4; miR-29 ID BREAST-CANCER CELLS; CONSTITUENT; APOPTOSIS; GROWTH AB Background: Gastric cancer, one of the most familiar adenocarcinomas of the gastrointestinal tract, ranks third in the world in cancer-related deaths. Traditional Chinese medicine can suppress the growth of tumors, and the underlying mechanism may be associated with the tumor microenvironment. Here, we investigated the anti-cancer effects of the Qingrexiaoji recipe on gastric cancer and the underlying molecular mechanism. Methods: An in vivo nude mouse model was established, and the expression of CD206, CD80, and M2 phenotype-related proteins (Arg-1, Fizz1) was obtained by flow cytometry and western blotting. The expressions of the M2 phenotype-related cytokines were examined by ELISA. Results: Qingrexiaoji recipe inhibited gastric tumor growth and downregulated the expression of CD206, IFN-gamma, IL-13, IL-4, and TNF-alpha in vivo. Qingrexiaoji recipe deceased M2 phenotypic polarization by upregulating microRNA (miR)-29a-3p level. Luciferase activity assays showed that HDAC4 is a potential target of miR-29a-3p. In cells co-transfected with HDAC4 siRNA and miR-29a-3p inhibitor and treated with IL-4 and Qingrexiaoji recipe, the miR-29a-3p inhibitor-induced increase of M2 phenotypic polarization was reversed. Conclusion: In summary, these results suggested that the Qingrexiaoji recipe regulated M2 macrophage polarization by regulating miR-29a-3p/HDAC4, providing a different and innovative treatment for gastric cancer. C1 [Zhang, Yiqiong] Zhejiang Chinese Med Univ, Dept Clin Med Coll 1, Hangzhou, Zhejiang, Peoples R China. [Chen, Luting] First Peoples Hosp Wenling, Dept Integrated Chinese & Western Med, Taizhou, Zhejiang, Peoples R China. [Fei, Yuchang] First Peoples Hosp Jiashan, Dept Integrated Chinese & Western Med, Jiaxing, Zhejiang, Peoples R China. [Chen, Peifeng; Pan, Lei] Zhejiang Chinese Med Univ, Affiliated Hosp 1, Dept Oncol, Hangzhou, Zhejiang, Peoples R China. C3 Zhejiang Chinese Medical University; Zhejiang Chinese Medical University RP Pan, L (corresponding author), Zhejiang Chinese Med Univ, Affiliated Hosp 1, Dept Oncol, Hangzhou, Zhejiang, Peoples R China. EM panlei21316@163.com RI Fei, Yuchang/GWR-1356-2022 FU Zhejiang Provincial Natural Science Foundation of China [LY20H270009]; School-level Young and Middle-aged Scientific Research Innovation Foundation of Zhejiang Chinese Medical University [KC201929] FX This work was supported by the Zhejiang Provincial Natural Science Foundation of China (grant no. LY20H270009) and the 2019 School-level Young and Middle-aged Scientific Research Innovation Foundation of Zhejiang Chinese Medical University (KC201929). 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High Throughput Screen PY 2024 VL 27 IS 18 BP 2764 EP 2775 DI 10.2174/0113862073263776231009115524 PG 12 WC Biochemical Research Methods; Chemistry, Applied; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA H0G8M UT WOS:001320325800001 PM 39428821 DA 2026-03-26 ER PT J AU Li, ZY Zhang, QY Gao, YH Wan, F Wang, YC Hou, B Cui, WW Wang, YA Feng, W Hou, YL AF Li, Ziyu Zhang, Qiuyan Gao, Yuhe Wan, Fang Wang, Yincang Hou, Bin Cui, Wenwen Wang, Yanan Feng, Wei Hou, Yunlong TI Luobitong Potentiates MTX's Anti-Rheumatoid Arthritis Activity via Targeting Multiple Inflammatory Pathways SO JOURNAL OF INFLAMMATION RESEARCH LA English DT Article DE rheumatoid arthritis; traditional Chinese medicine; methotrexate; network pharmacology ID THERAPEUTIC TARGET; T-CELLS; IL-17; METHOTREXATE; ANNOTATION; AUTOIMMUNE; CYTOSCAPE; NECROSIS; DATABASE AB Background: The LuoBiTong (LBT) capsule, a novel traditional Chinese medicine formulation, is currently in Phase III clinical trials. Preliminary preclinical and Phase II clinical studies suggest its efficacy and safety in treating rheumatoid arthritis (RA). However, the underlying mechanisms of its action remain to be elucidated.This research aims to explore the effects and mechanisms of LBT in conjunction with a maintenance dose of methotrexate (M-MTX) on RA. Methods: A Collagen-Induced Arthritis (CIA) mouse model was used to evaluate the anti-RA effects of LBT combined with M-MTX. Assessments included foot swelling, arthritis scoring, serum inflammatory factor analysis, and histopathological examination of the foot. These effects were compared with those of high-dose MTX (H-MTX). Network pharmacology was employed to construct a compound-target network for RA, based on drug composition, to predict its potential mechanism of action. Flow cytometry, Western Blot, and immunohistochemical analyses in animal models identified multiple inflammatory pathways targeted by LBT to augment the anti-RA effects of MTX. Results: The study revealed that LBT combined with M-MTX significantly alleviated CIA-induced arthritis without adverse effects. The combination of LBT and M-MTX showed similar or superior efficacy in regulating macrophage polarization, NF-kappa B, MAPK signaling pathways, and in the suppression of TH-17 expression in proinflammatory cells. These findings suggest that LBT may exert a multi-pathway therapeutic effect in RA treatment. The predicted pharmacological targets and mechanisms align well with this hypothesis. Conclusion: LBT, when combined with MTX, enhances the anti-RA effect by targeting multiple inflammatory pathways, demonstrating significant therapeutic potential. C1 [Li, Ziyu] Nanjing Univ Chinese Med, Suzhou TCM Hosp, Suzhou, Peoples R China. [Zhang, Qiuyan; Hou, Bin; Wang, Yanan; Feng, Wei] Shijiazhuang Yiling Pharmaceut Co Ltd, New Drug Evaluat Ctr, Shijiazhuang, Peoples R China. [Gao, Yuhe; Wan, Fang; Wang, Yincang] Heilongjiang Univ Chinese Med, Grad Sch, Harbin, Peoples R China. [Cui, Wenwen; Hou, Yunlong] Shijiazhuang Yiling Pharmaceut Co Ltd, Natl Key Lab Innovat & Transformat Luobing Theory, Shijiazhuang, Peoples R China. [Cui, Wenwen; Hou, Yunlong] Key Lab State Adm TCM Cardiocerebral VesselCollate, Shijiazhuang, Peoples R China. C3 Nanjing University of Chinese Medicine; Heilongjiang University of Chinese Medicine RP Hou, YL (corresponding author), Shijiazhuang Yiling Pharmaceut Co Ltd, Natl Key Lab Innovat & Transformat Luobing Theory, Shijiazhuang, Peoples R China.; Hou, YL (corresponding author), Key Lab State Adm TCM Cardiocerebral VesselCollate, Shijiazhuang, Peoples R China. EM houyunlonghrb@Hotmail.com RI ; Hou, Yunlong/C-4885-2014 OI 李, 子瑜/0000-0002-2385-5701; Hou, Yunlong/0000-0002-6989-8221 FU National Key Research and Development Program [2023YFC3504300]; S&T Program of Hebei [23379902L] FX Funding This work was supported by the National Key Research and Development Program "Modernization of Traditional Chinese Medicine" (No. 2023YFC3504300) , S&T Program of Hebei (No.23379902L) Support Project. 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PY 2024 VL 17 BP 4389 EP 4403 DI 10.2147/JIR.S461093 PG 15 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA XX2Z5 UT WOS:001264923400001 PM 38994468 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Liu, HQ Yan, S Yang, RM Huang, CD Guo, KY Wang, S Huang, YM Shen, DY Lin, Y Cao, ZY Zhong, HY Lin, JM Chen, XZ AF Liu, Haiqin Yan, Shuo Yang, Ruiming Huang, Caidi Guo, Kangyue Wang, Shi Huang, Yunmei Shen, Dongyi Lin, Ying Cao, Zhiyun Zhong, Hangyan Lin, Jiumao Chen, Xuzheng TI Jiedu Xiaozheng Yin Inhibits the Progression of Colitis Associated Colorectal Cancer by Stimulating Macrophage Polarization Towards an M1 Phenotype via the TLR4 Pathway SO INTEGRATIVE CANCER THERAPIES LA English DT Article DE Jiedu Xiaozheng Yin; colitis associated colon cancer; RAW264.7; macrophage polarization; TLR4 ID CHINESE HERBAL FORMULA; IN-VIVO; CELL-PROLIFERATION; TUMOR ANGIOGENESIS; CARCINOMA CELLS; MODEL; APOPTOSIS; INDUCTION AB To investigate the effect of Jiedu Xiaozheng Yin (JXY) on the polarization of macrophages in colitis-associated colon cancer (CAC). An orthotopic model of CAC was established to monitor changes in the pathological state of mice. Colon length, number of colon tumors were recorded, and indices for liver, spleen, and thymus were calculated. Hematoxylin and eosin (H&E) staining was employed to observe intestinal mucosal injury and tumor formation. Immunohistochemistry (IHC) staining was utilized to investigate the effect of JXY on M1 and M2 polarization of macrophages in the colonic mucosa of CAC mice. For in vitro experiments, RT-qPCR (Reverse Transcription-quantitative PCR) and flow cytometry were used to observe the effect of JXY on various M1-related molecules such as IL-1 beta, TNF-alpha, iNOS, CD80, CD86, and its phagocytic function as well as M2-related molecules including Arg-1, CD206, and IL-10. Subsequently, after antagonizing the TLR4 pathway with antagonists (TAK242, PDTC, KG501, SR11302, LY294002), the expression of IL-6, TNF-alpha, iNOS, and IL-1 beta mRNA were detected by RT-qPCR. In vivo experiments, the results showed that JXY improved the pathological condition of mice in general. And JXY treatment decreased the shortening of colon length and number of tumors as compared to non-treated CAC mice. Additionally, JXY treatment improved the lesions in the colonic tissue and induced a polarization of intestinal mucosal macrophages towards the M1 phenotype, while inhibiting polarization towards the M2 phenotype. In vitro experiments further confirmed that JXY treatment promoted the activation of macrophages towards the M1 phenotype, leading to increased expression of IL-1 beta, TNF-alpha, iNOS, CD80, CD86, as well as enhanced phagocytic function. JXY treatment concomitantly inhibited the expression of M2-phenotype related molecules Arginase-1 (Arg-1), CD206, and IL-10. Furthermore, JXY inhibited M1-related molecules such as IL-6, TNF-alpha, iNOS, and IL-1 beta after antagonizing the TLR4 pathway. Obviously, JXY could exhibit inhibitory effects on the development of colon tumors in mice with CAC by promoting M1 polarization through TLR4-mediated signaling and impeding M2 polarization of macrophages. C1 [Liu, Haiqin; Yan, Shuo; Yang, Ruiming; Guo, Kangyue; Wang, Shi; Huang, Yunmei; Shen, Dongyi; Cao, Zhiyun; Zhong, Hangyan; Lin, Jiumao; Chen, Xuzheng] Fujian Univ Tradit Chinese Med, Acad Integrat Med, 1 Qiuyang Rd, Fuzhou 350122, Peoples R China. [Liu, Haiqin; Yan, Shuo; Yang, Ruiming; Huang, Yunmei; Cao, Zhiyun; Lin, Jiumao; Chen, Xuzheng] Fujian Key Lab Integrat Med Geriatr, Fuzhou, Peoples R China. [Liu, Haiqin; Yan, Shuo; Yang, Ruiming; Huang, Yunmei; Cao, Zhiyun; Lin, Jiumao; Chen, Xuzheng] Fujian Prov Univ, Coll Integrat Med, Fuzhou, Peoples R China. [Huang, Caidi; Lin, Ying] Fujian Med Univ, Shengli Clin Med Coll, Fuzhou, Peoples R China. [Huang, Caidi; Lin, Ying] Fujian Prov Hosp, Dept Pathol, Fuzhou, Peoples R China. [Zhong, Hangyan] Shanghang Hosp Tradit Chinese Med, Longyan, Peoples R China. C3 Fujian University of Traditional Chinese Medicine; Fujian Medical University; Fujian Provincial Hospital RP Chen, XZ (corresponding author), Fujian Univ Tradit Chinese Med, Acad Integrat Med, 1 Qiuyang Rd, Fuzhou 350122, Peoples R China. EM 471235814@qq.com FU Natural Science Foundation of Fujian Province, China [2020J01747]; Chen Ke-Ji Integrative Medicine Development Funds [CKJ2022006]; Innovation and entrepreneurship training program for Fujian university students [S202210393028] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by the Natural Science Foundation of Fujian Province, China (2020J01747), Chen Ke-Ji Integrative Medicine Development Funds (CKJ2022006), Innovation and entrepreneurship training program for Fujian university students (NO. S202210393028). 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Recent studies have highlighted that the Grb2-associated binder 2 (Gab2) is a critical gene involved in the development of various types of tumor, including CRC. However, the precise role of Gab2 in mediating TAM polarization remains incompletely elucidated. In the present study, it was discovered that Gab2 was highly expressed within CRC tissue TAMs, and was associated with a poor prognosis of patients with CRC. Functionally, it was identified that the tumor-conditioned medium (TCM) induced Gab2 expression, facilitating the TAMs towards an M2-like phenotype polarization. Of note, the suppression of Gab2 expression using shRNA markedly inhibited the TCM-induced expression of M2-associated molecules, without affecting M1-type markers. Furthermore, the xenotransplantation model demonstrated that Gab2 deficiency in TAMs inhibited tumor growth in the mouse model of CRC. Mechanistically, Gab2 induced the M2 polarization of TAMs by regulating the AKT and ERK signaling pathways, promoting CRC growth and metastasis. In summary, the present study study elucidates that decreasing Gab2 expression hinders the transition of TAMs towards the M2 phenotype, thereby suppressing the growth of CRC. The exploration of the regulatory mechanisms of Gab2 in TAM polarization may enhance the current understanding of the core molecular pathways of CRC development and may thus provide a foundation for the development of novel immunotherapeutic strategies targeted against TAMs. C1 [Gao, Xuehan; Long, Runying; Qin, Ming; Wei, Linna; Dong, Pinzhi; Chen, Jin; Luo, Junmin] Zunyi Med Univ, Special Key Lab Gene Detect & Therapy & Base Talen, Zunyi 563000, Guizhou, Peoples R China. [Gao, Xuehan; Long, Runying; Qin, Ming; Wei, Linna; Dong, Pinzhi; Chen, Jin; Luo, Junmin] Zunyi Med Univ, Dept Immunol, 6 Xuefu West Rd, Zunyi 563000, Guizhou, Peoples R China. [Long, Runying] Univ Hong Kong, Li Ka Shing Fac Med, Sch Clin Med, Dept Obstet & Gynaecol, Hong Kong 999077, Peoples R China. [Zhu, Wenfang; Feng, Jihong] Wenzhou Med Univ, Lishui Peoples Hosp, Affiliated Hosp 6, Dept Oncol, 1188 Liyang St, Lishui 323000, Zhejiang, Peoples R China. C3 Zunyi Medical University; Zunyi Medical University; University of Hong Kong; Wenzhou Medical University RP Luo, JM (corresponding author), Zunyi Med Univ, Dept Immunol, 6 Xuefu West Rd, Zunyi 563000, Guizhou, Peoples R China.; Feng, JH (corresponding author), Wenzhou Med Univ, Lishui Peoples Hosp, Affiliated Hosp 6, Dept Oncol, 1188 Liyang St, Lishui 323000, Zhejiang, Peoples R China. EM luojm16128@163.com; jh_f@163.com RI Long, Runying/MIK-6321-2025 FU Program of the Natural Science Foundation of Zhejiang Province FX The authors would like to sincerely thank Dr Ding Chenbo for his valuable suggestions (Shanghai Jiao Tong University, Shanghai, China). 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J. Mol. Med. PD JAN PY 2024 VL 53 IS 1 AR 3 DI 10.3892/ijmm.2023.5327 PG 14 WC Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine GA OF5V7 UT WOS:001205873600001 PM 37937666 OA Green Submitted, hybrid DA 2026-03-26 ER PT J AU Huang, YH Zhao, CR Zheng, GD Yuan, YJ Gong, L Liu, R An, JA AF Huang, Yihan Zhao, Chenrui Zheng, Guodong Yuan, Yujuan Gong, Ling Liu, Rui An, Jingang TI Dictamnine Ameliorates DNFB-Induced Atopic Dermatitis Like Skin Lesions in Mice by Inhibiting M1 Macrophage Polarization and Promoting Autophagy SO BIOLOGICAL & PHARMACEUTICAL BULLETIN LA English DT Article DE dictamnine; atopic dermatitis; macrophage; autophagy; 2,4-dinitrofluorobenzene ID ALLERGIC CONTACT-DERMATITIS; INFLAMMATION; PHYTOCHEMISTRY; PHARMACOLOGY; DASYCARPUS; ACTIVATION; DIAGNOSIS; PATHWAY AB Autophagy and M1 macrophage polarization play important roles in the regulation of inflammation in atopic dermatitis (AD). Dictamnine is one of the main ingredients in Cortex Dictamni, a widely used traditional Chinese medicine for the treatment of dermatitis. In the present study, we investigated the anti-inflammatory effects of dictamnine on AD like skin lesions and M1 macrophage polarization. A 2,4-dinitrofluorobenzene (DNFB) triggered AD like skin lesions models in mice was established to identify the ameliorative effects of dictamnine on AD in vivo. In addition, an M1 macrophage polarization model was co-stimulated by lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) using phorbol myristate acetate (PMA) differentiated THP-1 cells, to investigate the effect of dictamnine on promoting autophagy and inhibiting inflammatory factor release. Dictamnine suppressed DNFB-induced skin inflammation by inhibiting M1 macrophage polarization, up-regulating the expression of microtubule-associated protein 1A/1B-light chain 3 (LC3) expression, and promoting macrophage autophagy at inflammatory sites. Dictamnine also could reduce the release of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8), and down-regulate the mRNA expression of these genes in LPS-IFN-gamma triggered M1 polarized macrophages. Dictamnine ameliorates AD like skin lesions by inhibiting M1 macrophage polarization and promoting autophagy. Hence, dictamnine is expected to be a potential therapeutic candidate for AD. C1 [Huang, Yihan; Zhao, Chenrui; Zheng, Guodong; Yuan, Yujuan; Gong, Ling; Liu, Rui] Xi An Jiao Tong Univ, Sch Pharm, Xian 710061, Peoples R China. [An, Jingang] Xi An Jiao Tong Univ, Affiliated Hosp 2, Sch Med, Dept Dermatol, Xian 710004, Peoples R China. C3 Xi'an Jiaotong University; Xi'an Jiaotong University RP Liu, R (corresponding author), Xi An Jiao Tong Univ, Sch Pharm, Xian 710061, Peoples R China.; An, JA (corresponding author), Xi An Jiao Tong Univ, Affiliated Hosp 2, Sch Med, Dept Dermatol, Xian 710004, Peoples R China. EM rliu2018@xjtu.edu.cn; anjg2008@126.com RI Huang, Yihan/KGL-9913-2024; Liu, Rui/HTM-5674-2023 FU National Natural Science Foundation of China [81872837]; Natural Science Basic Research Program of Shaanxi Province [2019JQ-979, 2023-JC-YB-737]; Xi'an Science and Technology Planning Project [J201901005] FX This work was supported by the National Natural Science Foundation of China (Grant Number: 81872837) , Natural Science Basic Research Program of Shaanxi Province (Grant Number: 2023-JC-YB-737) , Natural Science Basic Research Program of Shaanxi Province (Grant Number: 2019JQ-979) , and Xi'an Science and Technology Planning Project (J201901005) . 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Pharm. Bull. PD JAN PY 2024 VL 47 IS 1 BP 175 EP 186 PG 12 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA FS9Q8 UT WOS:001147966600002 PM 38092386 DA 2026-03-26 ER PT J AU Wang, HB Chu, ZW Ni, TY Chen, DW Dai, XJ Jiang, W Sunagawa, M Liu, YQ AF Wang, Haibo Chu, Zewen Ni, Tengyang Chen, Dawei Dai, Xiaojun Jiang, Wei Sunagawa, Masataka Liu, Yanqing TI Effect and mechanism of aqueous extract of Chinese herbal prescription (TFK) in treating gout arthritis SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Aqueous extract of TFK; Gouty arthritis; Hyperuricemia; Immunoinflammatory factor; Arthritis ID ALTERS MACROPHAGE POLARIZATION; RISK-FACTORS; MOUSE MODEL; TNF-ALPHA; HYPERURICEMIA; INFLAMMATION; PANICULATUM; EXPRESSION AB Ethnopharmacological relevance: With the rapid development of China's economic level, great changes have taken place in people's diet structure, gout has become a common disease that puzzles people's health, seriously affects the realization of China's "Healthy China" strategic goal. Gouty arthritis (GA) is a common joint disease caused by chronic purine metabolism disorder. Currently, drugs used to treat GA are allopurinol and colchicine. However, these drugs can only temporarily relieve the clinical symptoms of GA with significant side effects. More and more basic and clinical studies have confirmed that Traditional Chinese medicine has definite curative effect on GA.Aim of the study: To elucidate the potential molecular mechanism of Tongfengkang (TFK) in the treatment of GA, and to provide experimental basis for the search and development of efficient and low-toxicity Chinese medicine for GA treatment.Materials and methods: Aqueous extract of TFK (AETFK) were determined by liquid phase high resolution mass spectrometry and the possible effective constituents were screened out. Acute GA model rats were established to detect the anti-inflammatory and detumification effects of AETFK on GA and explore the potential mechanism. The effect of AETFK on serum uric acid and urinary uric acid levels in acute GA rats was determined by automatic biochemical analyzer, and the effect of AETFK on the expression of acute GA-related immunoinflammatory factors were determined by protein thermal fluorescence chip. The effect of AETFK on the concentration of neutrophils in the joint fluid of acute GA rats were determined by Reichs-Giemsa staining. The effect of AETFK on macrophage activation was detected by ELISA. In order to further investigate the mechanism of AETFK in the treatment of GA, a rat model of hyperuricemia was established to detect the effect of AETFK on the level of uric acid in hyperuricemia model rats. Biochemical indexes of liver and kidney and hematoxylin-eosin staining (HE) were used to evaluate the effects of AETFK on the organs, and to preliminatively evaluate the safety of ventilation confufang.Results: Compared with the model group, the joint swelling degree of GA rats in AETFK treatment group were significantly reduced, and the levels of blood uric acid and urine uric acid were also significantly decreased. Protein thermal fluorescence microarray results showed that the levels of gout -related inflammatory factors in GA rats in AETFK treatment group were significantly lower than those in control group. Reichsen-giemsa staining and ELISA showed that AETFK could reduce the activation of macrophages and the accumulation of neutrophils in the joint fluid. The results of liver and kidney biochemical indexes and HE staining showed that no obvious tissue damage was observed in the organs of rats treated with AETFK.Conclusions: AETFK not only has significant anti-inflammatory effects on GA, but also can significantly reduce the level of blood uric acid in GA rats, without obvious toxic and side effects. These effects may be related to AETFK's inhibition of neutrophil enrichment and macrophage activation during early inflammation. C1 [Wang, Haibo; Chu, Zewen; Ni, Tengyang; Dai, Xiaojun; Liu, Yanqing] Yangzhou Univ, Inst Translat Med, Med Coll, Yangzhou 225001, Peoples R China. [Wang, Haibo; Chu, Zewen; Ni, Tengyang; Liu, Yanqing] Yangzhou Univ, State Adm Tradit Chinese Med, Key Lab Syndrome Differentiat & Treatment Gastr Ca, Yangzhou 225001, Peoples R China. [Chen, Dawei] Chinese Acad Med Sci 2019RU014, China Natl Ctr Food Safety Risk Assessment CFSA, Res Unit Food Safety, NHC Key Lab Food Safety Risk Assessment, Beijing 100022, Peoples R China. [Jiang, Wei] Yangzhou Univ, Coll Environm Sci & Engn, Yangzhou 225127, Jiangsu, Peoples R China. [Sunagawa, Masataka] Showa Univ, Sch Med, Dept Physiol, Tokyo 142, Japan. [Wang, Haibo; Liu, Yanqing] Yangzhou Univ, Med Coll, 3rd Floor,Bldg 41,North Campus,Jiangyang Rd, Yangzhou, Peoples R China. C3 Yangzhou University; Yangzhou University; Yangzhou University; Showa Medical University; Yangzhou University RP Wang, HB; Liu, YQ (corresponding author), Yangzhou Univ, Med Coll, 3rd Floor,Bldg 41,North Campus,Jiangyang Rd, Yangzhou, Peoples R China. EM whbosy@163.com; 17521176065@163.com; yzunitengyang@sina.com; chendw@cfsa.net.cn; dxj2319@sina.com; Weijiang@yzu.edu.cn; suna@med.showa-u.ac.jp; yzumpi@163.com RI ; Sunagawa, Masataka/ABE-4996-2021 OI Wang, Haibo/0000-0002-7549-5613; FU National Natural Science Foundation of China [82104946, 82274603]; Natural Science Foundation of Jiangsu Province [BK20210817]; Traditional Chinese Medicine Science and Technology Development Project of Jiangsu Province [QN202008] FX National Natural Science Foundation of China (Project code: 82104946, 82274603) ; Natural Science Foundation of Jiangsu Province (BK20210817) ; The Traditional Chinese Medicine Science and Technology Development Project of Jiangsu Province (Project code: QN202008) . 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Ethnopharmacol. PD MAR 1 PY 2024 VL 321 AR 117527 DI 10.1016/j.jep.2023.117527 EA DEC 2023 PG 13 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA DW2H7 UT WOS:001135048300001 PM 38056535 DA 2026-03-26 ER PT J AU Wang, W Xu, XW Xu, Y Zhan, YP Wu, CY Xiao, X Cheng, C Gao, CF AF Wang, Wei Xu, Xuewen Xu, Yang Zhan, Yueping Wu, Chuanyong Xiao, Xiao Cheng, Cheng Gao, Chunfang TI Quercetin, a key active ingredient of Jianpi Zishen Xiehuo Formula, suppresses M1 macrophage polarization and platelet phagocytosis by inhibiting STAT3 activation based on network pharmacology SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE Primary immune thrombocytopenia; Quercetin; Macrophage; Jianpi Zishen Xiehuo Formula; Network pharmacology ID ARTHRITIS; CELLS AB Primary immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease, and abnormal M1 macrophage polarization participates in the pathogenesis of ITP. Jianpi Zishen Xiehuo (JZX) Formula has a good therapeutic effect on ITP. However, its key active ingredients and molecular mechanisms remain unclear. In this study, we explored the key active ingredients and potential targets of JZX in treating ITP using network pharmacology combined with in vitro experimental verification. A total of 157 active ingredients of JZX were identified from public databases, and quercetin was the most important one. One hundred sixty-five intersection targets of active ingredients in JZX, ITP, and macrophage polarization were obtained by Venn diagram. The top three potential targets were signal transducer and activator of transcription 3 (STAT3), protein kinase B (PKB/AKT) 1, and c-JUN through protein-protein interaction analysis. Molecular docking showed that quercetin had strong binding affinities with them all. In vitro experiment, CD16+ monocytes increased in ITP patients compared with healthy controls, which indicated a M1/M2 polarization imbalance in ITP. The expression levels of M1 polarization markers, CD86, CD80, and inducible nitric oxide synthase (iNOS), M1 polarization-associated cytokines, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6), and antibody-opsonized platelet phagocytosis significantly increased in THP-1 macrophages stimulated with lipopolysaccharide (LPS). Quercetin markedly inhibited the expressions of M1 markers, decreased the levels of TNF-alpha and IL-6, and down-regulated the phosphorylated STAT3 (p-STAT3) protein, which confirmed the prediction by network pharmacology and molecular docking. Importantly, quercetin significantly reduced the phagocytosis of antibody opsonised platelet. In conclusion, quercetin suppressed platelet phagocytosis in M1 macrophages via its anti-inflammatory effects and may serve as a potential drug for the treatment of ITP. Quercetin could be a key ingredient for JZX against ITP. C1 [Wang, Wei; Xu, Xuewen; Xu, Yang; Zhan, Yueping; Wu, Chuanyong; Xiao, Xiao; Cheng, Cheng; Gao, Chunfang] Shanghai Univ Tradit Chinese Med, Yueyang Hosp Integrated Tradit Chinese & Western M, Clin Lab Med Ctr, 110 Gan He Rd, Shanghai 200437, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine RP Gao, CF (corresponding author), Shanghai Univ Tradit Chinese Med, Yueyang Hosp Integrated Tradit Chinese & Western M, Clin Lab Med Ctr, 110 Gan He Rd, Shanghai 200437, Peoples R China. EM gaocf1115@163.com FU Innovation Group Project of Shanghai Municipal Health Commission [2019CXJQ03] FX This study was supported by the Innovation Group Project of Shanghai Municipal Health Commission [2019CXJQ03]. 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Pharmacol. PD JUN PY 2024 VL 397 IS 6 BP 4219 EP 4233 DI 10.1007/s00210-023-02870-2 EA DEC 2023 PG 15 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA RS4A9 UT WOS:001115161000001 PM 38055068 DA 2026-03-26 ER PT J AU Qu, PD Wang, HY Wang, W Hu, Q Du, SY Peng, ZR Tang, XH AF Qu, Pengda Wang, Haiyang Wang, Wei Hu, Qian Du, Shiyu Peng, Zhaorong Tang, Xiaohu TI Clinical efficacy evaluation and potential mechanism prediction on Guizhi-Shaoyao-Zhimu decoction in the treatment of gouty arthritis based on meta-analysis, network pharmacology analysis, and molecular docking SO MEDICINE LA English DT Review DE gouty arthritis; Guizhi-Shaoyao-Zhimu decoction; meta-analysis; molecular docking; network pharmacology; traditional Chinese medicine ID URIC-ACID LEVELS; BETA-SITOSTEROL; TNF-ALPHA; MACROPHAGE POLARIZATION; RHEUMATOID-ARTHRITIS; AMERICAN-COLLEGE; GLOBAL BURDEN; INFLAMMATION; LUTEOLIN; DISEASE AB Background:Guizhi-Shaoyao-Zhimu decoction (GSZD) is a Chinese herb formula. Previous studies have reported that the clinical symptoms and laboratory indicators of gouty arthritis patients could be improved by GSZD. However, no previous study has evaluated and analyzed its efficacy, safety, underlying mechanisms, and the relationship between related ingredients of herbs and targets of gouty arthritis.Methods:Randomized controlled trials of GSZD for gouty arthritis were retrieved from various databases. Meta-analysis was performed by Stata 17 software. Galbraith plot was used to find studies with possible heterogeneity. Publication bias was assessed by Egger test and funnel plot. The related ingredients of herbs and the targets of herbs and gouty arthritis were obtained from several databases, such as TCMSP, HERB, and DrugBank. The protein-protein interaction network was conducted by the STRING platform. DAVID database was used to perform GO and KEGG analysis. Molecular docking and visualization of docking results were carried out by AutoDock and PyMOL software.Results:Twenty studies with 1633 patients were included. Meta-analysis indicated that GSZD could better improve the clinical efficiency and visual analogue scale score, and reduce the level of blood uric acid and inflammatory biomarkers (including C-reactive protein, erythrocyte sedimentation rate, interleukin 6, interleukin 8, and tumor necrosis factor-alpha) than conventional treatment. In addition, we retrieved 157 active compounds, 517 herb target genes, 3082 disease targets, and 295 intersection targets of herb and disease. The results of network pharmacology analysis showed that the core related ingredients included quercetin, kaempferol, sitosterol, luteolin, catechin, etc. The core intersection targets contained AKT1, TNF-alpha, TP53, IL6, etc. And the critical signaling pathways included IL-17, HIF-1, TNF, PI3K-Akt, etc. Among the 56 molecular docking results, only 8 results had binding energy values greater than -5.0 kcal/mol.Conclusion:GSZD could be a satisfactory complementary and alternative therapy for treating gouty arthritis. However, it should be verified by further studies. Future research on gouty arthritis could be conducted from the active components including beta-sitosterol and sitosterol, the targets including TNF-1, IL1B, and ESR1, and the signaling pathways including IL-17 and HIF-1. C1 [Qu, Pengda; Wang, Haiyang; Du, Shiyu; Peng, Zhaorong; Tang, Xiaohu] Yunnan Univ Chinese Med, Clin Med Coll 1, Kunming, Peoples R China. [Wang, Wei; Hu, Qian] Yunnan Univ Chinese Med, Sch Basic Med Sci, Kunming, Peoples R China. [Tang, Xiaohu] Yunnan Prov Hosp Tradit Chinese Med, Dept Rheumatol, Kunming, Peoples R China. [Tang, Xiaohu] Yunnan Prov Hosp Tradit Chinese Med, 1 Huachen Rd, Kunming, Yunnan, Peoples R China. C3 Yunnan University of Chinese Medicine; Yunnan University of Chinese Medicine; Yunnan University of Chinese Medicine; Yunnan University of Chinese Medicine RP Tang, XH (corresponding author), Yunnan Prov Hosp Tradit Chinese Med, 1 Huachen Rd, Kunming, Yunnan, Peoples R China. EM qupengda06@outlook.com; 1004519168@qq.com; 1004519168@qq.com; 15559877315@163.com; 1534098586@qq.com; 809512052@qq.com; h.tang0718@163.com RI Tang, Xiaohu/AAX-4577-2021 FU Famous Doctor Special Project for Ten Thousand Talent Plans of Yunnan Province [2022YB02]; Yunnan Provincial Department of Education Science Research Fund Project [1]; Project of first-class discipline construction in Yunnan Province [2022Y362] FX This study was supported by the Famous Doctor Special Project for Ten Thousand Talent Plans of Yunnan Province (Yun Wei Ren Fa [2019] No. 1), the Yunnan Provincial Department of Education Science Research Fund Project (No. 2022Y362), and the Project of first-class discipline construction in Yunnan Province (No. 2022YB02). 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In recent years, LHQW exerts significant therapeutic effects in treating influenza and Coronavirus Disease 2019 (COVID-19). However, the potential mechanisms are not yet understood and need further study.Aim of study: This study aims to look into the influence of LHQW on lung inflammation and macrophage phenotype, and to clarify the connection between macrophage plasticity and LHQW. Methods: The cell viability, marker expression, response to LPS stimulation, and phagocytosis of Raw264.7 were detected after LHQW treatment. In an LPS-induced acute lung injury (ALI) mouse model, the alleviating effect of LHQW on lung injury was investigated. The total macrophages and M2 macrophages in mice lungs and the peripheral blood monocytes after LHQW treatment were detected. The cell viability and polarization of peripheral blood macrophages treated with LHQW were detected.Results: Here, we demonstrate that LHQW protects LPS-induced ALI by promoting M2 macrophage infiltration. LHQW treatment inhibited the inflammatory response and pro-inflammatory phenotype of Raw264.7 macro-phages. High concentrations of LHQW promoted the phagocytic capacity of Raw264.7 macrophages. In an ALI mouse model, LHQW alleviated lung injury and no significant hepatotoxicity was observed. By Immunohisto-chemistry (IHC) analysis, LHQW increased the infiltration of macrophages, mainly M2 macrophages. Consistent with Raw264.7, LHQW also decreased the expression of M1 markers in peripheral blood macrophages. In addition, LHQW blood plasma promoted the M2-type polarization of peripheral blood macrophages. Conclusions: Taken together, our data demonstrate that LHQW reduces the inflammatory response and amelio-rates acute lung injury by promoting anti-inflammatory polarization of macrophages. C1 [Li, Shanshan; Wang, Wanqiao; Li, Yanxin] Shanghai Jiao Tong Univ, Shanghai Childrens Med Ctr, Key Lab Pediatr Hematol & Oncol, Sch Med,Pediat Translat Med Inst,Dept Hematol & On, Shanghai 200127, Peoples R China. [Feng, Tianyue] Gezhi Sr High Sch Shanghai China, Shanghai 200001, Peoples R China. [Zhang, Yingwen; Shi, Qiqi] Shanghai Jiao Tong Univ, Ren Ji Hosp, Renji Med Clin Stem Cell Res Ctr 10, Shanghai Canc Inst,Sch Med,State Key Lab Syst Med, Shanghai 200127, Peoples R China. [Ren, Jingyu; Shen, Gangyi] Minzu Univ China, Sch Pharm, Minist Educ, Key Lab Ethn Med, Beijing 100081, Peoples R China. [Gu, Haihui] Naval Med Univ, Affiliated Hosp 1, Dept Transfus Med, Shanghai 200433, Peoples R China. [Luo, Chengjuan] Fujian Med Univ, Fujian Childrens Hosp, Coll Clin Med Obstet & Gynecol & Pediat, Fujian Branch,Shanghai Childrens Med Ctr, Fuzhou, Peoples R China. C3 Shanghai Jiao Tong University; Shanghai Jiao Tong University; Naval Medical University; Fujian Medical University RP Li, YX (corresponding author), Shanghai Jiao Tong Univ, Shanghai Childrens Med Ctr, Key Lab Pediatr Hematol & Oncol, Sch Med,Pediat Translat Med Inst,Dept Hematol & On, Shanghai 200127, Peoples R China.; Shen, GY (corresponding author), Minzu Univ China, Sch Pharm, Minist Educ, Key Lab Ethn Med, Beijing 100081, Peoples R China.; Gu, HH (corresponding author), Naval Med Univ, Affiliated Hosp 1, Dept Transfus Med, Shanghai 200433, Peoples R China.; Luo, CJ (corresponding author), Fujian Med Univ, Fujian Childrens Hosp, Coll Clin Med Obstet & Gynecol & Pediat, Fujian Branch,Shanghai Childrens Med Ctr, Fuzhou, Peoples R China. EM shengy@muc.edu.cn; haihuigu@126.com; luochengjuan@scmc.com.cn; liyanxin@scmc.com.cn RI Li, Yanxin/OXB-0109-2025; li, shsh/GPS-9260-2022 FU National Natural Science Foundation of China [81972341, 32271007, 81970165, 81400152]; Shanghai Natural Science Foundation [23ZR1441000]; Natural Science Foundation of Fujian Province [2022J011069]; Shanghai Municipal Science and Technology Commission [201409002700]; Local High-Level University Construction Project of Shanghai Jiao Tong University School of Medicine; Foundation of Key Laboratory of Ethnomedicine (Minzu University of China) , Ministry of Education [KLEM-ZZ202302] FX This work was supported in part by the National Natural Science Foundation of China (81972341, 32271007 to Y. Li, No.81970165 and No. 81400152 to H. Gu) , Shanghai Natural Science Foundation (23ZR1441000) to Y. Li. Natural Science Foundation of Fujian Province (2022J011069) to C. Luo. Shanghai Municipal Science and Technology Commission (201409002700) , and Local High-Level University Construction Project of Shanghai Jiao Tong University School of Medicine to Y. Li; the foundation of Key Laboratory of Ethnomedicine (Minzu Uni-versity of China) , Ministry of Education (No. KLEM-ZZ202302) to G. Shen. 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Ethnopharmacol. PD FEB 10 PY 2024 VL 320 AR 117467 DI 10.1016/j.jep.2023.117467 EA NOV 2023 PG 9 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA CM3B6 UT WOS:001125617700001 PM 37981112 DA 2026-03-26 ER PT J AU Huang, MY Chen, YC Lyu, WY He, XY Ye, ZH Huang, CY He, XL Chen, XP Chen, XB Zhang, BX Kai, GY Zhang, XL Li, T Huang, MQ Lu, JJ AF Huang, Mu-Yang Chen, Yu-Chi Lyu, Wen-Yu He, Xin-Yu Ye, Zi-Han Huang, Can-Yu He, Xin-Ling Chen, Xiuping Chen, Xiaobing Zhang, Baoxian Kai, Guoyin Zhang, Xiaolei Li, Ting Huang, Mingqing Lu, Jin-Jian TI Ginsenoside Rh2 augmented anti-PD-L1 immunotherapy by reinvigorating CD8+T cells via increasing intratumoral CXCL10 SO PHARMACOLOGICAL RESEARCH LA English DT Article DE PD-1/PD-L1; Ginsenoside Rh2; T cells; Tumor microenvironment; Combination treatment ID COMBINATION; STATES; PHASE; PD-1; RG3 AB Profiting from the sustained clinical improvement and prolonged patient survival, immune checkpoint blockade of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis has emerged as a revolutionary cancer therapy approach. However, the anti-PD-1/PD-L1 antibodies only achieve a clinical response rate of approximately 20%. Herein, we identified a novel combination strategy that Chinese medicine ginsengderived ginsenoside Rh2 (Rh2) markedly improved the anti-cancer efficacy of anti-PD-L1 antibody in mice bearing MC38 tumor. Rh2 combined with anti-PD-L1 antibody (combo treatment) further triggered the infiltration, proliferation and activation of CD8+ T cells in the tumor microenvironment (TME). Depletion of CD8+ T cells by mouse CD8 blocking antibody abolished the anti-cancer effect of combo treatment totally. Mechanistically, combo treatment further increased the expression of CXCL10 through activating TBK1-IRF3 signaling pathway, explaining the increased infiltration of T cells. Employing anti- CXC chemokine receptor 3 (CXCR3) blocking antibody prevented the T cells infiltration and abolished the anti-cancer effect of combo treatment. Meanwhile, combo treatment increased the percentage of M1-like macrophages and raised the ratio of M1/M2 macrophages in TME. By comparing the anti-cancer effect of combo treatment among MC38, CT26 and 4T1 tumors, resident T cells were considered as a prerequisite for the effectiveness of combo treatment. These findings demonstrated that Rh2 potentiated the anti-cancer effect of PD-L1 blockade via promoting the T cells infiltration and activation, which shed a new light on the combination strategy to enhance anti-PD-L1 immunotherapy by using natural product Rh2. C1 [Huang, Mu-Yang; Chen, Yu-Chi; Lyu, Wen-Yu; He, Xin-Yu; Ye, Zi-Han; Huang, Can-Yu; He, Xin-Ling; Chen, Xiuping; Li, Ting; Lu, Jin-Jian] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China. [Chen, Xiuping; Lu, Jin-Jian] Univ Macau, Fac Hlth Sci, Dept Pharmaceut Sci, Macau, Peoples R China. [Chen, Xiaobing; Zhang, Baoxian] Increasepharm Hengqin Innovat Med Inst Ltd, Zhuhai, Peoples R China. [Kai, Guoyin] Zhejiang Chinese Med Univ, Affiliated Hosp 3, Sch Pharmaceut Sci, Zhejiang Prov Int S&T Cooperat Base Act Ingredient, Hangzhou, Peoples R China. [Zhang, Xiaolei] Sun Yat Sen Univ, Sch Pharmaceut Sci, Natl Local Joint Engn Lab Druggabil & New Drug Eva, Guangdong Key Lab Chiral Mol & Drug Discovery, Guangzhou, Peoples R China. [Huang, Mingqing] Fujian Univ Tradit Chinese Med, Coll Pharm, Fuzhou, Peoples R China. [Lu, Jin-Jian] Univ Macau, MoE Frontiers Sci Ctr Precis Oncol, Macau, Peoples R China. [Lu, Jin-Jian] Univ Macau, Guangdong Hong Kong Macau Joint Lab Chinese Med &, Macau, Peoples R China. C3 University of Macau; University of Macau; Zhejiang Chinese Medical University; Sun Yat Sen University; Fujian University of Traditional Chinese Medicine; University of Macau; University of Macau RP Li, T; Lu, JJ (corresponding author), Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China.; Huang, MQ (corresponding author), Fujian Univ Tradit Chinese Med, Coll Pharm, Fuzhou, Peoples R China. EM tingli@um.edu.mo; hmq1115@126.com; jinjianlu@um.edu.mo RI ; Lu, Jinjian/X-2083-2019; He, Xinyu/HLG-7831-2023; Chen, Xiuping/O-8927-2017; Kai, Guoyin/GWC-5827-2022; Mingqing, Huang/AFQ-7104-2022 OI Li, Ting/0000-0001-8733-4625; Chen, Yu-Chi/0000-0003-0010-9308; FU Science and Technology Development Fund, Macau SAR [0053-2021-AGJ, 0015-2022-A1]; Joint Foundation of Guangdong and Macau for Science and Technology Innovation [2022A0505020024]; National Natural Science Foundation of China [81973516]; The 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund [2020B1212030006]; Internal Research Grant of the State Key Laboratory of Quality Research in Chinese Medicine, University of Macau [SKL-QRCM- IRG2023-011] FX We sincerely appreciate Prof. Jun Chen (Sun Yat-sen University, China) for providing MC38 cell line, and Prof. Yonghua Zhao (University of Macau, China) for providing HT29 cell line. In addition, we thank the members of the SPF animal facility of Faculty of Health Sciences at the University of Macau for experimental and technical supports. This study was supported by the Science and Technology Development Fund, Macau SAR (File No. 0053-2021-AGJ and 0015-2022-A1) , the Joint Foundation of Guangdong and Macau for Science and Technology Innovation (2022A0505020024) , the National Natural Science Foundation of China (File No. 81973516) , the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund (Guangdong-Hong Kong-Macau Joint Lab, File No. 2020B1212030006) , as well as the Internal Research Grant of the State Key Laboratory of Quality Research in Chinese Medicine, University of Macau (File No. SKL-QRCM- IRG2023-011). 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Res. PD DEC PY 2023 VL 198 AR 106988 DI 10.1016/j.phrs.2023.106988 EA NOV 2023 PG 13 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA FP4K3 UT WOS:001147034000001 PM 37984507 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Lu, CY Cheng, RJ Zhang, QP Hu, YD Pu, YY Wen, J Zhong, YT Tang, ZG Wu, L Wei, SX Tsou, PS Fox, DA Li, SS Luo, YB Liu, Y AF Lu, Chenyang Cheng, Rui-Juan Zhang, Qiuping Hu, Yidan Pu, Yaoyu Wen, Ji Zhong, Yutong Tang, Zhigang Wu, Liang Wei, Shixiong Tsou, Pei-Suen Fox, David A. Li, Shasha Luo, Yubin Liu, Yi TI Herbal compound cepharanthine attenuates inflammatory arthritis by blocking macrophage M1 polarization SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Cepharanthine; Rheumatoid arthritis; Monocyte; Macrophage polarization; Glycolytic metabolism ID IRAK4 KINASE-ACTIVITY; SYNOVIAL TISSUE; DENDRITIC CELL; IRF5; GLYCOLYSIS; ACTIVATION AB Objective: Cepharanthine (CEP) is a drug candidate for tumor, viral infection, and some inflammatory diseases, but its effect on rheumatoid arthritis (RA) and the underlying mechanism are incompletely understood. Methods: CEP was administered intraperitoneally to a collagen-induced arthritis (CIA) model. Joints went radiological and histological examination and serum cytokines were examined with cytometry-based analysis. M1 macrophages were induced from THP-1 cells or mouse bone marrow-derived macrophages with LPS and IFN-gamma. Bulk RNA-seq was performed on macrophage undergoing M1-polarizatioin. Western blotting was applied to determine pathways involved in monocyte chemotaxis and polarization. Glycolysis metabolites were measured by chemiluminescence while glycolytic enzymes were examined by quantitative PCR. Results: We found CEP significantly ameliorated synovial inflammation and joint destruction of CIA mice. It downregulated TNF-alpha levels in serum and in joints. The number of M1 macrophages were reduced in CEP-treated mice. In vitro, CEP inhibited monocyte chemotaxis to MCP-1 by downregulating CCR2 and reducing ERK1/2 signaling. Additionally, CEP suppressed M1 polarization of macrophages induced by LPS and IFN-gamma. Genes involved in IFN-gamma signaling, IL-6-JAK/STAT3 signaling, glycolysis, and oxidative phosphorylation process were downregulated by CEP. Several enzymes critically involved in glycolytic metabolism were suppressed by CEP, which resulted in reduced citrate in M1-polarizing macrophages. The inhibitory effect of CEP on macrophage polarization might be attributed to the blockage of TLRs-MyD88/IRAK4-IRF5 signaling pathway together with suppression of overactivated glycolytic metabolism in M1-polarizing macrophages. Conclusion: CEP attenuated joint inflammation by suppressing monocyte chemotaxis and proinflammatory differentiation. It has the potential to be developed into a complementary or alternative therapy for RA. C1 [Cheng, Rui-Juan; Zhang, Qiuping; Hu, Yidan; Pu, Yaoyu; Wen, Ji; Zhong, Yutong; Tang, Zhigang; Wu, Liang; Luo, Yubin; Liu, Yi] Sichuan Univ, West China Hosp, Dept Rheumatol & Immunol, Chengdu 610041, Peoples R China. [Lu, Chenyang] Sun Yat Sen Univ, Affiliated Hosp 3, Dept Internal Med, Div Rheumatol, Guangzhou 510630, Peoples R China. [Wei, Shixiong] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Rheumatol & Clin Immunol, 1 Shuai Fu Yuan,Wang Fu Jing St, Beijing 100730, Peoples R China. [Li, Shasha] Sun Yat Sen Univ, Affiliated Hosp 3, Guangdong Prov Key Lab Diabetol, Med Ctr Comprehens Weight Control, Guangzhou 510630, Peoples R China. [Li, Shasha] Sun Yat Sen Univ, Affiliated Hosp 3, Med Ctr Comprehens Weight Control, Guangzhou Municipal Key Lab Mechanist & Translat O, Guangzhou 510630, Peoples R China. [Tsou, Pei-Suen; Fox, David A.] Univ Michigan, Dept Internal Med, Div Rheumatol, Ann Arbor, MI USA. [Tsou, Pei-Suen; Fox, David A.] Univ Michigan, Clin Autoimmun Ctr Excellence, Ann Arbor, MI USA. [Liu, Yi] 37 Guoxue Alley, Chengdu 610047, Peoples R China. [Luo, Yubin] 88 Keyuan South Rd, Chengdu, Peoples R China. [Li, Shasha] 600 Tianhe Rd, Guangzhou 510630, Peoples R China. C3 Sichuan University; Sun Yat Sen University; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Peking Union Medical College Hospital; Sun Yat Sen University; Sun Yat Sen University; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan RP Liu, Y (corresponding author), 37 Guoxue Alley, Chengdu 610047, Peoples R China.; Luo, YB (corresponding author), 88 Keyuan South Rd, Chengdu, Peoples R China.; Li, SS (corresponding author), 600 Tianhe Rd, Guangzhou 510630, Peoples R China. EM lishsh85@mail.sysu.edu.cn; luoyubin2016@163.com; yiliu8999@wchscu.cn RI ; Wei, Shixiong/AAS-7009-2020; 程, 瑞娟/KFQ-2834-2024; Wen, Jirui/GRX-8236-2022 OI Tsou, Pei-Suen/0000-0002-7149-9115; FU National Natural Science Foundation of China [82104484]; Post-Doctor Research Project, West China Hospital, Sichuan University [2021HXBH014]; Natural Science Foundation of Sichuan Province [2022NSFSC1542] FX This study was supported by the National Natural Science Foundation of China (No. 82104484) , the Post-Doctor Research Project, West China Hospital, Sichuan University (2021HXBH014) , and the Natural Science Foundation of Sichuan Province (2022NSFSC1542) . 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Immunopharmacol. PD DEC PY 2023 VL 125 AR 111175 DI 10.1016/j.intimp.2023.111175 EA NOV 2023 PN B PG 12 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA Z9AL2 UT WOS:001114926400001 PM 37976601 DA 2026-03-26 ER PT J AU Zhao, MR Qiao, C Cui, ZL Zhang, W Yang, SY Zhu, CM Du, F Ning, TT Xie, S Liu, S Li, P Xu, JX Zhu, ST AF Zhao, Mengran Qiao, Chen Cui, Zilu Zhang, Wen Yang, Shuyue Zhu, Congmin Du, Feng Ning, Tingting Xie, Sian Liu, Si Li, Peng Xu, Junxuan Zhu, Shengtao TI Moluodan promotes DSS-induced intestinal inflammation involving the reprogram of macrophage function and polarization SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Moluodan; Gastrointestinal inflammation; Macrophage polarization; AKT/NF-kappa B ID SIGNALING PATHWAY; GASTRITIS AB Ethnopharmacological relevance: Moluodan (MLD) is a traditional Chinese medicine that is composed of 18 herbal medicines based on traditional Chinese medicine theory and practice. It has long been used in treating chronic gastritis and its components were traditionally used in dealing with intestinal inflammation. However, its specific pharmacological mechanism is still unclear. Aim of the study: The upper and lower digestive tract diseases are correlated. In clinical practice, some chronic gastritis patients are also accompanied by intestinal inflammation. Due to the unclear pharmacological mech-anism of MLD and its effect on intestinal inflammation, there is doubt whether MLD is still suitable for this type of patient. Therefore, this study aims to elucidate the pharmacological mechanism of MLD and identify its effect in the mouse model of intestinal inflammation. Materials and methods: Mice intestinal inflammation model was induced by 2.5% dextran sulfate sodium (DSS). The mice were given different concentrations of MLD via oral gavage (0.25, 0.5 g/kg b.w.). Pharmacodynamic indicators were assessed including body weight, colon length, disease activity index (DAI), bloody stool score, inflammatory factors, histological change, etc. RAW264.7 macrophage cells were used for in vitro experiments that illuminated the role of MLD in reprogramming macrophage function and polarization. RT-qPCR and western blots were performed to measure the mRNA and protein levels of macrophage polarization marker and effector molecules. The functions of polarized macrophages were tested using ROS detection probes, Edu assay and wound healing assay. Results: The administration of MLD exhibited obvious hemostatic effects, while unexpectedly accentuating various aspects of the DSS-induced intestinal inflammation in mice, including increased body weight loss and colon shortening, elevated disease activity index, and intensified colonic tissue damage. Additionally, MLD treatment induced more severe inflammatory cell infiltration and higher proinflammatory cytokines expression in colon tissue. Further results showed that MLD promoted M1 macrophage polarization and stimulated its proinflammatory cytokines expression, while only slightly affecting the function of M2 macrophage. Western blot analysis revealed that MLD induced the phosphorylation of AKT and NF-kappa B. The polarization of M1 mac-rophages induced by MLD was inhibited by either an Akt inhibitor or a NF-kappa B inhibitor. Conclusions: Although MLD has an obvious hemostatic effect, it generally promoted the severity of DSS-induced colitis in mice by facilitating macrophage polarization toward the M1 phenotype through the AKT/NF-kappa B pathway. Our study suggested that MLD may not be suitable for colitis, especially during the acute inflammation stage. C1 [Zhao, Mengran; Qiao, Chen; Cui, Zilu; Yang, Shuyue; Du, Feng; Ning, Tingting; Xie, Sian; Liu, Si; Li, Peng; Xu, Junxuan; Zhu, Shengtao] Capital Med Univ, State Key Lab Digest Hlth, Dept Gastroenterol, Natl Clin Res Ctr Digest Dis,Beijing Friendship Ho, Beijing 100050, Peoples R China. [Zhang, Wen] Beijing Univ Chinese Med, Dongzhimen Hosp, Dept Gastroenterol, Beijing 100700, Peoples R China. [Zhu, Congmin] Capital Med Univ, Sch Biomed Engn, Beijing Key Lab Fundamental Res Biomech Clin Appli, Beijing, Peoples R China. C3 Capital Medical University; Beijing University of Chinese Medicine; Capital Medical University RP Xu, JX; Zhu, ST (corresponding author), Capital Med Univ, State Key Lab Digest Hlth, Dept Gastroenterol, Natl Clin Res Ctr Digest Dis,Beijing Friendship Ho, Beijing 100050, Peoples R China. EM junxuan.xu.jerry@mail.ccmu.edu.cn; zhushengtao@ccmu.edu.cn RI Du, Feng/KTH-9559-2024; zhu, congmin/GRR-8463-2022 OI Du, Feng/0000-0001-9886-5317; Zhang, Wen/0000-0003-0115-7440 FU National Natural Science Foundation of China [82070550, 82202299]; Natural Science Foundation of Capital Medical University [2022-ZZ-028]; Beijing Postdoctoral Research Foundation; [PYZ21048] FX This study was supported by National Natural Science Foundation of China (82070550 and 82202299) , Beijing Postdoctoral Research Foundation (2022-ZZ-028) , and Natural Science Foundation of Capital Medical University (PYZ21048) . 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PD FEB 10 PY 2024 VL 320 AR 117393 DI 10.1016/j.jep.2023.117393 EA NOV 2023 PG 12 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA AA0B8 UT WOS:001115602700001 PM 37952735 DA 2026-03-26 ER PT J AU Wang, W Li, H Shi, Y Zhou, J Khan, GJ Zhu, J Liu, FW Duan, H Li, LL Zhai, KF AF Wang, Wei Li, Han Shi, Ying Zhou, Jing Khan, Ghulam Jilany Zhu, Juan Liu, Fawang Duan, Hong Li, Lili Zhai, Kefeng TI Targeted intervention of natural medicinal active ingredients and traditional Chinese medicine on epigenetic modification: Possible strategies for prevention and treatment of atherosclerosis SO PHYTOMEDICINE LA English DT Article DE Atherosclerosis; Traditional Chinese medicine; Natural medicinal active ingredients; Epigenetic modification ID SMOOTH-MUSCLE-CELL; DNA METHYLATION; VASCULAR INFLAMMATION; CHOLESTEROL EFFLUX; OXIDATIVE STRESS; TANSHINONE IIA; NONCODING RNAS; PPAR-GAMMA; AUTOPHAGY; PATHWAY AB Background: Atherosclerosis is a deadly consequence of cardiovascular disease and has very high mortality rate worldwide. The epigenetic modifications can regulate the pervasiveness and progression of atherosclerosis through its involvement in regulation of inflammation, oxidative stress, lipid metabolism and several other factors. Specific non-coding RNAs, DNA methylation, and histone modifications are key regulatory factors of atherosclerosis. Natural products from traditional Chinese medicine have shown promising therapeutic potential against atherosclerosis by means of regulating the expression of specific genes, stabilizing arterial plaques and protecting vascular endothelial cells. Objective: Our study is focusing to explore the pathophysiology and probability of traditional Chinese medicine and natural medicinal active ingredients to treat atherosclerosis. Methods: Comprehensive literature review was conducted using PubMed, Web of Science, Google Scholar and China National Knowledge Infrastructure with a core focus on natural medicinal active ingredients and traditional Chinese medicine prying in epigenetic modification related to atherosclerosis. Results: Accumulated evidence demonstrated that natural medicinal active ingredients and traditional Chinese medicine have been widely studied as substances that can regulate epigenetic modification. They can participate in the occurrence and development of atherosclerosis through inflammation, oxidative stress, lipid metabolism, cell proliferation and migration, macrophage polarization and autophagy respectively. Conclusion: The function of natural medicinal active ingredients and traditional Chinese medicine in regulating epigenetic modification may provide a new potential strategy for the prevention and treatment of atherosclerosis. However, more extensive research is essential to determine the potential of these natural medicinal active ingredients to treat atherosclerosis because of least clinical data. C1 [Wang, Wei; Li, Han; Shi, Ying; Zhou, Jing; Zhu, Juan; Liu, Fawang; Duan, Hong; Zhai, Kefeng] Suzhou Univ, Engn Res Ctr Dev & High Value Utilizat Genuine Med, Sch Biol & Food Engn, Suzhou 234000, Anhui, Peoples R China. [Wang, Wei; Li, Han; Shi, Ying; Zhou, Jing; Duan, Hong; Zhai, Kefeng] Anhui Polytech Univ, Coll Biol & Food Engn, Wuhu 241000, Anhui, Peoples R China. [Zhu, Juan; Zhai, Kefeng] Bengbu Med Coll, Fac Pharm, Bengbu 233030, Anhui, Peoples R China. [Li, Lili] Anhui Wanbei Coal Elect Grp Gen Hosp, Gen Clin Res Ctr, Suzhou 234000, Peoples R China. [Liu, Fawang] Anhui Prov Key Lab Res & Dev Chinese Med, Hefei 230012, Anhui, Peoples R China. [Khan, Ghulam Jilany] Univ Cent Punjab, Fac Pharm, Dept Pharmacol & Therapeut, Lahore 54000, Pakistan. C3 Suzhou University; Anhui Polytechnic University; Bengbu Medical University; University of Central Punjab RP Duan, H; Zhai, KF (corresponding author), Suzhou Univ, Engn Res Ctr Dev & High Value Utilizat Genuine Med, Sch Biol & Food Engn, Suzhou 234000, Anhui, Peoples R China.; Li, LL (corresponding author), Anhui Wanbei Coal Elect Grp Gen Hosp, Gen Clin Res Ctr, Suzhou 234000, Peoples R China. EM szxydh@163.com; lilili07@163.com; kefengzhai@163.com RI Zhai, Kefeng/C-4780-2018; Li, Lili/MTC-8108-2025; Khan, Ghulam Jilany/C-2135-2017 OI Zhai, Kefeng/0000-0002-5198-4332; Li, Lili/0000-0002-6095-3853; Khan, Ghulam Jilany/0000-0002-2748-5314 FU National Natural Science Foundation of China [82170481]; Anhui Natural Science Foundation [2008085J39, 2108085MH314]; Excellent top-notch Talents Training Program of Anhui Universities [gxbjZD2022073]; Anhui Province Innovation Team of Authentic Medicinal Materials Development and High Value Utilization [2022AH010080]; Suzhou University Joint Cultivation Post-graduate Research Innovation Fund Project [2023KYCX04]; Foundation of Anhui Province Key Laboratory of Research & Development of Chinese Medicine [AKLPDCM202302]; Suzhou University PhD Research Startup Fund [2022BSK033] FX This work was supported by the National Natural Science Foundation of China (82170481) , Anhui Natural Science Foundation (2008085J39 and 2108085MH314) , Excellent top-notch Talents Training Program of Anhui Universities (gxbjZD2022073) , Anhui Province Innovation Team of Authentic Medicinal Materials Development and High Value Utilization (2022AH010080) , Suzhou University Joint Cultivation Post-graduate Research Innovation Fund Project (2023KYCX04) , Foundation of Anhui Province Key Laboratory of Research & Development of Chinese Medicine (AKLPDCM202302) , Suzhou University PhD Research Startup Fund (2022BSK033) . 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Tome, Fernanda D. Arruda, Felipe S. da Fonseca, Simone Goncalves Nagib, Patricia R. A. Celes, Mara R. N. TI Curcumin as a Stabilizer of Macrophage Polarization during Plasmodium Infection SO PHARMACEUTICS LA English DT Article DE RAW 264.7 cells; curcumin; malaria; iNOS; arginase; phagocytosis ID MALARIA; PHAGOCYTOSIS; ACTIVATION; TOXICITY AB Malaria is a parasitic infection responsible for high morbidity and mortality rates worldwide. During the disease, phagocytosis of infected red blood cells by the macrophages induces the production of reactive oxygen (ROS) and nitrogen species (RNS), culminating in parasite death. Curcumin (CUR) is a bioactive compound that has been demonstrated to reduce the production of pro-inflammatory cytokines and chemokines produced by macrophages but to reduce parasitemia in infected mice. Hence, the main purpose of this study is to investigate whether curcumin may interfere with macrophage function and polarization after Plasmodium berghei infection in vitro. In our findings, non-polarized macrophage (M0), classically activated (M1), and alternatively activated (M2) phenotypes showed significantly increased phagocytosis of infected red blood cells (iRBCs) when compared to phagocytosis of uninfected red blood cells (RBCs) 3 h after infection. After 24 h, M1 macrophages exposed to RBCs + CUR showed greater elimination capacity when compared to macrophages exposed to iRBCs + CUR, suggesting the interference of curcumin with the microbicidal activity. Additionally, curcumin increased the phagocytic activity of macrophages when used in non-inflammatory conditions (M0) and reduced the inducible nitric oxide synthase (iNOS) and arginase activities in all macrophage phenotypes infected (M0, M1, and M2), suggesting interference in arginine availability by curcumin and balance promotion in macrophage polarization in neutral phenotype (M0). These results support the view of curcumin treatment in malaria as an adjuvant, promoting a balance between pro- and anti-inflammatory responses for a better clinical outcome. C1 [Cordeiro, Maria Clara C.; Tome, Fernanda D.; Arruda, Felipe S.; da Fonseca, Simone Goncalves; Celes, Mara R. N.] Univ Fed Goias, Inst Trop Pathol & Publ Hlth, Dept Biosci & Technol, BR-74605050 Goiania, GO, Brazil. [Nagib, Patricia R. A.] Univ Fed Juiz de Fora, Biol Sci Inst, Dept Microbiol Immunol & Parasitol, BR-36036900 Juiz De Fora, MG, Brazil. C3 Universidade Federal de Goias; Universidade Federal de Juiz de Fora RP Celes, MRN (corresponding author), Univ Fed Goias, Inst Trop Pathol & Publ Hlth, Dept Biosci & Technol, BR-74605050 Goiania, GO, Brazil. EM mariac.coelho07@gmail.com; fernandadiast@gmail.com; arrudaf@ymail.com; sfonseca@ufg.br; patricia.nagib@ufjf.br; mrubia_celes@ufg.br RI ; FONSECA, SIMONE/U-9278-2019; Celes, Mara Rubia/I-8707-2019 OI Nagib, Patrícia/0000-0002-1331-0441; GONÇALVES FONSECA, SIMONE/0000-0002-5126-6306; DOS SANTOS ARRUDA, FELIPE/0000-0002-6775-390X; Celes, Mara Rubia/0000-0002-4733-007X; Coêlho Cordeiro, Maria Clara/0000-0003-4700-9646 FU Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [88881.845026/2023-01]; Fundacao de Amparo a Pesquisa do Estado de Goias (FAPEG) [201810267001566] FX This research was funded by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), grant number AUXPE n. 88881.845026/2023-01, and Fundacao de Amparo a Pesquisa do Estado de Goias (FAPEG), grant number-201810267001566-Edital FAPEG n. 06/2018. 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This research is aimed at gaining a comprehensive understanding of the pathogenesis of liver cancer, particularly focusing on the potential role of the traditional Chinese herbal medicine Astragaloside IV (AS-IV) in liver cancer treatment. To achieve this, this study employs mouse and human liver cancer cells as experimental materials. The primary objective is to investigate the mechanisms through which AS-IV inhibits the development of tumour cells in HCC. The research aims to elucidate the specific actions and functions of AS-IV in the course of HCC cell development. Furthermore, it seeks to clarify the interrelationships between miR-135b-5p, immune-mediated PD-L1, and AS-IV during the process of liver cancer cell migration. This study not only holds significant implications for predicting and preventing HCC metastasis but also provides novel theoretical foundations and research directions for clinical approaches to the treatment of liver cancer.Abstract Background: Astragaloside IV (AS-IV) is a pivotal contributor to anti-tumour effects and has garnered extensive attention in research. Tumour cell immune suppression is closely related to the increase in Programmed Death-Ligand 1 (PD-L1). Hepatocellular carcinoma (HCC) is a malignant tumour originating from hepatic epithelial tissue, and the role of AS-IV in regulating PD-L1 in anti-HCC activity remains unclear. Methods: Various concentrations of AS-IV were administered to both human liver immortalised cells (THEL2) and HCC (Huh-7 and SMMC-7721), and cell growth was assessed using the CCK-8 assay. HCC levels and cell apoptosis were examined using flow cytometry. Mice were orally administered AS-IV at different concentrations to study its effects on HCC in vivo. Immunohistochemistry was employed to evaluate PD-L1 levels. Western blotting was employed to determine PD-L1 and CNDP1 protein levels. We carried out a qRT-PCR to quantify the levels of miR-135b-3p and CNDP1. Finally, a dual-luciferase reporter assay was employed to validate the direct interaction between miR-135b-3p and the 3 ' UTR of CNDP1. Results: AS-IV exhibited a dose-dependent inhibition of proliferation in Huh-7 and SMMC-7721 while inhibiting PD-L1 expression induced by interferon-gamma (IFN-gamma), thus attenuating PD-L1-mediated immune suppression. MiR-135b-5p showed significant amplification in HCC tissues and cells. AS-IV mitigated PD-L1-mediated immune suppression through miR-135b-5p. MiR-135b-5p targeted CNDP1, and AS-IV mitigated PD-L1-induced immunosuppression by modulating the miR-135b-5p/CNDP1 pathway. Conclusion: AS-IV decreases cell surface PD-L1 levels and alleviates PD-L1-associated immune suppression via the miR-135b-5p/CNDP1 pathway. AS-IV may be a novel component for treating HCC. C1 [Ma, Yang; Li, Yan; Wu, Taotao; Li, Yingshuai; Wang, Qi] Beijing Univ Chinese Med, Natl Inst TCM Constitut & Prevent Med, Beijing 100029, Peoples R China. [Li, Yan; Wu, Taotao] Beijing Univ Chinese Med, Sch Tradit Chinese Med, Beijing 100029, Peoples R China. C3 Beijing University of Chinese Medicine; Beijing University of Chinese Medicine RP Li, YS; Wang, Q (corresponding author), Beijing Univ Chinese Med, Natl Inst TCM Constitut & Prevent Med, Beijing 100029, Peoples R China. EM mayang@bucm.edu.cn; 700181@bucm.edu.cn; 601392@bucm.edu.cn OI Wu, Taotao/0000-0002-2991-774X FU I would like to express my heartfelt thanks to the National Institute of Traditional Chinese Medicine Constitution and Prevention of Disease, Beijing University of Chinese Medicine for the support of this study.; National Institute of Traditional Chinese Medicine Constitution and Prevention of Disease, Beijing University of Chinese Medicine FX I would like to express my heartfelt thanks to the National Institute of Traditional Chinese Medicine Constitution and Prevention of Disease, Beijing University of Chinese Medicine for the support of this study. 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Meanwhile, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway affects AS progression by regulating macrophage autophagy. We previously reported that the herbal formula San Jie Tong Mai Fang (SJTMF) elicits lipid regulatory and anti-inflammatory properties. Hence, the current study used an ApoE(-/-) high-fat diet-fed mouse model to determine whether SJTMF elicits protective effects against AS progression by means of the regulation of macrophage autophagy through the PI3K/AKT/mTOR signaling pathway. Our results show that SJTMF reduced the number of atherosclerotic plaques, foam cell formation, and intimal thickness in mouse aorta. In addition, SJTMF improved blood lipid metabolism and inflammatory levels in mice. We also observed that SJTMF caused macrophages to be polarized toward the M2 phenotype through the inhibition of the PI3K/AKT/mTOR signaling pathway. In addition, the abundances of LC3-II/I and beclin1 proteins-key autophagy molecules-were increased, whereas that of p62 was decreased, resulting in the promotion of macrophage autophagy. Taken together, these findings indicate that SJTMF may regulate the polarization of macrophages by inhibiting the PI3K/AKT/mTOR signaling pathway, thereby reducing atherosclerotic plaque damage in ApoE(-/-) mice, thereby promoting macrophage autophagy and eliciting a significant antiarteriosclerosis effect. Hence, SJTMF may represent a promising new candidate drug for the treatment of AS. C1 [Li, Pengfei; Xu, Hanying; Xin, Yuning] Changchun Univ Chinese Med, Coll Tradit Chinese Med, Changchun 130117, Peoples R China. [Li, Hongyu; Liu, Aidong] Changchun Univ Chinese Med, Dept Cardiol, Affiliated Hosp 3, Changchun, Peoples R China. [Li, Xiaohui] Henan Univ Chinese Med, Dept Cardiol, Affiliated Hosp 1, Zhengzhou, Peoples R China. [Li, Shuangdi; Xu, Xiaolin] Changchun Univ Chinese Med, Dept Cardiol, Affiliated Hosp, Changchun, Peoples R China. [Cui, Junfeng] Changchun Univ Chinese Med, Off Party Comm, Affiliated Hosp, Changchun, Peoples R China. [Cheng, Guangyu] Changchun Univ Chinese Med, Res Ctr Tradit Chinese Med, Affiliated Hosp, Changchun 130117, Peoples R China. [Liu, Yinghui] Changchun Univ Chinese Med, Dept Basic Teaching & Res Tradit Chinese Med, Changchun, Peoples R China. [Liu, Aidong] Changchun Univ Chinese Med, Dept Cardiol, Affiliated Hosp 3, Changchun 130117, Peoples R China. C3 Changchun University of Chinese Medicine; Changchun University of Chinese Medicine; Henan University of Traditional Chinese Medicine; Changchun University of Chinese Medicine; Changchun University of Chinese Medicine; Changchun University of Chinese Medicine; Changchun University of Chinese Medicine; Changchun University of Chinese Medicine RP Liu, AD (corresponding author), Changchun Univ Chinese Med, Dept Cardiol, Affiliated Hosp 3, Changchun 130117, Peoples R China. EM 356888281@qq.com; 303398070@qq.com; 478103511@qq.com; lishuangdi007@126.com; 421006829@qq.com; cuijunfengdoc@163.com; 616012938@qq.com; 1029906143@qq.com; xuxiaolin4303@163.com; 695637920@qq.com; Laddoc8808@163.com RI Pengfei, Li/ABE-4835-2021 CR Ala M, 2021, OXID MED CELL LONGEV, V2021, DOI 10.1155/2021/8790369 Ardestani SB, 2020, SCI REP-UK, V10, DOI 10.1038/s41598-020-72338-3 Baidzajevas K, 2020, ATHEROSCLEROSIS, V305, P10, DOI 10.1016/j.atherosclerosis.2020.05.003 Bermudez MA, 2021, BIOMEDICINES, V9, DOI 10.3390/biomedicines9121891 Chen WN, 2019, INT IMMUNOPHARMACOL, V70, P486, DOI 10.1016/j.intimp.2019.02.054 Daugherty A, 2015, ARTERIOSCL THROM VAS, V35, P11, DOI 10.1161/ATVBAHA.114.304833 Ding Y., 2020, Jilin J Chin Med, V40, P1213 Ding Y., 2020, Jilin J Chin Med, V40, P1062 Fredman G, 2021, CARDIOVASC RES, V117, P2563, DOI 10.1093/cvr/cvab309 Giampieri F, 2019, ANTIOXID REDOX SIGN, V30, P577, DOI 10.1089/ars.2017.7234 Hansson GK, 2015, J INTERN MED, V278, P483, DOI 10.1111/joim.12406 Hansson GK, 2011, NAT IMMUNOL, V12, P204, DOI 10.1038/ni.2001 Ko M, 2020, BMB REP, V53, P652, DOI 10.5483/BMBRep.2020.53.12.184 Kopf M, 2010, NAT REV DRUG DISCOV, V9, P703, DOI 10.1038/nrd2805 Kowara M, 2021, INT J MOL SCI, V22, DOI 10.3390/ijms22073513 Li WF, 2021, PHYTOTHER RES, V35, P2220, DOI 10.1002/ptr.6980 Li Y, 2016, EUR REV MED PHARMACO, V20, P3863 Lin ES, 2020, INT J MOL SCI, V21, DOI 10.3390/ijms21155511 Liu CP, 2021, FRONT PHARMACOL, V12, DOI 10.3389/fphar.2021.724670 Liu K, 2015, AUTOPHAGY, V11, P271, DOI 10.1080/15548627.2015.1009787 Liu XF, 2020, BIOMED PHARMACOTHER, V129, DOI 10.1016/j.biopha.2020.110433 Liu Y, 2019, J AGR FOOD CHEM, V67, P807, DOI 10.1021/acs.jafc.8b05719 Liuzzo G, 2001, Rays, V26, P221 Luo Y, 2020, AGING-US, V12, P1685, DOI 10.18632/aging.102708 Ma CR, 2022, BRIT J PHARMACOL, V179, P252, DOI 10.1111/bph.15720 Meyers A, 2017, LIPIDS, V52, P465, DOI 10.1007/s11745-017-4263-0 Momtazi-Borojeni AA, 2019, HEART FAIL REV, V24, P399, DOI 10.1007/s10741-018-09764-z Shao WH, 2022, AGING-US, V14, P2418, DOI 10.18632/aging.203951 Sica A, 2015, CELL MOL LIFE SCI, V72, P4111, DOI 10.1007/s00018-015-1995-y Song T, 2021, BIOENGINEERED, V12, P8135, DOI 10.1080/21655979.2021.1987130 Sun MQ, 2021, MOL MED REP, V24, DOI 10.3892/mmr.2021.12403 Sun YT, 2021, INT IMMUNOPHARMACOL, V99, DOI 10.1016/j.intimp.2021.107956 Tabas I, 2015, J CELL BIOL, V209, P13, DOI 10.1083/jcb.201412052 Tabas I, 2010, NAT REV IMMUNOL, V10, P36, DOI 10.1038/nri2675 Wan Q, 2021, ECOTOX ENVIRON SAFE, V208, DOI 10.1016/j.ecoenv.2020.111440 Wang BY, 2018, AGING-US, V10, P2772, DOI 10.18632/aging.101586 Wang Y, 2014, BIOCHEM BIOPH RES CO, V455, P119, DOI 10.1016/j.bbrc.2014.10.135 Xie YY, 2020, J TRADIT CHIN MED, V40, P28 Xu LX, 2019, CLIN EXP HYPERTENS, V41, P220, DOI 10.1080/10641963.2018.1465076 Yang H, 2022, CURR PHARM DESIGN, V28, P671, DOI 10.2174/1381612828666220128104636 Yu LY, 2022, APPL BIOCHEM BIOTECH, V194, P5717, DOI 10.1007/s12010-022-04044-x Zhai CG, 2014, PLOS ONE, V9, DOI 10.1371/journal.pone.0090563 Zhang J, 2021, LIFE SCI, V276, DOI 10.1016/j.lfs.2020.118957 Zhao YG, 2021, NAT REV MOL CELL BIO, V22, P733, DOI 10.1038/s41580-021-00392-4 Zhu YH, 2018, BIOMOLECULES, V8, DOI 10.3390/biom8030080 NR 45 TC 4 Z9 4 U1 1 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0160-2446 EI 1533-4023 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD OCT PY 2023 VL 82 IS 4 BP 333 EP 343 DI 10.1097/FJC.0000000000001452 PG 11 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA T9CH5 UT WOS:001080885400011 PM 37506377 OA Green Submitted, hybrid DA 2026-03-26 ER PT J AU Liu, Y Wu, JY Liang, S Xu, JW Wei, MG Du, ZF Qiang, S AF Liu, Yue Wu, Jingyi Liang, Shuo Xu, Jiawei Wei, Minggang Du, Zhenfang Qiang, Sheng TI Guben Xiezhuo Decoction inhibits M1 polarization through the Raf1/p-Elk1 signaling axis to attenuate renal interstitial fibrosis SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Renal interstitial fibrosis; Macrophage polarization; Raf1; Elk1; Guben Xiezhuo Decoction ID KIDNEY INJURY; MECHANISMS AB Ethnopharmacological relevance: Guben Xiezhuo Decoction (GBXZD) is an herbal compound used to treat chronic kidney disease (CKD) under the guidance of traditional Chinese medicine (TCM). Its main components are Astragalus membranaceus (Fisch.) Bunge, Codonopsis pilosula (Franch.) Nannf., Centella asiatica (L.) Urb., Salvia miltiorrhiza Bunge, Cuscuta chinensis Lam., and Rheum palmatum L.. Clinical studies have shown that it can relieve fatigue, nausea and other symptoms and improve kidney function in patients; however, its specific mechanism of action requires further study.Aim of the study: Renal interstitial fibrosis (RIF) is the ultimate characteristic manifestation of various CKD, that cannot be cured, and appropriate treatments to delay its progression require further exploration. GBXZD, widely used in clinical practice for RIF treatment, can effectively relieve the syndrome in patients with CKD. However, the specific mechanism of action of GBXZD in RIF is unknown and requires further study. This study aimed to explore the specific effects of GBXZD on RIF through the regulation of M1 macrophages.Materials and methods: An in vivo RIF model was obtained through unilateral ureteral obstruction (UUO), and the Sprague-Dawley (SD) rats were randomly divided into sham operation, UUO, UUO + GBXZD-low dose (GBXZDL) and UUO + GBXZD-high dose (GBXZD-H) groups. Pathological changes in rat kidney specimens were observed using hematoxylin and eosin (HE) and Masson staining. The expression of collagen I (COL I), fibronectin (FN), alpha-smooth muscle actin (alpha-SMA), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha) was detected using immunohistochemistry, and immunofluorescence was used to detect the expression of CD86 and inducible nitric-oxide synthase (iNOS) in kidney tissue. An in vitro experiment was performed using M1 polarization model in RAW264.7 macrophages induced by lipopolysaccharide (LPS). Cells were divided into control, LPS, LPS + GBXZD-low dose (GBXZD-L) and LPS + GBXZD-high dose (GBXZD-H) groups. The changes in expression of CD86, iNOS, IL-1 beta, IL-6, and TNF-alpha were measured using western blotting, flow cytometry, immunofluorescence and enzyme-linked immunosorbent assay (ELISA). We analyzed the action pathway of GBXZD in regulating M1 polarization of macrophages using antibody microarray and verified the results using western blotting.Results: Histopathological results showed that the UUO group exhibited significant fibrotic injury compared to the sham group. After GBXZD treatment, the degree of kidney injury, RIF, and inflammatory factor expression were lower than those in the UUO group. Compared with LPS-treated cells, the expression of the M1 markers CD86, iNOS, and pathway proteins Raf1 and p-Elk1 was down-regulated in RAW 264.7 cells treated with LPS and GBXZD. The secretion of the inflammatory factors IL-1 beta, IL-6, and TNF-alpha in the LPS group was more than that in the control group. However, the levels of these factors were significantly reduced in the GBXZD-H group compared to those in the LPS group.Conclusions: This study indicates that GBXZD ameliorates RIF and inhibits the inflammatory response and macrophage M1 polarization by a potential mechanism related to the downregulation of Raf1 and p-Elk1. GBXZD therefore has therapeutic potential value for patients with CKD. C1 [Liu, Yue; Wu, Jingyi; Liang, Shuo; Xu, Jiawei; Du, Zhenfang; Qiang, Sheng] Nanjing Univ Chinese Med, Zhangjiagang TCM Hosp, Dept Nephropathy, Zhangjiagang 215600, Jiangsu, Peoples R China. [Liu, Yue; Wu, Jingyi] Nanjing Univ Chinese Med, Zhangjiagang TCM Hosp, Translat Med Innovat Ctr, Zhangjiagang 215600, Jiangsu, Peoples R China. [Wei, Minggang] Soochow Univ, Affiliated Hosp 1, Tradit Chinese Med Dept, Suzhou 215006, Jiangsu, Peoples R China. [Du, Zhenfang; Qiang, Sheng] Nanjing Univ Chinese Med, Zhangjiagang TCM Hosp, Dept Nephropathy, 77 Changan Rd, Zhangjiagang 215600, Jiangsu, Peoples R China. [Wei, Minggang] Soochow Univ, Affiliated Hosp 1, Dept Tradit Chinese Med, 899 Pinghai Rd, Suzhou 215006, Jiangsu, Peoples R China. C3 Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine; Soochow University - China; Nanjing University of Chinese Medicine; Soochow University - China RP Du, ZF; Qiang, S (corresponding author), Nanjing Univ Chinese Med, Zhangjiagang TCM Hosp, Dept Nephropathy, 77 Changan Rd, Zhangjiagang 215600, Jiangsu, Peoples R China.; Wei, MG (corresponding author), Soochow Univ, Affiliated Hosp 1, Dept Tradit Chinese Med, 899 Pinghai Rd, Suzhou 215006, Jiangsu, Peoples R China. EM weiminggang@suda.edu.cn; zjgzy089@njucm.edu.cn; zjgzy018@njucm.edu.cn RI ; wu, jingyi/OVY-8846-2025 OI Qiang, Sheng/0009-0005-9455-6804; Qiang, Sheng/0000-0003-1252-1834; FU Jiangsu Pharmaceutical Society project [A202126, Q202125]; Suzhou science and technology development plan [SKJYD2021176, SYSD2020221, SYSD2019222]; Zhangjiagang science and technology plan project [ZKS2135, ZKS2147]; Youth science and technology project of Zhangjiagang Municipal Health Commission [ZJGQNKJ202211]; Natural Science Foundation project of Nanjing University of Traditional Chinese Medi-cine [XZR2020060] FX This research was supported by Jiangsu Pharmaceutical Society project (A202126 and Q202125) , Suzhou science and technology development plan (SKJYD2021176, SYSD2020221 and SYSD2019222) , Zhangjiagang science and technology plan project (ZKS2135 and ZKS2147) , Youth science and technology project of Zhangjiagang Municipal Health Commission (ZJGQNKJ202211) , Natural Science Foundation project of Nanjing University of Traditional Chinese Medicine (XZR2020060) . 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PD JAN 30 PY 2024 VL 319 AR 117189 DI 10.1016/j.jep.2023.117189 EA SEP 2023 PN 2 PG 12 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA U6RR4 UT WOS:001086061600001 PM 37716490 DA 2026-03-26 ER PT J AU Lin, L Deng, KM Gong, ZR Fan, HF Zhang, DW Lu, G AF Lin, Lin Deng, Kuimiao Gong, Zongrong Fan, Huifeng Zhang, Dongwei Lu, Gen TI Sinensetin Attenuated Macrophagic NLRP3 Inflammasomes Formation via SIRT1-NRF2 Signaling SO ACS OMEGA LA English DT Article AB Macrophage-mediated inflammation plays essential roles in multiple-organ injury. Sinensetin (SNS) at least exhibits anti-inflammation, antioxidant, and antitumor properties. However, the underlying mechanism of SNS-targeted macrophage-mediated inflammation remains elusive. In the present study, our results showed that SNS suppressed lipopolysaccharide (LPS)-induced inflammation to ameliorate lung and liver injuries. Mechanistically, SNS significantly inhibited M1-type macrophage polarization and its NLRP3 inflammasome formation to significantly decrease tumor necrosis factor a (TNFa) and IL-6 expression, while increasing IL-10 expression. Moreover, SNS interacted and activated SIRT1 to promote NRF2 and its target gene SOD2 transcription, which subsequently decreased LPS-induced inflammation. SIRT1 knockdown impaired the effects of SNS on the inhibition of macrophage polarization, NLRP3 inflammasome formation, and NRF2/SOD2 signaling. Taken together, our results showed that SNS is a potential and promising natural active ingredient to ameliorate inflammatory injury via activating SIRT1/NRF2/SOD2 signaling. C1 [Lin, Lin; Deng, Kuimiao; Gong, Zongrong; Fan, Huifeng; Zhang, Dongwei; Lu, Gen] Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Dept Respirat, Guangzhou 510120, Guangdong, Peoples R China. C3 Guangzhou Medical University RP Lu, G (corresponding author), Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Dept Respirat, Guangzhou 510120, Guangdong, Peoples R China. EM genl2023@163.com RI zhang, dongwei/GWU-7896-2022 FU Not applicable. FX Not applicable. 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Astragali Radix (AR) and Solanum nigrum L. (SN) are traditional antitumor combinations in Chinese herbal medicine, but their roles and mechanisms against glioma are not yet clear. Aim of the study: The effects of AR and SN compound (ARSN) on the polarization of GAMs and glioma cells in vitro and in vivo were studied, providing new ideas for the treatment of glioma. Materials and methods: The UPLC-QTOF-MS method was used to examine the quality of ARSN extracts. The effects of ARSN on proliferation, migration and apoptosis of C6 cells were investigated using CCK-8 assay, colonyforming assay, wound healing assay and flow cytometry. The impact of ARSN on the polarization of GAMs was verified by PCR, ELISA, and flow cytometry. In addition, a rat glioma model was established to assess the effects of ARSN on glioma growth, infiltration, and polarization of GAMs. Results: In vitro experiments, ARSN can effectively inhibit the proliferation and migration of C6 cells and promote apoptosis. In the rat orthotopic tumor model, ARSN also effectively inhibited tumor growth and infiltration. The SN part of ARSN has strong cytotoxicity. Meanwhile the AR part can effectively inhibit the M2 polarization of GAMs and chemokine production induced by tumor, promote the M1 phenotype of GAMs, and regulate the tumor immune microenvironment to indirectly kill glioma. Conclusions: ARSN inhibited glioma growth both in vitro and in vivo. SN takes effect through direct cytotoxicity, while AR works by regulating GAMs polarization. ARSN extracts can be used as a potential agent for glioma treatment. C1 [Shen, Mingxue; Liu, Suo; Wei, Qin; Zhang, Xiong; Wen, Shiyu; Qiu, Runze; Fan, Hongwei] Nanjing Med Univ, Nanjing Hosp 1, Dept Clin Pharmacol Lab, Nanjing 210006, Peoples R China. [Li, Yingbin] Nanjing Med Univ, Dept Neurosurg, Affiliated Hosp 2, Nanjing 210011, Peoples R China. 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Ethnopharmacol. PD JAN 30 PY 2024 VL 319 AR 117067 DI 10.1016/j.jep.2023.117067 EA SEP 2023 PN 1 PG 10 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA HZ9Y5 UT WOS:001163466100001 PM 37619857 OA hybrid DA 2026-03-26 ER PT J AU Manríquez-Núñez, J Mora, O Villarroya, F Reynoso-Camacho, R Pérez-Ramírez, IF Ramos-Gómez, M AF Manriquez-Nunez, Josue Mora, Ofelia Villarroya, Francesc Reynoso-Camacho, Rosalia Perez-Ramirez, Iza Fernanda Ramos-Gomez, Minerva TI Macrophage Activity under Hyperglycemia: A Study of the Effect of Resveratrol and 3H-1,2-Dithiole-3-thione on Potential Polarization SO MOLECULES LA English DT Article DE hyperglycemia; macrophage polarization; bioactive compounds; inflammation; resveratrol; 3H-1,2-dithiole-3-thione ID TISSUE; PROLIFERATION; INFLAMMATION; IL-10 AB Currently, research is focused on bioactive compounds with the potential to promote macrophage polarization with the aim of reducing the development of inflammatory-related diseases. However, the effect of bioactive compounds under oxidative-stress-induced hyperglycemia on macrophage polarization has been scarcely investigated. RAW264.7 macrophages were incubated under standard (SG) or high glucose (HG) conditions and stimulated with lipopolysaccharide (LPS) (10, 60 and 100 ng/mL) to monitor macrophage polarization after resveratrol (RSV) or 3H-1,2-dithiole3-thione (D3T) supplementation (2.5, 5, 10 and 20 mu M). Under SG and HG conditions without LPS stimulation, RSV significantly decreased macrophage viability at the highest concentration (20 mu M), whereas D3T had no or low effect. LPS stimulation at 60 and 100 ng/mL, under SG and HG conditions, increased significantly macrophage viability. Both RSV and D3T significantly decreased NO production in LPS-stimulated macrophages under HG condition, whereas only D3T increased GSH levels at 100 ng/mL and normalized MDA values at 60 ng/mL of LPS under HG condition. Under 60 ng/mL LPS stimulation and HG, mRNA IL-1 and IL-6 were higher. Interestingly, RSV decreased pro-inflammatory interleukins; meanwhile, D3T increased Arg1 and IL-10 relative expression. Overall, our results indicate that hyperglycemia plays a fundamental role in the modulation of macrophage-induced inflammation in response to bioactive compounds. C1 [Manriquez-Nunez, Josue; Reynoso-Camacho, Rosalia; Perez-Ramirez, Iza Fernanda; Ramos-Gomez, Minerva] Univ Autonoma Queretaro, Fac Quim, Dept Invest & Posgrad Alimentos, Ctr Univ S N, Queretaro 76010, Mexico. [Mora, Ofelia] Univ Nacl Autonoma Mexico, Fac Estudios Super Cuautitlan, Queretaro 76230, Mexico. [Villarroya, Francesc] Univ Barcelona, Dept Biochem & Mol Biomed, Inst Biomed, Barcelona 08007, Spain. C3 Universidad Autonoma de Queretaro; Universidad Nacional Autonoma de Mexico; University of Barcelona RP Ramos-Gómez, M (corresponding author), Univ Autonoma Queretaro, Fac Quim, Dept Invest & Posgrad Alimentos, Ctr Univ S N, Queretaro 76010, Mexico. EM minervaramos9297@gmail.com RI ; Ramos, Milagros/K-5369-2014; Pérez-Ramírez, Iza/G-9275-2019 OI Ramos-Gomez, Minerva/0000-0002-0763-4108; Manríquez Núñez, Josué/0009-0008-5074-0791; Mora, Ofelia/0000-0002-7073-7740; FU Universidad Autonoma de Queretaro [FCQ202126]; CONAHCYT scholarship for JMN [559214] FX This study was supported by the Universidad Autonoma de Queretaro (Project FCQ202126) and CONAHCYT scholarship for JMN (Grant 559214). 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However, YXSMG can inhibit the progression of atherosclerotic plaque and stabilize vulnerable plaque needs to be further explored and studied. This research, mass spectrometry analysis, network pharmacology, in vivo and in vitro experimental studies were conducted to explore the mechanism of YXSMG on atherosclerosis.Aim of the study: To decipher the mechanism of atherosclerotic plaque, stabilization for YXSMG by analysis of its active ingredients and biological network and activity in whole animal and at cellular and molecular levels.Methods: The active components of YXSMG were determined using high performance liquid chromatography-mass spectrometry/mass spectrometry (HPLC-MS/MS) analysis. The 'Disease-Compound-Target-Pathway' network diagram was constructed using network pharmacology, and the stability of binding between core targets and core compounds was analyzed with molecular docking. After intervention with YXSMG, the pathology of aortic plaque, inflammation in the surrounding tissue, expression of TLR9/MyD88/NF-& kappa;B pathway protein in plaque and M1/M2 polarization of plaque macrophages were evaluated in vivo in apolipoprotein E-deficient (ApoE-/-) mice fed with high-fat diet. To verify whether it suppressed inflammation by inhibiting Toll-like receptor 9 (TLR9) reprogramming of macrophage polarization, we used RAW264.7 macrophages treated with specific TLR9 agonist (ODN1826) and inhibitor (ODN2088).Results: Five active compounds were identified in YXSMG: catechin, formononetin, tanshinone IIA, cryptotan-shinone and glycitein. Network pharmacology studies revealed TLR9 as one of the core targets of YXSMG intervention in atherosclerosis. Computer simulation of molecular docking showed that TLR9 could interact with the core compound to form a stable complex. In vivo experiments confirmed that YXSMG could significantly inhibit atherosclerotic plaque, reduce levels of blood lipids and inflammatory factors, downregulate TLR9/ MyD88/NF-& kappa;B pathway protein and inhibit aortic sinus macrophages polarization to M1, but promote their polarization to M2 to inhibit inflammation. In vitro experiments revealed that YXSMG could downregulate expression of TLR9 gene and protein in ODN1826-activated RAW264.7 macrophages. ODN2088 had a syner-gistic effect with YXSMG on the TLR9/MyD88/NF-& kappa;B signaling pathway, and reprogrammed macrophages po-larization from M1 to M2 by inhibiting TLR9, thus reducing immuno-inflammatory response. Conclusion: YXSMG can reduce the level of blood lipid and improve the size of atherosclerotic plaque and in-flammatory infiltration in ApoE-/-mice fed with high fat. It is concluded that YXSMG can improve the mechanism of atherosclerotic plaque by inhibiting TLR9/MyD88/NF-& kappa;B pathway reprogramming macrophage M1/M2 polarization and reducing arterial inflammation. C1 [Huang, Hong; Sun, Zeqi; Xu, Junyao; Wang, Linjie; Zhao, Jing; Li, Jie; Zhang, Siqi; Yuan, Fang; Liu, Ming; Fang, Zhuyuan] Nanjing Univ Chinese Med, Jiangsu Prov Hosp Chinese Med, Affiliated Hosp, Nanjing 210029, Jiangsu, Peoples R China. [Zhang, Siqi; Liu, Ming; Fang, Zhuyuan] Nanjing Univ Chinese Med, Jiangsu Prov Hosp Chinese Med, Inst Hypertens, Affiliated Hosp, Nanjing 210029, Jiangsu, Peoples R China. [Fang, Zhuyuan] Jiangsu Prov Hosp Chinese Med, 155 Hanzhong Rd, Nanjing, Jiangsu, Peoples R China. C3 Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine RP Liu, M; Fang, ZY (corresponding author), Nanjing Univ Chinese Med, Jiangsu Prov Hosp Chinese Med, Affiliated Hosp, Nanjing 210029, Jiangsu, Peoples R China.; Fang, ZY (corresponding author), Jiangsu Prov Hosp Chinese Med, 155 Hanzhong Rd, Nanjing, Jiangsu, Peoples R China. EM 18064078637@163.com; szqdoct@163.com; liuming@njucm.edu.cn; fangzhuyuan@njucm.edu.cn RI 李, 洁玭/HCH-7056-2022; zhang, siqi/KWU-0918-2024 FU Research Innovation Program for College Graduates of Jiangsu Province, China [KYCX20_1470] FX Funding This work was supported by the Research Innovation Program for College Graduates of Jiangsu Province, China (KYCX20_1470) . 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PD JAN 10 PY 2024 VL 318 AR 116868 DI 10.1016/j.jep.2023.116868 EA JUL 2023 PN A PG 18 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA P4GV3 UT WOS:001050255100001 PM 37454749 DA 2026-03-26 ER PT J AU Wang, YX Han, Q Zhang, SX Xing, XY Sun, XB AF Wang, Yixin Han, Qin Zhang, Shuxia Xing, Xiaoyan Sun, Xiaobo TI New perspective on the immunomodulatory activity of ginsenosides: Focus on effective therapies for post-COVID-19 SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE Ginsenosides; Immunomodulation; Post-COVID-19; Epidemic disease ID KOREAN RED GINSENG; METABOLITE COMPOUND K; ACUTE LUNG INJURY; FACTOR-KAPPA-B; PANAX-GINSENG; INFLAMMATORY RESPONSES; DENDRITIC CELLS; NLRP3 INFLAMMASOME; HUMAN MACROPHAGES; OXIDATIVE STRESS AB More than 700 million confirmed cases of Coronavirus Disease-2019 (COVID-19) have been reported globally, and 10-60% of patients are expected to exhibit "post-COVID-19 symptoms," which will continue to affect human life and health. In the absence of safer, more specific drugs, current multiple immunotherapies have failed to achieve satisfactory efficacy. Ginseng, a traditional Chinese medicine, is often used as an immunomodulator and has been used in COVID-19 treatment as a tonic to increase blood oxygen saturation. Ginsenosides are the main active components of ginseng. In this review, we summarize the multiple ways in which ginsenosides affect postCOVID-19 symptoms, including inhibition of lipopolysaccharide, tumor necrosis factor signaling, modulation of chemokine receptors and inflammasome activation, induction of macrophage polarization, effects on Toll-like receptors, nuclear factor kappa-B, the mitogen-activated protein kinase pathway, lymphocytes, intestinal flora, and epigenetic regulation. Ginsenosides affect virus-mediated tissue damage, local or systemic inflammation, immune modulation, and other links, thus alleviating respiratory and pulmonary symptoms, reducing the cardiac burden, protecting the nervous system, and providing new ideas for the rehabilitation of patients with postCOVID-19 symptoms. Furthermore, we analyzed its role in strengthening body resistance to eliminate pathogenic factors from the perspective of ginseng-epidemic disease and highlighted the challenges in clinical applications. However, the benefit of ginsenosides in modulating organismal imbalance post-COVID-19 needs to be further evaluated to better validate the pharmacological mechanisms associated with their traditional efficacy and to determine their role in individualized therapy. C1 [Wang, Yixin; Han, Qin; Zhang, Shuxia; Xing, Xiaoyan; Sun, Xiaobo] Peking Union Med Coll & Chinese Acad Med Sci, Inst Med Plant Dev, Beijing Key Lab Innovat Drug Discovery Tradit Chin, Beijing, Peoples R China. [Wang, Yixin; Han, Qin; Zhang, Shuxia; Xing, Xiaoyan; Sun, Xiaobo] Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Plant Dev, Key Lab Bioact Subst & Resources Utilizat Chinese, Minist Educ, Beijing 100193, Peoples R China. [Wang, Yixin; Han, Qin; Zhang, Shuxia; Xing, Xiaoyan; Sun, Xiaobo] Peking Union Med Coll & Chinese Acad Med Sci, Inst Med Plant Dev, Key Lab Efficacy Evaluat Chinese Med Glycolipid Me, State Adm Tradit Chinese Med, Beijing, Peoples R China. C3 Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Institute of Medicinal Plant Development - CAMS; Chinese Academy of Medical Sciences - Peking Union Medical College; Institute of Medicinal Plant Development - CAMS; Peking Union Medical College; Chinese Academy of Medical Sciences - Peking Union Medical College; Institute of Medicinal Plant Development - CAMS; Peking Union Medical College RP Xing, XY; Sun, XB (corresponding author), Peking Union Med Coll & Chinese Acad Med Sci, Inst Med Plant Dev, Beijing Key Lab Innovat Drug Discovery Tradit Chin, Beijing, Peoples R China.; Xing, XY; Sun, XB (corresponding author), Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Plant Dev, Key Lab Bioact Subst & Resources Utilizat Chinese, Minist Educ, Beijing 100193, Peoples R China.; Xing, XY; Sun, XB (corresponding author), Peking Union Med Coll & Chinese Acad Med Sci, Inst Med Plant Dev, Key Lab Efficacy Evaluat Chinese Med Glycolipid Me, State Adm Tradit Chinese Med, Beijing, Peoples R China. EM lilyclxy@163.com; sun-xiaobo@163.com RI xing, xiaoyan/GNP-8275-2022 FU Major Program of the National Natural Science Foundation of China [81891012]; CAMS Innovation Fund for Medical Sciences (CIFMS) [2022-I2M-1-018]; CAMS Fundamental Research Funds for central public welfare research institutes, the first batch of talent introduction and training project in 2022 [2022-RC360-01] FX This study was supported by Major Program of the National Natural Science Foundation of China (No. 81891012), CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2022-I2M-1-018), and CAMS Fundamental Research Funds for central public welfare research institutes, the first batch of talent introduction and training project in 2022 (No. 2022-RC360-01). 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PD SEP PY 2023 VL 165 AR 115154 DI 10.1016/j.biopha.2023.115154 EA JUL 2023 PG 17 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA O4TW4 UT WOS:001043764500001 PM 37454595 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Liu, XQ Wang, Y Shao, PW Chen, YY Yang, CS Wang, JS Cui, SA AF Liu, Xiaoqin Wang, Ying Shao, Puwei Chen, Yuanyuan Yang, Changshui Wang, Junsong Cui, Shuna TI Sargentodoxa cuneata and Patrinia villosa extract inhibits LPS-induced inflammation by shifting macrophages polarization through FAK/PI3K/Akt pathway regulation and glucose metabolism reprogramming SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Sargentodoxa cuneata; Patrinia villosa; Anti-inflammation; Macrophages polarization; Glucose metabolism; FAK; PI3K; Akt pathway ID FOCAL ADHESION KINASE; PROMOTES AB Ethnopharmacological relevance: Sargentodoxa cuneata and Patrinia villosa (S & P) are two natural herbal medicine widely used for treatment of various inflammatory diseases in Traditional Chinese Medicine, whereas the mode of action needs to be further investigated. Aim of the study: This study aimed to explore the anti-inflammatory effects and unravel the involved mechanism of S & P extract. Materials and methods: The components of S & P extract were first detected using the liquid chromatographytandem mass spectrometry (LC-MS/MS). The effects of S & P extract on the viability and migration ability of macrophages were detected using CCK8, LDH, adhesion and transwell assays. Cytokine release and macrophage phenotype transition were measured using a cytometric bead array and flow cytometry. The potential mechanism was uncovered using an integrative approach combining RNA sequencing and LC-MS/MS-based metabolic analysis. The expression of related proteins was further validated using western blotting. Results: S & P extract inhibited the proliferation and migration of LPS-induced macrophages, changed the morphology of macrophages, and inhibited the production of NO and the expression of iNOS. Furthermore, the extract inhibited tumor necrosis factor-& alpha; (TNF-& alpha;) and interleukin-6 (IL-6) production and the expression of the M1 phenotype markers CD11c and CD16/32, whereas it promoted interleukin-10 (IL-10) production and the expression of the M2 phenotype markers CD206 and arginase 1 (Arg1). RNA sequencing analysis demonstrated that the upregulated genes by S & P extract treatment were involved in M2 macrophages: Il10, Ccl17, Ccl22, Cd68. The downregulated genes were involved in M1 macrophages and glycolysis processes: Stat1, Il18, Cd80, Cd86, Nos2, Il6, Pik3ap1, Raf1, Pdhb, etc. Metabolomics results showed that the S & P extract strongly ameliorated lipopolysaccharide (LPS)-induced metabolic disturbances. KEGG analysis indicated that most of these metabolites were involved in glucose metabolism, which is involved in the tumor necrosis factor (TNF), phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt), Glycolysis, and mitogen-activated protein kinase (MAPK) pathways. In vitro experiments further confirmed that the extract significantly inhibited the phosphorylation of focal adhesion kinase (FAK), PI3K and Akt, and the expression of glucose metabolism-related proteins. Adding a FAK inhibitor (defactinib) further inhibited the expression of M1/M2 phenotypic markers and the phosphorylation of FAK, PI3K, and Akt. Conclusions: S & P extract can induce M2 polarization and shift macrophages from M1 to M2 tissue repair in LPSinduced inflammation by regulating glucose metabolism and the FAK/PI3K/Akt pathway. C1 [Liu, Xiaoqin; Wang, Ying; Shao, Puwei; Chen, Yuanyuan; Yang, Changshui; Cui, Shuna] Med Coll Yangzhou Univ, Jiangsu Key Lab Integrated Tradit Chinese & Wester, Yangzhou 225009, Peoples R China. [Cui, Shuna] Yangzhou Univ, Dept Gynecol & Obstet, Affiliated Hosp, Yangzhou 225009, Peoples R China. [Wang, Junsong] Nanjing Univ Sci & Technol, Sch Environm & Biol Engn, Xiao Ling Wei 200, Nanjing 210094, Peoples R China. C3 Yangzhou University; Nanjing University of Science & Technology RP Cui, SA (corresponding author), Med Coll Yangzhou Univ, Jiangsu Key Lab Integrated Tradit Chinese & Wester, Yangzhou 225009, Peoples R China.; Wang, JS (corresponding author), Nanjing Univ Sci & Technol, Sch Environm & Biol Engn, Xiao Ling Wei 200, Nanjing 210094, Peoples R China. EM wang.junsong@gmail.com; sncui@yzu.edu.cn RI Cui, Shuna/GPW-5982-2022 OI Yang, Changshui/0000-0003-3910-5005; Liu, Xiaoqin/0009-0005-4527-7681 FU National Natural Science Foundation of China (NSFC) [82174432]; Scientific Research Foundation of Jiangsu Province, China [BK20211327]; Jiangsu Province Qinglan Project; Yangzhou University "Top Talent" project; Natural Science Foundation of Jiangsu Higher Education Institutions of China; [21KJA360004] FX This research was supported by the National Natural Science Foundation of China (NSFC) (82174432) ; Scientific Research Foundation of Jiangsu Province, China (BK20211327) ; Jiangsu Province Qinglan Project (2022) ; Yangzhou University "Top Talent" project (2020) ; The Natural Science Foundation of Jiangsu Higher Education Institutions of China (21KJA360004) . 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PD JAN 10 PY 2024 VL 318 AR 116855 DI 10.1016/j.jep.2023.116855 EA JUL 2023 PN A PG 15 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA P3SW7 UT WOS:001049885900001 PM 37390878 DA 2026-03-26 ER PT J AU Xu, XS Cui, LH Zhang, LQ Yang, L Zhuo, YZ Li, CX AF Xu, Xinsheng Cui, Lihua Zhang, Lanqiu Yang, Lei Zhuo, Yuzhen Li, Caixia TI Saikosaponin d modulates the polarization of tumor-associated macrophages by deactivating the PI3K/AKT/mTOR pathway in murine models of pancreatic cancer SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Saikosaponin d; Pancreatic Cancer; M2 macrophage; STAT6; PI3K; AKT; mTOR ID SIGNALING AXIS; ACTIVATION; CELLS; PHENOTYPE; APOPTOSIS; PROGRESSION; PROGNOSIS; TISSUE AB The tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) poses a major obstacle to traditional and immunomodulatory cancer therapies and is closely associated with macrophage polarization. Saikosaponin d (SSd), a major active component of triterpene saponins derived from Bupleurum falcatum, has anti-inflammatory and antitumor activities. However, whether SSd can regulate immune cells during the development of the TME in PDAC remains unknown. In the present study, we aimed to analyze the role of SSd in regulating immune cells in the PDAC TME, especially the polarization of macrophages, and examine the related mechanisms. An orthotopic PDAC cancer model was used to investigate the antitumor activities and the regulation of immune cells in vivo. In vitro, bone marrow mononuclear (BM-MNC) cells and RAW 264.7 cells were used to induce the M2 macrophage phenotype and examine the effects and molecular mechanism of SSd on M2 macrophage polarization. The results revealed that SSd could directly inhibit the apoptosis and invasion of pancreatic cancer cells, modulate the immunosuppressive microenvironment and reactivate the local immune response, especially by decreasing the shift toward M2 macrophage polarization by downregulating phosphorylated STAT6 levels and the PI3K/AKT/mTOR signaling pathway. Furthermore, 740-Y-P (PI3K activator) was used to verify that SSd inhibited M2 polarization in RAW264.7 cells via the PI3K/AKT/mTOR signaling pathway. In conclusion, this study provided experimental evidence of the antitumor effect of SSd, especially in the regulation of M2 macrophage polarization, and demonstrated that SSd may be a promising therapeutic agent in PDAC. C1 [Cui, Lihua; Zhang, Lanqiu; Yang, Lei; Zhuo, Yuzhen; Li, Caixia] Tianjin Med Univ, Tianjin Nankai Hosp, Inst Acute Abdominal Dis Integrated Tradit Chinese, Nankai Clin Coll,Tianjin Key Lab Acute Abdomen Dis, Tianjin, Peoples R China. [Xu, Xinsheng] Tianjin Med Univ, Tianjin Nankai Hosp, Nankai Clin Coll, Hepatopancreatobiliary Surg Dept, Tianjin, Peoples R China. C3 Tianjin Medical University; Tianjin Medical University RP Li, CX (corresponding author), Tianjin Med Univ, Tianjin Nankai Hosp, Inst Acute Abdominal Dis Integrated Tradit Chinese, Nankai Clin Coll,Tianjin Key Lab Acute Abdomen Dis, Tianjin, Peoples R China. EM licaixia2013@163.com RI ; Yang, Lie/JXY-1497-2024 OI cui, lihua/0000-0002-7921-4225; FU Chen Xiao-ping Foundation for the Development of Science and Technology of Hubei Province [CXPJJH12000001-2020335]; Scientific Research Projects in Key Areas of Traditional Chinese Medicine of Tianjin Municipal Health Committee [2021041, 2021007] FX This work was supported by the Chen Xiao-ping Foundation for the Development of Science and Technology of Hubei Province (CXPJJH12000001-2020335) and the Scientific Research Projects in Key Areas of Traditional Chinese Medicine of Tianjin Municipal Health Committee (2021041 and 2021007) . 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PD SEP PY 2023 VL 122 AR 110579 DI 10.1016/j.intimp.2023.110579 EA JUL 2023 PG 12 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA N8TD6 UT WOS:001039664000001 PM 37433245 DA 2026-03-26 ER PT J AU Yang, LL Yan, LJ Tan, WF Zhou, XJ Yang, GL Yu, JT Lu, ZB Liu, Y Zou, LY Li, W Yu, LZ AF Yang, Liling Yan, Lijun Tan, Weifu Zhou, Xiangjun Yang, Guangli Yu, Jingtao Lu, Zibin Liu, Yong Zou, Liyi Li, Wei Yu, Linzhong TI Liang-Ge-San: a classic traditional Chinese medicine formula, attenuates acute inflammation via targeting GSK3β SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE Liang-Ge-San; traditional Chinese medicine; sepsis; acute inflammation; LPS; GSK-3 beta; macrophage; immunomodulatory ID NEUTROPHILS; ACTIVATION; MANAGEMENT; SHOCK; TOOL; LPS AB Sepsis is a serious life-threatening health disorder with high morbidity and mortality rates that burden the world, but there is still a lack of more effective and reliable drug treatment. Liang-Ge-San (LGS) has been shown to have anti-inflammatory effects and is a promising candidate for the treatment of sepsis. However, the anti-sepsis mechanism of LGS has still not been elucidated. In this study, a set of genes related to inflammatory chemotaxis pathways was downloaded from Encyclopedia of Genes and Genomes (KEGG) and integrated with sepsis patient information from the Gene Expression Omnibus (GEO) database to perform differential gene expression analysis. Glycogen synthase kinase-3 beta (GSK-3 beta) was found to be the feature gene after these important genes were examined using the three algorithms Random Forest, support vector machine recursive feature elimination (SVM-REF), and least absolute shrinkage and selection operator (LASSO), and then intersected with possible treatment targets of LGS found through the search. Upon evaluation, the receiver operating characteristic (ROC) curve of GSK-3 beta indicated an important role in the pathogenesis of sepsis. Immune cell infiltration analysis suggested that GSK-3 beta expression was associated with a variety of immune cells, including neutrophils and monocytes. Next, lipopolysaccharide (LPS)-induced zebrafish inflammation model and macrophage inflammation model was used to validate the mechanism of LGS. We found that LGS could protect zebrafish against a lethal challenge with LPS by down-regulating GSK-3 beta mRNA expression in a dose-dependent manner, as indicated by a decreased neutrophils infiltration and reduction of inflammatory damage. The upregulated mRNA expression of GSK-3 beta in LPS-induced stimulated RAW 264.7 cells also showed the same tendency of depression by LGS. Critically, LGS could induce M1 macrophage polarization to M2 through promoting GSK-3 beta inactivation of phosphorylation. Taken together, we initially showed that antiseptic effects of LGS is related to the inhibition on GSK-3 beta, both in vitro and in vivo. C1 [Yang, Liling] Jinan Univ, Dongguan Affiliated Hosp, Binhaiwan Cent Hosp Dongguan, Med Coll,Dept Pharm, Dongguan, Peoples R China. [Yang, Liling; Yan, Lijun; Yu, Jingtao; Lu, Zibin; Yu, Linzhong] Southern Med Univ, Sch Tradit Chinese Med, Level Res Lab State Adm Tradit Chinese Med 3, Guangzhou, Peoples R China. [Tan, Weifu; Li, Wei] Jinan Univ, Dongguan Affiliated Hosp, Binhaiwan Cent Hosp Dongguan, Med Coll,Dept Neonatol, Dongguan, Peoples R China. [Zhou, Xiangjun; Liu, Yong; Zou, Liyi] Guangdong Med Univ, Sch Pharm, Guangdong Prov Key Lab Res & Dev Nat Drugs, Dongguan, Peoples R China. [Yang, Guangli] Jinan Univ, Binhaiwan Cent Hosp Dongguan, Dongguan Affiliated Hosp, Med Coll,Dept Cent Lab, Dongguan, Peoples R China. C3 Jinan University; Southern Medical University - China; Jinan University; Guangdong Medical University; Jinan University RP Yu, LZ (corresponding author), Southern Med Univ, Sch Tradit Chinese Med, Level Res Lab State Adm Tradit Chinese Med 3, Guangzhou, Peoples R China. EM yulzh@smu.edu.cn RI yan, linxia/K-7044-2017; Zhou, Xiangjun/PEV-3551-2025; Lu, Zi-Bin/ABF-3245-2020; Yang, Liling/A-9410-2018 OI Tan, Weifu/0000-0002-6192-3920; Yang, Liling/0000-0003-1552-9508 FU Dongguan Science and Technology of Social Development Program [20221800905232, 20211800904592]; National Natural Science Foundation of China [82204718, 82141221, 82074317]; Guangdong Basic and Applied Basic Research Foundation [2019A1515110369]; Administration of Traditional Chinese Medicine of Guangdong Province [20211411]; Binhaiwan Central Hospital of Dongguan [2022003] FX This work was supported by the Dongguan Science and Technology of Social Development Program (ID: 20221800905232, 20211800904592), National Natural Science Foundation of China (ID: 82204718, 82141221, 82074317), Guangdong Basic and Applied Basic Research Foundation (ID: 2019A1515110369), Administration of Traditional Chinese Medicine of Guangdong Province (ID: 20211411), and Binhaiwan Central Hospital of Dongguan (ID: 2022003). 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Pharmacol. PD JUN 29 PY 2023 VL 14 AR 1181319 DI 10.3389/fphar.2023.1181319 PG 15 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA M2UX1 UT WOS:001028792700001 PM 37456759 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Tian, XR Wei, Y Hou, RS Liu, XG Tian, YE Zhao, P Li, JS AF Tian, Xinrong Wei, Yu Hou, Runsu Liu, Xinguang Tian, Yange Zhao, Peng Li, Jiansheng TI Yangqing Chenfei formula alleviates silica-induced pulmonary inflammation in rats by inhibiting macrophage M1 polarization SO CHINESE MEDICINE LA English DT Article DE Silicosis; Yangqing Chenfei formula; Macrophage polarization; Inflammation; Network pharmacology; Transcriptomic ID OXIDATIVE STRESS; TISSUE-REPAIR; FIBROSIS; PLASTICITY; ACTIVATION; PATHWAY; DISEASE AB BackgroundYangqing Chenfei formula (YCF) is a traditional Chinese medicine formula for early-stage silicosis. However, the therapeutic mechanism is unclear. The purpose of this study was to determine the mechanism for the effects of YCF on early-stage experimental silicosis.MethodsThe anti-inflammatory and anti-fibrotic effects of YCF were determined in a silicosis rat model, which was established by intratracheal instillation of silica. The anti-inflammatory efficacy and molecular mechanisms of YCF were examined in a lipopolysaccharide (LPS)/interferon (IFN)-& gamma;-induced macrophage inflammation model. Network pharmacology and transcriptomics were integrated to analyze the active components, corresponding targets, and anti-inflammatory mechanisms of YCF, and these mechanisms were validated in vitro.ResultsOral administration of YCF attenuated the pathological changes, reduced inflammatory cell infiltration, inhibited collagen deposition, decreased the levels of inflammatory factors, and reduced the number of M1 macrophages in the lung tissue of rats with silicosis. YCF5, the effective fraction of YCF, significantly attenuated the inflammatory factors induced by LPS and IFN-& gamma; in M1 macrophages. Network pharmacology analysis showed that YCF contained 185 active components and 988 protein targets, which were mainly associated with inflammation-related signaling pathways. Transcriptomic analysis showed that YCF regulated 117 reversal genes mainly associated with the inflammatory response. Integrative analysis of network pharmacology and transcriptomics indicated that YCF suppressed M1 macrophage-mediated inflammation by regulating signaling networks, including the mTOR, mitogen-activated protein kinases (MAPK), PI3K-Akt, NF-& kappa;B, and JAK-STAT signaling pathways. In vitro studies confirmed that the active components of YCF significantly decreased the levels of p-mTORC1, p-P38, and p-P65 by suppressing the activation of related-pathways.ConclusionYCF significantly attenuated the inflammatory response in rats with silicosis via the suppression of macrophage M1 polarization by inhibiting a "multicomponent-multitarget-multipathway" network. C1 [Tian, Xinrong; Wei, Yu; Hou, Runsu; Liu, Xinguang; Tian, Yange; Zhao, Peng; Li, Jiansheng] Henan Univ Chinese Med, Henan Key Lab Chinese Med Resp Dis, Zhengzhou 450046, Henan Province, Peoples R China. [Tian, Xinrong; Wei, Yu; Hou, Runsu; Liu, Xinguang; Tian, Yange; Zhao, Peng; Li, Jiansheng] Henan Prov & Educ Minist PR China, Collaborat Innovat Ctr Chinese Med & Resp Dis Co C, Zhengzhou 450046, Henan, Peoples R China. [Tian, Xinrong; Wei, Yu; Hou, Runsu; Liu, Xinguang; Tian, Yange; Zhao, Peng] Henan Univ Chinese Med, Acad Chinese Med Sci, Zhengzhou 450000, Peoples R China. [Tian, Yange; Li, Jiansheng] Henan Univ Chinese Med, Dept Resp Dis, Affiliated Hosp 1, Zhengzhou 450000, Peoples R China. C3 Henan University of Traditional Chinese Medicine; Henan University of Traditional Chinese Medicine; Henan University of Traditional Chinese Medicine RP Zhao, P; Li, JS (corresponding author), Henan Univ Chinese Med, Henan Key Lab Chinese Med Resp Dis, Zhengzhou 450046, Henan Province, Peoples R China.; Zhao, P; Li, JS (corresponding author), Henan Prov & Educ Minist PR China, Collaborat Innovat Ctr Chinese Med & Resp Dis Co C, Zhengzhou 450046, Henan, Peoples R China.; Zhao, P (corresponding author), Henan Univ Chinese Med, Acad Chinese Med Sci, Zhengzhou 450000, Peoples R China.; Li, JS (corresponding author), Henan Univ Chinese Med, Dept Resp Dis, Affiliated Hosp 1, Zhengzhou 450000, Peoples R China. EM zhaopeng@hactcm.edu.cn; li_js8@hactcm.edu.cn RI Zhao, Peng/LWK-6324-2024; Li, Jian-sheng/AGT-3370-2022 FU Special Project of Traditional Chinese Medicine Research of Henan Province [20-21ZYZD01]; National Natural Science Fund of China [81973822] FX AcknowledgementsThis work was financially supported by Special Project of Traditional Chinese Medicine Research of Henan Province (20-21ZYZD01), National Natural Science Fund of China (81973822). 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Med. PD JUN 28 PY 2023 VL 18 IS 1 AR 79 DI 10.1186/s13020-023-00787-9 PG 21 WC Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine; Pharmacology & Pharmacy GA K7WZ8 UT WOS:001018519500001 PM 37381044 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhang, ZH Zheng, YH Chen, N Xu, CQ Deng, J Feng, X Liu, W Ma, C Chen, J Cai, TK Xu, YC Wang, S Cao, YM Ge, GB Jia, CL Cao, YB AF Zhang, Zhihui Zheng, Yihan Chen, Nan Xu, Chenqin Deng, Jie Feng, Xia Liu, Wei Ma, Chao Chen, Jian Cai, Tongkai Xu, Yicheng Wang, Song Cao, Yemin Ge, Guangbo Jia, Chenglin Cao, Yongbing TI San Huang Xiao Yan recipe modulates the HMGB1-mediated abnormal inflammatory microenvironment and ameliorates diabetic foot by activating the AMPK/Nrf2 signalling pathway SO PHYTOMEDICINE LA English DT Article DE Diabetic foot; Chinese herbal compound; Nrf2; Inflammation; M1 macrophage; Wound healing ID MACROPHAGE POLARIZATION; INJURY; HMGB1; NRF2; NEPHROPATHY; MELLITUS; MICE; SKIN AB Background: Diabetic foot (DF) is one of the serious complications of diabetes and lacks of therapeutic drugs. Abnormal and chronic inflammation promoting foot infection and wound healing delay are the main patho-genesis of DF. The traditional prescription San Huang Xiao Yan Recipe (SHXY) has been used in the clinical treatment of DF for several decades as approved hospital experience prescription and showed remarkable therapeutic effect, but the mechanisms by which SHXY treats DF are still unclear. Purpose: Objectives of this study were to investigate SHXY anti-inflammatory effect on DF and explore the molecular mechanism for SHXY. Methods: We detected the effects of SHXY on DF in C57 mouse and SD rat DF models. Animal blood glucose, weight and wound area were detected every week. Serum inflammatory factors were detected by ELISA. H&E and Masson's trichrome were used to observe tissue pathology. Single-cell sequencing data reanalysis revealed the role of M1 macrophages in DF. Venn analysis showed the co-target genes between DF M1 macrophages and compound-disease network pharmacology. Western blotting was used to explored target protein expression. Meanwhile, RAW264.7 cells were treated with drug-containing serum of SHXY to further unravel the roles of target proteins during high glucose-induced inflammation in vitro. The Nrf2 inhibitor ML385 was used on RAW 264.7 cells to further explore the relationship between Nrf2, AMPK and HMGB1. The main components of SHXY were analysed by HPLC. Finally, the treatment effect of SHXY on DF were detected on rat DF model. Results: In vivo, SHXY can ameliorate inflammatory, accelerate wound healing and upregulate expression of Nrf2, AMPK and downregulate of HMGB1. Bioinformatic analysis showed that M1 macrophages were the main in-flammatory cell population in DF. Moreover, the Nrf2 downstream proteins HO-1 and HMGB1 were potential DF therapeutic targets for SHXY. In vitro, we also found that SHXY increased AMPK and Nrf2 protein levels and downregulated HMGB1 expression in RAW264.7 cells. Inhibiting the expression of Nrf2 impaired the inhibition effect of SHXY on HMGB1. SHXY promoted Nrf2 translocation into the nucleus and increased the phosphory-lation of Nrf2. SHXY also inhibited HMGB1 extracelluar release under high glucose. In rat DF models, SHXY also exhibited significant anti-inflammatory effect. Conclusion: The SHXY activated AMPK/Nrf2 pathway to suppress abnormal inflammation on DF via inhibiting HMGB1 expression. These findings provide novel insight into the mechanisms by which SHXY treats DF. C1 [Zhang, Zhihui; Zheng, Yihan; Chen, Nan; Xu, Chenqin; Deng, Jie; Feng, Xia; Ma, Chao; Chen, Jian; Cai, Tongkai; Xu, Yicheng; Cao, Yemin; Jia, Chenglin; Cao, Yongbing] Shanghai Univ Tradit Chinese Med, Shanghai TCM Integrated Hosp, Inst Vasc Anomalies, 303 Changyang Rd, Shanghai 200082, Peoples R China. [Liu, Wei] Shanghai Univ Tradit Chinese Med, Dept Pharm, SATCM Grade Lab Tradit Chinese Med Preparat 3, Shuguang Hosp, Shanghai 201203, Peoples R China. [Wang, Song] Shanghai Univ Tradit Chinese Med, Shanghai TCM Integrated Hosp, Pharm Dept, Shanghai 200082, Peoples R China. [Ge, Guangbo] Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai Frontiers Sci Ctr Chinese Med Chem Biol, Shanghai, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine RP Zhang, ZH; Jia, CL; Cao, YB (corresponding author), Shanghai Univ Tradit Chinese Med, Shanghai TCM Integrated Hosp, Inst Vasc Anomalies, 303 Changyang Rd, Shanghai 200082, Peoples R China.; Ge, GB (corresponding author), Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai Frontiers Sci Ctr Chinese Med Chem Biol, Shanghai, Peoples R China. EM 18715112312@163.com; geguangbo@shutcm.edu.cn; jiachenglin0716@126.com; ybcao@vip.sina.com RI Ma, Chao/ABC-9692-2020; Chen, Jian/GNM-7929-2022 OI Ma, Chao/0000-0003-2100-8776; chen, nan/0000-0003-4353-0127; Chen, Jian/0000-0001-5230-7141 FU National Natural Science Foundation of China [82,104,486]; Shanghai Hong kong District Family Planning Commission project [Hongwei1903-03]; Shanghai Municipal Science and Technology Commission Yang fan plan [20YF1445700]; Shanghai Municipal Health Commission clinical project [20204Y0411, 22S21901400]; Shanghai University of Traditional Chinese Medicine [2020LK082]; Shanghai hubei animal Experimental Center of Tongji University [TJ-HB-LAC-2022-15, TJ-HB-LAC-2022-16] FX This work was supported by the National Natural Science Foundation of China (No. 82,104,486) , the Shanghai Hong kong District Family Planning Commission project (No. Hongwei1903-03) , Shanghai Municipal Science and Technology Commission Yang fan plan (No. 20YF1445700) , Shanghai Municipal Health Commission clinical project (No. 20204Y0411 and No. 22S21901400) , the budget research project of Shanghai University of Traditional Chinese Medicine (No. 2020LK082) . Animal ethics number is granted by Shanghai hubei animal Experimental Center of Tongji University (No. TJ-HB-LAC-2022-15 and No. TJ-HB-LAC-2022-16) . Rat and mouse pictures were obtained from Figdraw (https:// www.figdraw.com /static/index.html) . Fig. 8 was created with BioRender.com . 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Chin., P159, DOI [10.13193/j.issn.1673-7717.2021.10.038, DOI 10.13193/J.ISSN.1673-7717.2021.10.038] Zhu YY, 2022, ACTA PHARM SIN B, V12, P4011, DOI 10.1016/j.apsb.2022.08.022 NR 43 TC 32 Z9 38 U1 9 U2 56 PU ELSEVIER GMBH PI MUNICH PA HACKERBRUCKE 6, 80335 MUNICH, GERMANY SN 0944-7113 EI 1618-095X J9 PHYTOMEDICINE JI Phytomedicine PD SEP PY 2023 VL 118 AR 154931 DI 10.1016/j.phymed.2023.154931 EA JUN 2023 PG 15 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA HZ7Q5 UT WOS:001163404600001 PM 37364421 DA 2026-03-26 ER PT J AU Qiu, FS Wang, JF Guo, MY Li, XJ Shi, CY Wu, F Zhang, HH Ying, HZ Yu, CH AF Qiu, Fen-Sheng Wang, Jia-Feng Guo, Mei-Ying Li, Xue-Jian Shi, Chang-Yi Wu, Fang Zhang, Huan-Huan Ying, Hua-Zhong Yu, Chen-Huan TI Rgl-exomiR-7972, a novel plant exosomal microRNA derived from fresh Rehmanniae Radix, ameliorated lipopolysaccharide-induced acute lung injury and gut dysbiosis SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE MicroRNA; GPR161; Hedgehog pathway; Gut microbiota; Biofilm form; Virulence gene ID TRADITIONAL CHINESE MEDICINE; CANCER; CELLS; OSTEOPOROSIS; INFLAMMATION; GLUTINOSA; HEDGEHOG; GROWTH AB Plant-derived exosome-like nanoparticles (ELNs) have been proposed as a novel therapeutic tool for preventing human diseases. However, the number of well-verified plant ELNs remains limited. In this study, the microRNAs in ELNs derived from fresh Rehmanniae Radix, a well-known traditional Chinese herb for treating inflammatory and metabolic diseases, were determined by using microRNA sequencing to investigate the active components in the ELNs and the protection against lipopolysaccharide (LPS)-induced acute lung inflammation in vivo and in vitro. The results showed that rgl-miR-7972 (miR-7972) was the main ingredient in ELNs. It exerted stronger protective activities against LPS-induced acute lung inflammation than catalpol and acteoside, which are two well-known chemical markers in this herb. Moreover, miR-7972 decreased the production of pro-inflammatory cytokines (IL-1 & beta;, IL-6, and TNF-& alpha;), reactive oxygen species (ROS) and nitric oxide (NO) in LPS-exposed RAW264.7 cells, thereby facilitating M2 macrophage polarization. Mechanically, miR-7972 downregulated the expression of G protein-coupled receptor 161 (GPR161), activating the Hedgehog pathway, and inhibited the biofilm form of Escherichia coli via targeting virulence gene sxt2. Therefore, miR-7972 derived from fresh R. Radix alleviated LPS-induced lung inflammation by targeting the GPR161-mediated Hedgehog pathway, recovering gut microbiota dysbiosis. It also provided a new direction for gaining novel bioactivity nucleic acid drugs and broadening the knowledge on cross-kingdom physiological regulation through miRNAs. C1 [Qiu, Fen-Sheng; Guo, Mei-Ying; Li, Xue-Jian; Shi, Chang-Yi; Wu, Fang; Zhang, Huan-Huan; Ying, Hua-Zhong; Yu, Chen-Huan] Zhejiang Acad Med Sci, Hangzhou Med Coll, Key Lab Expt Anim & Safety Evaluat, Hangzhou 310013, Peoples R China. [Wang, Jia-Feng] Zhejiang Univ, Affiliated Hangzhou Peoples Hosp 1, Dept Pharm, Sch Med, Hangzhou, Peoples R China. [Shi, Chang-Yi] Westlake Univ, Hangzhou 310024, Peoples R China. [Yu, Chen-Huan] Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Hangzhou 310022, Peoples R China. [Yu, Chen-Huan] Chinese Acad Sci, Inst Basic Med & Canc, Hangzhou 310018, Peoples R China. C3 Zhejiang Academy of Medical Sciences; Hangzhou Medical College; Zhejiang University; Westlake University; Zhejiang Cancer Hospital; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Chinese Academy of Sciences RP Ying, HZ; Yu, CH (corresponding author), Zhejiang Acad Med Sci, Hangzhou Med Coll, Key Lab Expt Anim & Safety Evaluat, Hangzhou 310013, Peoples R China. EM HZYing0101@163.com; yuchenhuan2002@ucas.ac.cn RI ; Wang, Jiafeng/LZE-8700-2025 OI Yu, Chen-Huan/0000-0002-0542-9362; , Gian Raya Salsabila/0009-0001-5467-4145 FU Natural Science Foundation of Zhejiang Province [LZ17H280001]; National Natural Science Foundation of China [81473339, 81573591] FX This research was funded by Natural Science Foundation of Zhejiang Province (No. LZ17H280001) , and National Natural Science Foundation of China (No. 81473339 and 81573591) . 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PD SEP PY 2023 VL 165 AR 115007 DI 10.1016/j.biopha.2023.115007 EA JUN 2023 PG 16 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA L4NL0 UT WOS:001023047500001 PM 37327587 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Cui, LW Liu, YZ Hu, YY Dong, JT Deng, Q Jiao, BY Sun, Y Wu, Y Liu, TH Wang, W Li, C AF Cui, Lingwen Liu, Yizhou Hu, Yueyao Dong, Jianteng Deng, Qiong Jiao, Boyang Sun, Ying Wu, Yan Liu, Tianhua Wang, Wei Li, Chun TI Shexiang Tongxin Dropping Pill alleviates M1 macrophage polarization-induced inflammation and endothelial dysfunction to reduce coronary microvascular dysfunction via the Dectin-1/Syk/IRF5 pathway SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Coronary microvascular dysfunction; Shexiang Tongxin Dropping Pill (STDP); Endothelial dysfunction; Sterile inflammation; M1 macrophage polarization; Dectin-1; Syk; IRF5 pathway ID ADHERENS JUNCTIONS; ANGIOGENESIS; PATHOGENESIS; SPECTRUM AB Ethnopharmacological relevance: Shexiang Tongxin Dropping Pill (STDP), a traditional Chinese medicine com-pound, is fragrant, invigorates the qi, unblocks pulses, activates the blood circulation, removes blood stasis, and relieves pain. It is used clinically to treat coronary heart disease and angina pectoris. Coronary microvascular dysfunction (CMD) is associated with increased morbidity and mortality from cardiovascular events. Endothelial dysfunction and inflammation have been verified as its underlying causes. STDP can ameliorate CMD, but the mechanism has not been fully elucidated. Aim of the study: To explore the effects of STDP on M1 macrophage polarization-induced inflammation and endothelial dysfunction as an inhibitor of CMD, and to determine its mechanisms of action. Materials and methods: The CMD rat model was established by left anterior descending artery (LAD) ligation. The efficacy of STDP against CMD was evaluated by echocardiography, optical microangiography, Evans blue staining, and histological examination. The OGD/R-induced endothelial injury model, the endothelial injury -induced sterile inflammation model, the Dectin-1 overexpression model, and the Dectin-1-overexpressing RAW264.7 macrophage supernatant-stimulated HUVEC-induced secondary injury of endothelial function model were established to confirm the efficacy of STDP against M1 macrophage polarization-induced inflam-mation and endothelial dysfunction.Results: STDP blunted the deterioration of cardiac function and ameliorated CMD by reducing inflammatory cell infiltration and endothelial dysfunction in CMD rats. Endothelial injury and Dectin-1 overexpression induced M1 macrophage polarization and inflammation. Mechanically, STDP hindered M1 macrophage polarization and inflammation by inhibiting the Dectin-1/Syk/IRF5 pathway both in vivo and in vitro. STDP alleviated endo-thelial dysfunction induced by Dectin-1 overexpression in macrophages. Conclusion: STDP can alleviate M1 macrophage polarization-induced inflammation and endothelial dysfunction against CMD via the Dectin-1/Syk/IRF5 pathway. Dectin-1-associated M1 macrophage polarization might be developed as a novel target for ameliorating CMD. C1 [Cui, Lingwen; Li, Chun] Beijing Univ Chinese Med, Modern Res Ctr Tradit Chinese Med, Beijing 100029, Peoples R China. [Liu, Yizhou; Hu, Yueyao; Dong, Jianteng; Deng, Qiong; Jiao, Boyang; Sun, Ying; Wu, Yan; Liu, Tianhua; Wang, Wei] Beijing Univ Chinese Med, Sch Tradit Chinese Med, Beijing 100029, Peoples R China. [Wang, Wei; Li, Chun] Beijing Univ Chinese Med, Key Lab TCM Syndrome & Formula, Minist Educ, Beijing 100029, Peoples R China. [Wang, Wei] Guangzhou Univ Chinese Med, Guangzhou, Peoples R China. [Li, Chun] Beijing Univ Chinese Med, Modern Res Ctr Tradit Chinese Med, Sch Chinese Mat Med, Beijing 100029, Peoples R China. C3 Beijing University of Chinese Medicine; Beijing University of Chinese Medicine; Beijing University of Chinese Medicine; Guangzhou University of Chinese Medicine; Beijing University of Chinese Medicine RP Liu, TH; Wang, W (corresponding author), Beijing Univ Chinese Med, Sch Tradit Chinese Med, Beijing 100029, Peoples R China.; Li, C (corresponding author), Beijing Univ Chinese Med, Modern Res Ctr Tradit Chinese Med, Sch Chinese Mat Med, Beijing 100029, Peoples R China. EM liutianhua@bucm.edu.cn; 010700@gzucm.edu.cn; 700442@bucm.edu.cn RI Li, Chun/MTD-8257-2025 OI Li, Chun/0000-0001-8643-9679 FU National Natural Sci- ence Foundation of China [81930113] FX Funding This work was supported by Grants from the National Natural Sci- ence Foundation of China (No. 81930113) . 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PD NOV 15 PY 2023 VL 316 AR 116742 DI 10.1016/j.jep.2023.116742 EA JUN 2023 PG 14 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA L7AN9 UT WOS:001024750200001 PM 37290736 DA 2026-03-26 ER PT J AU Li, Z Ouyang, H Zhu, JF AF Li, Zhen Ouyang, Hao Zhu, Junfeng TI Traditional Chinese medicines and natural products targeting immune cells in the treatment of metabolic-related fatty liver disease SO FRONTIERS IN PHARMACOLOGY LA English DT Review DE metabolic-related fatty liver disease; immune cells; traditional Chinese medicine prescription; natural product; herb component; treatment ID INDUCED NONALCOHOLIC STEATOHEPATITIS; ENDOPLASMIC-RETICULUM STRESS; RHUS-VERNICIFERA STOKES; MACROPHAGE POLARIZATION; INSULIN-RESISTANCE; LIPID-METABOLISM; ADIPOSE-TISSUE; KAPPA-B; INFLAMMATION; MICE AB MAFLD stands for metabolic-related fatty liver disease, which is a prevalent liver disease affecting one-third of adults worldwide, and is strongly associated with obesity, hyperlipidemia, and type 2 diabetes. It encompasses a broad spectrum of conditions ranging from simple liver fat accumulation to advanced stages like chronic inflammation, tissue damage, fibrosis, cirrhosis, and even hepatocellular carcinoma. With limited approved drugs for MAFLD, identifying promising drug targets and developing effective treatment strategies is essential. The liver plays a critical role in regulating human immunity, and enriching innate and adaptive immune cells in the liver can significantly improve the pathological state of MAFLD. In the modern era of drug discovery, there is increasing evidence that traditional Chinese medicine prescriptions, natural products and herb components can effectively treat MAFLD. Our study aims to review the current evidence supporting the potential benefits of such treatments, specifically targeting immune cells that are responsible for the pathogenesis of MAFLD. By providing new insights into the development of traditional drugs for the treatment of MAFLD, our findings may pave the way for more effective and targeted therapeutic approaches. C1 [Li, Zhen; Ouyang, Hao; Zhu, Junfeng] Shanghai Univ Tradit Chinese Med, Yueyang Hosp Integrated Tradit Chinese & Western M, Dept Liver, Shanghai, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine RP Zhu, JF (corresponding author), Shanghai Univ Tradit Chinese Med, Yueyang Hosp Integrated Tradit Chinese & Western M, Dept Liver, Shanghai, Peoples R China. EM zhujftongling@163.com RI Ouyang, Hao/JDW-2548-2023 FU Preclinical study of a new Chinese herbal medicine for the treatment of ascites of liver cirrhosis (spleen and kidney yang deficiency type) [23S21900100] FX & nbsp;Preclinical study of a new Chinese herbal medicine for the treatment of ascites of liver cirrhosis (spleen and kidney yang deficiency type) with the clinical formula of Qigui Xiaogu Patch. (No. 23S21900100). 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Pharmacol. PD JUN 9 PY 2023 VL 14 AR 1195146 DI 10.3389/fphar.2023.1195146 PG 22 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA L0DR1 UT WOS:001020051000001 PM 37361209 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Tienda-Vázquez, MA Hanel, JM Márquez-Arteaga, EM Salgado-alvarez, AP Scheckhuber, CQ Alanis-Gómez, JR Espinoza-Silva, JI Ramos-Kuri, M Hernández-Rosas, F Melchor-Martínez, EM Parra-Saldívar, R AF Tienda-Vazquez, Mario Adrian Hanel, Juan Manuel Marquez-Arteaga, Elsa Margarita Salgado-alvarez, Ana Paola Scheckhuber, Christian Quintus Alanis-Gomez, Jose Rafael Espinoza-Silva, Janette Ivone Ramos-Kuri, Manuel Hernandez-Rosas, Fabiola Melchor-Martinez, Elda M. Parra-Saldivar, Roberto TI Exosomes: A Promising Strategy for Repair, Regeneration and Treatment of Skin Disorders SO CELLS LA English DT Review DE exosomes; mesenchymal stem cell-derived; wound care; skin damage; diabetic wounds ID INFRARED RADIATION; EXPRESSION; EXPOSURE; PATHWAY; PROTECT; HEAT AB The skin is the organ that serves as the outermost layer of protection against injury, pathogens, and homeostasis with external factors; in turn, it can be damaged by factors such as burns, trauma, exposure to ultraviolet light (UV), infrared radiation (IR), activating signaling pathways such as Toll-like receptors (TLR) and Nuclear factor erythroid 2-related factor 2 (NRF2), among others, causing a need to subsequently repair and regenerate the skin. However, pathologies such as diabetes lengthen the inflammatory stage, complicating the healing process and, in some cases, completely inhibiting it, generating susceptibility to infections. Exosomes are nano-sized extracellular vesicles that can be isolated and purified from different sources such as blood, urine, breast milk, saliva, urine, umbilical cord bile cells, and mesenchymal stem cells. They have bioactive compounds that, thanks to their paracrine activity, have proven to be effective as anti-inflammatory agents, inducers of macrophage polarization and accelerators of skin repair and regeneration, reducing the possible complications relating to poor wound repair, and prolonged inflammation. This review provides information on the use of exosomes as a promising therapy against damage from UV light, infrared radiation, burns, and skin disorders. C1 [Tienda-Vazquez, Mario Adrian; Scheckhuber, Christian Quintus; Melchor-Martinez, Elda M.; Parra-Saldivar, Roberto] Tecnol Monterrey, Sch Engn & Sci, Monterrey 64849, Mexico. [Tienda-Vazquez, Mario Adrian; Hanel, Juan Manuel; Marquez-Arteaga, Elsa Margarita; Salgado-alvarez, Ana Paola; Alanis-Gomez, Jose Rafael; Hernandez-Rosas, Fabiola] Anahuac Queretaro Univ, Fac Engn, Biomed Engn Program, Queretaro 76246, Mexico. [Scheckhuber, Christian Quintus] Tecnol Monterrey, Sch Engn & Sci, Campus Mexico City, Mexico City 14380, Mexico. [Alanis-Gomez, Jose Rafael] Autonomous Univ Queretaro, Fac Engn, Div Res, Queretaro 76010, Mexico. [Alanis-Gomez, Jose Rafael] Autonomous Univ Queretaro, Fac Engn, Postgrad Div, Queretaro 76010, Mexico. [Espinoza-Silva, Janette Ivone] Gen Hosp Queretaro, Dept Internal Med, Queretaro 76175, Mexico. [Ramos-Kuri, Manuel] Tecnol Monterrey, Escuela Med & Ciencias Salud, Monterrey 64710, Mexico. [Hernandez-Rosas, Fabiola] Anahuac Queretaro Univ, Res Ctr, Queretaro 76246, Mexico. [Melchor-Martinez, Elda M.; Parra-Saldivar, Roberto] Tecnol Monterrey, Inst Adv Mat Sustainable Mfg, Monterrey 64849, Mexico. C3 Tecnologico de Monterrey; Tecnologico de Monterrey; Universidad Autonoma de Queretaro; Universidad Autonoma de Queretaro; Tecnologico de Monterrey; Tecnologico de Monterrey RP Melchor-Martínez, EM; Parra-Saldívar, R (corresponding author), Tecnol Monterrey, Sch Engn & Sci, Monterrey 64849, Mexico.; Melchor-Martínez, EM; Parra-Saldívar, R (corresponding author), Tecnol Monterrey, Inst Adv Mat Sustainable Mfg, Monterrey 64849, Mexico. EM a01204468@tec.mx; juan.hanel15@anahuac.mx; elsa.marquez01@anahuac.mx; ana.salgado96@anahuac.mx; c.scheckhuber@tec.mx; rafael.alanis@anahuac.mx; jannymed07@gmail.com; manuel.ramos@tec.mx; fabiola.hernandez86@anahuac.mx; elda.melchor@tec.mx; r.parra@tec.mx RI ; Gómez, José/AAQ-6171-2021; Hernandez-Rosas, Fabiola/U-9961-2019; Scheckhuber, Christian/A-6462-2012; Melchor-Martínez, Elda/GNH-3265-2022; Tienda-Vázquez, Mario Aián/HNP-2641-2023; Parra, Roberto/ABA-6768-2020 OI Hanel, Juan/0009-0001-3831-6129; Hernandez-Rosas, Fabiola/0000-0003-2287-7041; Scheckhuber, Christian/0000-0002-2924-7547; Salgado Alvarez, Ana Paola/0000-0001-8524-8280; Melchor, Elda/0000-0002-5434-2765; Tienda-Vázquez, Mario Aián/0000-0003-2800-9122; Parra, Roberto/0000-0002-4958-5797 FU Consejo Nacional de Ciencia y Tecnologia (CONACYT) [858269]; CONACYT [CVU: 743687, CVU: 273003, CVU: 230784, CVU: 35753] FX & nbsp;& nbsp;Consejo Nacional de Ciencia y Tecnologia (CONACYT) is thankfully acknowledged for for the scholarship granted to Mario Adrian Tienda Vazquez, CVU: 858269 and Tecnologico de Monterrey. CONACYT is thankfully acknowledged for partially supporting this work under the Sistema Nacional de Investigadores (SNI) program awarded to Christian Quintus Scheckhuber (CVU: 743687), Fabiola Hernandez-Rosas (CVU: 273003), Elda M. Melchor-Martinez (CVU: 230784) and Roberto Parra-Saldivar (CVU: 35753). The authors appreciate the support from Tecnologico de Monterrey for the literature services. 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10.3390/cells12121625 PG 26 WC Cell Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology GA K5SN9 UT WOS:001017039900001 PM 37371095 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zeng, WC Wang, YH Cao, Y Xing, FL Yang, XH AF Zeng, Wucheng Wang, Yihan Cao, Yi Xing, Fengling Yang, Xiaohong TI Study of dietary-induced progression of psoriasis-like mice based on gut macrophage polarization SO EXPERIMENTAL AND THERAPEUTIC MEDICINE LA English DT Article DE stimulating food; dampness-heat constitution; macrophage polarization; systemic proinflammatory cytokines; psoriasis AB The aim of the present study was to investigate the influence of stimulating food (SF), a Traditional Chinese Medicine term for a high protein, high fat diet, on psoriasis exacerbation. It was hypothesized that SF disposed psoriasis-like aggravation might be related to inflammatory pathways induction via gut dysbiosis. In the present study, mice were fed either an SF or normal diet for 4 weeks. In the last week, their back hair was removed to establish psoriasis-like dermatitis by imiquimod. After sacrifice, blood samples, alimentary tissues and skin lesions were collected and tested by enzyme-linked immunosorbent assay, western blotting, immunohistochemistry and immunofluorescence. Compared with normal diet groups, body weight and blood glucose of SF diet mice were not increased, but they exhibited higher modified Psoriasis Area and Severity Index scores and corresponding epithelial hyperproliferation. Unexpectedly, skin lesions showed abnormal lower protein expressions of Notch and TLR-2/NF-kappa B p65 signaling pathway, which was attributable to severe skin damage. No difference was observed in the structure and inflammatory cell infiltration of the gut between groups. Instead, macrophage polarization (M1/M2) in the gut of the SF diet group marked by high expression of CD11b (a marker of macrophage, M1) and mild low expression of MRC1 (a marker of macrophage, M2), which resulted in increased TNF-alpha, decreased IL-10, IL-35, and unchanged IL-17 in serum. Furthermore, serum derived from SF diet mice promoted translocation of NF-kappa B p65 in HaCaT cells, which indirectly suggested a systemic inflammation. These results suggested that mice fed a continuous SF diet for a time could change gut macrophage polarization, which secretes proinflammatory cytokines into blood circulation. Once transported to skin lesions, these cytokines activate psoriasis tissue resident immune cells and present as psoriasis exacerbation. C1 [Zeng, Wucheng; Xing, Fengling] Zhejiang Chinese Med Univ, Hangzhou TCM Hosp, Dept Dermatol & Venereol, Hangzhou 310007, Zhejiang, Peoples R China. [Wang, Yihan] Zhejiang Chinese Med Univ, Dept Dermatol, Hangzhou 310053, Zhejiang, Peoples R China. [Cao, Yi; Yang, Xiaohong] Zhejiang Chinese Med Univ, Affiliated Hosp 1, Dept Dermatol, Hangzhou 310006, Zhejiang, Peoples R China. [Xing, Fengling] Zhejiang Chinese Med Univ, Hangzhou TCM Hosp, Dept Dermatol & Venereol, 453 Tiyuchang Rd, Hangzhou 310007, Zhejiang, Peoples R China. [Yang, Xiaohong] Zhejiang Chinese Med Univ, Affiliated Hosp 1, Dept Dermatol, 54 Youdian Rd, Hangzhou 310006, Zhejiang, Peoples R China. C3 Zhejiang Chinese Medical University; Zhejiang Chinese Medical University; Zhejiang Chinese Medical University; Zhejiang Chinese Medical University; Zhejiang Chinese Medical University RP Xing, FL (corresponding author), Zhejiang Chinese Med Univ, Hangzhou TCM Hosp, Dept Dermatol & Venereol, 453 Tiyuchang Rd, Hangzhou 310007, Zhejiang, Peoples R China.; Yang, XH (corresponding author), Zhejiang Chinese Med Univ, Affiliated Hosp 1, Dept Dermatol, 54 Youdian Rd, Hangzhou 310006, Zhejiang, Peoples R China. EM xfl2013@163.com RI Yang, Xiaohong/K-3029-2018; Wang, Yihan/ABE-9094-2021 CR Adawi M, 2019, NUTRIENTS, V11, DOI 10.3390/nu11030601 Balic A, 2020, INT J MOL SCI, V21, DOI 10.3390/ijms21030741 Barrea L, 2017, REV ENDOCR METAB DIS, V18, P195, DOI 10.1007/s11154-017-9411-6 Benhadou F, 2019, DERMATOLOGY, V235, P91, DOI 10.1159/000495291 BOERICKE H, 1952, Dtsch Gesundheitsw, V7, P919 Brembilla NC, 2018, FRONT IMMUNOL, V9, DOI 10.3389/fimmu.2018.01682 Chen WQ, 2019, BIOL TRACE ELEM RES, V191, P313, DOI 10.1007/s12011-018-1626-1 De Angelis M, 2019, CURR MED CHEM, V26, P3567, DOI 10.2174/0929867324666170428103848 De Simone C, 2022, INT J DERMATOL, V61, P1543, DOI 10.1111/ijd.16192 Ely PH, 2018, CLIN DERMATOL, V36, P376, DOI 10.1016/j.clindermatol.2018.03.011 Fernández-Armenteros JM, 2019, J EUR ACAD DERMATOL, V33, P128, DOI 10.1111/jdv.15159 Gentile CL, 2018, SCIENCE, V362, P776, DOI 10.1126/science.aau5812 Griffiths CEM, 2021, LANCET, V397, P1301, DOI 10.1016/S0140-6736(20)32549-6 Jena PK, 2019, J DERMATOL SCI, V95, P13, DOI 10.1016/j.jdermsci.2019.05.007 Kashem SW, 2017, ANNU REV IMMUNOL, V35, P469, DOI 10.1146/annurev-immunol-051116-052215 Kim ES, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-01983-y KRAGBALLE K, 1989, ACTA DERM-VENEREOL, V69, P23 Madden SK, 2020, CLIN NUTR, V39, P1026, DOI 10.1016/j.clnu.2019.05.006 Mahil SK, 2019, BRIT J DERMATOL, V181, P946, DOI 10.1111/bjd.17741 Marasca C, 2019, BRIT J DERMATOL, V180, P950, DOI 10.1111/bjd.17509 Millsop JW, 2014, J AM ACAD DERMATOL, V71, P561, DOI 10.1016/j.jaad.2014.03.016 Mohammadi A, 2019, J NUTR BIOCHEM, V66, P1, DOI 10.1016/j.jnutbio.2018.12.005 National Psoriasis Epidemic Survey Group, 1989, J DERMATOL VENEREOL, V11, P66 Passali M, 2020, NUTRIENTS, V12, DOI 10.3390/nu12082316 Petrozzi J W, 1968, JAMA, V205, P345 Phan C, 2018, JAMA DERMATOL, V154, P1017, DOI 10.1001/jamadermatol.2018.2127 [乔菊 Qiao Ju], 2017, [中国皮肤性病学杂志, The Chinese Journal of Dermatovenereology], V31, P1301 Reich K, 2020, BRIT J DERMATOL, V182, P869, DOI 10.1111/bjd.18384 Semenov YR, 2021, J AM ACAD DERMATOL, V85, P396, DOI 10.1016/j.jaad.2019.08.011 Siebel C, 2017, PHYSIOL REV, V97, P1235, DOI 10.1152/physrev.00005.2017 SPIERA H, 1967, LANCET, V2, P1418 Takeshita J, 2017, J AM ACAD DERMATOL, V76, P377, DOI 10.1016/j.jaad.2016.07.064 Thatikonda S, 2020, CELL DEATH DIS, V11, DOI 10.1038/s41419-019-2212-y Tran HQ, 2020, CELL MOL GASTROENTER, V9, P313, DOI 10.1016/j.jcmgh.2019.09.009 Xu Y., 2011, SCI TECHNOL INFORM, V10, P241 Yang BY, 2019, MOLECULES, V24, DOI 10.3390/molecules24112157 Ye C, 2021, J INTERF CYTOK RES, V41, P391, DOI 10.1089/jir.2021.0147 Yilmaz SB, 2012, ARCH DERMATOL RES, V304, P465, DOI 10.1007/s00403-012-1229-1 Yu S, 2020, J DERMATOL SCI, V97, P194, DOI 10.1016/j.jdermsci.2020.01.011 Yu S, 2019, J INVEST DERMATOL, V139, P1404, DOI 10.1016/j.jid.2018.12.002 ZACKHEIM HS, 1969, ARCH DERMATOL, V99, P580, DOI 10.1001/archderm.99.5.580 Zackheim HS., 1982, ARCH DERMATOL, V118 [朱飞叶 Zhu Feiye], 2018, [中华中医药杂志, China Journal of Traditional Chinese Medicine and Pharmacy], V33, P3104 NR 43 TC 6 Z9 6 U1 1 U2 8 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1792-0981 EI 1792-1015 J9 EXP THER MED JI Exp. Ther. Med. PD JUN PY 2023 VL 25 IS 6 AR 278 DI 10.3892/etm.2023.11976 PG 10 WC Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine GA G4SJ8 UT WOS:000989069000001 PM 37206572 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Nie, X Fu, L Cheng, YF Wu, XP Lv, KP Li, RK Wu, YH Leung, GPH Fu, CM Lee, SMY Seto, SW Zhang, JM Li, JJ AF Nie, Xin Fu, Li Cheng, Yanfen Wu, Xiaoping Lv, Kongpeng Li, Renkai Wu, Yihan Leung, George Pak-Heng Fu, Chaomei Lee, Simon Ming-Yuen Seto, Sai-Wang Zhang, Jinming Li, Jingjing TI Garcinone E suppresses breast cancer growth and metastasis by modulating tumor-associated macrophages polarization via STAT6 signaling SO PHYTOTHERAPY RESEARCH LA English DT Article DE breast cancer metastasis; Garcinone E; STAT6 signaling; tumor-associated macrophages ID MEDICINAL PROPERTIES; MANGOSTANA L.; PHYTOCHEMICALS; IDENTIFICATION AB Cancer metastasis remains the most common cause of death in breast cancer patients. Tumor-associated macrophages (TAMs) are a novel therapeutic target for the treatment of metastatic breast cancer. Despite the good anti-cancer activity of garcinone E (GE), there are no reports on its therapeutic effects on breast cancer metastasis. The objective of this study was to examine the anti-cancer effects of GE on metastatic breast cancer. RAW 264.7 and THP-1 cells were polarized to M2 macrophages by IL-4/IL-13 in vitro. A 4T1 mouse breast cancer model and the tail vein breast cancer metastasis model were used to explore the effect of GE on breast cancer growth and metastasis in vivo. In vitro studies showed that GE dose-dependently suppressed IL-4 + IL-13-induced expression of CD206 in both RAW 264.7 cells and differentiated THP-1 macrophages. However, GE did not affect the LPS + IFN-gamma-induced polarization to the M1-like macrophages in vitro. GE inhibited the expression of the M2 macrophage specific genes in RAW 264.7 cells, and simultaneously impaired M2 macrophage-induced breast cancer cell proliferation and migration, and angiogenesis. In animal studies, GE significantly suppressed tumor growth, angiogenesis, and lung metastasis in 4T1 tumor-bearing mice, without causing toxicity. In both tumor and lung tissues, the proportion of M2-like TAMs was significantly decreased while the proportion of M1-like TAMs was markedly increased by GE treatment. Mechanistically, GE inhibited phosphorylation of STAT6 in vitro and in vivo. Our results demonstrate for the first time that GE suppresses breast cancer growth and pulmonary metastasis by modulating M2-like macrophage polarization through the STAT6 signaling pathway. C1 [Nie, Xin; Fu, Li; Cheng, Yanfen; Wu, Yihan; Fu, Chaomei; Zhang, Jinming] Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, Chengdu, Peoples R China. [Nie, Xin; Lee, Simon Ming-Yuen] Univ Macau, State Key Lab Qual Res Chinese Med, Macau, Peoples R China. [Nie, Xin; Lee, Simon Ming-Yuen] Univ Macau, Inst Chinese Med Sci, Macau, Peoples R China. [Wu, Xiaoping; Li, Renkai; Leung, George Pak-Heng] Univ Hong Kong, Li Ka Shing Fac Med, Dept Pharmacol & Pharm, Hong Kong, Peoples R China. [Lv, Kongpeng] Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Intervent Radiol, Shenzhen, Peoples R China. [Lv, Kongpeng] Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen, Peoples R China. [Seto, Sai-Wang] Hong Kong Polytech Univ, Fac Sci, Dept Food Sci & Nutr, Hong Kong, Peoples R China. [Seto, Sai-Wang; Li, Jingjing] Hong Kong Polytech Univ, Res Ctr Chinese Med Innovat, Hong Kong, Peoples R China. [Li, Jingjing] Hong Kong Polytech Univ, Fac Hlth & Social Sci, Dept Rehabil Sci, Hong Kong, Peoples R China. [Zhang, Jinming] Chengdu Univ Tradit Chinese Med, Coll Pharm, State Key Lab Southwestern Chinese Med Resources, 1166 Liutai Ave, Chengdu, Peoples R China. [Li, Jingjing] Hong Kong Polytech Univ, Kowloon, Room ST527, 11 Yuk Choi Rd, Hong Kong, Peoples R China. C3 Chengdu University of Traditional Chinese Medicine; University of Macau; University of Macau; University of Hong Kong; Jinan University; Southern University of Science & Technology; Hong Kong Polytechnic University; Hong Kong Polytechnic University; Hong Kong Polytechnic University; Chengdu University of Traditional Chinese Medicine; Hong Kong Polytechnic University RP Zhang, JM (corresponding author), Chengdu Univ Tradit Chinese Med, Coll Pharm, State Key Lab Southwestern Chinese Med Resources, 1166 Liutai Ave, Chengdu, Peoples R China.; Li, JJ (corresponding author), Hong Kong Polytech Univ, Kowloon, Room ST527, 11 Yuk Choi Rd, Hong Kong, Peoples R China. EM cdutcmzjm@126.com; kim07.li@polyu.edu.hk RI lee, Simon Ming Yuen/NOE-8462-2025; FU, Li/AAD-4775-2019; Leung, Gabriel/C-4336-2009; Wu, Xiaoping/JLL-1228-2023; Leung, George Pak Heng/B-4529-2009 OI lee, Simon Ming Yuen/0000-0002-3966-6569; NIE, XIN/0009-0003-5275-4912; Leung, George Pak Heng/0000-0003-3529-9367; Li, Jingjing/0000-0003-3636-0537 FU National Natural Science Foundation of China [8227142138]; Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine [ZYYCXTD-D-202209]; Start-up Fund for research assistant professors under the Strategic Hiring Scheme [A0040914] FX National Natural Science Foundation of China, Grant/Award Number: 8227142138;Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine, Grant/Award Number: ZYYCXTD-D-202209; Start-up Fund for research assistant professors under the Strategic Hiring Scheme, Grant/Award Number: A0040914 CR Agarwal G, 2020, BIOTECHNOL 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PD OCT PY 2023 VL 37 IS 10 BP 4442 EP 4456 DI 10.1002/ptr.7909 EA MAY 2023 PG 15 WC Chemistry, Medicinal; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA U5KS4 UT WOS:000999224400001 PM 37259475 OA Green Published, hybrid DA 2026-03-26 ER PT J AU Chu, W Li, YL Li, JJ Lin, J Li, M Wang, J He, JZ Zhang, YM Yao, J Jin, XJ Cai, H Liu, YQ AF Chu, Wei Li, Ya-ling Li, Jun-jie Lin, Jia Li, Mi Wang, Jiao He, Jian-zheng Zhang, Yue-mei Yao, Juan Jin, Xiao-jie Cai, Hui Liu, Yong-qi TI Guiqi Baizhu prescription ameliorates cytarabine-induced intestinal mucositis by targeting JAK2 to inhibit M1 macrophage polarization SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE Intestinal mucositis; JAK2; STAT1; Macrophage polarization; Acridine; Senkyunolide A ID ALTERNATIVE ACTIVATION; CANCER-CELLS; RUXOLITINIB; SUPPRESSES; MECHANISM; APOPTOSIS; EFFICACY; COLITIS; PATHWAY; MODEL AB Background: Intestinal mucositis (IM) is characterized by damage to the intestinal mucosa resulting from inhi-bition of epithelial cell division and loss of renewal capacity following anticancer chemotherapy and radio-therapy. Cytarabine (Ara-C), the main chemotherapy drug for the treatment of leukemia and lymphoma, is a frequent cause of IM. Guiqi Baizhu prescription (GQBZP) is a traditional Chinese medicine with anti-cancer and anti-inflammatory effects.Purpose: To determine if GQBZP can ameliorate Ara-C induced IM and identify and characterize the pharma-cologic and pharmacodynamic mechanisms.Study design and methods: IM was induced in mice with Ara-C and concurrently treated with orally administered GQBZP. Body weight and food intake was monitored, with HE staining to calculate ileal histomorphometric scoring and villus length/crypt depth. Immunoblotting was used to detect intestinal tissue inflammatory factors. M1 macrophages (M1) were labeled with CD86 by flow cytometry and iNOS + F4/80 by immunofluorescence. Virtual screening was used to find potentially active compounds in GQBZP that targeted JAK2. In vitro, RAW264.7 cells were skewed to M1 macrophage polarization by lipopolysaccharide (LPS) and interferon-gamma (INF-gamma) and treated orally with GQBZP or potential active compounds. M1 was labeled with CD86 by flow cytometry and iNOS by immunofluorescence. ELISA was used to detect inflammatory factor expression. Active compounds against JAK2, p-JAK2, STAT1 and p-STAT1 were identified by western blotting and HCS fluorescence. Molecular dynamics simulations and pharmacokinetic predictions were carried out on representative active compounds.Results: Experimental results with mice in vivo suggest that GQBZP significantly attenuated Ara-C-induced ileal damage and release of pro-inflammatory factors by inhibiting macrophage polarization to M1. Molecular docking was used to identify potentially active compounds in GQBZP that targeted JAK2, a key factor in macrophage polarization to M1. By examining the main components of each herb and applying Lipinski's rules, ten poten-tially active compounds were identified. In vitro experimental results suggested that all 10 compounds of GQBZP targeted JAK2 and could inhibit M1 polarization in RAW264.7 cells treated with LPS and INF-gamma. Among them, acridine and senkyunolide A down-regulated the expression of JAK2 and STAT1. MD simulations revealed that acridine and senkyunolide A were stable in the active site of JAK2 and exhibited good interactions with the surrounding amino acids.Conclusions: GQBZP can ameliorate Ara-C-induced IM by reducing macrophage polarization to M1, and acridine and senkyunolide A are representative active compounds in GQBZP that target JAK2 to inhibit M1 polarization. Targeting JAK2 to regulate M1 polarization may be a valuable therapeutic strategy for IM. C1 [Chu, Wei; Li, Ya-ling; Li, Jun-jie; He, Jian-zheng; Jin, Xiao-jie; Liu, Yong-qi] Gansu Univ Chinese Med, Gansu Univ Key Lab Mol Med & Chinese Med Prevent &, Lanzhou 730000, Peoples R China. [Chu, Wei; Li, Ya-ling; Li, Jun-jie; He, Jian-zheng; Jin, Xiao-jie; Liu, Yong-qi] Gansu Univ Chinese Med, Chinese Med Prevent & Treatment Major Dis, Lanzhou 730000, Peoples R China. [Li, Ya-ling; Liu, Yong-qi] Gansu Univ Chinese Med, Key Lab Dun Huang Med & Transformat, Minist Educ Peoples Republ China, Lanzhou 730000, Peoples R China. [Lin, Jia; Li, Mi; Wang, Jiao; Yao, Juan; Jin, Xiao-jie] Gansu Univ Chinese Med, Coll Pharm, Lanzhou 730000, Peoples R China. [Zhang, Yue-mei] First Hosp Lanzhou Univ, Ophthalmol Dept, Lanzhou 730000, Peoples R China. [Cai, Hui] Gansu Prov Hosp, Key Lab Mol Diagnost & Precis Med Surg Oncol Gansu, Lanzhou 730000, Peoples R China. [Cai, Hui] Gansu Prov Hosp, NHC Key Lab Diag & Therapy Gastrointestinal Tumor, Lanzhou 730000, Peoples R China. [Jin, Xiao-jie; Liu, Yong-qi] Gansu Univ Chinese Med, 35 Dingxi East Rd, Lanzhou 730000, Peoples R China. [Cai, Hui] Gansu Prov Hosp, Lanzhou 730000, Peoples R China. C3 Gansu University of Chinese Medicine; Gansu University of Chinese Medicine; Gansu University of Chinese Medicine; Gansu University of Chinese Medicine; Gansu University of Chinese Medicine RP Jin, XJ (corresponding author), Gansu Univ Chinese Med, Coll Pharm, Lanzhou 730000, Peoples R China.; Jin, XJ; Liu, YQ (corresponding author), Gansu Univ Chinese Med, 35 Dingxi East Rd, Lanzhou 730000, Peoples R China.; Cai, H (corresponding author), Gansu Prov Hosp, Lanzhou 730000, Peoples R China. EM jinlovedream@163.com; caialon@163.com; liuyongqi73@163.com RI ; Ling, Li/JYO-7043-2024 OI Li, Junjie/0009-0007-9654-9223; FU National Natural Science Foundation of China [82260927, 82160857]; Youth Science and Technology Fund in Gansu [21JR11RA149]; Foundation of Key Laboratory of Dunhuang Medicine and Transformation Constructed by Chinese Ministry of Education and Gansu Province [DHYX20-07]; Basic Research Innovation Group in Gansu [20JR10RA332] FX This study was supported by the National Natural Science Foundation of China (No. 82260927, 82160857), the Youth Science and Technology Fund in Gansu (21JR11RA149), the Foundation of Key Laboratory of Dunhuang Medicine and Transformation Constructed by Chinese Ministry of Education and Gansu Province (No. DHYX20-07) and Basic Research Innovation Group in Gansu (20JR10RA332). 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Pharmacother. PD AUG PY 2023 VL 164 AR 114902 DI 10.1016/j.biopha.2023.114902 EA MAY 2023 PG 15 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA I3PH2 UT WOS:001001926700001 PM 37209628 OA Green Submitted, gold DA 2026-03-26 ER PT J AU He, PK Wang, H Cheng, SB Hu, F Zhang, LF Chen, WC Xu, YL Zhang, YX Gu, YY Li, ZY Jin, Y Liu, XY Jia, YH AF He, Peikun Wang, Hao Cheng, Saibo Hu, Fang Zhang, Lifang Chen, Weicong Xu, Yuling Zhang, Yaxin Gu, Yuyan Li, Zhaoyong Jin, Yao Liu, Xiaoyu Jia, Yuhua TI Geniposide ameliorates atherosclerosis by regulating macrophage polarization via perivascular adipocyte-derived CXCL14 SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Geniposide; Atherosclerosis; Macrophage polarization; Perivascular adipose tissue; CXCL14 ID INFLAMMATION; PHENOTYPE; FAT; MECHANISMS; ARTERIES AB Ethnopharmacological relevance: Gardenia jasminoides Ellis is a traditional Chinese medicine that has been used for treatment of various diseases, including atherosclerosis by clearing heat and detoxication. Geniposide is considered as the effective compounds responsible for the therapeutic efficacy of Gardenia jasminoides Ellis against atherosclerosis.Aim of the study: To investigate the effect of geniposide on atherosclerosis burden and plaque macrophage po-larization, with focus on its potential impact on CXCL14 expression by perivascular adipose tissue (PVAT).Materials and methods: ApoE-/-mice fed a western diet (WD) were used to model atherosclerosis. In vitro cultures of mouse 3T3-L1 preadipocytes and RAW264.7 macrophages were used for molecular assays.Results: The results revealed that geniposide treatment reduced atherosclerotic lesions in ApoE-/-mice, and this effect was correlated with increased M2 and decreased M1 polarization of plaque macrophages. Of note, geni-poside increased the expression of CXCL14 in PVAT, and both the anti-atherosclerotic effect of geniposide, as well as its regulatory influence on macrophage polarization, were abrogated upon in vivo CXCL14 knockdown. In line with these findings, exposure to conditioned medium from geniposide-treated 3T3-L1 adipocytes (or to recombinant CXCL14 protein) enhanced M2 polarization in interleukin-4 (IL-4) treated RAW264.7 macrophages, and this effect was negated after CXCL14 silencing in 3T3-L1 cells.Conclusion: In summary, our findings suggest that geniposide protects ApoE-/-mice against WD-induced atherosclerosis by inducing M2 polarization of plaque macrophages via enhanced expression of CXCL14 in PVAT. These data provide novel insights into PVAT paracrine function in atherosclerosis and reaffirm geniposide as a therapeutic drug candidate for atherosclerosis treatment. C1 [He, Peikun; Wang, Hao; Cheng, Saibo; Hu, Fang; Zhang, Lifang; Chen, Weicong; Zhang, Yaxin; Gu, Yuyan; Li, Zhaoyong; Jin, Yao; Jia, Yuhua] Southern Med Univ, Sch Tradit Chinese Med, Guangzhou, Guangdong, Peoples R China. [Xu, Yuling] Fujian Med Univ, Coll Hlth, Fuzhou, Fujian, Peoples R China. [Liu, Xiaoyu] Southern Med Univ, Pingshan Gen Hosp, Shenzhen Pingshan Dist Med Healthcare Grp, Shenzhen, Guangdong, Peoples R China. [Jia, Yuhua] Southern Med Univ, Sch Tradit Chinese Med, 1023 Shatai Rd, Guangzhou 510515, Guangdong, Peoples R China. C3 Southern Medical University - China; Fujian Medical University; Southern Medical University - China; Southern Medical University - China RP Liu, XY (corresponding author), Southern Med Univ, Pingshan Gen Hosp, Shenzhen Pingshan Dist Med Healthcare Grp, Shenzhen, Guangdong, Peoples R China.; Jia, YH (corresponding author), Southern Med Univ, Sch Tradit Chinese Med, 1023 Shatai Rd, Guangzhou 510515, Guangdong, Peoples R China. EM lxy875834580@163.com; yuhuajia_smu@126.com RI liu, xiaoyu/LZE-2244-2025; zhang, lifang/ITT-4448-2023; zhaoyong, li/MGB-4145-2025 FU National Natural Science Foundation of China [81973802, 82174299]; Guangdong Nat- ural Science Foundation [2021A1515011603] FX This work was supported by grants from National Natural Science Foundation of China (No. 81973802, No. 82174299) , Guangdong Nat- ural Science Foundation (No. 2021A1515011603) . CR [Anonymous], 2017, CIRCULATION, V135, pe146, DOI 10.1161/CIR.0000000000000485 Barrett TJ, 2020, ARTERIOSCL THROM VAS, V40, P20, DOI 10.1161/ATVBAHA.119.312802 Bermudez B, 2017, ARTERIOSCL THROM VAS, V37, P1157, DOI 10.1161/ATVBAHA.116.308187 Cereijo R., 2018, CELL METABOL Cereijo R, 2021, INT J OBESITY, V45, P706, DOI 10.1038/s41366-020-00732-y Chatterjee TK, 2013, PHYSIOL GENOMICS, V45, P697, DOI 10.1152/physiolgenomics.00042.2013 Chatterjee TK, 2009, CIRC RES, V104, P541, DOI 10.1161/CIRCRESAHA.108.182998 Chen LP, 2020, J ETHNOPHARMACOL, V257, DOI 10.1016/j.jep.2020.112829 Chen SY, 2021, J NUTR BIOCHEM, V90, DOI 10.1016/j.jnutbio.2020.108575 Cheng SB, 2019, IMMUNOBIOLOGY, V224, P296, DOI 10.1016/j.imbio.2018.12.005 Colin S, 2014, IMMUNOL REV, V262, P153, DOI 10.1111/imr.12218 Dib LH, 2014, ENDOCRINOLOGY, V155, P40, DOI 10.1210/en.2013-1607 Hanna RN, 2012, CIRC RES, V110, P416, DOI 10.1161/CIRCRESAHA.111.253377 Hansson GK, 2005, NEW ENGL J MED, V352, P1685, DOI 10.1056/NEJMra043430 Hiramatsu-Ito M, 2016, CARDIOVASC RES, V110, P107, DOI 10.1093/cvr/cvv282 Huby AC, 2016, HYPERTENSION, V67, P1020, DOI 10.1161/HYPERTENSIONAHA.115.06642 Iacobellis G, 2015, NAT REV ENDOCRINOL, V11, P363, DOI 10.1038/nrendo.2015.58 Kim HW, 2020, ARTERIOSCL THROM VAS, V40, P2569, DOI 10.1161/ATVBAHA.120.312470 Kuznetsova T, 2020, NAT REV CARDIOL, V17, P216, DOI 10.1038/s41569-019-0265-3 Lee HT, 2017, THERANOSTICS, V7, P855, DOI 10.7150/thno.17558 Li XZ, 2019, FASEB J, V33, P12704, DOI 10.1096/fj.201901548R Liu JX, 2022, PHYTOMEDICINE, V95, DOI 10.1016/j.phymed.2021.153862 Liu JX, 2020, PHARMACOL RES, V152, DOI 10.1016/j.phrs.2020.104631 Liu XY, 2021, FRONT PHARMACOL, V12, DOI 10.3389/fphar.2021.687394 Mahabadi AA, 2010, ATHEROSCLEROSIS, V211, P195, DOI 10.1016/j.atherosclerosis.2010.02.013 Martel J, 2017, NAT REV ENDOCRINOL, V13, P149, DOI 10.1038/nrendo.2016.142 Nosalski R, 2017, BRIT J PHARMACOL, V174, P3496, DOI 10.1111/bph.13705 Orekhov AN, 2015, OXID MED CELL LONGEV, V2015, DOI 10.1155/2015/463797 Qi XY, 2018, CARDIOVASC DIABETOL, V17, DOI 10.1186/s12933-018-0777-x Sanjurjo L, 2018, FRONT IMMUNOL, V9, DOI 10.3389/fimmu.2018.00480 Scheja L, 2019, NAT REV ENDOCRINOL, V15, P507, DOI 10.1038/s41574-019-0230-6 Sena CM, 2017, BRIT J PHARMACOL, V174, P3514, DOI 10.1111/bph.13756 Shen YH, 2022, FRONT PHARMACOL, V13, DOI 10.3389/fphar.2022.879870 Tabas I, 2016, CIRC RES, V118, P653, DOI 10.1161/CIRCRESAHA.115.306256 Tian HY, 2022, OXID MED CELL LONGEV, V2022, DOI 10.1155/2022/7616696 Tu YY, 2021, OXID MED CELL LONGEV, V2021, DOI 10.1155/2021/9247947 Victorio JA, 2016, FRONT PHYSIOL, V7, DOI 10.3389/fphys.2016.00295 Virdis A, 2015, EUR HEART J, V36, P784, DOI 10.1093/eurheartj/ehu072 Wang Y., 2022, JCI Insight, V7 Wu MM, 2021, PHARMACOL RES, V172, DOI 10.1016/j.phrs.2021.105796 Xu YL, 2020, AM J CHINESE MED, V48, P1821, DOI 10.1142/S0192415X20500913 Xue J, 2014, IMMUNITY, V40, P274, DOI 10.1016/j.immuni.2014.01.006 Ying W, 2017, CELL, V171, P372, DOI 10.1016/j.cell.2017.08.035 Yudkin JS, 2005, LANCET, V365, P1817, DOI 10.1016/S0140-6736(05)66585-3 Zhao CH, 2020, PHARMACOL THERAPEUT, V216, DOI 10.1016/j.pharmthera.2020.107698 NR 45 TC 23 Z9 26 U1 1 U2 42 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-8741 EI 1872-7573 J9 J ETHNOPHARMACOL JI J. Ethnopharmacol. PD OCT 5 PY 2023 VL 314 AR 116532 DI 10.1016/j.jep.2023.116532 EA MAY 2023 PG 13 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA H8HZ6 UT WOS:000998320400001 PM 37149071 OA hybrid DA 2026-03-26 ER PT J AU Zhou, HF Yang, C Li, JY He, YY Huang, Y Qin, RJ Zhou, QL Sun, F Hu, DS Yang, J AF Zhou, Hai-feng Yang, Chao Li, Jun-yi He, Yu-yao Huang, Yun Qin, Ren-jie Zhou, Qiao-li Sun, Fei Hu, De-sheng Yang, Jia TI Quercetin serves as the major component of Xiang-lian Pill to ameliorate ulcerative colitis via tipping the balance of STAT1/PPARγ and dictating the alternative activation of macrophage SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Xiang-lian pill (XLP); Quercetin; Ulcerative colitis (UC); Macrophage ID PPAR-GAMMA; SIGNALING PATHWAY; POLARIZATION; SUPPRESSES; TARGET; MOUSE AB Ethnopharmacological relevance: The traditional Chinese herbal formula, Xiang-lian Pill (XLP), is commonly prescribed for ulcerative colitis (UC) patients to relieve their clinical symptom. Nonetheless, the underlying cellular and molecular mechanisms of XLP's anti-UC effect remain incompletely understood.Aim of the study: To evaluate the therapeutic effect and elucidate the possible working mechanisms of XLP in UC treatment. The major active component of XLP was also characterized.Materials and methods: Colitis was induced in C57BL/6 mice with 3% dextran sulfate sodium (DSS) dissolved in drinking water for 7 consecutive days. The UC mice were grouped and treated with XLP (3640 mg/kg) or vehicle orally during the procedure of DSS induction. Mouse body weight, disease activity index (DAI) score and colon length were recorded. Histopathological changes and inflammatory cell infiltration were evaluated by pathological staining and flow cytometric analysis (FACS). Network pharmacology, bioinformatic analysis, widely targeted and targeted metabolomics analysis were performed to screen the potential effective ingredients and key targets. Bone marrow derived macrophages (BMDMs), peripheral blood mononuclear cells (PBMCs), RAW264.7 and THP-1 cells were used to dissect the anti-inflammatory effect of XLP.Results: Oral administration of XLP ameliorated DSS induced mouse colitis, as evidenced by reduced DAI and colonic inflammatory destruction. FACS results demonstrated that XLP treatment effectively restored immune tolerance in colon, inhibited the generation of monocyte derived macrophages and skewed macrophage polarization into M2 phenotype. Network pharmacology analysis suggested that innate effector modules related to macrophage activation comprise the major targets of XLP, and the counter-regulatory STAT1/PPAR gamma signaling possibly serves as the critical downstream pathway. Subsequent experiments unveiled an imbalance of STAT1/ PPAR gamma signaling in monocytes derived from UC patients, and validated that XLP suppressed LPS/IFN-gamma induced macrophage activation (STAT1 mediated) but facilitated IL-4 induced macrophage M2 polarization (PPAR gamma dependent). Meanwhile, our data showed that quercetin served as the major component of XLP to recapitulate the regulatory effect on macrophages. C1 [Zhou, Hai-feng; Li, Jun-yi; Qin, Ren-jie; Zhou, Qiao-li; Hu, De-sheng; Yang, Jia] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Integrated Tradit Chinese & Western Med, Wuhan 430022, Peoples R China. [Yang, Chao] Hubei Prov Hosp Integrated Chinese & Western Med, Dept Geratol, Wuhan 430015, Peoples R China. [He, Yu-yao] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Anesthesiol, Wuhan 430022, Peoples R China. [Huang, Yun] Zhengzhou Univ, Affiliated Hosp 3, Dept Clin Lab, Zhengzhou 450000, Peoples R China. [Sun, Fei] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Ctr Biomed Res,Dept Resp & Crit Care Med,Key Lab P, Wuhan 430030, Peoples R China. C3 Huazhong University of Science & Technology; Huazhong University of Science & Technology; Zhengzhou University; Huazhong University of Science & Technology RP Hu, DS; Yang, J (corresponding author), Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Integrated Tradit Chinese & Western Med, Wuhan 430022, Peoples R China.; Sun, F (corresponding author), Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Ctr Biomed Res,Dept Resp & Crit Care Med,Key Lab P, Wuhan 430030, Peoples R China. EM 309624203@qq.com; ychbtcm@163.com; lijunyi19901990@163.com; 1747390551@qq.com; 924541899@qq.com; 547045325@qq.com; 1434942106@qq.com; phil_sunfei@163.com; desheng.hu@hust.edu.cn; 2017XH0142@hust.edu.cn RI Sun, Fei/IZP-7789-2023 OI Sun, Fei/0000-0001-8184-6718 FU National Natural Science Founda-tion of China [81904015, 82104488, 82200923] FX Funding This study was supported by the National Natural Science Founda-tion of China (No. 81904015, 82104488, 82200923) . 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Ethnopharmacol. PD SEP 15 PY 2023 VL 313 AR 116557 DI 10.1016/j.jep.2023.116557 EA MAY 2023 PG 17 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA H8CX2 UT WOS:000998188000001 PM 37142141 DA 2026-03-26 ER PT J AU Li, XY Huang, X Feng, YM Wang, YQ Guan, JB Deng, BT Chen, QP Wang, YJ Chen, YM Wang, JH Yeong, J Hao, JF AF Li, Xiaoyu Huang, Xin Feng, Yongmin Wang, Yaqing Guan, Jibin Deng, Botian Chen, Qiuping Wang, Yanjing Chen, Yongming Wang, Jiahe Yeong, Joe Hao, Junfeng TI Cylindrin from Imperata cylindrica inhibits M2 macrophage formation and attenuates renal fibrosis by downregulating the LXR-α/PI3K/AKT pathway SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE Chronic kidney disease; Macrophage polarization; Cylindrin; Renal fibrosis ID PROLIFERATION; PROGRESSION AB Imperata cylindrica, a medicinal plant used in Traditional Chinese Medicine, has been used to treat chronic kidney disease. Extracts of I. cylindrica display anti-inflammatory, immunomodulatory, and anti-fibrotic properties. However, the active components of the extracts and their protective mechanisms have not been fully elucidated. In this study, we explored the ability of cylindrin, the main active compound extracted from I. cylindrica, to protect against renal fibrosis and to investigate the potential mechanisms involved. At high doses, cylindrin exerted protective effects against folic acid-induced kidney fibrosis in mice. Bioinformatic analysis predicted the LXR-alpha/PI3K/AKT pathway as a target of regulation by cylindrin. This was supported by our in vitro and in vivo results showing that cylindrin significantly downregulated the expression of LXR-alpha and phosphorylated PI3K/ AKT in M2 macrophages and mouse renal tissues. Furthermore, high-dose cylindrin inhibited M2 polarization of IL-4-stimulated macrophages in vitro. Our results suggest that cylindrin alleviates renal fibrosis by attenuating M2 macrophage polarization through inhibition of the PI3K/AKT pathway via downregulation of LXR-alpha. C1 [Li, Xiaoyu; Feng, Yongmin; Deng, Botian; Wang, Yanjing; Chen, Yongming; Hao, Junfeng] Guangdong Med Univ, Affiliated Hosp, Dept Nephrol, Zhanjiang 524001, Peoples R China. [Li, Xiaoyu; Feng, Yongmin; Deng, Botian; Chen, Yongming; Hao, Junfeng] Guangdong Med Univ, Guangdong Prov Key Lab Autophagy & Major Chron Non, Affiliated Hosp, Zhanjiang 524001, Peoples R China. [Huang, Xin; Wang, Jiahe; Hao, Junfeng] China Med Univ, Dept Family Med, Shengjing Hosp, Shenyang 110022, Peoples R China. [Wang, Yaqing] China Med Univ, Dept Nephrol, Affiliated Hosp 1, Shenyang 110000, Liaoning, Peoples R China. [Guan, Jibin] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA. [Chen, Qiuping] Guangdong Med Univ, Affiliated Hosp, Dept Geriatr, Zhanjiang 524001, Peoples R China. [Yeong, Joe] ASTAR, Inst Mol Cell Biol IMCB, Singapore, Singapore. [Yeong, Joe] Singapore Gen Hosp, Dept Anat Pathol, Singapore 169856, Singapore. C3 Guangdong Medical University; Guangdong Medical University; China Medical University; China Medical University; University of Minnesota System; University of Minnesota Twin Cities; Guangdong Medical University; Agency for Science Technology & Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology (IMCB); Singapore General Hospital RP Hao, JF (corresponding author), Guangdong Med Univ, Affiliated Hosp, Dept Nephrol, Zhanjiang 524001, Peoples R China.; Hao, JF (corresponding author), Guangdong Med Univ, Guangdong Prov Key Lab Autophagy & Major Chron Non, Affiliated Hosp, Zhanjiang 524001, Peoples R China.; Wang, JH; Hao, JF (corresponding author), China Med Univ, Dept Family Med, Shengjing Hosp, Shenyang 110022, Peoples R China.; Yeong, J (corresponding author), ASTAR, Inst Mol Cell Biol IMCB, Singapore, Singapore. EM wangjh1@sj-hospital.org; yeongps@imcb.a-star.edu.sg; ygzhjf85@gmail.com RI Wang, Jiahe/MTB-0607-2025; Chen, qiu/LCE-1743-2024; GUAN, JIBIN/HTR-4113-2023; feng, yongmin/JJF-1031-2023; Yeong, Joe/AFS-6236-2022; Huang, Xin/CAF-8251-2022 OI Yeong, Joe/0000-0002-6674-7153; Deng, Botian/0000-0003-4273-6625; Huang, Xin/0000-0001-5192-4906 FU National Natural Science Founda-tion of China [82000647]; GuangDong Basic and Applied Basic Research Foundation [2020A1515111080]; Discipline Con-struction Project of Guangdong Medical University [4SG21229G] FX Funding This research was funded by the National Natural Science Founda-tion of China (82000647) , the GuangDong Basic and Applied Basic Research Foundation (No. 2020A1515111080) and the Discipline Con-struction Project of Guangdong Medical University (4SG21229G) . 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PD JUL 5 PY 2023 VL 950 AR 175771 DI 10.1016/j.ejphar.2023.175771 EA MAY 2023 PG 12 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA I2JP8 UT WOS:001001102100001 PM 37146709 OA hybrid DA 2026-03-26 ER PT J AU Wang, XH Wei, SS Li, WZ Wei, XJ Zhang, C Dai, SL Ma, M Zhao, LM Shan, BE AF Wang, Xiaohan Wei, Sisi Li, Wanzhao Wei, Xiaojian Zhang, Cong Dai, Suli Ma, Ming Zhao, Lianmei Shan, Baoen TI P-Hydroxylcinnamaldehyde induces tumor-associated macrophage polarization toward the M1 type by regulating the proteome and inhibits ESCC in vivo and in vitro SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE p-Hydroxylcinnamaldehyde (CMSP); Tumor-associated macrophages; Polarization; Esophageal squamous cell carcinoma; Proteomics ID ROLES AB P-Hydroxylcinnamaldehyde (CMSP) was firstly isolated from Chinese medicine Cochinchinnamomordica seed (CMS) by our team and has been verified to have growth-inhibiting abilities in malignant tumors including esophageal squamous cell carcinoma (ESCC). However, the detailed mechanism of its function is still unclear. Tumor-associated macrophages (TAMs) are an essential component of the tumor microenvironment (TME), playing important roles in tumor growth, metastasis, angiogenesis, and epithelial-mesenchymal transition (EMT). In the present study, we found that the percentage of M1-like macrophages was significantly increased in TME of ESCC cell derived xenograft tumor model after CMSP treatment, while the ratios of other immune cells showed relatively low variation. To confirm these results, we further examined the effect of CMSP on macro-phage polarization in vitro. The results revealed that CMSP also could induce phorbol-12-myristate-13-acetate (PMA)-induced M0 macrophages from THP-1 and mouse peritoneal macrophages toward the M1-like macro-phages. Furthermore, CMSP could exert anti-tumor effect through TAMs in vitro co-culture model, in addition, the growth inhibition effect of CMSP was partly abolished in macrophage depletion model. To determine the potential pathway of CMSP induced polarization, we used quantitative proteomics (label-free) technology to explore the proteomic changes under CMSP treatment. The results revealed that immune-activating protein and M1 macrophage biomarkers were significantly increased after CMSP treatment. More importantly, CMSP stim-ulated pathways related to M1 macrophage polarization, such as the NF-kappa B signaling pathway and Toll-like receptor pathway, indicating that CMSP might induce M1-type macrophage polarization through these path-ways. In conclusion, CMSP can regulate immune microenvironment in vivo and induce TAM polarization toward the M1 type by promoting proteomic changes, and exert anti-tumor effect through TAMs. C1 [Wei, Sisi; Li, Wanzhao; Wei, Xiaojian; Zhang, Cong; Dai, Suli; Zhao, Lianmei; Shan, Baoen] Hebei Med Univ, Hosp 4, Res Ctr, Jiankang Rd 12, Shijiazhuang 050011, Peoples R China. [Wei, Sisi; Li, Wanzhao; Wei, Xiaojian; Zhang, Cong; Dai, Suli; Zhao, Lianmei; Shan, Baoen] Clin Oncol Res Ctr, Key Lab Tumor Gene Diag Prevent & Therapy, Shijiazhuang 050001, Hebei, Peoples R China. [Ma, Ming] Hebei Med Univ, Hosp 4, Dept Clin Lab, Shijiazhuang 050021, Peoples R China. [Zhao, Lianmei; Shan, Baoen] 12 Jiankang Rd, Shijiazhuang, Peoples R China. C3 Hebei Medical University; Hebei Medical University RP Zhao, LM; Shan, BE (corresponding author), 12 Jiankang Rd, Shijiazhuang, Peoples R China. EM zhaolianmei@hbydsy.com; shanbaoen@163.com RI ; wei, xiaojian/HJP-8349-2023 OI Wei, Sisi/0000-0001-5959-653X; FU Natural Science Foundation of China [U21A20415]; Hebei Provincial Key Research Projects [223777157D]; Natural Science Foundation of Hebei Province [H2020206131]; Key Research Projects of Hebei Province [223777107D] FX Funding This work was supported by the Natural Science Foundation of China (Grant No. U21A20415) , the Hebei Provincial Key Research Projects (Grant No. 223777157D) , Natural Science Foundation of Hebei Province (Grant No. H2020206131) and the Key Research Projects of Hebei Province (Grant No. 223777107D) . 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PD JUN PY 2023 VL 119 AR 110213 DI 10.1016/j.intimp.2023.110213 EA MAY 2023 PG 14 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA G8WO7 UT WOS:000991896600001 PM 37137266 DA 2026-03-26 ER PT J AU Wang, K Mao, TY Lu, XY Wang, MY Yun, YF Jia, ZY Shi, L Jiang, HX Li, JX Shi, R AF Wang, Ke Mao, Tangyou Lu, Xinyu Wang, Muyuan Yun, Yifei Jia, Zeyu Shi, Lei Jiang, Haoxi Li, Junxiang Shi, Rui TI A potential therapeutic approach for ulcerative colitis: targeted regulation of macrophage polarization through phytochemicals SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE macrophage; phenotype; polarization; phytochemicals; therapeutic effects; ulcerative colitis ID INFLAMMATORY-BOWEL-DISEASE; SIGNALING PATHWAY; INTESTINAL INFLAMMATION; EPITHELIAL-CELLS; M1 POLARIZATION; MONOCYTE; M2; MALIGNANCIES; CONTRIBUTES; ARTEMISININ AB Ulcerative colitis (UC), a type of inflammatory bowel disease characterized by recurring and incurable symptoms, causes immense suffering and economic burden for patients due to the limited treatment options available. Therefore, it is imperative to develop novel and promising strategies, as well as safe and effective drugs, for the clinical management of UC. Macrophages play a critical role as the initial line of defense in maintaining intestinal immune homeostasis, and their phenotypic transformation significantly influences the progression of UC. Scientific studies have demonstrated that directing macrophage polarization toward the M2 phenotype is an effective strategy for the prevention and treatment of UC. Phytochemicals derived from botanical sources have garnered the interest of the scientific community owing to their distinct bioactivity and nutritional value, which have been shown to confer beneficial protective effects against colonic inflammation. In this review, we explicated the influence of macrophage polarization on the development of UC and collated data on the significant potential of natural substances that can target the macrophage phenotype and elucidate the possible mechanism of action for its treatment. These findings may provide novel directions and references for the clinical management of UC. C1 [Wang, Ke; Lu, Xinyu; Wang, Muyuan; Yun, Yifei; Jia, Zeyu; Jiang, Haoxi] Beijing Univ Chinese Med, Grad Sch, Beijing, Peoples R China. [Wang, Ke; Mao, Tangyou; Lu, Xinyu; Wang, Muyuan; Yun, Yifei; Jia, Zeyu; Shi, Lei; Jiang, Haoxi; Li, Junxiang; Shi, Rui] Beijing Univ Chinese Med, Dongfang Hosp, Beijing, Peoples R China. C3 Beijing University of Chinese Medicine; Beijing University of Chinese Medicine RP Li, JX; Shi, R (corresponding author), Beijing Univ Chinese Med, Dongfang Hosp, Beijing, Peoples R China. EM lijunxiang1226@163.com; shiai588@163.com RI Lu, Xinyu/KIB-5798-2024; mao, tangyou/AFI-4620-2022; Shi, Rui/R-7159-2019; Wang, Muyuan/MZQ-1948-2025 OI Wang, Ke/0009-0008-3098-107X; FU National Natural Science Foundation of China [81874386]; Chinese Medicine Inheritance and Innovation "OneHundred Million" Talent Project Qihuang Scholar; Capital's Funds for Health Improvement and Research [shoufa 2022-4-4205] FX Funding This work was supported by the National Natural Science Foundation of China (No. 81874386), Chinese Medicine Inheritance and Innovation "OneHundred Million" Talent Project Qihuang Scholar (to JL) and Capital's Funds for Health Improvement and Research (shoufa 2022-4-4205). 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Immunol. PD MAY 1 PY 2023 VL 14 AR 1155077 DI 10.3389/fimmu.2023.1155077 PG 15 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA G2FZ4 UT WOS:000987392100001 PM 37197668 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Yang, X Wu, ML Yan, X Zhang, C Luo, YY Yu, J AF Yang, Xin Wu, Miaolin Yan, Xin Zhang, Cheng Luo, Yingying Yu, Jun TI Pulsatilla Saponins Inhibit Experimental Lung Metastasis of Melanoma via Targeting STAT6-Mediated M2 Macrophages Polarization SO MOLECULES LA English DT Article DE Pulsatilla saponins; M2 macrophages; STAT6; tumor metastasis ID TUMOR-ASSOCIATED MACROPHAGES; CANCER; ACTIVATION; MICROENVIRONMENT; COLITIS; CELLS AB Pulsatilla saponins (PS) extracts from Pulsatilla chinensis (Bge.) Regel, are a commonly used traditional Chinese medicine. In the previous study, we found Pulsatilla saponins displayed anti-tumor activity without side effects such as bone marrow suppression. However, the mechanism of the anti-tumor effect was not illustrated well. Since M2-like tumor-associated macrophages (TAMs) that required activation of the signal transducer and activator of transcription 6 (STAT6) for polarization are the important immune cells in the tumor microenvironment and play a key role in tumor progress and metastasis, this study aimed to confirm whether Pulsatilla saponins could inhibit the development and metastasis of tumors by inhibiting the polarization of M2 macrophages. We investigated the relevance of M2 macrophage polarization and the anti-tumor effects of Pulsatilla saponins in vitro and in vivo. In vitro, Pulsatilla saponins could decrease the mRNA level of M2 marker genes Arg1, Fizz1, Ym1, and CD206, and the down-regulation effect of phosphorylated STAT6 induced by IL-4; moreover, the conditioned medium (CM) from bone marrow-derived macrophages (BMDM) treated with Pulsatilla saponins could inhibit the proliferation and migration of B16-F0 cells. In vivo, Pulsatilla saponins could reduce the number of lung metastasis loci, down-regulate the expression of M2 marker genes, and suppress the expression of phosphorylated STAT6 in tumor tissues. Furthermore, we used AS1517499 (AS), a STAT6 inhibitor, to verify the role of PS on M2 macrophage polarization both in vitro and in vivo. We found that Pulsatilla saponins failed to further inhibit STAT6 activation; the mRNA level of Arg1, Fizz1, Ym1, and CD206; and the proliferation and migration of B16-F0 cells after AS1517499 intervention in vitro. Similar results were obtained in vivo. These results illustrated that Pulsatilla saponins could effectively suppress tumor progress by inhibiting the polarization of M2 macrophages via the STAT6 signaling pathway; this revealed a novel mechanism for its anti-tumor activity. C1 [Yang, Xin; Wu, Miaolin; Luo, Yingying] Jiangxi Univ Chinese Med, Ctr Translat Med, Jiangxi Key Lab Tradit Chinese Med Prevent & Treat, Nanchang 330006, Peoples R China. [Yan, Xin] Jiangxi Univ Chinese Med, Affiliated Hosp 2, Nanchang 330006, Peoples R China. [Zhang, Cheng; Luo, Yingying; Yu, Jun] Temple Univ, Ctr Metab Dis Res, Lewis Katz Sch Med, Dept Cardiovasc Sci, Philadelphia, PA 19140 USA. [Luo, Yingying] State Key Lab Innovat Drug & Efficient Energy Savi, 56 Yangming Rd, Nanchang 330006, Peoples R China. C3 Jiangxi University of Traditional Chinese Medicine; Jiangxi University of Traditional Chinese Medicine; Pennsylvania Commonwealth System of Higher Education (PCSHE); Temple University RP Luo, YY (corresponding author), Jiangxi Univ Chinese Med, Ctr Translat Med, Jiangxi Key Lab Tradit Chinese Med Prevent & Treat, Nanchang 330006, Peoples R China.; Luo, YY; Yu, J (corresponding author), Temple Univ, Ctr Metab Dis Res, Lewis Katz Sch Med, Dept Cardiovasc Sci, Philadelphia, PA 19140 USA.; Luo, YY (corresponding author), State Key Lab Innovat Drug & Efficient Energy Savi, 56 Yangming Rd, Nanchang 330006, Peoples R China. EM luoying0302@163.com; jun.yu@temple.edu RI ; Cheng, Zhang/NCV-2587-2025 OI Zhang, Cheng/0000-0001-8932-0585; FU National Natural Science Foundation of China [82060735, 81660683]; first-class discipline of Traditional Chinese Pharmacology of Jiangxi Province [JXSYLXK-ZHYAO122]; Jiangxi Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Vascular Remodeling Related Diseases [20202BCD42014] FX This work was partly supported by grants from the National Natural Science Foundation of China (No. 82060735, 81660683), first-class discipline of Traditional Chinese Pharmacology of Jiangxi Province (No. JXSYLXK-ZHYAO122), and Jiangxi Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Vascular Remodeling Related Diseases (No. 20202BCD42014). 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Y., 2018, MOD CHIN MED, V20, P791, DOI 10.13313/j.issn.1673-4890.20180119007 Yu T, 2019, NAT COMMUN, V10, DOI 10.1038/s41467-019-12384-2 Yuan A, 2015, SCI REP-UK, V5, DOI 10.1038/srep14273 Zhang BC, 2011, CLINICS, V66, P1879, DOI 10.1590/S1807-59322011001100006 Zhu CB, 2017, NEURO-ONCOLOGY, V19, P648, DOI 10.1093/neuonc/now251 NR 57 TC 11 Z9 13 U1 2 U2 31 PU MDPI PI BASEL PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND EI 1420-3049 J9 MOLECULES JI Molecules PD APR 24 PY 2023 VL 28 IS 9 AR 3682 DI 10.3390/molecules28093682 PG 14 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry GA G2FV9 UT WOS:000987388600001 PM 37175092 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Wang, J Gao, HY Xie, Y Wang, P Li, Y Zhao, JL Wang, CL Ma, X Wang, YW Mao, QW Xia, HB AF Wang, Juan Gao, Huiying Xie, Yuan Wang, Peng Li, Yu Zhao, Junli Wang, Chunlin Ma, Xin Wang, Yuwen Mao, Qinwen Xia, Haibin TI Lycium barbarum polysaccharide alleviates dextran sodium sulfate-induced inflammatory bowel disease by regulating M1/M2 macrophage polarization via the STAT1 and STAT6 pathways SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE inflammatory bowel disease; lycium barbarum polysaccharides; macrophage polarization; STAT1; STAT6 ID ULCERATIVE-COLITIS; ACTIVATION; RESPONSES; REPAIR; M2 AB Disruption of colonic homeostasis caused by aberrant M1/M2 macrophage polarization contributes to the development of inflammatory bowel disease (IBD). Lycium barbarum polysaccharide (LBP) is the primary active constituent of traditional Chinese herbal Lycium barbarum L., which has been widely demonstrated to have important functions in regulating immune activity and anti-inflammatory. Thus, LBP may protect against IBD. To test this hypothesis, the DSS-induced colitis model was established in mice, then the mice were treated with LBP. The results indicated that LBP attenuated the weight loss, colon shortening, disease activity index (DAI), and histopathological scores of colon tissues in colitis mice, suggesting that LBP could protect against IBD. Besides, LBP decreased the number of M1 macrophages and the protein level of Nitric oxide synthase 2(NOS2) as a marker of M1 macrophages and enhanced the number of M2 macrophages and the protein level of Arginase 1(Arg-1) as a marker of M2 macrophages in colon tissues from mice with colitis, suggesting that LBP may protect against IBD by regulating macrophage polarization. Next, the mechanistic studies in RAW264.7 cells showed that LBP inhibited M1-like phenotype by inhibiting the phosphorylation of STAT1, and promoted M2-like phenotype by promoting the phosphorylation of STAT6. Finally, immunofluorescence double-staining results of colon tissues showed that LBP regulated STAT1 and STAT6 pathways in vivo. The results in the study demonstrated that LBP could protect against IBD by regulating macrophage polarization through the STAT1 and STAT6 pathways. C1 [Wang, Juan; Gao, Huiying; Xie, Yuan; Wang, Peng; Li, Yu; Zhao, Junli; Wang, Chunlin; Ma, Xin; Wang, Yuwen; Xia, Haibin] Shaanxi Normal Univ, Coll Life Sci, Dept Biochem, Lab Gene Therapy, Xian, Peoples R China. [Wang, Juan] Ningxia Med Univ, Sch Basic Med Sci, Dept Pathol, Yinchuan, Ningxia, Peoples R China. [Mao, Qinwen] Univ Utah, Huntsman Canc Inst, Dept Pathol, Salt Lake City, UT USA. C3 Shaanxi Normal University; Ningxia Medical University; Utah System of Higher Education; University of Utah; Huntsman Cancer Institute RP Xia, HB (corresponding author), Shaanxi Normal Univ, Coll Life Sci, Dept Biochem, Lab Gene Therapy, Xian, Peoples R China. EM hbxia2001@163.com RI Wang, Yuwen/PDY-5089-2025 OI Wang, Yuwen/0009-0006-9405-6276 FU Fundamental Research Funds for the Central Universities [2019TS081, GK202007023, GK202107018]; National Natural Science Foundation of China [81773265]; Key Research and Development Plan of Shaanxi Province [2018SF-106]; National Center for Advancing Translational Sciences [UL1TR002538] Funding Source: NIH RePORTER FX Funding This work was supported by the Fundamental Research Funds for the Central Universities (No. 2019TS081, No. GK202007023, and No. GK202107018), the National Natural Science Foundation of China (No. 81773265), and the Key Research and Development Plan of Shaanxi Province (No. 2018SF-106). 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PD APR 18 PY 2023 VL 14 AR 1044576 DI 10.3389/fphar.2023.1044576 PG 15 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA F1QF7 UT WOS:000980155800001 PM 37144216 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Xiao, Y Zhang, JX Zhu, XY Zhao, WX Li, YQ Jin, NY Lu, HJ Han, JC AF Xiao, Yan Zhang, Jinxin Zhu, Xiangyu Zhao, Wenxin Li, Yiquan Jin, Ningyi Lu, Huijun Han, Jicheng TI Fu-Zheng-Xuan-Fei formula promotes macrophage polarization and Th17/ Treg cell homeostasis against the influenza B virus (Victoria strain) infection SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Influenza B virus; Antiviral drugs; Traditional Chinese medicines; Macrophage polarization; Th17; Treg homeostasis ID RESPIRATORY MORTALITY; RADIX; ACTIVATION; CASPASES; EXTRACTS; CHINA; GSDMD AB Ethnopharmacological relevance: Fu-Zheng-Xuan-Fei formula (FF) is a prescription that has been clinically used through the basic theory of traditional Chinese medicine (TCM) for treating viral pneumonia. Although FF possesses a prominent clinical therapeutic effect, seldom pharmacological studies have been reported on its antiinfluenza B virus (IBV) activity.Aim of the study: Influenza is an acute infectious respiratory disease caused by the influenza virus, which has high annual morbidity and mortality worldwide. With a global decline in the COVID-19 control, the infection rate of influenza virus is gradually increasing. Therefore, it is of great importance to develop novel drugs for the effective treatment of influenza virus. Apart from conventional antiviral drugs, TCM has been widely used in the clinical treatment of influenza in China. Therefore, studying the antiviral mechanism of TCM can facilitate the scientific development of TCM.Materials and methods: Madin-Darby canine kidney cells (MDCK) and BALB/c mice were infected with IBV, and FF was added to evaluate the anti-IBV effects of FF both in vitro and in vivo by Western blotting, immunofluorescence, flow cytometry, and pathological assessment. Results: It was found that FF exhibited anti-viral activity against IBV infection both in vivo and in vitro, while inducing macrophage activation and promoting M1 macrophage polarization. In addition, FF effectively regulated the signal transducer and activator of transcription (STAT) signaling pathway-mediated Th17/Treg balance to improve the lung tissue damage caused by IBV infection-induced inflammation. The findings provided the scientific basis for the antiviral mechanism of FF against IBV infection.Conclusions: This study shows that FF is a potentially effective antiviral drug against IBV infection. C1 [Xiao, Yan; Jin, Ningyi] Northwest A&F Univ, Coll Vet Med, Yangling 712100, Peoples R China. [Zhang, Jinxin; Li, Yiquan; Han, Jicheng] Changchun Univ Chinese Med, Academician Workstat, Changchun 130117, Peoples R China. [Xiao, Yan; Zhu, Xiangyu; Zhao, Wenxin; Jin, Ningyi; Lu, Huijun; Han, Jicheng] Chinese Acad Agr Sci, Changchun Vet Res Inst, Changchun 130122, Peoples R China. C3 Northwest A&F University - China; Changchun University of Chinese Medicine; Chinese Academy of Agricultural Sciences RP Jin, NY (corresponding author), Northwest A&F Univ, Coll Vet Med, Yangling 712100, Peoples R China.; Han, JC (corresponding author), Changchun Univ Chinese Med, Academician Workstat, Changchun 130117, Peoples R China.; Jin, NY; Lu, HJ; Han, JC (corresponding author), Chinese Acad Agr Sci, Changchun Vet Res Inst, Changchun 130122, Peoples R China. EM 1986721142@qq.com; 1330432818@163.com; zhuxiangyu00@126.com; zhaowenxin9908@163.com; 905381255@qq.com; ningyik@126.com; huijun_lu@126.com; 373108406@qq.com RI Zhu, Xiangyu/NBY-2483-2025 OI Zhu, Xiangyu/0009-0003-0203-0342 FU Natural Science Foundation of Jilin Province [YDZJ202201ZYTS254]; China Postdoctoral Science Foundation [2022M713867]; Jilin Province Young Science and Technology Talent Support Project [QT202228]; Jilin Province Traditional Chinese Medicine Science and Technology Project [2022129]; Changchun Science and Technology Development Project [21ST03] FX Funding This work was supported by Natural Science Foundation of Jilin Province [Grant No. YDZJ202201ZYTS254] , China Postdoctoral Science Foundation [Grant No. 2022M713867] , Jilin Province Young Science and Technology Talent Support Project [Grant No. QT202228] , the Jilin Province Traditional Chinese Medicine Science and Technology Project [Grant No. 2022129] , and the Changchun Science and Technology Development Project [Grant No. 21ST03] . 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Ethnopharmacol. PD AUG 10 PY 2023 VL 312 AR 116485 DI 10.1016/j.jep.2023.116485 EA APR 2023 PG 13 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA F6YQ5 UT WOS:000983784600001 PM 37044232 OA hybrid DA 2026-03-26 ER PT J AU Lin, YR Zheng, FT Xiong, BJ Chen, ZH Chen, ST Fang, CN Yu, CX Yang, J AF Lin, Ya-rong Zheng, Feng-ting Xiong, Bo-jun Chen, Ze-hong Chen, Shi-ting Fang, Chao-nan Yu, Chang-xi Yang, Jian TI Koumine alleviates rheumatoid arthritis by regulating macrophage polarization SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Koumine; Rheumatoid arthritis; Macrophage polarization; M1 macrophage; M2 macrophage; PI3K/AKT signaling Pathway ID GELSEMIUM-ELEGANS BENTH.; DIFFERENTIATION; METASTASIS; CELLS AB Ethnopharmacological relevance: The imbalance between M1-and M2-polarized macrophages is one of the major pathophysiological changes in RA. Therefore, targeted macrophage polarization may be an effective therapy for RA. Koumine, an alkaloid monomer with the highest content and low toxicity in Gelsemium elegans Benth., has the effect of treating RA by playing an immunomodulatory role by influencing various immune cells. However, whether koumine affects macrophage polarization in RA and the associated molecular mechanisms remain unknown.Aim of the study: To investigate the mechanism of the anti-RA effect of koumine on macrophage polarization. Materials and methods: The effect of koumine on macrophage polarization was investigated in vivo and in vitro. We first explored the effects of koumine on AIA rats and detected the levels of M1/M2 macrophage polarization markers in the spleen by western blotting. Then, we explored the regulatory effect of koumine on M1/M2 macrophage polarization and the effect on the PI3K/AKT signaling pathway in vitro. Finally, we verified the effects of koumine on macrophage polarization in CIA mice. Results: We found that koumine alleviated symptoms, including relieving pain, reducing joint redness and swelling in AIA rats and restoring the M1/M2 macrophage balance in vivo. Interestingly, koumine had an inhibitory effect on both M1 and M2 macrophage polarization in vitro, but it had a stronger inhibitory effect on M1 macrophage. In a mixed polarization experiment, koumine mainly inhibited M1 macrophage polarization and had an inhibitory effect on the PI3K/AKT signaling pathway. Finally, we found that koumine had therapeutic effects on CIA mice, regulated macrophage polarization and inhibited the PI3K/AKT signaling pathway.Conclusions: Our results reveal that koumine regulates macrophage polarization through the PI3K/AKT signaling pathway. This may be one of the important mechanisms of its anti-RA effect, which provides a theoretical and scientific basis for the possible clinical application of koumine. C1 [Xiong, Bo-jun; Yu, Chang-xi; Yang, Jian] Fujian Med Univ, Sch Pharm, Dept Pharmacol, Fuzhou 350122, Peoples R China. [Yu, Chang-xi] Fujian Med Univ, Sch Pharm, Fujian Key Lab Drug Target Discovery & Struct & Fu, Fuzhou 350122, Peoples R China. [Lin, Ya-rong; Zheng, Feng-ting; Chen, Shi-ting; Fang, Chao-nan; Yu, Chang-xi; Yang, Jian] Fujian Med Univ, Sch Pharm, Fujian Key Lab Nat Med Pharmacol, Fuzhou 350122, Peoples R China. [Chen, Ze-hong] Fujian Med Univ, Basic Med Expt Teaching Ctr, Sch Basic Med Sci, Lab Med Funct, Fuzhou 350122, Peoples R China. [Yu, Chang-xi; Yang, Jian] Fujian Med Univ, Sch Pharm, Fuzhou 350122, Fujian, Peoples R China. C3 Fujian Medical University; Fujian Medical University; Fujian Medical University; Fujian Medical University; Fujian Medical University RP Yu, CX; Yang, J (corresponding author), Fujian Med Univ, Sch Pharm, Fuzhou 350122, Fujian, Peoples R China. EM fjmu_lyr@163.com; zft15759129270@163.com; xiongbojun@mail.fjmu.edu.cn; czh838515449@mail.fjmu.edu.cn; 1715306912@qq.com; 348984859@qq.com; changxiyu@mail.fjmu.edu.cn; fjmukent@mail.fjmu.edu.cn RI Chen, Zehong/NFT-2062-2025 FU Joint Funds for the Innovation of Science and Technology of Fujian Province [2018Y9073, 81872879]; National Natural Science Foundation of China [81973309, 087376]; Fujian Provincial Talent Project; [2020Y9010] FX This work was supported by the Joint Funds for the Innovation of Science and Technology of Fujian Province (Nos. 2020Y9010 and 2018Y9073) , the National Natural Science Foundation of China (Nos. 81872879 and 81973309) , and the Fujian Provincial Talent Project (No.087376). 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Ethnopharmacol. PD JUL 15 PY 2023 VL 311 AR 116474 DI 10.1016/j.jep.2023.116474 EA APR 2023 PG 15 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA P9XF2 UT WOS:001054130900001 PM 37031823 DA 2026-03-26 ER PT J AU Duraisamy, P Ravi, S Krishnan, M Martin, LC Manikandan, B Raman, T Munusamy, A Ramar, M AF Duraisamy, Parimalanandhini Ravi, Sangeetha Krishnan, Mahalakshmi Martin, Livya Catherene Manikandan, Beulaja Raman, Thiagarajan Munusamy, Arumugam Ramar, Manikandan TI Scoparia dulcis and Indigofera tinctoria as potential herbal remedies against 7-ketocholesterol-induced pro-inflammatory mediators of macrophage polarization SO JOURNAL OF HERBAL MEDICINE LA English DT Article DE Polarization; Atherosclerosis; Anti-inflammatory; 7-ketocholesterol; Lipopolysaccharide ID MEDICINAL-PLANTS; ANTIOXIDANT; EXTRACT; OXYSTEROLS; DIFFERENTIATION; PATHOGENESIS; MECHANISMS; MONOCYTE; STRESS; CELLS AB Introduction: Herbs with medicinal properties contribute to atheroprotective effects through their preventive and therapeutic interactions with macrophages. Scoparia dulcis and Indigofera tinctoria are examples of such medicinal owing to their antiinflammatory, antioxidant, antibacterial and anticancer properties. The aim of this study was to investigate the antiatherogenic potential of hot- and cold-water extracts of Scoparia dulcis (HwSd and CwSd) and Indigofera tinctoria (HwIt and CwIt). Methods: S. dulcis and I. tinctoria extracts were primarily analyzed for phytochemical constituents. In vitro model of atherosclerosis was established using IC-21 M2 phenotypic macrophages, which were stimulated using 7-ketocholesterol (7KCh) and lipopolysaccharide (LPS). In addition, their antiinflammatory and antioxidant potential against 7KCh and LPS-induced macrophage polarization mediators like intracellular ROS/ RNS and gene expression of pro-inflammatory mediators were studied. Results: HwSd, CwSd, HwIt and CwIt contained alkaloids, amino acids, flavonoids, glycosides, reducing sugar, saponins, tannins and terpenoids. In addition, they improved oxidative stress caused by nitric oxide and reactive oxygen species, as well as exhibited anti-inflammatory activity. Furthermore, they modulated gene expression of pro-inflammatory mediators (iNOS, IL-1 beta, COX-2, TLR-4, MMP-9 and IL-6). Conclusions: Based on these results, we concluded that Scoparia dulcis and Indigofera tinctoria possess antiatherogenic potential and can be beneficial in treating several illnesses associated with chronic inflammation. C1 [Duraisamy, Parimalanandhini; Ravi, Sangeetha; Krishnan, Mahalakshmi; Martin, Livya Catherene; Munusamy, Arumugam; Ramar, Manikandan] Univ Madras, Dept Zool, Guindy Campus, Chennai 600025, India. [Manikandan, Beulaja] Annai Veilankannis Coll Women, Dept Biochem, Chennai 600015, India. [Raman, Thiagarajan] Vivekananda Coll, Dept Zool, Ramakrishna Mission, Chennai 600004, India. C3 University of Madras RP Ramar, M (corresponding author), Univ Madras, Dept Zool, Guindy Campus, Chennai 600025, India. 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PD JUN PY 2023 VL 39 AR 100652 DI 10.1016/j.hermed.2023.100652 EA APR 2023 PG 13 WC Integrative & Complementary Medicine WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine GA F2GF9 UT WOS:000980574500001 DA 2026-03-26 ER PT J AU Li, MY Wu, YZ Qiu, JG Lei, JX Li, MX Xu, N Liu, YH Jin, Z Su, ZR Lee, SMY Zheng, XB Xiao-qi, H AF Li, Min-yao Wu, Yu-zhu Qiu, Jian-guo Lei, Jun-xuan Li, Mu-xia Xu, Nan Liu, Yu -hong Jin, Zhen Su, Zi-ren Lee, Simon Ming-Yuen Zheng, Xue-bao Xiao-qi, Huang TI Huangqin Decoction ameliorates ulcerative colitis by regulating fatty acid metabolism to mediate macrophage polarization via activating FFAR4-AMPK-PPAR? pathway SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Huangqin decoction; Ulcerative colitis; Gut microbiota; Fatty acid metabolism; Macrophage polarization; FFAR4-AMPK-PPAR? pathway ID INFLAMMATORY-BOWEL-DISEASE; GUT MICROBIOTA; INHIBITION; RESOLUTION; DRIVES AB Ethnopharmacological relevance: Huangqin Decoction (HQD), a traditional Chinese medicine (TCM) formula chronicled in Shang Han Lun, is safe and effective for treatment of ulcerative colitis (UC).Aim of the study: To investigate the effect of HQD against dextran sulfate sodium (DSS)-induced UC mice by regulating gut microbiota and metabolites, and further explore the mechanism of fatty acid metabolism on macrophage polarization.Materials and methods: Based on 3% dextran sulfate sodium (DSS)-induced UC mice model, clinical symptoms observation (body weight, DAI, and colon length) and histological inspection were used to evaluate the efficacy of HQD and fecal microbiota transplantation (FMT) from HQD-treated mice. The gut microbiota and metabolites were detected by 16S rRNA sequencing and metabolomics analysis. The parameters of fatty acid metabolism, macrophage polarization, and FFAR1/FFAR4-AMPK-PPAR alpha pathway were analyzed by immunofluorescence analysis, western blotting, and real-time PCR. Then, the effects of FFAR1 and FFAR4 on macrophage polarization were examined by agonists based on LPS-induced RAW264.7 cell model.Results: The results showed that FMT, like HQD, ameliorated UC by improving weight loss, restoring colon length, and reducing DAI scores and histopathological scores. Besides, HQD and FMT both enhanced the richness of gut microbiota, and modulated intestinal bacteria and metabolites to achieve a new balance. Untargeted metabolomics analysis revealed that fatty acids, especially long-chain fatty acids (LCFAs), dominated in HQD against DSS-induced UC by regulating the gut microenvironment. Further, FMT and HQD recovered the expression of fatty acid metabolism-related enzymes, and simultaneously activated FFAR1/FFAR4-AMPK-PPAR alpha pathway but suppressed NF-kappa B pathway. Combined with cell experiment, HQD and FMT promoted macrophage polarization from M1 toward M2, which were well associated with anti-inflammatory cytokines and combined with the activated FFAR4.Conclusions: The mechanism of HQD against UC was related to regulating fatty acid metabolism to mediate M2 macrophage polarization by activating the FFAR4-AMPK-PPAR alpha pathway. C1 [Li, Min-yao; Wu, Yu-zhu; Qiu, Jian-guo; Lei, Jun-xuan; Zheng, Xue-bao; Xiao-qi, Huang] Guangzhou Univ Chinese Med, Sch Pharmaceut Sci, Guangzhou, Peoples R China. [Li, Mu-xia] Guangzhou Univ Chinese Med, Dongguan Inst, Dongguan, Peoples R China. [Jin, Zhen] Guangzhou Univ Chinese Med, Shenzhen Key Lab Hosp Chinese Med Preparat, Shenzhen Tradit Chinese Med Hosp, Clin Med Coll 4, Shenzhen, Peoples R China. [Xu, Nan; Lee, Simon Ming-Yuen] Guangzhou Univ Chinese Med, Clin Med Coll 1, Guangzhou, Peoples R China. [Lee, Simon Ming-Yuen] Univ Macau, State Key Lab Qual Res Chinese Med, Macau, Peoples R China. [Lee, Simon Ming-Yuen] Univ Macau, Inst Chinese Med Sci, Macau, Peoples R China. [Zheng, Xue-bao; Xiao-qi, Huang] Univ Macau, Fac Hlth Sci, Dept Pharmaceut Sci, Macau, Peoples R China. [Zheng, Xue-bao; Xiao-qi, Huang] Guangzhou Univ Chinese Med, Sch Pharmaceut Sci, 232, Waihuan East Rd, Guangzhou 510006, Peoples R China. C3 Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine; Shenzhen Traditional Chinese Medicine Hospital; Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine; University of Macau; University of Macau; University of Macau; Guangzhou University of Chinese Medicine RP Zheng, XB; Xiao-qi, H (corresponding author), Guangzhou Univ Chinese Med, Sch Pharmaceut Sci, 232, Waihuan East Rd, Guangzhou 510006, Peoples R China. EM xuebaozheng@gzucm.edu.cn; huangxiaoqi@gzucm.edu.cn RI Su, Zi-Ren/O-5014-2019; lee, Simon Ming Yuen/NOE-8462-2025; Liu, Yuhong/AAT-9680-2021; Xiaoqi, Huang/AAK-7124-2020; LEI, Junxuan/LGZ-1380-2024; Qiu, Jianguo/LIF-1049-2024 OI lee, Simon Ming Yuen/0000-0002-3966-6569; Xiaoqi, Huang/0000-0003-3401-5000; FU National Natural Foundation of China [82274227]; National Natural Science Foundation of Guangdong, China [2019A1515010673, 2022A1515010092]; Science and Technology Program of Guangzhou [202002030222]; "Double First-Class" and High Level University Discipline Collaborative Innovation Team Cultivation Project of Guangzhou University of Chinese Medicine [2021xk34]; Guangdong Basic and Applied Basic Research Foundation [2021B1515140043]; International Program for Postgraduates, Guangzhou University of Chinese Medicine FX This work was supported by National Natural Foundation of China (grant number: 82274227); National Natural Science Foundation of Guangdong, China (grant number: 2019A1515010673 & 2022A1515010092); Science and Technology Program of Guangzhou (grant number: 202002030222); "Double First-Class" and High Level University Discipline Collaborative Innovation Team Cultivation Project of Guangzhou University of Chinese Medicine (grant number: 2021xk34); Guangdong Basic and Applied Basic Research Foundation (grant number: 2021B1515140043); International Program for Postgraduates, Guangzhou University of Chinese Medicine. 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Ethnopharmacol. PD JUL 15 PY 2023 VL 311 AR 116430 DI 10.1016/j.jep.2023.116430 EA APR 2023 PG 13 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA F4HA3 UT WOS:000981961200001 PM 36997133 DA 2026-03-26 ER PT J AU Ding, HY Dong, JX Wang, YQ Huang, Q Xu, J Qiu, ZD Yao, F AF Ding, Hongyue Dong, Jinxiang Wang, Yuqi Huang, Qiang Xu, Jie Qiu, Zhidong Yao, Fan TI Ginsenoside Rb1 Interfered with Macrophage Activation by Activating PPARγ to Inhibit Insulin Resistance in Obesity SO MOLECULES LA English DT Article DE ginsenoside Rb1; insulin resistance; inflammation; PPAR gamma; network pharmacology ID RECEPTOR AB Type 2 diabetes (T2D) is characterized by insulin resistance (IR), often accompanied by inflammation. Macrophage activation acts as an inflammatory response, which is characterized by macrophage recruitment in the initial stage. Ginsenoside Rb1 (Rb1) is a main active ingredient, which is known for its fat-reducing, anti-inflammatory effects. To clarify that Rb1 regulates macrophage activation in adipose tissue and improves tissue inflammation, network pharmacology and molecular docking were used for target prediction and preliminary validation. By constructing the co-culture model of adipose-derived stem cells (ADSC) and primary macrophage (PM), the body adipose tissue microenvironment was simulated to observe the adipogenesis degree of adipocytes under the effect of Rb1. The levels of cytokines, macrophage polarization, and protein or RNA expression in the inflammatory signaling pathway were finally detected. The results showed that 89 common targets of T2D-Rb1 were obtained after their intersection. Furthermore, according to the results of the KEGG pathway and PPI analysis, PTGS2 (COX-2) is the downstream protein of PPAR gamma-NF-kappa B. The molecular binding energy of PPAR gamma-Rb1 is 6.8 kcal/mol. Rb1 significantly inhibited the increase in MCP-1, TNF-alpha, and IL-1 beta induced by hypertrophic adipocytes supernatant and promoted the expression of IL-10. Rb1 inhibited the activation of inflammatory macrophages and PM migration and upregulated PPAR gamma expression with the blocking of NF- kappa B activation. Additionally, Rb1 promoted the expression of IRS1 and PI3K in the insulin signal pathway, which had a similar effect with ROS. Therefore, Rb1 might affect macrophage activation through PPAR gamma, which might alleviate obese insulin resistance in T2D early stage. C1 [Ding, Hongyue; Dong, Jinxiang; Wang, Yuqi; Huang, Qiang; Xu, Jie; Qiu, Zhidong; Yao, Fan] Changchun Univ Chinese Med, Sch Pharmaceut Sci, Changchun 130117, Peoples R China. C3 Changchun University of Chinese Medicine RP Qiu, ZD; Yao, F (corresponding author), Changchun Univ Chinese Med, Sch Pharmaceut Sci, Changchun 130117, Peoples R China. EM qiuzhongdong@ccucm.edu.cn; yaofan@ccucm.edu.cn OI Yao, Fan/0000-0003-1888-621X FU National Natural Science Foundation of China [81803796]; Major Science and technology projects of Jilin province [20200504005YY] FX This research was funded by National Natural Science Foundation of China, grant number: 81803796 and Major Science and technology projects of Jilin province, grant number: 20200504005YY. 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Tumor-associated macrophages (TAMs) have been considered as potential targets for treating breast cancer metas-tasis because they promote tumor growth and development. Glycyrrhetinic acid (GA) is one of the most important phytochemicals of licorice which has shown promising anti-cancer efficacies in pre-clinical trials. However, the regulatory effect of GA on the polarization of TAMs remains elusive. Purpose: To investigate the role of GA in regulating the polarization of M2 macrophages and inhibiting breast cancer metastasis, and to further explore its underlying mechanisms of action. Study Design: IL-4 / IL-13-treated RAW 264.7 and THP-1 cells were used as the M2-polarized macrophages in vitro. A 4T1 mouse breast cancer model and the tail vein breast cancer metastasis model were applied to study the effect of GA on breast cancer growth and metastasis in vivo. Results: In vitro studies showed that GA significantly inhibited IL-4 / IL 13-induced M2-like polarization in RAW 264.7 and THP-1 macrophages without affecting M1-like polarization. GA strongly decreased the expression of M2 macrophage markers CD206 and Arg-1, and reduced the levels of the pro-angiogenic molecules VEGF, MMP9, MMP2 and IL-10 in M2 macrophages. GA also increased the phosphorylation of JNK1/2 in M2 macro-phages. Moreover, GA significantly suppressed M2 macrophage-induced cell proliferation and migration in 4T1 cancer cells and HUVECs. Interestingly, the inhibitory effects of GA on M2 macrophages were abolished by a JNK inhibitor. Animal studies showed that GA significantly suppressed tumor growth, angiogenesis, and lung metastasis in BALB/c mice bearing breast tumor. In tumor tissues, GA reduced the number of M2 macrophages but elevated the proportion of M1 macrophages, accompanied by activation of JNK signaling. Similar results were found in the tail vein breast cancer metastasis model. C1 [Cheng, Yanfen; Zhong, Xuemei; Gu, Huan; Wu, Yihan; Fu, Chaomei; Zhang, Jinming; Li, Jingjing] Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, Chengdu, Peoples R China. [Wu, Xiaoping; Li, Renkai; Leung, George Pak-Heng; Li, Jingjing] Univ Hong Kong, Li Ka Shing Fac Med, Dept Pharmacol & Pharm, Hong Kong, Peoples R China. [Lv, Kongpeng] Jinan Univ, Shenzhen Peoples Hosp, Dept Intervent Radiol, Clin Med Coll 2, Shenzhen, Peoples R China. [Lv, Kongpeng] Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen, Peoples R China. [Lee, Simon Ming-Yuen] Univ Macau, State Key Lab Qual Res Chinese Med, Macau, Peoples R China. [Lee, Simon Ming-Yuen] Univ Macau, Inst Chinese Med Sci, Macau, Peoples R China. [Zhang, Jinming; Li, Jingjing] Chengdu Univ Tradit Chinese Med, Coll Pharm, State Key Lab Southwestern Chinese Med Resources, 1166 Liutai Ave, Chengdu, Peoples R China. C3 Chengdu University of Traditional Chinese Medicine; University of Hong Kong; Jinan University; Southern University of Science & Technology; University of Macau; University of Macau; Chengdu University of Traditional Chinese Medicine RP Zhang, JM; Li, JJ (corresponding author), Chengdu Univ Tradit Chinese Med, Coll Pharm, State Key Lab Southwestern Chinese Med Resources, 1166 Liutai Ave, Chengdu, Peoples R China. EM cdutcmzjm@126.com; ljj805812@163.com RI Leung, George Pak Heng/B-4529-2009; lee, Simon Ming Yuen/NOE-8462-2025; Leung, Gabriel/C-4336-2009; Wu, Xiaoping/KVX-9826-2024 OI Leung, George Pak Heng/0000-0003-3529-9367; lee, Simon Ming Yuen/0000-0002-3966-6569; Li, Jingjing/0000-0003-3636-0537; FU National Natural Science Foundation of China [82104462, 81973662, 82274112]; China Postdoctoral Science Foundation [2022M710499]; Xinglin Scholar Research Promotion Project of Chengdu University of Traditional Chinese Medicine [BSH2021005]; Innovation Team and Talents Cultivation Program of National Administration of TraditionalChinese Medicine [ZYYCXTD-D-202209] FX This study was supported by the National Natural Science Foundation of China (Grant No. 82104462, 81973662, 82274112) , China Postdoctoral Science Foundation (Grant No. 2022M710499) , Xinglin Scholar Research Promotion Project of Chengdu University of Traditional Chinese Medicine (Grant No. BSH2021005) , Innovation Team and Talents Cultivation Program of National Administration of TraditionalChinese Medicine (Grant No: ZYYCXTD-D-202209) . 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As a member of the human innate immune cells, macrophages usually show different phenotypes in different diseases. The macrophage phenotype (M1/M2) imbalance caused by the increase of M1 macrophages or the decrease of M2 macrophages is common in inflammatory dermatosis. In recent years, with the deepening research on inflammatory skin diseases, more and more natural medicines/traditional Chinese medicines (TCMs), represented by Shikonin and Angelica Dahurica, have shown their therapeutic effects by affecting the polarization of macrophages. This review introduced macrophage polarization in different inflammatory dermatosis, such as psoriasis. Then summarized the natural medicines/TCMs that have potential therapeutic effects so far and introduced their mechanisms of action and the proteins/signal pathways involved. We found that the TCMs with therapeutic effects listed in this review are closely related to the theory of five flavors and four properties of Chinese medicinal, and most of them are bitter, acrid and sweet. Bitter TCMs have antipyretic, anti-inflammatory and antibacterial effects, which may improve the persistent inflammation of M1 macrophage infiltration. Acrid TCMs have the effect of promoting blood circulation, while sweet TCMs have the effect of nourishing. These 2 flavors may accelerate the repair of skin lesions of inflammatory dermatosis by affecting M2 macrophages. In conclusion, we hope to provide sufficient knowledge for natural medicine research and the development of inflammatory dermatosis related to macrophage phenotype imbalance. C1 [Sun, Qingru; Hu, Shiyu; Lou, Zhaohuan; Gao, Jianli] Zhejiang Chinese Med Univ, Sch Pharmaceut Sci, Hangzhou 310053, Zhejiang, Peoples R China. C3 Zhejiang Chinese Medical University RP Gao, JL (corresponding author), Zhejiang Chinese Med Univ, Sch Pharmaceut Sci, Hangzhou 310053, Zhejiang, Peoples R China. EM jianligao@zcmu.edu.cn RI GAO, JianLi/J-4997-2017 OI GAO, JianLi/0000-0002-5977-0021; Sun, Qingru/0009-0005-4751-1718 FU Zhejiang Provincial Key Laboratory Project [2012E10002]; National Natural Science Foundation of China [82274621] FX Funding This work was supported by Zhejiang Provincial Key Laboratory Project (No. 2012E10002) , and National Natural Science Foundation of China (82274621) . 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Pharmacother. PD MAY PY 2023 VL 161 AR 114469 DI 10.1016/j.biopha.2023.114469 EA MAR 2023 PG 17 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA C8QJ1 UT WOS:000964496300001 PM 37002572 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Xun, J Zhou, SY Lv, ZJ Wang, BT Luo, H Zhang, LQ Yang, L Zhang, AM Wu, XL Wang, ZY Wang, XM Yu, XY Zhang, Q AF Xun, Jing Zhou, Siying Lv, Zongjing Wang, Botao Luo, Hai Zhang, Lanqiu Yang, Lei Zhang, Aimin Wu, Xueliang Wang, Zhenyu Wang, Ximo Yu, Xiangyang Zhang, Qi TI Dioscin modulates macrophages polarization and MDSCs differentiation to inhibit tumorigenesis of colitis-associated colorectal cancer SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Colitis -associated colorectal cancer; Tumorigenesis; Dioscin; Macrophage polarization; Myeloid -derived suppressor cells ID INFLAMMATORY-BOWEL-DISEASE; ULCERATIVE-COLITIS; SUPPRESSOR-CELLS; MECHANISMS; FIBROSIS; IMMUNITY; RISK; MICE; VIVO AB It has been reported that colitis is one of risk factors in colorectal cancer (CRC). Intervention of intestinal inflammation and in the early stage of tumorigenesis is of great significance to control the incidence and mortality of CRC. In recent years, natural active products of traditional Chinese medicine have been confirmed that they had made great progress in disease prevention. Here, we showed that Dioscin, a natural active product of Dioscorea nipponica Makino, inhibited initiation and tumorigenesis of AOM/DSS-induced colitis-associated colon cancer (CAC), including alleviating colonic inflammation, improving intestinal barrier function and decreasing tumor burden. In addition, we also explored the immunoregulatory effect of Dioscin on mice. The results showed that Dioscin modulated M1/M2 macrophages phenotype in spleen and decreased monocytic myeloid-derived suppressor cells (M-MDSCs) population in blood and spleen of mice. The in vitro assay demonstrated that Dioscin promoted M1 as well as inhibited M2 macrophages phenotype in LPS- or IL-4-induced bone marrow-derived macrophages (BMDMs) model. Based on the plasticity of MDSCs and its ability to differentiate into M1/M2 macrophages, we here found that Dioscin increased M1- and decreased M2-like phenotype during the process of MDSCs differentiation in vitro, suggesting Dioscin promoted MDSCs differentiate into M1 as well as inhibited its differentiation into M2 macrophages. Taken together, our study indicated that Dioscin had the inhibitory effect on the initial of tumorigenesis at early stage of CAC via the ant-inflammatory effect, which provided a natural active candidate for effective prevention of CAC. C1 [Xun, Jing; Zhang, Lanqiu; Yang, Lei; Zhang, Aimin; Wang, Zhenyu; Yu, Xiangyang; Zhang, Qi] Tianjin Med Univ, Tianjin Nankai Hosp, Tianjin Key Lab Acute Abdomen Dis Associated Organ, Tianjin 300100, Peoples R China. [Xun, Jing; Zhang, Lanqiu; Yang, Lei; Wang, Zhenyu; Wang, Ximo; Yu, Xiangyang; Zhang, Qi] Tianjin Univ, Integrated Chinese & Western Med Hosp, Tianjin 300100, Peoples R China. [Zhou, Siying; Lv, Zongjing; Luo, Hai] Tianjin Med Univ, Grad Sch, Tianjin 300100, Peoples R China. [Wang, Botao] Chongqing Tradit Chinese Med Hosp, Chongqing 400021, Peoples R China. [Wu, Xueliang] Hebei North Univ, Affiliated Hosp 1, Dept Gen Surg, Zhangjiakou 075000, Peoples R China. [Wang, Ximo] Tianjin Med Univ, Inst Integrat Med Acute Abdominal Dis, Tianjin 300100, Peoples R China. C3 Tianjin Medical University; Tianjin University; Tianjin Medical University; Hebei North University; Tianjin Medical University RP Yu, XY; Zhang, Q (corresponding author), Tianjin Med Univ, Tianjin Nankai Hosp, Tianjin Key Lab Acute Abdomen Dis Associated Organ, Tianjin 300100, Peoples R China. EM yxynankai@126.com; zhangqi8501@126.com RI Yang, Lie/JXY-1497-2024 FU National Natural Science Foundation of China [81978158]; Natural Science Foundation of Tianjin [17ZXMFSY00220]; Key Areas of Traditional Chinese Medicine in Tianjin [2023008]; Tianjin Health Commission [2021043, 2021008] FX This research was supported by the National Natural Science Foundation of China (NO. 81978158) , Natural Science Foundation of Tianjin (No. 17ZXMFSY00220) , The Key Areas of Traditional Chinese Medicine in Tianjin (No. 2023008) , Project of Tianjin Health Commission (No. 2021043, No.2021008) . We thank Tianjin KingMed Center for Clinical Laboratory for the platform support. 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Immunopharmacol. PD APR PY 2023 VL 117 AR 109839 DI 10.1016/j.intimp.2023.109839 EA FEB 2023 PG 13 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA A4MZ5 UT WOS:000954897700001 PM 36809720 DA 2026-03-26 ER PT J AU Cheng, WJ Wang, X Wu, YH Li, W Fu, CM Zou, L Zhang, JM AF Cheng, Weijian Wang, Xiao Wu, Yihan Li, Wei Fu, Chaomei Zou, Liang Zhang, Jinming TI Huanglian-Houpo extract attenuates DSS-induced UC mice by protecting intestinal mucosal barrier and regulating macrophage polarization SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Ulcerative colitis; Coptis chinensis Franch; Magnoliae officinalis; Intestinal barrier; Macrophage polarization ID COLITIS; INFLAMMATION; MAGNOLOL AB Ethnopharmacological relevance: Huanglian-Houpo Decoction (HLHP), a classical prescription, has been used to treat gastrointestinal diseases for hundreds of years in TCM. However, the effective constituents and underlying mechanisms of HLHP in the treatment of ulcerative colitis (UC) have not been fully investigated.Aim of the study: This study aimed to reveal the potential anti-UC mechanisms of 50% ethanol extraction of HL and HP (EHLHP), combining transcriptomes and network pharmacology, as well as the animal experiment verification.Methods: Primarily, we identified the chemical composition of EHLHP via UPLC-QE-MS analysis. A visualization network with components-targets-pathways on UC treatment were constructed using network pharmacology. And then, the transcriptomics sequencing method was applied to screen out the differentially expressed genes (DEGs) of EHLHP in the treatment of UC. The key targets and pathways of EHLHP were selected by the com-bination of the network pharmacology and transcriptomics results. Ultimately, the potential mechanisms of EHLHP on DSS-induced UC mice were verified.Results: A total of 34 components of EHLHP were identified by UPLC-QE-MS analysis. Combined with the analysis of network pharmacology and transcriptomics, there were 262 DEGs between the normal group and the model group, and 151 DEGs between the model group and the EHLHP group. At the same time, there are 79 interaction paths, such as PI3K-Akt signaling pathway, MAPK signaling pathway, etc. These results indicated that the anti-UC mechanisms would be involved in calcium signaling pathway, inflammatory signaling pathway (JAK-STAT, TNF-alpha, cGMP-PKG) and immune regulation (IL-17, B cell receptor). After 160 mg/kg and 320 mg/kg EHLHP were given to DSS induced UC mice, these typical symptoms could be significantly alleviated, such as the decrease of DAI value and inflammation level. The IHC staining results of ZO-1, Occludin and Claudin-1 sug-gested that the intestinal barrier of UC mice was enhanced by EHLHP. The expression of macrophages and immune cells in F4/80+, CD11c+, Gr-1+, NK1.1+by FCM determination indicated that EHLHP could suppress UC by immunosuppression and macrophage polarization M1 to M2.Conclusion: The potential mechanisms of HLHP extract on DSS-induced UC mice were revealed, by the prediction of integrated analysis of transcriptomes and network pharmacology, and subsequently animal test verification. It would provide a viable strategy to elucidate the mechanisms of TCM classical formula. C1 [Cheng, Weijian; Wang, Xiao; Wu, Yihan; Fu, Chaomei; Zhang, Jinming] Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, Chengdu 611137, Peoples R China. [Li, Wei] Chengdu Univ, Sch Preclin Med, Chengdu 610106, Peoples R China. [Zou, Liang] Chengdu Univ, Sch Food & Biol Engn Preclin Med, Chengdu 610106, Peoples R China. C3 Chengdu University of Traditional Chinese Medicine; Chengdu University; Chengdu University RP Zhang, JM (corresponding author), Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, Chengdu 611137, Peoples R China.; Zou, L (corresponding author), Chengdu Univ, Sch Food & Biol Engn Preclin Med, Chengdu 610106, Peoples R China. EM zouliangcdu@126.com; cdutcmzjm@126.com RI Li, Wei/HJP-1988-2023 OI Li, Wei/0000-0002-1074-9213 FU National Interdisciplinary Innovation Team of Traditional Chinese Medicine [ZYYCXTD-D-202209] FX Funding This work was supported by National Interdisciplinary Innovation Team of Traditional Chinese Medicine (Nos. ZYYCXTD-D-202209) . 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Ethnopharmacol. PD MAY 10 PY 2023 VL 307 AR 116181 DI 10.1016/j.jep.2023.116181 EA FEB 2023 PG 14 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA C8SN4 UT WOS:000964553900001 PM 36738944 DA 2026-03-26 ER PT J AU Fan, QQ Liu, YY Sheng, L Lv, S Yang, L Zhang, ZM Guo, JP Fan, YF Hu, D AF Fan, Qiqi Liu, Yuanyue Sheng, Lei Lv, Shuang Yang, Li Zhang, Zhaoming Guo, Jiaping Fan, Yafei Hu, Dan TI Chaihu-Shugan-San inhibits neuroinflammation in the treatment of post-stroke depression through the JAK/STAT3-GSK38/PTEN/Akt pathway SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE Chaihu-Shugan-San; Post -stroke depression; GSK38; Neuroinflammation; Microglia polarization ID NLRP3 INFLAMMASOME ACTIVATION; MODULATING MICROGLIA/MACROPHAGE POLARIZATION; ISCHEMIC-STROKE; CUMS RATS; STRESS; INJURY; METABOLISM; MECHANISMS; LIVER AB Post-stroke depression (PSD) is one of the most common neuropsychiatric consequence of stroke, affecting cognitive function, recovery of somatic function, and patient survival. The aim of this study was to evaluate whether Chaihu-Shugan-San, a traditional Chinese medicine formula used clinically to treat depression, could improve symptoms in a rat model for PSD, to investigate the potential mechanisms, and to validate the findings in an in vitro oxygen and glucose deprivation (OGD) model. Male rats were subjected to middle cerebral artery occlusion (MCAO) and to chronic unpredictable mild stress (CUMS). The rats were then allocated to experimental groups (n = 15) that were treated with Chaihu-Shugan-San, a JAK-STAT3 inhibitor, a GSK38 overexpressing virus, or an empty virus (control). The subjects allocated to each group, as well as those that received no treatment and rats that did not undergo MCAO/CUMS, were then subjected to forced swimming, tail suspension, and sugar water preference tests, and their neurological deficit score was determined. Inflammatory factor levels and the expression of proteins related to the JAK/STAT3-GSK38/PTEN/Akt pathway were measured, and the synaptic ultrastructure was observed using transmission electron microscopy. Flow cytometry showed microglia polarization towards the M1 phenotype in an in vitro PSD model, which was reversed after treatment with a GSK38 overexpression virus, Chaihu-Shugan-San, or a JAK-STAT3 inhibitor. The results showed that Chaihu-Shugan-San has a therapeutic effect on an in vivo model for PSD and can regulate microglia polarization through the activation of the JAK/STAT3-GSK38/PTEN/Akt pathway, suggesting that it exerts its effect via the inhibition of neuroinflammation. C1 [Fan, Qiqi; Liu, Yuanyue; Sheng, Lei; Lv, Shuang; Yang, Li; Zhang, Zhaoming; Guo, Jiaping; Fan, Yafei; Hu, Dan] Nanjing Univ Chinese Med, Affiliated Hosp 2, Dept Neurol, Nanjing 210017, Jiangsu, Peoples R China. [Hu, Dan] Nanjing Univ Chinese Med, Sch Chinese Med, Nanjing 210023, Jiangsu, Peoples R China. C3 Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine RP Hu, D (corresponding author), Nanjing Univ Chinese Med, Affiliated Hosp 2, Dept Neurol, Nanjing 210017, Jiangsu, Peoples R China. EM fsyy00801@njucm.edu.cn FU National Natural Science Foundation of China [81904136, 82205013] FX This work was supported by the National Natural Science Foundation of China [grant numbers 81904136, 82205013] . 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Pharmacother. PD APR PY 2023 VL 160 AR 114385 DI 10.1016/j.biopha.2023.114385 EA FEB 2023 PG 15 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 9R4SU UT WOS:000945645700001 PM 36774722 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Jiang, XQ Sun, J Guo, SC Zhao, ZY Chen, YX Cao, JX Liu, YP Cheng, GG Tian, L Li, Y AF Jiang, Xiaoqian Sun, Jin Guo, Shancheng Zhao, Zhiye Chen, Yuxu Cao, Jianxin Liu, Yaping Cheng, Guiguang Tian, Lei Li, Ye TI Elsholtzia bodinieri Vaniot ameliorated acute lung injury in mice by regulating pyroptosis, inflammation, oxidative stress and macrophage polarization SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Elsholtzia bodinieri Vaniot; ALI; Pyroptosis; Inflammation; Oxidative stress; Macrophage polarization AB Ethnopharmacological relevance: Elsholtzia bodinieri Vaniot, perennial herbs, a traditional Yunnan Chinese herbal medicine. Its whole herb can be used as commonly used herbs to cure fever, headache, inflammation, indigestion etc., and its tender tip can also be used as tea in Yunnan of China. However, the protective mechanism of Elsholtzia bodinieri Vaniot on acute lung injury (ALI) still needs to be explored. Aim of study: ALI is characterized by acute respiratory inflammation, which remains a significant source of morbidity and mortality. The current study with the aim of determining the therapeutic the efficacy of E. bodinieri Vaniot on lipopolysaccharide-induced ALI, moreover uncovered the underlying gene-regulated framework, so E. bodinieri Vaniot might serve as functional food for adjuvant therapy or therapeutic agent. Materials and methods: These potential pharmacological targets of E. bodinieri Vaniot against ALI were analyzed by multiple bioinformatics databases. E. bodinieri Vaniot methanol extract (EBE) was obtained by ultrasonic -assisted extraction method, and detected by UHPLC-ESI-HRMS/MS. These pyroptosis, inflammation and oxidative stress associated factors were measured using ELISA assay, western blotting, and histopathological examination to assess the effects of EBE. EcoTyper and immunofluorescence staining were employed to estimate macrophage polarization states in ALI lungs tissue. Results: In ALI lung tissues, EBE treatment could increase B cell leukemia/lymphoma 2 (BCL2) to inhibit pyroptosis, downregulate prostaglandin-endoperoxide synthase 2 (PTGS2) to attenuate inflammation, upregu-lating NAD(P)H dehydrogenase, quinone 1 (NQO1) to alleviate oxidative stress and induce macrophage polar-ization toward the M2 phenotype. Conclusion: E. bodinieri Vaniot ameliorated ALI thought regulating pyroptosis, inflammation, oxidative stress and macrophage polarization, as well as could be a promising source for therapeutic agent. C1 [Jiang, Xiaoqian; Sun, Jin; Guo, Shancheng; Zhao, Zhiye; Chen, Yuxu; Cao, Jianxin; Liu, Yaping; Cheng, Guiguang; Tian, Lei] Kunming Univ Sci & Technol, Fac Food Sci & Engn, Kunming 650500, Peoples R China. [Li, Ye] Kunming Univ Sci & Technol, Sch Med, Kunming 650500, Peoples R China. C3 Kunming University of Science & Technology; Kunming University of Science & Technology RP Tian, L (corresponding author), Kunming Univ Sci & Technol, Fac Food Sci & Engn, Kunming 650500, Peoples R China.; Li, Y (corresponding author), Kunming Univ Sci & Technol, Sch Med, Kunming 650500, Peoples R China. EM leotian@kust.edu.cn; liye918@kust.edu.cn RI Jiang, Xiaoqian/K-6752-2012; Cheng, Guiguang/GOE-3906-2022 FU National Natural Science Foundation of China [32160106]; Yunan Ten Thousand Talents Plan Young & Elite Talents Project [YNWR-QNBJ-2018-126]; Yunnan Major Natural Science [2019ZF010] FX This research was funded by the National Natural Science Foundation of China (32160106 to Lei Tian) , Yunan Ten Thousand Talents Plan Young & Elite Talents Project (YNWR-QNBJ-2018-126 to Ye Li) and Yunnan Major Natural Science (2019ZF010 to Guiguang Cheng) . 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Ethnopharmacol. PD MAY 10 PY 2023 VL 307 AR 116232 DI 10.1016/j.jep.2023.116232 EA FEB 2023 PG 12 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 9P9IE UT WOS:000944589100001 PM 36764561 DA 2026-03-26 ER PT J AU Wang, WY Chu, YR Zhang, PY Liang, Z Fan, ZL Guo, XQ Zhou, GD Ren, WJ AF Wang, Weiyun Chu, Yaru Zhang, Pengyuan Liang, Zhuo Fan, Zhenlin Guo, Xueqiang Zhou, Guangdong Ren, Wenjie TI Targeting macrophage polarization as a promising therapeutic strategy for the treatment of osteoarthritis SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Osteoarthritis; Synovitis; Macrophage polarization; Disease -modifying OA drugs (DMOADs) ID PLATELET-RICH PLASMA; MESENCHYMAL STEM-CELLS; KNEE OSTEOARTHRITIS; CHONDROITIN SULFATE; DEGENERATIVE OSTEOARTHRITIS; SYNOVIAL MACROPHAGES; CARTILAGE REPAIR; II COLLAGEN; PAIN; INFLAMMATION AB Osteoarthritis (OA) is a chronic osteoarthropathy characterized by the progressive degeneration of articular cartilage and synovial inflammation. Early OA clinical treatments involve intra-articular injection of glucocorticoids, oral acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), which are used for antiinflammation and pain relief. However, long-term use of these agents will lead to inevitable side effects, even aggravate cartilage loss. At present, there are no disease-modifying OA drugs (DMOADs) yet approved by regulatory agencies. Polarization regulation of synovial macrophages is a new target for OA treatment. Inhibiting M1 polarization and promoting M2 polarization of synovial macrophages can alleviate synovial inflammation, relieve joint pain and inhibit articular cartilage degradation, which is a promising strategy for OA treatment. In this study, we describe the molecular mechanisms of macrophage polarization and its key role in the development of OA. Subsequently, we summarize the latest progress of strategies for OA treatment through macrophage reprogramming, including small molecule compounds (conventional western medicine and synthetic compounds, monomer compounds of traditional Chinese medicine), biomacromolecules, metal/metal oxides, cells, and cell derivatives, and interprets the molecular mechanisms, hoping to provide some information for DMOADs development. C1 [Wang, Weiyun; Chu, Yaru; Liang, Zhuo; Fan, Zhenlin; Guo, Xueqiang; Zhou, Guangdong; Ren, Wenjie] Xinxiang Med Univ, Third Affiliated Hosp Xinxiang Med Univ, Inst Hlth Cent Plain, Clin Med Ctr Tissue Engn & Regenerat, Xinxiang, Peoples R China. [Zhang, Pengyuan] Xinxiang Med Univ, Affiliated Hosp 3, Dept Trauma Med, Xinxiang, Peoples R China. [Zhou, Guangdong] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Plast & Reconstruct Surg, Shanghai Key Lab Tissue Engn,Sch Med, Shanghai, Peoples R China. C3 Henan Medical University; Henan Medical University; Shanghai Jiao Tong University RP Zhou, GD; Ren, WJ (corresponding author), Xinxiang Med Univ, Third Affiliated Hosp Xinxiang Med Univ, Inst Hlth Cent Plain, Clin Med Ctr Tissue Engn & Regenerat, Xinxiang, Peoples R China.; Zhou, GD (corresponding author), Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Plast & Reconstruct Surg, Shanghai Key Lab Tissue Engn,Sch Med, Shanghai, Peoples R China. EM weiyun@xxmu.edu.cn; chuyaru5625@163.com; zhangpengyuan0303@163.com; liangzhuo@xxmu.edu.cn; fanzl0214@163.com; gxqxll@163.com; guangdongzhou@126.com; wjren1966@163.com RI ; Guo, Xueqiang/GYR-2551-2022; Ren, Wenjie/JFK-8231-2023 OI Wang, Weiyun/0000-0001-7152-1565; Guo, Xueqiang/0000-0003-2318-8678; Ren, Wenjie/0000-0003-4711-2352 FU National Natural Science Foundation of China [32200754]; Key Research and Development Program of Henan province [221111310100]; Major Science and Technology Projects of Xinxiang City [21ZD006]; Open Project Program of the Third Affiliated Hospital of Xinxiang Medical University [KFKTZD202105, KFKTYB202107, KFKTYB202119] FX This study was supported by the grants from National Natural Science Foundation of China (No. 32200754) for Weiyun Wang; the Key Research and Development Program of Henan province (No. 221111310100) for Wenjie Ren; the Major Science and Technology Projects of Xinxiang City (No. 21ZD006) for Wenjie Ren; and the Open Project Program of the Third Affiliated Hospital of Xinxiang Medical University (No. KFKTZD202105 for Wenjie Ren; No. KFKTYB202107 for Zhenlin Fan; No. KFKTYB202119 for Xueqiang Guo) . 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Immunopharmacol. PD MAR PY 2023 VL 116 AR 109790 DI 10.1016/j.intimp.2023.109790 EA FEB 2023 PG 15 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA E2GF9 UT WOS:000973776800001 PM 36736223 DA 2026-03-26 ER PT J AU Sun, YX Tao, Q Cao, Y Yang, TT Zhang, L Luo, YF Wang, L AF Sun, Yaoxiang Tao, Qing Cao, Yang Yang, Tingting Zhang, Ling Luo, Yifeng Wang, Lei TI Kaempferol has potential anti-coronavirus disease 2019 (COVID-19) targets based on bioinformatics analyses and pharmacological effects on endotoxin-induced cytokine storm SO PHYTOTHERAPY RESEARCH LA English DT Article DE COVID-19; kaempferol; key targets; macrophage polarization; molecular docking; network pharmacology ID MECHANISM; STRATEGY AB COVID-19 has infected 272 million patients and caused 5.33 million deaths around the world, and it remains the main global threat. Previous studies revealed that Chinese traditional medicine is an effective treatment for COVID-19 infection. This study aims to reveal the pharmacological effects of kaempferol, which is the active component of Radix Bupleuri and Tripterygii Radix, and potential mechanisms for the treatment of COVID-19. Here, we employed the bioinformatics methods to filter the anti-COVID-19 candidate genes of kaempferol, which mainly enriched in inflammation (TNF, JUN, etc.) and virus infection (AKT1, JNK, etc.). The Transcription levels of AKT1, JNK and JUN were significantly reduced by kaempferol treatment in the LPS-activated macrophages. In addition, kaempferol reduced the secretion of inflammatory factors by LPS-stimulated macrophages, inhibited MAPK/NF-kappa B signaling and regulated macrophage polarization to M2 type in vitro, and suppressed endotoxin-induced cytokine storm and improved survival in mice. Molecular docking analysis demonstrated that kaempferol was probable to bind the COVID-19 protein 5R84 and formatted hydrogen bond with the residues, the free binding energy of which was lower than the original ligand. In summary, our current work indicates that kaempferol has anti-COVID-19 potential through the reduction of COVID-19-induced body dysfunction and molecule-protein interaction, and bioinformatics results clarify that some of these key target genes might serve as potential molecular markers for detecting COVID-19. C1 [Sun, Yaoxiang; Yang, Tingting; Zhang, Ling; Luo, Yifeng] Jiangsu Univ, Dept Clin Lab, Affiliated Yixing Hosp, Yixing, Peoples R China. [Tao, Qing] Nanjing Univ, Ctr Translat Med, Nanjing, Peoples R China. [Tao, Qing] Nanjing Univ, Jiangsu Key Lab Mol Med, Med Sch, Nanjing, Peoples R China. [Cao, Yang] Vanderbilt Univ, Coll Arts & Sci, Nashville, TN USA. [Wang, Lei] Jiangsu Prov Acad Tradit Chinese Med, Jiangsu Prov Hosp Integrat Chinese & Western Med, Dept Clin Lab, Nanjing, Peoples R China. [Wang, Lei] Jiangsu Prov Hosp Integrat Chinese & Western Med, Jiangsu Prov Acad Tradit Chinese Med, Dept Clin Lab, Nanjing 210028, Peoples R China. [Luo, Yifeng] Jiangsu Univ, Dept Clin Lab, Affiliated Yixing Hosp, Yixing 214200, Jiangsu, Peoples R China. C3 Jiangsu University; Nanjing University; Nanjing University; Vanderbilt University; Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine; Jiangsu University RP Wang, L (corresponding author), Jiangsu Prov Hosp Integrat Chinese & Western Med, Jiangsu Prov Acad Tradit Chinese Med, Dept Clin Lab, Nanjing 210028, Peoples R China.; Luo, YF (corresponding author), Jiangsu Univ, Dept Clin Lab, Affiliated Yixing Hosp, Yixing 214200, Jiangsu, Peoples R China. 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Res. PD JUN PY 2023 VL 37 IS 6 BP 2290 EP 2304 DI 10.1002/ptr.7740 EA FEB 2023 PG 15 WC Chemistry, Medicinal; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA H9YX0 UT WOS:000924031300001 PM 36726236 DA 2026-03-26 ER PT J AU Han, J Wang, JW Wang, YC Zhu, ZQ Zhang, SW Wu, BR Meng, MS Zhao, JN Wang, DS AF Han, Jing Wang, Jingwen Wang, Yicun Zhu, Zhiqi Zhang, Siwang Wu, Bingrong Meng, Mingsong Zhao, Jianning Wang, Dongsheng TI Sesquiterpene lactones-enriched fractions from Xanthium mongolicum Kitag alleviate RA by regulating M1 macrophage polarization via NF-κB and MAPK signaling pathway SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE rheumatoid arthritis; Xanthium mongolicum kitag; sesquiterpene lactone; macrophage; traditional Chinese medicine ID ARTHRITIS; INHIBITION; EXPRESSION; GENE AB Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease, characterized by activated M1-like macrophage in the joint. Xanthium mongolicum Kitag (X. mongolicum) is a traditional medicinal plant that has long been used to treat RA and other immune diseases in China.Methods: Fractions of X. mongolicum were separated based on polarity. Anti-RA activity of the fractions were screened by LPS-stimulated RAW264.7 macrophage in vitro. The major active compounds were identified by UPLC-MS and quantified by HPLC. The anti-RA effects of the active fraction was evaluated in complete freund's adjuvant (CFA)-induced arthritis and collagen-induced arthritis (CIA) mouse models in vivo and LPS-stimulated macrophage in vitro.Results: Sesquiterpene lactones-enriched fraction from X. mongolicum (SL-XM) exhibited the strongest anti-RA activity among all components in vitro. Five major constituents i.e., Xanthinosin (1), Xanthatin (2), Mogolide D (3), Mogolide E (4), and Mogolide A (5) were identified as major compounds of SL-XM. SL-XM ameliorated symptoms of CFA and CIA induced arthritis mice model. Furthermore, SL-XM treatment inhibited LPS-induced M1 macrophages polarization. In addition, SL-XM inhibited the phosphorylation of NF-kappa B and MAPK signaling pathways in LPS-induced macrophage and CIA-challenged mice.Discussion: The main anti-RA active fraction of X. mongolicum may be the Sesquiterpene lactones, which includes five key compounds. SL-XM may exert its anti-RA effect by suppressing M1 macrophage polarization via the NF-kappa B and MAPK signaling pathway. C1 [Han, Jing; Zhu, Zhiqi; Zhang, Siwang; Wu, Bingrong; Meng, Mingsong] Nanjing Univ Chinese Med, Sch Pharm, Nanjing, Peoples R China. [Wang, Jingwen] China Pharmaceut Univ, Sch Tradit Chinese Pharm, Dept TCMs Pharmaceut, Nanjing, Peoples R China. [Wang, Yicun; Zhao, Jianning; Wang, Dongsheng] Nanjing Univ, Jinling Hosp, Sch Med, Dept Orthoped, Nanjing, Peoples R China. C3 Nanjing University of Chinese Medicine; China Pharmaceutical University; Nanjing University RP Han, J (corresponding author), Nanjing Univ Chinese Med, Sch Pharm, Nanjing, Peoples R China.; Zhao, JN; Wang, DS (corresponding author), Nanjing Univ, Jinling Hosp, Sch Med, Dept Orthoped, Nanjing, Peoples R China. EM hanjing@njucm.edu.cn; zhaojianning.0207@163.com; wdssmmu@163.com RI ; Wu, Bingrong/NTQ-1332-2025 OI Wang, Jingwen/0000-0002-4651-9129; Han, jing/0009-0008-3050-7247; FU National Natural Science Foundation of China [31900283]; Natural Science Foundation of Nanjing University of Chinese Medicine [NZY31900283]; China Postdoctoral Science Foundation [2021T140786]; Nanjing Postdoctoral Science Foundation [48289]; Natural Science Foundation of Jiangsu province [BK20221556]; Jinling Hospital Postdoctoral Science Foundation [48289]; Jinling Hospital Science Foundation [YYQN2021075] FX This work was supported by the National Natural Science Foundation of China (No. 31900283 to JH); the Natural Science Foundation of Nanjing University of Chinese Medicine (No. NZY31900283 to JH); the China Postdoctoral Science Foundation (2021T140786 to DW); the Nanjing Postdoctoral Science Foundation (48289 to DW); Natural Science Foundation of Jiangsu province (No. BK20221556 to DW); the Jinling Hospital Postdoctoral Science Foundation (48289 to DW); and the Jinling Hospital Science Foundation (YYQN2021075 to DW). 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PD JAN 26 PY 2023 VL 14 AR 1104153 DI 10.3389/fphar.2023.1104153 PG 13 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 9B7UA UT WOS:000934937700001 PM 36778009 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Yang, CG Mao, XL Wu, JF An, X Cao, JJ Zhang, XY Li, M Zhang, FF AF Yang, Chen-Guang Mao, Xue-Li Wu, Jun-Fei An, Xiang Cao, Jia-Jia Zhang, Xiao-Yu Li, Min Zhang, Fang-Fang TI Amelioration of Lung Fibrosis by Total Flavonoids of Astragalus via Inflammatory Modulation and Epithelium Regeneration SO AMERICAN JOURNAL OF CHINESE MEDICINE LA English DT Article DE Total Flavonoids of Astragalus; Pulmonary Fibrosis; Macrophage Polarization; EMT; Wnt7b; Epithelium Regeneration ID MESENCHYMAL TRANSITION; MACROPHAGE PLASTICITY; TISSUE-REPAIR; POLARIZATION; MEMBRANACEUS; ACTIVATION; INDUCTION; TTF-1 AB Idiopathic Pulmonary Fibrosis (IPF) is identifiable by the excessive increase of mesenchyme paired with the loss of epithelium. Total flavonoids of Astragalus (TFA), the main biologically active ingredient of the traditional Chinese medicine, Astragalus membranaceus (Huangqi), shows outstanding effects on treating pulmonary disorders, including COVID-19-associated pulmonary dysfunctions. This study was designed to evaluate the efficacy of TFA on treating pulmonary fibrosis and the possible mechanisms behind these effects. A549 cells were treated with TGF-beta 1 and TFA to observe the potential effects of TFA on regulating alveolar epithelial cell proliferation, TGF-beta 1-induced EMT, and the underlying mechanisms in vitro. Then, mouse pulmonary fibrosis was induced with a single intra-tracheal injection of bleomycin, and TFA was administrated by i.p. injection. Lung fibrosis was evaluated through histological and molecular analyses, and the possible mechanisms were explored using immunological methods. The results demonstrated that TFA could promote cell proliferation but inhibit TGF-beta 1-induced EMT on A549 cells. TFA attenuated BLM-induced pulmonary fibrosis in mice by modulating inflammatory infiltration and M2 macrophage polarization; it furthermore modulated EMT through regulating the TGF-beta 1/Smad pathway. In addition, TFA augmented the expression of the Wnt7b protein, which plays an important role in alveolar epithelium reparation. In conclusion, TFA alleviated bleomycin-induced mouse lung fibrosis by preventing the fibrotic response and increasing epithelium regeneration. C1 [Yang, Chen-Guang; Wu, Jun-Fei; An, Xiang; Cao, Jia-Jia; Zhang, Xiao-Yu; Li, Min; Zhang, Fang-Fang] Lanzhou Univ, Sch Basic Med Sci, Lanzhou 730000, Gansu, Peoples R China. [Mao, Xue-Li] Cent South Univ, Xiangya Sch Med, Changsha 410078, Hunan, Peoples R China. [Li, Min; Zhang, Fang-Fang] Lanzhou Univ, Sch Basic Med Sci, 222 South Tianshui Rd, Lanzhou 730000, Gansu, Peoples R China. C3 Lanzhou University; Central South University; Lanzhou University RP Li, M; Zhang, FF (corresponding author), Lanzhou Univ, Sch Basic Med Sci, Lanzhou 730000, Gansu, Peoples R China.; Li, M; Zhang, FF (corresponding author), Lanzhou Univ, Sch Basic Med Sci, 222 South Tianshui Rd, Lanzhou 730000, Gansu, Peoples R China. EM limin@lzu.edu.cn; zhangff@lzu.edu.cn RI Zhang, xiaoyu/HTM-3222-2023; cao, jiajia/HFZ-8693-2022; Wu, Junfei/OAJ-8855-2025; yang, cg/LRC-7871-2024; Zhang, Fangfang/D-6776-2013 OI Mao, Xueli/0000-0002-2611-7712; FU National Natural Science Foundation of China [32070150]; Natural Science Foundation of Gansu Province [22JR5RA497] FX This research was supported by the National Natural Science Foundation of China(32070150) and the Natural Science Foundation of Gansu Province (22JR5RA497) CR Adhikari B, 2021, PHYTOTHER RES, V35, P1298, DOI 10.1002/ptr.6893 Agajanian M, 2015, BIOCHEM BIOPH RES CO, V465, P606, DOI 10.1016/j.bbrc.2015.08.071 Arora S, 2018, IMMUNOBIOLOGY, V223, P383, DOI 10.1016/j.imbio.2017.11.001 Auyeung KK, 2016, AM J CHINESE MED, V44, P1, DOI 10.1142/S0192415X16500014 Bao CM, 2021, J TRADIT CHIN MED, V41, P982, DOI 10.19852/j.cnki.jtcm.2021.06.016 Baouz S, 2005, INT IMMUNOL, V17, P1473, DOI 10.1093/intimm/dxh325 Biswas SK, 2010, NAT IMMUNOL, V11, P889, DOI 10.1038/ni.1937 Boye A, 2015, J ETHNOPHARMACOL, V169, P219, DOI 10.1016/j.jep.2015.04.013 Chen YS, 2021, J ETHNOPHARMACOL, V272, DOI 10.1016/j.jep.2021.113920 Chua F, 2005, AM J RESP CELL MOL, V33, P9, DOI 10.1165/rcmb.2005-0062TR Derynck R, 2003, NATURE, V425, P577, DOI 10.1038/nature02006 Duffield JS, 2013, ANNU REV PATHOL-MECH, V8, P241, DOI 10.1146/annurev-pathol-020712-163930 Fu S, 2018, BIOMED PHARMACOTHER, V100, P64, DOI 10.1016/j.biopha.2018.01.138 Gross TJ, 2001, NEW ENGL J MED, V345, P517, DOI 10.1056/NEJMra003200 Law S, 2020, HERBA POL, V66, P79, DOI [10.2478/hepo-2020-0023, DOI 10.2478/hepo-2020-0023, 10.2478/hepo-2020-0023, DOI 10.2478/HEPO-2020-0023] Liu P, 2017, AGING DIS, V8, P868, DOI 10.14336/AD.2017.0816 Macías-Barragán J, 2010, FIBROGENESIS TISSUE, V3, DOI 10.1186/1755-1536-3-16 Mantovani A, 2013, J PATHOL, V229, P176, DOI 10.1002/path.4133 Matsuno Y, 2012, INT J BIOCHEM CELL B, V44, P776, DOI 10.1016/j.biocel.2012.01.021 Minoo P, 1995, DEV BIOL, V172, P694, DOI 10.1006/dbio.1995.8080 Morrisey EE, 2003, AM J PATHOL, V162, P1393, DOI 10.1016/S0002-9440(10)64271-X Murray PJ, 2014, IMMUNITY, V41, P14, DOI 10.1016/j.immuni.2014.06.008 Oh SW, 2011, J ETHNOPHARMACOL, V136, P414, DOI 10.1016/j.jep.2010.07.026 Shahzad M, 2016, CURR DRUG TARGETS, V17, P1331, DOI 10.2174/1389450116666150907104742 Shu WG, 2002, DEVELOPMENT, V129, P4831 Wang DQ, 2012, OXID MED CELL LONGEV, V2012, DOI 10.1155/2012/282383 Weidenfeld J, 2002, J BIOL CHEM, V277, P21061, DOI 10.1074/jbc.M111702200 Willis BC, 2005, AM J PATHOL, V166, P1321, DOI 10.1016/S0002-9440(10)62351-6 NR 28 TC 12 Z9 19 U1 3 U2 37 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0192-415X EI 1793-6853 J9 AM J CHINESE MED JI Am. J. Chin. Med. PY 2023 VL 51 IS 02 BP 373 EP 389 DI 10.1142/S0192415X23500192 EA JAN 2023 PG 17 WC Integrative & Complementary Medicine; Medicine, General & Internal WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine; General & Internal Medicine GA A5IV5 UT WOS:000917216200001 PM 36655684 DA 2026-03-26 ER PT J AU Zheng, Y Zhao, Q Lin, J Dai, XY Zhu, CY Wang, YJ Fu, HY AF Zheng, Yun Zhao, Qiong Lin, Jing Dai, Xiaoyang Zhu, Chenyu Wang, Yujie Fu, Hongye TI Xijiao Dihuang decoction relieves the erlotinib-induced dermatitis SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE Xijiao Dihuang decoction; Erlotinib; Skin toxicity; Macrophage; Inflammatory response ID PROINFLAMMATORY CYTOKINES; SKIN INFLAMMATION; INHIBITION; KERATINOCYTES; TOXICITIES; CHEMOKINES; EXTRACT; MICE AB Background: Erlotinib treatment can lead to skin diseases that drastically affected the quality of life of patients. Quercetin (Que), the active component in Xijiao Dihuang Decoction (XDD), was identified to improve inflammatory skin diseases. However, the mechanism of XDD treating erlotinib-induced cutaneous toxicity was not clear at the molecular level.Methods: Keratinocytes were treated with erlotinib, and the expression of inflammatory cytokines and chemo-kines was revealed by ELISA and qRT-PCR. The macrophage polarization was determined by flow cytometry. The key component of XDD, Que, and the target genes of dermatitis were selected via network pharmacology analysis. The binding effects of Que and target genes were verified using molecular docking and cellular thermal shift assay (CETSA)-western blot assay. Animal experiments were performed in vivo to verify the therapeutic effect of XDD on erlotinib-induced skin toxicity.Results: Erlotinib induced M1 polarization of macrophages after stimulating epidermal keratinocytes. While this effect was associated with increased production of inflammatory cytokines and chemokines, such production was prominently decreased by XDD treatment. By combining network pharmacological analysis, molecular docking, and CETSA, it was confirmed that Que had a binding relationship with IL-2 and CXCL8. In vivo results implied that erlotinib abated tumor growth and stimulated dermatitis in HR-1 nude mice, while Que alleviated erlotinib-induced skin damage without affecting this tumor repression effect.Conclusion: The results indicated that XDD could relieve the dermatitis induced by erlotinib and provide a favorable theoretical basis for the clinical relief by using this method. C1 [Zheng, Yun; Zhao, Qiong; Lin, Jing; Zhu, Chenyu; Wang, Yujie; Fu, Hongye] Zhejiang Shuren Univ, Dept Thorac Oncol, Shulan Hangzhou Hosp, Shulan Int Med Coll, Hangzhou 310022, Peoples R China. [Dai, Xiaoyang] Zhejiang Univ, Coll Pharm, Hangzhou 310030, Peoples R China. [Zhao, Qiong] Zhejiang Shuren Univ, Dept Thorac Oncol, Shulan Hangzhou Hosp, Shulan Int Med Coll, 848 Dongxin Rd, Hangzhou 310022, Zhejiang, Peoples R China. C3 Zhejiang Shuren University; Zhejiang University; Zhejiang Shuren University RP Zhao, Q (corresponding author), Zhejiang Shuren Univ, Dept Thorac Oncol, Shulan Hangzhou Hosp, Shulan Int Med Coll, 848 Dongxin Rd, Hangzhou 310022, Zhejiang, Peoples R China. EM drqiongzhao@163.com OI Zhao, Qiong/0000-0002-7317-5931 FU Zhejiang Science and Technology Program of Traditional Chinese Medicine [2022ZA149] FX Funding This study was supported in part by grants from Zhejiang Science and Technology Program of Traditional Chinese Medicine (2022ZA149) . The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 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Cell Res. PD FEB 15 PY 2023 VL 423 IS 2 AR 113437 DI 10.1016/j.yexcr.2022.113437 EA JAN 2023 PG 10 WC Oncology; Cell Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Cell Biology GA C7UI2 UT WOS:000963920700001 PM 36435221 DA 2026-03-26 ER PT J AU Ma, C Wang, C Zhang, YF Li, YZ Fu, K Gong, LH Zhou, HL Li, YX AF Ma, Cheng Wang, Cheng Zhang, Yafang Li, Yanzhi Fu, Ke Gong, Lihong Zhou, Honglin Li, Yunxia TI Phillygenin inhibited M1 macrophage polarization and reduced hepatic stellate cell activation by inhibiting macrophage exosomal miR-125b-5p SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE Phillygenin; Liver fibrosis; Hepatic stellate cell activation; Macrophage polarization; Exosomes; MicroRNA ID LIVER FIBROSIS; INFLAMMATION; CROSSTALK; CANCER AB Liver fibrosis (LF) is an important stage in chronic liver disease development, characterized by hepatic stellate cell (HSC) activation and excessive extracellular matrix deposition. Phillygenin (PHI), an active component in the traditional Chinese medicine Forsythiae Fructus with a significant anti-inflammatory effect, has been proved to inhibit HSC activation. Macrophages can polarize to pro-inflammatory M1 phenotype and anti-inflammatory M2 phenotype, participating in LF development. Currently, Forsythiae Fructus and its many components have been proved to inhibit the inflammatory activation of macrophages. However, there is no direct evidence that PHI can regulate macrophage polarization, and the relationship between macrophage polarization and the anti-LF effect of PHI has not been studied. In this study, we found that PHI inhibited the co-expression of CD80 and CD86, and inhibited the mRNA expression and protein secretion of related inflammatory cytokines in RAW264.7 cells. For mechanism, PHI was found to inhibit the JAK1/JAK2-STAT1 and Notch1 signaling pathways. Subsequently, mHSCs were co-cultured with the conditioned media or exosomes from macrophages with different treatments. It was found that the conditioned media and exosomes from PHI-treated macrophages inhibited the expression of MMP2, TIMP1, TGF-beta, alpha-SMA, COL1 and NF-kappa B in mHSCs. Moreover, through bioinformatic analysis and cell transfection, we confirmed that PHI reduced HSC activation by inhibiting the overexpression of miR-125b-5p in M1 macrophage-derived exosomes and restoring Stard13 expression in mHSCs. On the whole, PHI could inhibit M1 macrophage polarization by suppressing the JAK1/JAK2-STAT1 and Notch1 signaling pathways, and reduce HSC activation by inhibiting macrophage exosomal miR-125b-5p targeting Stard13. Data Availability: The raw data supporting the conclusions of this study are available in the article/Supple-mentary figures, and can be obtained from the first or corresponding author. C1 [Ma, Cheng; Wang, Cheng; Zhang, Yafang; Li, Yanzhi; Fu, Ke; Gong, Lihong; Zhou, Honglin; Li, Yunxia] Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, Key Lab Standardizat Chinese Herbal Med,Minist Edu, Chengdu 611137, Peoples R China. [Li, Yunxia] 1166 Liu Tai Ave, Chengdu 611137, Peoples R China. C3 Chengdu University of Traditional Chinese Medicine RP Li, YX (corresponding author), 1166 Liu Tai Ave, Chengdu 611137, Peoples R China. EM 2020KS261@stu.cdutcm.edu.cn; wangcheng@stu.cdutcm.edu.cn; 2020KS255@stu.cdutcm.edu.cn; liyanzhi@stu.cdutcm.edu.cn; fuke1993@stu.cdutcm.edu.cn; 2018b086@stu.cdutcm.edu.cn; 2020KS262@stu.cdutcm.edu.cn; lyxtgyxcdutcm@163.com RI Wang, Cheng/NQE-8348-2025 FU National Natural Science Foundation of China [81891012, 81630101, U19A2010]; Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine [ZYYCXTD-D-202209]; Sichuan Province Science and Technology Support Program [2021JDRC0041, 22ZYZYTS0071] FX Funding The work was supported by National Natural Science Foundation of China (No. 81891012, 81630101, U19A2010) , Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No: ZYYCXTD-D-202209) , and Sichuan Province Science and Technology Support Program (No. 2021JDRC0041, 22ZYZYTS0071) . 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Pharmacother. PD MAR PY 2023 VL 159 AR 114264 DI 10.1016/j.biopha.2023.114264 EA JAN 2023 PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 8G2WX UT WOS:000920209500001 PM 36652738 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Ye, ZS Wang, PX Feng, GD Wang, Q Liu, C Lu, J Chen, JW Liu, PQ AF Ye, Zesen Wang, Panxia Feng, Guodong Wang, Quan Liu, Cui Lu, Jing Chen, Jianwen Liu, Peiqing TI Cryptotanshinone attenuates LPS-induced acute lung injury by regulating metabolic reprogramming of macrophage SO FRONTIERS IN MEDICINE LA English DT Article DE acute lung injury; Cryptotanshinone; macrophage polarization; metabolic reprogramming; AMPK ID OXIDATIVE-METABOLISM; AMPK; DYSFUNCTION; COMPOUND; DANSHEN; MICE; AXIS AB BackgroundAcute lung injury (ALI) is a life-threatening inflammatory disease without effective therapeutic regimen. Macrophage polarization plays a key role in the initiation and resolution of pulmonary inflammation. Therefore, modulating macrophage phenotype is a potentially effective way for acute lung injury. Cryptotanshinone (CTS) is a lipophilic bioactive compound extracted from the root of Salvia miltiorrhiza with a variety of pharmacological effects, especially the anti-inflammatory role. In this study, we investigated the therapeutic and immunomodulatory effects of CTS on ALI. Materials and methodsThe rat model of ALI was established by intratracheal instillation of LPS (5 mg/kg) to evaluate the lung protective effect of CTS in vivo and to explore the regulation of CTS on the phenotype of lung macrophage polarization. LPS (1 mu g/mL) was used to stimulate RAW264.7 macrophages in vitro to further explore the effect of CTS on the polarization and metabolic reprogramming of RAW264.7 macrophages and to clarify the potential mechanism of CTS anti-ALI. ResultsCTS significantly improved lung function, reduced pulmonary edema, effectively inhibited pulmonary inflammatory infiltration, and alleviated ALI. Both in vivo and in vitro results revealed that CTS inhibited the differentiation of macrophage into the M1 phenotype and promoted polarization into M2 phenotype during ALI. Further in vitro studies indicated that CTS significantly suppressed LPS-induced metabolic transition from aerobic oxidation to glycolysis in macrophages. Mechanistically, CTS blocked LPS-induced metabolic transformation of macrophages by activating AMPK. ConclusionThese findings demonstrated that CTS regulates macrophage metabolism by activating AMPK, and then induced M1-type macrophages to transform into M2-type macrophages, thereby alleviating the inflammatory response of ALI, suggesting that CTS might be a potential anti-ALI agent. C1 [Ye, Zesen; Feng, Guodong; Wang, Quan; Liu, Cui; Lu, Jing; Chen, Jianwen; Liu, Peiqing] Sun Yat sen Univ, Sch Pharmaceut Sci, Lab Pharmacol & Toxicol, Guangdong Prov Engn Lab Druggabil & New Drug Evalu, Guangzhou, Peoples R China. [Wang, Panxia] Guangzhou Med Univ, Sch Pharmaceut Sci, Guangzhou, Peoples R China. C3 Sun Yat Sen University; Guangzhou Medical University RP Lu, J; Chen, JW; Liu, PQ (corresponding author), Sun Yat sen Univ, Sch Pharmaceut Sci, Lab Pharmacol & Toxicol, Guangdong Prov Engn Lab Druggabil & New Drug Evalu, Guangzhou, Peoples R China. EM lujing0504@126.com; chenjwen@mail.sysu.edu.cn; liupq@mail.sysu.edu.cn RI Chen, Jianwen/KWU-3334-2024; Feng, Guodong/PJS-4356-2026; Lu, Jing/N-1190-2017 OI Lu, Jing/0000-0001-5766-2775 FU National Natural Science Foundation of China [U21A20419, 82104157]; Natural Science Foundation of Guangdong Province [2022A1515012322]; Fundamental Research Funds for the Central Universities, Sun Yat-sen University [22qntd4510]; Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program [2017BT01Y093]; National Engineering and Technology Research Center for New drug Druggability Evaluation [2017B090903004]; Guangdong Provincial Key Laboratory of Construction Foundation [2019B030301005]; Guangzhou Basic and Applied Basic Research Project [202102020173, 202206080007]; Discipline Construction Project of Guangdong Medical University [4SG21233G] FX All research were supported by grants from the National Natural Science Foundation of China (U21A20419 and 82104157), Natural Science Foundation of Guangdong Province (2022A1515012322), the Fundamental Research Funds for the Central Universities, Sun Yat-sen University (22qntd4510), Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2017BT01Y093), National Engineering and Technology Research Center for New drug Druggability Evaluation (Seed Program of Guangdong Province, 2017B090903004), Guangdong Provincial Key Laboratory of Construction Foundation (2017B030314030), and Guangdong Provincial Key Laboratory of Construction Foundation, No. 2019B030301005, Guangzhou Basic and Applied Basic Research Project (202102020173 and 202206080007), and the Discipline Construction Project of Guangdong Medical University (4SG21233G). 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Med. PD JAN 13 PY 2023 VL 9 AR 1075465 DI 10.3389/fmed.2022.1075465 PG 14 WC Medicine, General & Internal WE Science Citation Index Expanded (SCI-EXPANDED) SC General & Internal Medicine GA 8H2NE UT WOS:000920871400001 PM 36714100 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Wang, FF Yang, PM Wan, TH Liu, C Zhu, YJ Chen, XZ Liu, HY AF Wang, Feifei Yang, Peiming Wan, Tianhao Liu, Cong Zhu, Yujuan Chen, Xuzhuo Liu, Huanyan TI Osthole Inhibits M1 Macrophage Polarization and Attenuates Osteolysis in a Mouse Skull Model SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY LA English DT Article ID NF-KAPPA-B; BONE; OSTEOCLASTOGENESIS; DIFFERENTIATION; INFLAMMATION; MATURATION AB Excessive bone resorption due to increased inflammatory factors is a common feature of inflammatory lytic bone diseases. This group of diseases is effectively treated with drugs. In recent years, many studies have reported that traditional Chinese medicine herbs have substantial effects on inflammation, osteoclast differentiation and maturation, and bone destruction. Herein, we investigated the effects of osthole (OST) on lipopolysaccharide- (LPS-) induced macrophage polarization, inflammatory responses, and osteolysis. In vitro, we used immunofluorescence and quantitative real-time polymerase chain reaction assays to confirm whether bone marrow-derived macrophages showed an increased expression of inflammatory factors, such as interleukin-6, iNOS, CCR7, and CD86, in the presence of LPS. However, we found that such expression was suppressed and that the M2 macrophage expression increased in the presence of OST. OST reduced LPS- and RANKL-induced intracellular reactive oxygen species production in the bone marrow-derived macrophages. Further, it potently suppressed osteoclast differentiation and osteoclast-specific gene expression by suppressing the P38/MAPK and NF-kappa B pathways. Consistent with the in vitro observations, OST greatly ameliorated LPS-induced bone resorption and modulated the ratio of macrophages at the site of osteolysis. Taken together, OST has great potential for use in the management of osteolytic diseases. C1 [Wang, Feifei; Liu, Cong; Liu, Huanyan] Qingdao Univ, Affiliated Taian City Cent Hosp, Tai An 271000, Shandong, Peoples R China. [Yang, Peiming] Xuzhou Cent Hosp, Dept Stomatol, Xuzhou 221000, Jiangsu, Peoples R China. [Wan, Tianhao] Shanghai Jiao Tong Univ, Sch Med, Shanghai 200011, Peoples R China. [Zhu, Yujuan] Taian Second Hosp Tradit Chinese Med, Dept Stomatol, Tai An 271000, Shandong, Peoples R China. [Chen, Xuzhuo] Shanghai Jiao Tong Univ, Peoples Hosp 9, Dept Oral Surg, Shanghai Key Lab Stomatol,Coll Stomatol,Sch Med, 639 Zhi Zao Ju Rd, Shanghai 200011, Peoples R China. C3 Qingdao University; Shanghai Jiao Tong University; Shanghai Jiao Tong University RP Liu, HY (corresponding author), Qingdao Univ, Affiliated Taian City Cent Hosp, Tai An 271000, Shandong, Peoples R China.; Chen, XZ (corresponding author), Shanghai Jiao Tong Univ, Peoples Hosp 9, Dept Oral Surg, Shanghai Key Lab Stomatol,Coll Stomatol,Sch Med, 639 Zhi Zao Ju Rd, Shanghai 200011, Peoples R China. EM 1848308168@qq.com; yangpm187@163.com; 1161654235@qq.com; 976187593@qq.com; zhuyujuan1012@163.com; cxzzxcaa@126.com; 2307222877@qq.com RI chen, xuzhuo/ACC-3813-2022; 王, 菲菲/R-1936-2019; Zhu, Yujuan/KFB-2912-2024 OI chen, xuzhuo/0000-0002-1276-1662; Liu, Huanyan/0000-0001-5302-3618; FU Digaoda Program of Shanghai Education Commission [20152226]; Industrial Support Fund of Huangpu District [XK2020013]; Shanghai Shenkang Project [SHDC2020CR3060B]; Faculty of Medicine, Shanghai Jiao Tong University [1420Y503] FX This study was supported by the Digaoda Program of Shanghai Education Commission (No. 20152226), the Industrial Support Fund of Huangpu District (No. XK2020013), the Shanghai Shenkang Project (SHDC2020CR3060B), and the Faculty of Medicine, Shanghai Jiao Tong University (No. 1420Y503). 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PD JAN 12 PY 2023 VL 2023 AR 2975193 DI 10.1155/2023/2975193 PG 14 WC Cell Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology GA 8E7KG UT WOS:000919146900001 PM 36686380 OA Green Submitted, hybrid DA 2026-03-26 ER PT J AU Wang, ST Ji, TS Wang, L Qu, YW Wang, XH Wang, WT Lv, MJ Wang, YC Li, X Jiang, P AF Wang, Sutong Ji, Tianshu Wang, Lin Qu, Yiwei Wang, Xinhui Wang, Wenting Lv, Mujie Wang, Yongcheng Li, Xiao Jiang, Ping TI Exploration of the mechanism by which Huangqi Guizhi Wuwu decoction inhibits Lps-induced inflammation by regulating macrophage polarization based on network pharmacology SO BMC COMPLEMENTARY MEDICINE AND THERAPIES LA English DT Article DE Huangqi Guizhi Wuwu decoction; Macrophage polarization; Inflammation; alpha 7 nAchR ID ACTIVE-SITE; RECEPTOR; DISCOVERY; POTENT; LIPOPOLYSACCHARIDE; REVEALS; DOCKING; BINDING; MICE AB Background Huangqi Guizhi Wuwu decoction (HQGZWWD) is a traditional Chinese herbal medicine formulation with significant anti-inflammatory activity. However, its underlying mechanism remains unknown. Through network pharmacology and experimental validation, this study aimed to examine the potential mechanism of HQGZWWD in regulating macrophage polarization and inflammation.Methods The active components were obtained from the Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP), whereas the corresponding targets were obtained from the TCMSP and Swiss Target Prediction database. The GeneCards database identified targets associated with macrophage polarization and inflammation. Multiple networks were developed to identify the key compounds, principal biological processes, and pathways of HQGZWWD that regulate macrophage polarization and inflammation. Autodock Vina is utilized to assess the binding ability between targets and active compounds. Finally, confirm the experiment's central hypothesis. Human histiocytic lymphoma (U-937) cells were transformed into M1 macrophages following stimulation with Lipopolysaccharide (LPS) to evaluate the effect of HQGZWWD drug-containing mouse serum (HQGZWWD serum) on regulating macrophage polarization and inflammation.Results A total of 54 active components and 859 HQGZWWD targets were obtained. There were 9972 targets associated with macrophage polarization and 11,109 targets associated with inflammation. After screening, 34 overlapping targets were identified, of which 5 were identified as central targets confirmed by experiments, including the alpha 7 nicotinic acetylcholine receptor (alpha 7 nAchR), interleukin 6 (IL-6), Interleukin-1 beta (IL-1 beta), interleukin 10 (IL-10) and growth factor beta (TGF-beta 1). Pathway enrichment analysis revealed that 34 overlapping targets were enriched in multiple pathways associated with macrophage polarization and inflammation, including the TGF beta signaling pathway, NF-kappa B signaling pathway, JAK-STAT signaling pathway, and TNF signaling pathway. Molecular docking confirmed that the majority of HQGZWWD's compounds can bind to the target. In vitro experiments, HQGZWWD serum was shown to up-regulate the expression of alpha 7 nAchR, reduce the number of M1 macrophages, stimulate the production of M2 macrophages, inhibit the expression of pro-inflammatory cytokines IL-6 and IL1-beta, and increase the expression of anti-inflammatory cytokines IL-10 and TGF-beta 1.Conclusion HQGZWWD can regulate the number of M1/M2 macrophages and the level of inflammatory cytokines, and the underlying mechanism may be related to the up-regulation of alpha 7 nAchR expression. C1 [Wang, Sutong; Ji, Tianshu; Wang, Lin; Qu, Yiwei; Wang, Xinhui; Lv, Mujie] Shandong Univ Tradit Chinese Med, Jinan 250014, Shandong, Peoples R China. [Wang, Wenting] China Acad Chinese Med Sci, Xiyuan Hosp, Natl Clin Res Ctr Cardiovasc Dis Tradit Chinese Me, Beijing 100091, Peoples R China. [Wang, Yongcheng; Li, Xiao; Jiang, Ping] Shandong Univ Tradit Chinese Med, Affiliated Hosp, Jinan 250011, Peoples R China. C3 Shandong University of Traditional Chinese Medicine; China Academy of Chinese Medical Sciences; Xiyuan Hospital, CACMS; Shandong University of Traditional Chinese Medicine RP Jiang, P (corresponding author), Shandong Univ Tradit Chinese Med, Affiliated Hosp, Jinan 250011, Peoples R China. EM lmdlmd6617@163.com RI Wang, Lin/U-5749-2019 OI Wang, Lin/0000-0003-1219-7632; Qu, Yiwei/0000-0002-1076-7905 FU National Natural Science Foundation of China [81874449]; Postdoctoral Science Foundation of China [2021M702043]; Natural Science Foundation of Shandong Province (Youth Program) [ZR2020QH307, ZR2020QH319] FX Grants supported this study from the National Natural Science Foundation of China (No. 81874449), Postdoctoral Science Foundation of China (No. 2021M702043) and Natural Science Foundation of Shandong Province (Youth Program)(Nos. ZR2020QH307 and ZR2020QH319). 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QL, 2016, J IMMUNOL, V196, P1317, DOI 10.4049/jimmunol.1502134 Zhou F, 2019, ACTA PHARM SIN B, V9, P973, DOI 10.1016/j.apsb.2019.01.015 Zhou X, 2021, DRUG DELIV, V28, P2447, DOI 10.1080/10717544.2021.2000679 NR 99 TC 15 Z9 21 U1 7 U2 43 PU BMC PI LONDON PA CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND EI 2662-7671 J9 BMC COMPLEMENT MED JI BMC Complement. 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PD JAN 9 PY 2023 VL 23 IS 1 AR 8 DI 10.1186/s12906-022-03826-4 PG 23 WC Integrative & Complementary Medicine WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine GA 7W9DQ UT WOS:000913807100002 PM 36624435 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Li, JJ Li, YL Chu, W Li, GQ Zhang, M Dong, JJ Li, L Li, CH Zhang, JB Li, JW Jin, XJ Liu, YQ AF Li, Jun-Jie Li, Ya-Ling Chu, Wei Li, Gao-Qin Zhang, Min Dong, Juan-Juan Li, Ling Li, Cheng-Hao Zhang, Jin-Bao Li, Jia-Wei Jin, Xiao-Jie Liu, Yong-Qi TI Astragaloside IV alleviates cytarabine-induced intestinal mucositis by remodeling macrophage polarization through AKT signaling SO PHYTOMEDICINE LA English DT Article DE Cytarabine; Intestinal mucositis; Macrophage polarization; Astragaloside IV; AKT ID EPITHELIAL-CELLS; ACTIVATION; PROTEIN; PROGRESSION; CANCER; INJURY AB Background: Intestinal mucositis (IM) is one of the common side effects of chemotherapy with Cytarabine (Ara-C) and contributes to the major dose-limiting factor of chemotherapy, while the effective drug for IM is little. Astragalus, one of the main active components extrated from the roots of Astragalus membranaceus (AS-IV), is a common Chinese herbal medicine used in gastrointestinal diseases. However, the effect and mechanism of AS-IV on IM is unclear. Accumulating evidence suggests that M1 macrophages play a pivotal role in IM progression. Purpose: The purpose of the study was to explore the protection of AS-IV and its potential molecular mechanism on intestinal mucositis injury induced by Ara-C. Method: The protective effect of AS-IV was investigated in LPS-induced macrophages and Ara-C-induced intes-tinal mucositis mouse model. H&E, immunofluorescence and western blotting were used to evaluate the damage in different doses of Ara-C. Silencing AKT targeted by siRNA was performed to explore the potential mechanisms regulating macrophage polarization effect of Ara-C, which was investigated by CCK-8, immunofluorescence and western blotting. Flow cytometry, immunofluorescence and Western blotting were used to detect macrophage surface marker proteins and inflammatory genes to explore the potential molecular mechanism of AS-IV regu-lating macrophage polarization. Results: The Cytarabine intervention at dose of 100mg/kg significantly induced IM in mice, with the ileum the most obvious site of injury, accompanied by decreased intestinal barrier, intestinal macrophage polarization to M1 and inflammation response. The administration of AS-IV improved weight loss, food intake, ileal morpho-logical damage, intestinal barrier destruction and inflammatory factor release in mice induced by Ara-c, and also suppressed macrophage polarization to M1, regulating in phenotypic changes in macrophages. In vitro, the expression of M1 macrophage surface marker protein was markedly decreased in LPS-induced macrophages after silencing AKT. Similarly, the western blotting of intestinal tissues and molecular docking indicated that the key mechanisms of AS-IV were remodel AKT signaling, and finally regulating M1 macrophages and decrease inflammation response. Conclusion: Our study highlights that AS-IV exerts protective effect in Ara-C-induced IM through inhibit polar-ization to M1 macrophages based on AKT, and AS-IV may serve as a novel AKT inhibitor to counteract the in-testinal adverse effects of chemotherapeutic agents. [GRAPHICS] . C1 [Li, Jun-Jie; Li, Ya-Ling; Chu, Wei; Li, Gao-Qin; Dong, Juan-Juan; Li, Ling; Li, Cheng-Hao; Zhang, Jin-Bao; Li, Jia-Wei; Jin, Xiao-Jie; Liu, Yong-Qi] Gansu Univ Chinese Med, Gansu Univ Key Lab Mol Med & Chinese Med Prevent &, Lanzhou, Peoples R China. [Liu, Yong-Qi] Gansu Univ Chinese Med, Key Lab Dun Huang Med & Transformat, Minist Educ Peoples Republ China, Lanzhou, Peoples R China. [Zhang, Min; Zhang, Jin-Bao; Jin, Xiao-Jie] Gansu Univ Chinese Med, Coll Pharm, Lanzhou, Peoples R China. [Liu, Yong-Qi] Gansu Univ Chinese Med, 35 Dingxi East Rd, Lanzhou 730000, Peoples R China. C3 Gansu University of Chinese Medicine; Gansu University of Chinese Medicine; Gansu University of Chinese Medicine; Gansu University of Chinese Medicine RP Liu, YQ (corresponding author), Gansu Univ Chinese Med, 35 Dingxi East Rd, Lanzhou 730000, Peoples R China. EM liuyongqi73@163.com RI Li, Jiawei/GXM-4151-2022; Chu, Wei/I-4486-2013; Li, Ling/MAH-6264-2025 OI Li, Junjie/0009-0007-9654-9223 FU Basic Research Innovation Group in Gansu [20JR10RA332]; Young Doctoral Fund Project of Gansu Province Colleges and Universities [2021QB-076]; National Natural Science Foundation of China [82260927]; Youth Science and Technology Fund in Gansu [21JR11RA149] FX This study was supported by Basic Research Innovation Group in Gansu (20JR10RA332) , Young Doctoral Fund Project of Gansu Province Colleges and Universities (2021QB-076) , National Natural Science Foundation of China (82260927) and Youth Science and Technology Fund in Gansu (21JR11RA149) . 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Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 8L0BH UT WOS:000923455500001 PM 36610133 OA hybrid DA 2026-03-26 ER PT J AU Kou, Y Sun, QD Zhu, RT Lin, ZJ Li, ZQ Xu, HR Feng, X Liu, YQ AF Kou, Yu Sun, Qidi Zhu, Rentao Lin, Zhijie Li, Zhuoqun Xu, Hairong Feng, Xuan Liu, Yanqing TI Dioscin induces M1 macrophage polarization through Connexin-43 Channels in Tumor-associated-macrophages-mediated melanoma metastasis SO PHYTOMEDICINE LA English DT Article DE Connexin 43; Melanoma; Dioscin; Tumor-associated macrophages; Invasion and metastasis ID CANCER-CELL; ACTIVATION; PLASTICITY; PROMOTE AB Background: Tumor-associated macrophages (TAMs) are important constituent parts of tumor microenvironment that connected with tumor metastasis in melanoma. Connexin 43 (Cx43) was expressed in all the immune cells which modulated different aspects of immune response. However, the concrete molecular mechanism maintains unclear. Purpose: The study aimed to find a natural drug monomer effectively reversed the polarity of tumor-associated macrophages inhibiting melanoma metastasis and improving survival time. Methods: Flow cytometry was used to determine the effects of dioscin on the macrophage phenotype. Western bolt and ELISA were performed to explore the underlying mechanism of dioscin and a co-culture experiment in vitro was applied to assess the role of dioscin on TAMs-mediated melanoma proliferation, invasion and migration. Moreover, in vivo melanoma metastasis models were established for examining effects of dioscin on TAMs-mediated melanoma metastasis. Results: Dioscin repolarized macrophages from M2 towards M1-like phenotype. Dioscin suppressed M2-like phenotype macrophages through enhanced the expression and transport function of Cx43. Furthermore, the stimulation IFN-./STAT1 pathway and suppression IL-4/JAK2/STAT3 pathway were major mechanism of dioscin. Importantly, dioscin suppressed Cx43(G21R) mutation TAMs induced proliferation, invasion, migration and metastasis of melanoma cells. It worthily noting that dioscin ameliorated tumor-associated-macrophages-mediated melanoma metastasis in vitro and vivo. Conclusion: Dioscin re-polarized macrophages from M2 to M1 phenotype through activation of Cx43-gap-junction-intercellular-communications (Cx43-GJs)/IFN-gamma/STAT1 pathway and inhibition of Cx43-GJs/IL-4/JAK2/STAT3 suppressing migration, invasion and metastasis of melanoma, which provided a theoretical and experimental basis for treating melanoma metastasis. C1 [Kou, Yu; Sun, Qidi; Zhu, Rentao; Lin, Zhijie; Li, Zhuoqun; Xu, Hairong; Feng, Xuan; Liu, Yanqing] Yangzhou Univ, Inst Translat Med, Med Coll, Yangzhou 225000, Jiangsu, Peoples R China. [Kou, Yu; Sun, Qidi; Zhu, Rentao; Li, Zhuoqun; Xu, Hairong; Feng, Xuan; Liu, Yanqing] Gastr Canc State Adm Tradit Chinese Med, Key Lab Syndrome Differentiat & Treatment, Yangzhou 225000, Jiangsu, Peoples R China. [Kou, Yu; Sun, Qidi; Zhu, Rentao; Li, Zhuoqun; Xu, Hairong; Feng, Xuan; Liu, Yanqing] Yangzhou Univ, Med Coll, Jiangsu Key Lab Integrated Tradit Chinese & Wester, Yangzhou 225000, Jiangsu, Peoples R China. [Kou, Yu; Feng, Xuan] Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou 225000, Jiangsu, Peoples R China. C3 Yangzhou University; Yangzhou University; Yangzhou University RP Kou, Y; Liu, YQ (corresponding author), Yangzhou Univ, Inst Translat Med, Med Coll, Yangzhou 225000, Jiangsu, Peoples R China.; Kou, Y; Liu, YQ (corresponding author), Gastr Canc State Adm Tradit Chinese Med, Key Lab Syndrome Differentiat & Treatment, Yangzhou 225000, Jiangsu, Peoples R China.; Kou, Y; Liu, YQ (corresponding author), Yangzhou Univ, Med Coll, Jiangsu Key Lab Integrated Tradit Chinese & Wester, Yangzhou 225000, Jiangsu, Peoples R China.; Kou, Y (corresponding author), Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou 225000, Jiangsu, Peoples R China. EM kouyu@yzu.edu.cn; liuyq@yzu.edu.cn RI Xu, Hairong/C-1627-2012 FU National Natural Science Foundation of China [81803780, 82102901]; Natural Sci- ence Foundation of Jiangsu Province, China [BK20180928, BK20180925] FX This work was supported by grants from National Natural Science Foundation of China (No. 81803780 and No. 82102901) ; Natural Sci- ence Foundation of Jiangsu Province, China (No. BK20180928 and No. BK20180925) . 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ID TOLL-LIKE RECEPTORS; BLOOD-BRAIN-BARRIER; SIGNALING PATHWAY; MICROGLIA; ACTIVATION; MACROPHAGES; PROTECTS; EXPRESSION; FAMILY; INJURY AB Astragaloside IV (AST IV), a major saponin component and active ingredient isolated from Astragalus membranaceus, has been well known to exhibit neuroprotective effects on diverse models of neurological diseases. Accumulating evidence suggests that dynamic balance of microglia/macrophages and astrocytes plays a vital role in neuroprotection and remyelination. However, dysregulation of microglia/macrophages and astrocytes orchestrate the pathogenesis of nervous system disorders. Therefore, we hypothesized that switching the transformation of microglia/macrophages and astrocytes into the neuroprotective M2 and A2 phenotypes, respectively, could be a potential target for therapeutic intervention. In the present study, we evaluate the efficacy of AST IV intervention on the effects of microglia/macrophages and astrocytes in an experimental autoimmune encephalomyelitis (EAE) model. AST IV improved paralysis and pathology of EAE by inhibiting the neurotoxic M1 microglia/macrophage phenotype, promoting M2 phenotype, shifting astrocytes towards a neuroprotective A2 phenotype, and protecting neurons from apoptosis through inhibition of TLR4/Myd88/NF-kappa B signalling pathway. Our study showed that AST IV could be a potential and promising drug for multiple sclerosis treatment. C1 [Yu, Jingwen; Mu, Bingtao; Guo, Minfang; Liu, Chunyun; Meng, Tao; Yan, Yuqing] Shanxi Datong Univ, Inst Brain Sci, Shanxi Key Lab Inflammatory Neurodegenerat Dis, Datong, Peoples R China. [Song, Lijuan; Yu, Jiezhong; Ma, Cungen] Shanxi Univ Chinese Med, Res Ctr Neurobiol, Key Res Lab Benefiting Qi Acting Blood Circulat M, State Adm Tradit Chinese Med, Taiyuan, Peoples R China. [Kumar, Gajendra] City Univ Hong Kong, Dept Neurosci, Kowloon, Tat Chee Ave, Hong Kong, Peoples R China. C3 Shanxi Datong University; Shanxi University of Chinese Medicine; City University of Hong Kong RP Ma, CG (corresponding author), Shanxi Univ Chinese Med, Res Ctr Neurobiol, Key Res Lab Benefiting Qi Acting Blood Circulat M, State Adm Tradit Chinese Med, Taiyuan, Peoples R China. EM macungen2001@163.com RI YU, JINGWEN/KRQ-6490-2024 OI Kumar, Gajena/0000-0002-7437-6743 FU National Natural Science Foundation of China [81473577, 82004028]; Basic Research Program of Shanxi Province [20210302123337, 20210302123476, 20210302123478]; Shanxi Scholarship Council of China [HGKY2019089]; Shanxi Province Collaborative Innovation Research Center of astragalus resources industrialization [HQXTCXZX2016-022]; Applied Basic Research Project of Datong [2020145]; China Postdoctoral Science Foundation [2020M680912]; International Key Research & Development Cooperation Plan of Datong [2019123]; Young Scientists Cultivation Project of Shanxi University of Chinese Medicine [2021PY-QN-09]; Leading Team of Medical Science and Technology, Shanxi Province [2020TD05] FX This study was supported by the National Natural Science Foundation of China (81473577, 82004028), Basic Research Program of Shanxi Province (20210302123337, 20210302123476, 20210302123478), Shanxi Scholarship Council of China (HGKY2019089), Shanxi Province Collaborative Innovation Research Center of astragalus resources industrialization and internationalization (HQXTCXZX2016-022), Applied Basic Research Project of Datong (2020145), China Postdoctoral Science Foundation (2020M680912), International Key Research & Development Cooperation Plan of Datong (2019123), Young Scientists Cultivation Project of Shanxi University of Chinese Medicine (2021PY-QN-09), and Leading Team of Medical Science and Technology, Shanxi Province (2020TD05). 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PY 2023 VL 61 IS 3 BP 273 EP 290 DI 10.5114/fn.2023.129066 PG 18 WC Neurosciences; Pathology WE Science Citation Index Expanded (SCI-EXPANDED) SC Neurosciences & Neurology; Pathology GA W3LS4 UT WOS:001090682800006 PM 37818688 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Qian, XW Jiang, Y Luo, YY Jiang, YC AF Qian, Xvwu Jiang, Ying Luo, Yiyuan Jiang, Yuchen TI The Anti-hyperuricemia and Anti-inflammatory Effects of Atractylodes Macrocephala in Hyperuricemia and Gouty Arthritis Rat Models SO COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING LA English DT Article DE Atractylodes macrocephala; Hyperuricemia; Gouty arthritis; AMPK; SIRT1; NF-kappa B; Macrophage polarization ID MACROPHAGE POLARIZATION; INFLAMMATORY RESPONSES; AMPK; INHIBITION; DISEASE; SIRT1 AB Aims: Atractylodes macrocephala is a traditional Chinese medicine with a variety of pharmacological activities. This study aimed to evaluate its anti-hyperuricemia and anti-inflammatory effects on gout, and to preliminarily explore its mechanism. Methods: The hyperuricemia rat model was established by intraperitoneal injection of oteracil potassium and intragastric gavage of yeast powder solution. And the acute gouty arthritis (GA) model was established by injecting monosodium urate (MSU) suspension. In the study of the anti-hyperuricemia effect of Atractylodes macrocephala, the healthy male Sprague-Dawley rats were randomly divided into the blank group, hyperuricemia group allopurinol group as well as low, moderate and high dose groups of Atractylodes macrocephala decoction (N=8 rats in each group). Serum, liver and kidney tissue samples were collected from each group. Serum uric acid (UA), adenosine deaminase (ADA) and xanthine oxidase (XOD) levels in each group were detected by enzyme-linked immunosorbent assay (ELISA). Protein levels of ADA and XOD in liver tissues were detected by Western blot, and renal histological changes were observed by Hematoxylin-eosin (H & E) and Masson staining. In order to investigate the anti-inflammatory effect of Atractylodes macrocephala, the healthy male Sprague-Dawley rats were randomly divided into the blank group, GA group, colchicine group, high, moderate and low dose groups of Atractylodes macrocephala decoction (N=8 rats in each group), and serum and synovial tissue of each group were collected. Then the level of serum interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha was observed by ELISA, and the histological changes of synovial tissue were observed by H & E staining. Besides, the expression of adenosine monophosphate-activated protein kinase (AMPK) /silent information regulator (SIRT) 1/nuclear factor kappa B (NF-kappa B) protein in synovial tissue was observed by Western blot and immunohistochemistry. The markers of M1 and M2 macrophages, inducible nitric oxide synthase (iNOS) and arginase-1 (ARG1) were observed by Western blot and immunofluorescence. Results: Atractylodes macrocephala could reduce the production of UA by inhibiting the level of ADA and XOD, and could improve renal injury and fibrosis. In addition, Atractylodes macrophages could reduce the levels of IL-1 beta and TNF-alpha, activate AMPK/SIRT1 signaling pathway, and inhibit the activation of NF-kappa B and the polarization of macrophages to a pro-inflammatory phenotype. Conclusion: Atractylodes macrocephala shows good anti-hyperuricemic and anti-inflammatory effects, and its anti-inflammation pharmacological activity may be related to the inhibition of M1 macrophage polarization and NF-kappa B activation through activating AMPK/SIRT1. C1 [Qian, Xvwu; Luo, Yiyuan; Jiang, Yuchen] Zhejiang Pharmaceut Univ, Coll Tradit Chinese Med, Ningbo 315503, Peoples R China. [Jiang, Ying] Ningbo Municipal Hosp Tradit Chinese Med, Dept Gynecol, Ningbo 315010, Peoples R China. C3 Zhejiang Pharmaceutical University RP Luo, YY (corresponding author), Zhejiang Pharmaceut Univ, Coll Tradit Chinese Med, Ningbo 315503, Peoples R China. EM luoyiyuan0012@163.com RI jiang, yuchen/AAP-4879-2021 FU Ningbo Natural Science Foundation Project [2017A610195, 2018A610434]; Scientific research project of Zhejiang Pharmaceutical College [ZPCSR2015017]; Zhejiang Province Traditional Chinese Medicine Science and Technology Project [2016ZB117] FX Ningbo Natural Science Foundation Project (No.2017A610195, No.2018A610434)Scientific research project of Zhejiang Pharmaceutical College (No.ZPCSR2015017).Zhejiang Province Traditional Chinese Medicine Science and Technology Project (2016ZB117). 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Chem. High Throughput Screen PY 2023 VL 26 IS 5 BP 950 EP 964 DI 10.2174/1386207325666220603101540 PG 15 WC Biochemical Research Methods; Chemistry, Applied; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA E3FJ3 UT WOS:000974432400008 PM 35658881 DA 2026-03-26 ER PT J AU Li, YH Li, H He, QJ Yang, XC AF Li, Yunheng Li, Hui He, Qiaojun Yang, Xiaochun TI Potential of Compounds Originating from the Nature to Act in Hepatocellular Carcinoma Therapy by Targeting the Tumor Immunosuppressive Microenvironment: A Review SO MOLECULES LA English DT Review DE hepatocellular carcinoma; immunotherapy; immune suppression; TME; natural products ID TRADITIONAL CHINESE MEDICINE; HEPATIC STELLATE CELLS; REGULATORY T-CELLS; MACROPHAGE POLARIZATION; PD-L1 EXPRESSION; IMMUNE-RESPONSE; M2 POLARIZATION; CURCUMIN ANALOG; LIVER-CANCER; IN-VITRO AB Hepatocellular carcinoma (HCC), the most prevalent subtype of liver cancer, is the second main reason for cancer-related deaths worldwide. In recent decades, sufficient evidence supported that immunotherapy was a safe and effective treatment option for HCC. However, tolerance and frequent recurrence and metastasis occurred in patients after immunotherapy due to the complicated crosstalk in the tumor immunosuppressive microenvironment (TIME) in HCC. Therefore, elucidating the TIME in HCC and finding novel modulators to target TIME for attenuating immune suppression is critical to optimize immunotherapy. Recently, studies have shown the potentially immunoregulatory activities of natural compounds, characterized by multiple targets and pathways and low toxicity. In this review, we concluded the unique role of TIME in HCC. Moreover, we summarized evidence that supports the hypothesis of natural compounds to target TIME to improve immunotherapy. Furthermore, we discussed the comprehensive mechanisms of these natural compounds in the immunotherapy of HCC. Accordingly, we present a well-grounded review of the naturally occurring compounds in cancer immunotherapy, expecting to shed new light on discovering novel anti-HCC immunomodulatory drugs from natural sources. C1 [Li, Yunheng; Li, Hui; He, Qiaojun; Yang, Xiaochun] Zhejiang Univ, Coll Pharmaceut Sci, Ctr Drug Safety Evaluat & Res, Hangzhou 310058, Peoples R China. [Yang, Xiaochun] Zhejiang Univ, Innovat Inst Artificial Intelligence Med, Coll Pharmaceut Sci, Hangzhou 310058, Peoples R China. [Yang, Xiaochun] Zhejiang Univ, Shandong Linyi Inst Modern Agr, Linyi 276000, Peoples R China. [Yang, Xiaochun] Zhejiang Univ, Hangzhou Inst Innovat Med, Coll Pharmaceut Sci, Hangzhou 310058, Peoples R China. C3 Zhejiang University; Zhejiang University; Zhejiang University; Zhejiang University RP Yang, XC (corresponding author), Zhejiang Univ, Coll Pharmaceut Sci, Ctr Drug Safety Evaluat & Res, Hangzhou 310058, Peoples R China.; Yang, XC (corresponding author), Zhejiang Univ, Innovat Inst Artificial Intelligence Med, Coll Pharmaceut Sci, Hangzhou 310058, Peoples R China.; Yang, XC (corresponding author), Zhejiang Univ, Shandong Linyi Inst Modern Agr, Linyi 276000, Peoples R China.; Yang, XC (corresponding author), Zhejiang Univ, Hangzhou Inst Innovat Med, Coll Pharmaceut Sci, Hangzhou 310058, Peoples R China. EM yangxiaochun@zju.edu.cn RI ; Yang, Xiaochun/ABP-8866-2022; he, qiaojun/F-3198-2010 OI Li, Yunheng/0000-0002-5622-7787; FU National Natural Science Foundation of China; [82274018] FX This research was funded by the National Natural Science Foundation of China (Grant No. 82274018). 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Zuo HX, 2020, J ETHNOPHARMACOL, V257, DOI 10.1016/j.jep.2020.112835 NR 184 TC 6 Z9 7 U1 3 U2 30 PU MDPI PI BASEL PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND EI 1420-3049 J9 MOLECULES JI Molecules PD JAN PY 2023 VL 28 IS 1 AR 195 DI 10.3390/molecules28010195 PG 33 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry GA 7P7WY UT WOS:000908912200001 PM 36615387 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhou, LX Li, MP Chai, ZB Zhang, JL Cao, K Deng, L Liu, YM Jiao, C Zou, GM Wu, JB Han, FB AF Zhou, Liangxing Li, Mengpeng Chai, Zhengbin Zhang, Junli Cao, Kuan Deng, Lei Liu, Yanming Jiao, Cun Zou, Gang-Ming Wu, Jibiao Han, Fabin TI Anticancer effects and mechanisms of astragaloside-IV SO ONCOLOGY REPORTS LA English DT Review DE astragaloside-IV; antitumor; apoptosis; proliferation; metastasis; migration; tumor microenvironment; signaling pathway ID EPITHELIAL-MESENCHYMAL TRANSITION; TRADITIONAL CHINESE MEDICINE; INHIBITS CELL-PROLIFERATION; MACROPHAGE POLARIZATION; GASTRIC-CANCER; LUNG-CANCER; COLORECTAL-CANCER; SIGNALING PATHWAY; IMMUNE FUNCTION; DOWN-REGULATION AB Astragalus membranaceus Bunge is widely used in Traditional Chinese Medicine to treat various cancers. Astragaloside-IV (AS-IV) is one of the major compounds isolated from A. membranaceus Bunge and has been demonstrated to have antitumor effects by inhibiting cell proliferation, invasion and metastasis in various cancer types. Numerous studies have used in vitro cell culture and in vivo animal models of cancer to explore the antitumor activities of AS-IV. In the present study, the antitumor effects and mechanisms of AS-IV reported in studies recorded in the PubMed database were reviewed. First, the antitumor effects of AS-IV on proliferation, cell cycle, apoptosis, autophagy, invasion, migration, metastasis and epithelial-mesenchymal transition processes in cancer cells and the tumor microenvironment, including angiogenesis, tumor immunity and macrophage-related immune responses to cancer cells, were comprehensively discussed. Subsequently, the molecular mechanisms and related signaling pathways associated with antitumor effects of AS-IV as indicated by in vitro and in vivo studies were summarized, including the Wnt/AKT/GSK-3 beta (glycogen synthase kinase-3 beta)/beta-catenin, TGF-beta/PI3K/AKT/mTOR, PI3K/MAPK/mTOR, PI3K/AKT/NF-kappa B, Rac family small GTPase 1/RAS/MAPK/ERK, TNF-alpha/protein kinase C/ERK1/2-NF-kappa B and Tregs (T-regulatory cells)/IL-11/STAT3 signaling pathways. Of note, several novel mechanisms of Toll-like receptor 4 (TLR4)/NF-kappa B/STAT3, pSmad3C/3L, nuclear factor erythroid 2-related factor (NrF2)/heme oxygenase 1, circDLST/microRNA-489-3p/eukaryotic translation initiation factor 4A1 and macrophage-related high-mobility group box 1-TLR4 signaling pathways associated with the anticancer activity of AS-IV were also included. Finally, the limitations of current studies that must be addressed in future studies were pointed out to facilitate the establishment of AS-IV as a potent therapeutic drug in cancer treatment. C1 [Zhou, Liangxing; Chai, Zhengbin; Zhang, Junli; Cao, Kuan; Deng, Lei; Wu, Jibiao; Han, Fabin] Shandong Univ Tradit Chinese Med, Innovat Inst Tradit Chinese Med, Translat Res Lab Stem Cell & Tradit Chinese Med, 4665 Univ Ave, Jinan 250355, Shandong, Peoples R China. [Li, Mengpeng; Liu, Yanming; Han, Fabin] Liaocheng Univ, Liaocheng Peoples Hosp, Inst Tissue Engn & Regenerat Med, Lab Stem Cell & Regenerat Med, Liaocheng, Peoples R China. [Jiao, Cun] Liaocheng Peoples Hosp, Dept Tradit Chinese Med, Liaocheng 252000, Shandong, Peoples R China. [Zou, Gang-Ming] Univ Hawaii Manoa, Nancy Atmospera Walch Sch Nursing, Honolulu, HI 96822 USA. [Han, Fabin] Shandong Meijia Therapeut Biotechnol Co Ltd, Dept Res & Dev, Jinan 250100, Shandong, Peoples R China. C3 Shandong University of Traditional Chinese Medicine; Liaocheng University; University of Hawaii System; University of Hawaii Manoa RP Wu, JB; Han, FB (corresponding author), Shandong Univ Tradit Chinese Med, Innovat Inst Tradit Chinese Med, Translat Res Lab Stem Cell & Tradit Chinese Med, 4665 Univ Ave, Jinan 250355, Shandong, Peoples R China. 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Rep. PD JAN PY 2023 VL 49 IS 1 AR 5 DI 10.3892/or.2022.8442 PG 15 WC Oncology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology GA 6N6MG UT WOS:000889668100001 PM 36367181 OA Green Submitted, hybrid DA 2026-03-26 ER PT J AU Song, M Cui, XH Zhang, J Li, YJ Li, JJ Zang, YL Li, Q Yang, Q Chen, Y Cai, WY Weng, XG Wang, YJ Zhu, XX AF Song, Min Cui, Xihe Zhang, Jing Li, Yujie Li, Jingjing Zang, Yuanlong Li, Qi Yang, Qing Chen, Ying Cai, Weiyan Weng, Xiaogang Wang, Yajie Zhu, Xiaoxin TI Shenlian extract attenuates myocardial ischaemia-reperfusion injury via inhibiting M1 macrophage polarization by silencing miR-155 SO PHARMACEUTICAL BIOLOGY LA English DT Article DE MI; RI; apoptosis; Salvia miltiorrhiza; Andrographis paniculata ID APOPTOSIS AB Context Shenlian extract (SL) is a combination of Salvia miltiorrhiza Bge. (Labiatae) and Andrographis paniculata (Burm. F.) Wall. Ex Nees (Acanthaceae) extracts, which promote blood circulation and clear endogenous heat toxins. Myocardial ischaemia-reperfusion injury (MI/RI) is aggravated myocardial tissue damage induced by reperfusion therapy after myocardial infarction. Objectives This study explores the effect of SL on MI/RI and the underlying mechanism. Materials and methods Primary peritoneal macrophages (pMACs) were treated with LPS and SL (5, 10 or 20 mu g/mL) for 24 h. The myocardial ischaemia-reperfusion (MI/R) model was established after administration of different doses of SL (90, 180 or 360 mg/kg). Myocardial tissue injury was assessed by methylthiazolyl tetrazolium (TTC) staining and levels of creatine kinase (CK), lactate dehydrogenase (LDH) and superoxide dismutase (SOD) in mice. The double immunofluorescence staining of iNOS/F4/80 and CD86/F4/80 was used to detect macrophage M1 polarization. The levels of miR-155, inflammatory factors and chemokines were detected by qRT-PCR or ELISA. CD86, iNOS, SOCS3, JAK2, p-JAK2, STAT3 and p-STAT3 proteins expressions in macrophages were analyzed by western blotting. Conditioned medium transfer systems were designed to unite M1 macrophages with H/R cardiomyocytes, and cell apoptosis was detected by TUNEL staining, western blotting or immunohistochemistry. Results SL reduced apoptosis, diminished CK and LDH levels, raised SOD concentration and decreased infarct size in the MI/R model. Meanwhile, SL decreased miR-155 level, inhibited M1 macrophage polarization and inflammation. Furthermore, SL promoted SOCS3 expression and blocked JAK2/STAT3 pathway in vitro. Conclusions SL may be a promising TCM candidate for MI/RI. The underlying mechanisms could be associated with inhibition of M1 macrophage polarization via down-regulating miR-155. C1 [Song, Min; Cui, Xihe; Zhang, Jing; Li, Yujie; Li, Jingjing; Zang, Yuanlong; Li, Qi; Yang, Qing; Chen, Ying; Cai, Weiyan; Weng, Xiaogang; Wang, Yajie; Zhu, Xiaoxin] China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing, Peoples R China. C3 China Academy of Chinese Medical Sciences; Institute of Chinese Materia Medica, CACMS RP Wang, YJ; Zhu, XX (corresponding author), China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing, Peoples R China. EM yjwang@icmm.ac.cn; xxzhu@icmm.ac.cn RI Luo, yujie/KGK-3881-2024; Wang, Yajie/PHO-7210-2026 FU Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences [CI2021B015]; National Natural Science Foundation of China [81573649]; State Project for Essential Drug Research and Development [2017ZX09101002] FX We acknowledge Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences [CI2021B015], the National Natural Science Foundation of China [81573649], financial support of the project supported by the State Project for Essential Drug Research and Development [2017ZX09101002]. 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PD DEC 31 PY 2022 VL 60 IS 1 BP 2011 EP 2024 DI 10.1080/13880209.2022.2117828 PG 14 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA 5I2JY UT WOS:000868190900001 PM 36239618 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Pan, T Chang, YB He, M He, ZH Jiang, J Ren, XL Zhang, F AF Pan, Tao Chang, Yabin He, Min He, Zehui Jiang, Jun Ren, Xinling Zhang, Fang TI β-Hydroxyisovalerylshikonin regulates macrophage polarization via the AMPK/Nrf2 pathway and ameliorates sepsis in mice SO PHARMACEUTICAL BIOLOGY LA English DT Article DE Chinese herb extract; non-cytotoxic dose; lipopolysaccharide; anti-inflammatory effect ID ACUTE LUNG INJURY; TUMOR-ASSOCIATED MACROPHAGES; CELLS; APOPTOSIS; PROTECTS; NRF2; INFLAMMATION; ACTIVATION; OVEREXPRESSION; EXPRESSION AB Context The potential anti-inflammatory bioactivities of beta-hydroxyisovalerylshikonin (beta-HIVS) remain largely unknown. Objective This study investigated the anti-inflammatory effects and underlying mechanisms of beta-HIVS. Materials and methods RAW 264.7 cells stimulated with LPS (100 ng/mL) for 24 h were treated with the non-cytotoxic doses of beta-HIVS (0.5 or 1 mu M, determined by MTT and Trypan blue staining), qRT-PCR and FCM assay were used to examine macrophage polarization transitions. Western blotting was used to evaluate the activation of the AMPK/Nrf2 pathway. In vivo, C57BL/6 mice were randomly divided into vehicle control, LPS (10 mg/kg), and beta-HIVS (2.5 mg/kg) combined with LPS (10 mg/kg) groups, blood samples, BALF, and lung tissues of mice were subjected to ELISA, qRT-PCR, FCM, and H&E staining. Results beta-HIVS (1 mu M) inhibited LPS-induced expression of M1 macrophage markers (TNF-alpha: 0.29-fold, IL-1 beta: 0.32-fold), promoted the expression of M2 macrophage markers (CD206: 3.14-fold, Arginase-1: 3.98-fold) in RAW 264.7 cells; mechanistic studies showed that beta-HIVS increased the expression of nuclear Nrf2 (2.04-fold) and p-AMPK (3.65-fold) compared with LPS group (p < 0.05). In vivo, beta-HIVS decreased the levels of pro-inflammatory cytokines (TNF-alpha: 1130.41 vs. 334.88 pg/mL, IL-1 beta: 601.89 vs. 258.21 pg/mL in serum; TNF-alpha: 893.07 vs. 418.21 pg/mL, IL-1 beta: 475.22 vs. 298.54 pg/mL in BALF), decreased the proportion of M1 macrophages (77.83 vs. 68.53%) and increased the proportion of M2 macrophages (13.55 vs. 19.56%) in BALF, and reduced lung tissue damage and septic mice survival (p < 0.05). Conclusions These results indicate that beta-HIVS may be a new potential anti-inflammatory agent. C1 [Pan, Tao; Chang, Yabin; He, Min; He, Zehui] Guangzhou Med Univ, Translat Med Ctr, Affiliated Hosp 2, Guangzhou, Guangdong, Peoples R China. [Pan, Tao; Jiang, Jun; Ren, Xinling; Zhang, Fang] Air Force Med Univ, Xijing Hosp, Dept Resp Med, Xian 710032, Shaanxi, Peoples R China. [Pan, Tao] Xian Med Univ, Inst Basic Med Sci, Inst Basic & Translat Med, Shaanxi Key Lab Brain Disorders, Xian, Shaanxi, Peoples R China. [Ren, Xinling] Shenzhen Univ, Carson Int Canc Ctr, Shenzhen, Guangdong, Peoples R China. [Ren, Xinling] Shenzhen Univ, Clin Med Acad, Shenzhen, Guangdong, Peoples R China. C3 Guangzhou Medical University; Air Force Medical University; Xi'an Medical University; Shenzhen University; Shenzhen University RP Ren, XL; Zhang, F (corresponding author), Air Force Med Univ, Xijing Hosp, Dept Resp Med, Xian 710032, Shaanxi, Peoples R China. EM majrenxl@fmmu.edu.cn; 176177507@qq.com RI Jiang, Jun/NVM-7104-2025 OI Jiang, Jun/0000-0002-5971-3174 FU National Natural Science Foundation of China [82100008, 81871880]; Natural Science Foundation of Shaanxi Province [2019JQ889]; Foundation of the State Key Laboratory of Cancer Biology of China [CBSKL201710]; Foundation of Xi'an Medical University [2018DOC02] FX This work was supported by grants from the National Natural Science Foundation of China (Grant numbers: 82100008, 81871880); the Natural Science Foundation of Shaanxi Province (Grant number: 2019JQ889); the Foundation of the State Key Laboratory of Cancer Biology of China (Grant number: CBSKL201710); and the Foundation of Xi'an Medical University (Grant number: 2018DOC02). 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PD DEC 31 PY 2022 VL 60 IS 1 BP 729 EP 742 DI 10.1080/13880209.2022.2046111 PG 14 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA 0C9UM UT WOS:000775650000001 PM 35352622 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhang, H Zhang, MY Wang, XM Zhang, M Wang, XL Li, YY Cui, ZE Chen, XP Han, YT Zhao, WW AF Zhang, Hao Zhang, Mengyao Wang, Xumei Zhang, Mi Wang, Xuelian Li, Yiyang Cui, Zhuoer Chen, Xiuping Han, Yantao Zhao, Wenwen TI Electrospun multifunctional nanofibrous mats loaded with bioactive anemoside B4 for accelerated wound healing in diabetic mice SO DRUG DELIVERY LA English DT Article DE Traditional Chinese medicine; anemoside B4; inflammatory; diabetic wound healing ID NF-KAPPA-B; SUSTAINED-RELEASE; STEM-CELLS; INFLAMMATION; PROLIFERATION; PATHOGENESIS; MACROPHAGES; SCAFFOLDS; DESIGN AB With the worldwide prevalence of diabetes and considering the complicated microenvironment of diabetic wounds, the design and development of innovative multifunctional wound dressing materials are much wanted for the treatment of hard-to-heal wounds in diabetic patients. In the present study, anti-inflammatory ingredients loaded with nanofibrous wound dressing materials were manufactured by a promising blend-electrospinning strategy, and their capability for treating the diabetic wound was also systematically explored. A polymer blend consisting of Chitosan (CS) and polyvinyl alcohol (PVA) was electrospun into CS-PVA nanofibrous mats as control groups. In the meanwhile, a bioactive ingredient of Chinese medicine Pulsatilla, anemoside B4(ANE), with different contents were loaded into the electrospinning solution to construct CS-PVA-ANE nanofibrous mats. The developed CS-PVA-ANE wound dressing materials exhibited multifunctional properties including prominent water absorption, biomimetic elastic mechanical properties, and sustained ANE releasing behavior, as well as outstanding hemostatic properties. The in vitro studies showed that the CS-PVA-ANE nanofiber mats could significantly suppress lipopolysaccharide (LPS)-stimulated differentiation of pro-inflammatory (M1) macrophage subsets, and notably reduce the reactive oxygen species (ROS) generation, as well as obviously decrease inflammatory cytokine release. The in vivo animal studies showed that the CS-PVA-ANE nanofiber mats promoted the healing of diabetic wounds by significantly enhancing wound closure rates, accelerating excellent angiogenesis, promoting re-epithelization and collagen matrix deposition throughout all stages of wound healing. The present study demonstrated that CS-PVA-ANE nanofiber mats could effectively shorten the wound-healing time by inhibiting inflammatory activity, which makes them promising candidates for the treatment of hard-to-heal wounds caused by diabetes. C1 [Zhang, Hao; Zhang, Mengyao; Zhang, Mi; Wang, Xuelian; Li, Yiyang; Cui, Zhuoer; Han, Yantao; Zhao, Wenwen] Qingdao Univ Med Coll, 308 Ningxia Rd, Qingdao 266021, Shandong, Peoples R China. [Wang, Xumei; Chen, Xiuping; Zhao, Wenwen] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Taipa, Macao, Peoples R China. C3 Qingdao University; University of Macau RP Han, YT; Zhao, WW (corresponding author), Qingdao Univ Med Coll, 308 Ningxia Rd, Qingdao 266021, Shandong, Peoples R China. EM hanyt@edu.qdu.cn; wenwenzhao0313@163.com RI Chen, Xiuping/AAG-3086-2020; Zhang, Mengyao/NJT-3983-2025 FU National Natural Science Foundation of China [31900957, 81803766]; Shandong Provincial Natural Science Foundation [ZR2019QC007, ZR2018BH036]; Key Research and Discovery Program of Shandong Province [2019GSF107072]; Innovation and Technology Program for the Excellent Youth Scholars of Higher Education of Shandong Province [2019KJE015]; China Postdoctoral Science Foundation [2019M652326, 2019M652336]; Special Programs for Postdoctoral Fellows [2020T130334] FX The authors are very grateful for financial support from the National Natural Science Foundation of China [Grant Nos. 31900957 and 81803766], Shandong Provincial Natural Science Foundation [Grant Nos. ZR2019QC007 and ZR2018BH036], Key Research and Discovery Program of Shandong Province [2019GSF107072], Innovation and Technology Program for the Excellent Youth Scholars of Higher Education of Shandong Province [Grant No. 2019KJE015], China Postdoctoral Science Foundation [Grant Nos. 2019M652326 and 2019M652336], and Special Programs for Postdoctoral Fellows [No. 2020T130334]. 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Thai traditional medicine uses Maclura cochinchinensis (Lour.) Corner to treat chronic fever and various inflammatory diseases, as well as to maintain normal lymphatic function. Five flavonoids and five xanthones were isolated from the heartwood of M. cochinchinensis and we investigated the anti-inflammatory properties of the isolated compounds. All isolated compounds possessed an anti-inflammatory effect by decreasing prostaglandin E-2 (PGE(2)) synthesis in lipopolysaccharide (LPS)-activated murine macrophages with varying degrees of potency. The greatest decrease in M1 inflammatory mediators, nitric oxide, PGE(2), and proinflammatory cytokines was observed with 1,3,7-trihydroxyxanthone and 1,3,5-trihydroxyxanthone treatment of LPS-activated macrophages. The anti-inflammatory mechanism of the two xanthones is mediated by the suppression of inducible nitric oxide synthase, cyclooxygenase-2, and phosphatidylinositol 3-kinase/protein kinase B expression and the upregulation of M2 anti-inflammatory signalling proteins phosphorylated signal transducer and activator of transcription 6 and peroxisome proliferator-activated receptors-gamma. 1,3,7-Trihydroxyxanthone exhibits superior induction of anti-inflammatory M2 mediator of LPS-activated macrophages by upregulating arginase1 expression. Following the resolution of inflammation, the two xanthones enhanced surface TLR4 expression compared to LPS-stimulated cells, possibly preserving macrophage function. Our research highlights the role of the two xanthones in modulating the M1/M2 macrophage polarisation to reduce inflammation and retain surface TLR4 once inflammation has been resolved. These findings support the use of xanthones for their anti-inflammatory effects in treating inflammatory dysregulation. C1 [Jansakun, Chutima; Mueangson, Onchuma; Chunglok, Warangkana] Walailak Univ, Sch Allied Hlth Sci, Nakhon Si Thammarat 80160, Thailand. [Chulrik, Wanatsanan; Supaweera, Nassareen] Walailak Univ, Coll Grad Studies, Hlth Sci Int Program, Nakhon Si Thammarat 80160, Thailand. [Hata, Janejira; Pabuprapap, Wachirachai; Suksamrarn, Apichart] Ramkhamhang Univ, Fac Sci, Dept Chem, Bangkok 10240, Thailand. [Hata, Janejira; Pabuprapap, Wachirachai; Suksamrarn, Apichart] Ramkhamhang Univ, Fac Sci, Ctr Excellence Innovat Chem, Bangkok 10240, Thailand. [Utaipan, Tanyarath] Prince Songkla Univ, Fac Sci & Technol, Dept Sci, Pattani Campus, Pattani 94000, Thailand. [Chunglok, Warangkana] Walailak Univ, Res & Innovat Inst Excellence, Food Technol & Innovat Ctr Excellence, Nakhon Si Thammarat 80160, Thailand. C3 Walailak University; Walailak University; Ramkhamhaeng University; Ramkhamhaeng University; Prince of Songkla University; Walailak University RP Chunglok, W (corresponding author), Walailak Univ, Sch Allied Hlth Sci, Nakhon Si Thammarat 80160, Thailand.; Chunglok, W (corresponding author), Walailak Univ, Res & Innovat Inst Excellence, Food Technol & Innovat Ctr Excellence, Nakhon Si Thammarat 80160, Thailand. EM cwarang@wu.ac.th RI Utaipan, Tanyarath/G-1423-2017; Jansakun, Chutima/IZP-7394-2023; Suksamrarn, Apichart/R-8782-2019; Chulrik, Wanatsanan/KVY-0830-2024 OI Pabuprapap, Wachirachai/0000-0001-6445-7550; Jansakun, Chutima/0000-0002-7892-4436; Hata, Janejira/0000-0003-3358-8712; Suksamrarn, Apichart/0000-0001-8919-3555; Chulrik, Wanatsanan/0000-0003-2804-4921 FU Thai Traditional Medical Knowledge Fund, Department of Thai Traditional and Alternative Medicine, Ministry of Public Health and the new strategic research (P2P) project of Walailak University, Nakhon Si Thammarat, Thailand; Center of Excellence for Innovation in Chemistry, Ministry of Higher Education, Science, Research, and Innovation FX This research was supported by Thai Traditional Medical Knowledge Fund, Department of Thai Traditional and Alternative Medicine, Ministry of Public Health and the new strategic research (P2P) project of Walailak University, Nakhon Si Thammarat, Thailand. C. Jansakun expresses her gratitude to The Royal Golden Jubilee Ph.D. Program (Grant No. RGJ PHD/0216/2561). A. Suksamrarn, J. Hata, and W. Pabuprapap acknowledge partial support from the Center of Excellence for Innovation in Chemistry, Ministry of Higher Education, Science, Research, and Innovation. We would like to thank Editage (www.editage.com) for English language editing. 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Sotetsuflavone (SF) is a natural monomeric herbal compound with anti-inflammatory and cytoprotective effects that is mostly nontoxic. The effect of SF on CD-like spontaneous colitis was investigated in this study.Methods: Il-10 /mice were used as a CD model and were administered different doses of SF. Lipopolysaccharide (LPS) plus IFN-gamma-induced macrophages (RAW264.7) and a coculture system (RAW264.7 and organoids) were used in vitro. The protective effects of SF against CD-like colitis and macrophage differentiation and the mech-anisms were evaluated.Results: SF treatment markedly improved spontaneous colitis in the CD model, as shown by the following evi-dence: reductions in the DAI, macroscopic scores (3.63 +/- 1.30), colonic tissue inflammatory scores (2 +/- 0.76) and proinflammatory factor levels and the attenuation of colon shortening (8 +/- 0.93 cm) and weight loss (1.75 +/- 1.83 g). Decreased intestinal permeability and intestinal bacterial translocation rates provided evidence of the protective effect of SF on intestinal barrier function. We also found that SF suppressed M1 macrophage-induced inflammatory responses. In the coculture system of mouse colonic organoids and RAW264.7 cells, SF signifi-cantly ameliorated M1 macrophage-induced intestinal epithelial damage. In addition, SF inhibited JNK and MAPK (p38) signalling in both Il-10 / mice and LPS plus IFN-gamma-induced macrophages (RAW264.7).Conclusions: The protective effects of SF against CD-like colitis may be achieved partially by inhibiting M1 macrophage-induced intestinal barrier damage via JNK and p38 signalling. SF may have therapeutic potential for treating CD, especially considering its safety. C1 [Ge, Sitang; Sun, Xuejun] Xi An Jiao Tong Univ, Dept Gen Surg, Affiliated Hosp 1, Xian, Shanxi, Peoples R China. [Ge, Sitang; Yang, Yating; Zuo, Lugen; Wen, Hexin; He, Yifan; Xu, Zilong; Wu, Huatao; Shen, Mengdi] Bengbu Med Coll, Dept Gastrointestinal Surg, Affiliated Hosp 1, Bengbu, Anhui, Peoples R China. [Yang, Yating; Zuo, Lugen; Song, Xue; He, Yifan; Xu, Zilong; Wu, Huatao; Shen, Mengdi] Bengbu Med Coll, Anhui Key Lab Tissue Transplantat, Bengbu, Peoples R China. [Song, Xue; Geng, Zhijun] Bengbu Med Coll, Dept Cent Lab, Affiliated Hosp 1, Bengbu, Peoples R China. [Ge, Yuanyuan] Nanjing Univ Chinese Med, Dept Colorectal Surg, Affiliated Hosp 3, Nanjing, Peoples R China. [Sun, Xuejun] Xi An Jiao Tong Univ, Dept Gen Surg, Affiliated Hosp 1, 76 West Yanta Rd, Xian 710061, Shanxi, Peoples R China. C3 Xi'an Jiaotong University; Bengbu Medical University; Bengbu Medical University; Bengbu Medical University; Nanjing University of Chinese Medicine; Xi'an Jiaotong University RP Sun, XJ (corresponding author), Xi An Jiao Tong Univ, Dept Gen Surg, Affiliated Hosp 1, 76 West Yanta Rd, Xian 710061, Shanxi, Peoples R China. EM sunxy@mail.xjtu.edu.cn RI sun, xuejun/G-5212-2011 FU Natural Science Foundation of Anhui Province [1808085QH237]; 512 Talent Cultivation Plan of Bengbu Medical College [by51201322]; National Natural Science Foundation of China [82070561] FX This work was supported partly by funding from the Natural Science Foundation of Anhui Province (1808085QH237) , 512 Talent Cultivation Plan of Bengbu Medical College (by51201322) and National Natural Science Foundation of China (82070561) . 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J. Pharmacol. PD FEB 5 PY 2023 VL 940 AR 175464 DI 10.1016/j.ejphar.2022.175464 EA DEC 2022 PG 11 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 7U6XY UT WOS:000912275600001 PM 36566007 OA hybrid DA 2026-03-26 ER PT J AU Wei, QC Jin, ZM Zhang, WW Zhao, YF Wang, YX Wei, YX He, X Ma, GL Guo, YM Jiang, YQ Hu, ZG AF Wei, Qingcong Jin, Ziming Zhang, Weiwei Zhao, Yanfei Wang, Yaxing Wei, Yixing He, Xing Ma, Guanglei Guo, Yuming Jiang, Yuqin Hu, Zhiguo TI Honokiol@PF127 crosslinked hyaluronate-based hydrogel for promoting wound healing by regulating macrophage polarization SO CARBOHYDRATE POLYMERS LA English DT Article DE Honokiol; PF127; Hyaluronic acid; Hydrogel; Wound healing; Macrophage polarization ID RELEASE AB Bacterial infection, oxidative stress and inflammation are the main obstacles in wound healing. Hydrogels with moist and inherent properties are beneficial to wound healing. Here, we fabricated a honokiol-laden micellecrosslinked hyaluronate-based hydrogel by simply mixing honokiol-laden PF127-CHO micelles, 3,3 '-dithiobis (propionohydrazide) grafted hyaluronic acid and silver ions. PF127 could not only effectively load hydrophobic small molecules but also be macromolecular crosslinker for preparing hydrogels. Hyaluronic acid plays an essential role in wound healing processes including regulating macrophage polarization towards M2 phenotype. The chemical dynamic acylhydrazone crosslinking and physical crosslinking among PF127-CHO micelles constructed hydrogel's networks, which endowed hydrogel with excellent self-healing properties. PF-HA-3 hydrogel also exhibited outstanding antioxidant and antibacterial capabilities. In a full-thickness skin defect model, this degradable and biocompatible hydrogel could promote wound healing by remodeling wound tissues, regulating M2 polarization and angiogenesis. In summary, this inherent multifunctional hydrogel will provide a promising strategy for designing bioactive compounds-based wound dressings. C1 [Wei, Qingcong; Jin, Ziming; Zhang, Weiwei; Zhao, Yanfei; Wang, Yaxing; Wei, Yixing; He, Xing; Ma, Guanglei; Guo, Yuming; Jiang, Yuqin; Hu, Zhiguo] Henan Normal Univ, Collaborat Innovat Ctr Henan Prov Green Mfg Fine C, Henan Engn Res Ctr Chiral Hydroxyl Pharmaceut, Sch Chem & Chem Engn,Key Lab Green Chem Media & Re, Xinxiang 453007, Peoples R China. C3 Henan Normal University RP Wei, QC; Zhang, WW; Hu, ZG (corresponding author), Henan Normal Univ, Collaborat Innovat Ctr Henan Prov Green Mfg Fine C, Henan Engn Res Ctr Chiral Hydroxyl Pharmaceut, Sch Chem & Chem Engn,Key Lab Green Chem Media & Re, Xinxiang 453007, Peoples R China. EM qcwei@htu.edu.cn; zhangweiwei@htu.edu.cn; zghu@htu.cn RI wang, YA/K-9671-2016; Wei, Qingcong/A-7908-2019; Jiang, Yuqin/HZM-6018-2023 FU Foundation of Henan Educational Committee [20A150023, 21A150029, 23B430001]; Key Science and Technology Project of Henan Province [212102310856]; Natural Science Foundation of Henan Province [212300410009]; Technical Innovation Team of Henan Normal University [2022TD03] FX This work was financially supported by the following foundation: The Foundation of Henan Educational Committee (No. 20A150023, 21A150029, 23B430001), the Key Science and Technology Project of Henan Province (No. 212102310856), Natural Science Foundation of Henan Province (212300410009), the Technical Innovation Team of Henan Normal University (2022TD03). 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Polym. PD MAR 1 PY 2023 VL 303 AR 120469 DI 10.1016/j.carbpol.2022.120469 EA DEC 2022 PG 10 WC Chemistry, Applied; Chemistry, Organic; Polymer Science WE Science Citation Index Expanded (SCI-EXPANDED) SC Chemistry; Polymer Science GA 7T0CB UT WOS:000911115800001 PM 36657865 DA 2026-03-26 ER PT J AU Li, MH Lu, W Meng, YY Zhang, WJ Wang, FG Sun, L Xu, YK AF Li, Minghui Lu, Wei Meng, Yuanyuan Zhang, Wenjie Wang, Fengge Sun, Li Xu, Yuekang TI Tetrahydroxy Stilbene Glucoside Alleviates Ischemic Stroke by Regulating Conformation-Dependent Intracellular Distribution of PKM2 for M2 Macrophage Polarization SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE tetrahydroxy stilbene glucoside; ischemic stroke; macrophage polarization; PKM2 conformation ID PYRUVATE-KINASE M2; IMMUNOMETABOLISM; PHARMACOKINETICS; PHARMACOLOGY; MECHANISMS; TOXICITY AB Tetrahydroxy stilbene glucoside (TSG) is a bioactive ingredient with powerful anti-inflammatory and neuroprotective properties. However, the detailed mechanisms concerning the neuroprotective effect of TSG are not fully understood. This study aims to address the molecular mechanism involved in the protective effects of TSG on murine ischemic stroke. We found that TSG meliorated the phenotypes of ischemic stroke in vivo, which was correlated with the increased percentage of infiltrated M2 macrophages in brain after stroke. Mechanistically, TSG regulated macrophage polarization by significantly downregulating the transcriptional levels of M1 marker genes (iNOS and IL-1 beta) but upregulating that of the M2 marker genes (arg-1 and IL-4) following lipopolysaccharide/interferon-gamma stimulation. Consistently, TSG reversed the metabolic profiling of M1 macrophage toward the M2 status at intracellular energy levels. Surprisingly, the knockdown of an established metabolic enzyme pyruvate kinase M2 (PKM2) that is important for M1 switch in macrophages abolished the promotive effect of TSG on the M2 polarization. Further investigation revealed that TSG markedly downregulated the intracellular ratio of dimer/monomer to the tetramer of PKM2 without affecting its total protein expression, leading to a suppressed nuclear translocation of functioning PKM2 in macrophages for M1 differentiation. Taken together, we identified a novel mechanism for macrophage M2 polarization regulation by a small-molecule chemical that controls the quality (conformation) rather than the quantity (expression) of an intracellular M1-promoting metabolic enzyme, which offers a better understanding of the mechanisms of macrophage plasticity and has serious implication in translational strategies for the treatment of macrophage-mediated neurological diseases with natural bioactive products. C1 [Li, Minghui; Lu, Wei; Meng, Yuanyuan; Zhang, Wenjie; Wang, Fengge; Sun, Li; Xu, Yuekang] Anhui Normal Univ, Anhui Prov Key Lab Mol Enzymol & Mech Major Dis, Coll Life Sci, Wuhu 241000, Peoples R China. [Li, Minghui; Lu, Wei; Meng, Yuanyuan; Zhang, Wenjie; Wang, Fengge; Sun, Li; Xu, Yuekang] Anhui Normal Univ, Coll Life Sci, Anhui Prov Key Lab Conservat & Exploitat Biol Reso, Wuhu 241000, Peoples R China. [Li, Minghui; Lu, Wei; Meng, Yuanyuan; Zhang, Wenjie; Wang, Fengge; Sun, Li; Xu, Yuekang] Anhui Normal Univ, Anhui Higher Educ Inst, Coll Life Sci, Key Lab Biomed Gene Dis & Hlth, Wuhu 241000, Peoples R China. C3 Anhui Normal University; Anhui Normal University; Anhui Normal University RP Xu, YK (corresponding author), Anhui Normal Univ, Anhui Prov Key Lab Mol Enzymol & Mech Major Dis, Coll Life Sci, Wuhu 241000, Peoples R China.; Xu, YK (corresponding author), Anhui Normal Univ, Coll Life Sci, Anhui Prov Key Lab Conservat & Exploitat Biol Reso, Wuhu 241000, Peoples R China.; Xu, YK (corresponding author), Anhui Normal Univ, Anhui Higher Educ Inst, Coll Life Sci, Key Lab Biomed Gene Dis & Hlth, Wuhu 241000, Peoples R China. EM yuekang.xu@hotmail.com RI Zhang, Wenjie/HLH-3968-2023; Li, Minghui/NBY-4161-2025; MENG, Yuanyuan/ODI-6578-2025 OI Zhang, Wenjie/0000-0002-3302-6675; Li, Minghui/0000-0003-4643-2303; FU Anhui Provincial Natural Science Foundation; Major Research Project in National Natural Science Foundation of China; Open Project of Guangxi Key Laboratory of Precision Medicine in Cardiocerebrovascular Diseases Control and Prevention; [1908085QH342]; [91742101]; [GXXNXG202102] FX ? ACKNOWLEDGMENTS This project was funded by the Anhui Provincial Natural Science Foundation (1908085QH342) , Major Research Project in National Natural Science Foundation of China (91742101) , and Open Project of Guangxi Key Laboratory of Precision Medicine in Cardiocerebrovascular Diseases Control and Prevention (GXXNXG202102) . 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Agric. Food Chem. PD DEC 14 PY 2022 VL 70 IS 49 BP 15449 EP 15463 DI 10.1021/acs.jafc.2c03923 PG 15 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology WE Science Citation Index Expanded (SCI-EXPANDED) SC Agriculture; Chemistry; Food Science & Technology GA 6Z5ER UT WOS:000897800300001 PM 36468551 DA 2026-03-26 ER PT J AU Wu, RX Zhou, T Xiong, JQ Zhang, Z Tian, S Wang, YL Chen, JD Tian, XF AF Wu, Ruoxia Zhou, Ting Xiong, Jiaqing Zhang, Zhen Tian, Sha Wang, Yongli Chen, Jindong Tian, Xuefei TI Quercetin, the Ingredient of Xihuang Pills, Inhibits Hepatocellular Carcinoma by Regulating Autophagy and Macrophage Polarization SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Article DE hepatocellular carcinoma; Xihuang Pills; quercetin; autophagy; macrophage; NF-kappa B ID TUMOR-ASSOCIATED MACROPHAGES; HCC CELLS; APOPTOSIS; CANCER; LIVER; CARCINOGENESIS; PATHWAY AB Background: The key active component(s) in an anti-tumor preparation used in traditional Chinese medicine, Xihuang Pills, remains unclear. Methods: We used a network pharmacology analysis to construct a component-disease-target network diagram and used this to determine quercetin as a critical active ingredient in Xihuang Pills. Subsequently, human hepatocellular carcinoma (HCC) cell lines, H22 and HepG2 cells, were treated with quercetin, and BALB/c mice were injected with H22 cells and treated with different concentrations of quercetin. Tumor volume and weight were determined in these mice with and without quercetin administration. Immune and pro-inflammatory factors were measured using Enzyme Linked Immunosorbent Assay (ELISA). Macrophage polarization was assessed by western blot and flow cytometry. Finally, PD-L1, autophagy-related proteins, and the NF-kappa B pathway were also analyzed. Results: Quercetin could significantly inhibit the proliferation, migration, and invasion characteristics of HCC cells and promote apoptosis in a concentration-dependent manner in vitro. After quercetin treatment, tumor volume and weight significantly decreased in vivo. Granulocyte-macrophage and granulocyte colony-stimulating factor (GM-CSF and G-CSF, respectively) levels were blunted in response to quercetin, as well as the PD-L1 level. CD86+ cell ratio was increased, while the CD206+ cell ratio was decreased, suggesting that macrophages tend to undergo M1 polarization in response to quercetin. The expression of LC3 II/I was increased, while the expression of p62 was down-regulated. The pro-inflammatory factors TNF-alpha, IL-6, and IL-17A, as well as NF-kappa B signaling were suppressed in a quercetin concentration-dependent manner. Conclusions: Quercetin is a key ingredient of anti-HCC activity in Xihuang Pills by regulating macrophage polarization and promoting autophagy via the NF-.B pathway. C1 [Wu, Ruoxia] Hunan Univ Chinese Med, Sch Tradit Chinese Med, Changsha 410208, Hunan, Peoples R China. [Zhou, Ting] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Hunan, Peoples R China. [Xiong, Jiaqing] Hunan Univ Chinese Med, Hosp 1, Teaching & Res Sect Tradit Chinese Med Surg, Changsha 410021, Hunan, Peoples R China. [Zhang, Zhen; Tian, Xuefei] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Hunan, Peoples R China. [Tian, Sha] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Dept Internal Med, Changsha 410208, Hunan, Peoples R China. [Wang, Yongli] Hunan Univ Chinese Med, Hosp 1, Oncol Dept, Changsha 410021, Hunan, Peoples R China. [Chen, Jindong] Hunan Univ Chinese Med, Med Sch, Changsha 410208, Hunan, Peoples R China. C3 Hunan University of Chinese Medicine; Hunan University of Chinese Medicine; Hunan University of Chinese Medicine; Hunan University of Chinese Medicine; Hunan University of Chinese Medicine; Hunan University of Chinese Medicine; Hunan University of Chinese Medicine RP Tian, XF (corresponding author), Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Hunan, Peoples R China. EM txf1718@163.com RI ; tian, xuefei/OJV-1564-2025; zhou, ting/KMX-1693-2024; WANG, YONGLI/ABB-6990-2020 OI Xiong, Jiaqing/0000-0002-2483-9420; FU Youth program of Natural Science Foundation of Hunan Province [2021JJ40407]; Youth project of Hunan Administration of traditional Chinese Medicine [202101]; Outstanding youth project of Hunan Education Department [20B451]; National Natural Science Foundation of China [U20A20408, 82074450] FX This work was supported by the Youth program of Natural Science Foundation of Hunan Province (2021JJ40407); the Youth project of Hunan Administration of traditional Chinese Medicine (202101); the Outstanding youth project of Hunan Education Department (20B451); and the National Natural Science Foundation of China (U20A20408 and 82074450). CR Abbas FA, 2007, NAT PROD RES, V21, P383, DOI 10.1080/14786410600942025 Allaire M, 2019, J HEPATOL, V70, P985, DOI 10.1016/j.jhep.2019.01.026 [Anonymous], 2018, Nucl. 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Biosci. PD DEC PY 2022 VL 27 IS 12 DI 10.31083/j.fbl2712323 PG 12 WC Biochemistry & Molecular Biology; Cell Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Cell Biology GA 8C8DG UT WOS:000917832600005 PM 36624942 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Li, YY He, YX Wu, YQ Liu, C Ren, LZ Lu, XY Wang, YM Yu, Y AF Li, Yan-Yang He, Yue-Xian Wu, Ye-Qun Liu, Chang Ren, Ling-Zhi Lu, Xiang-Yi Wang, Yu-Mei Yu, Yang TI Compatibility between cold-natured medicine CP and hot-natured medicine AZ synergistically mitigates colitis mice through attenuating inflammation and restoring gut barrier SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Huanglian ganjiang decoction; Compatibility; Cold-natured medicine CP; Hot-natured medicine AZ; Colitis; Intestinal inflammation ID PERMEABILITY; POLARIZATION; PARADIGM; PROTECT; M1 AB Ethnopharmacological relevance: Ulcerative colitis (UC) is a nonspecific intestinal inflammation with complex pathogenesis. Traditional Chinese Medicine (TCM) formula consists of several TCM herbs following the principle of herbal property and compatibility. Our previous studies found that Huanglian Ganjiang decoction (HGD) exhibited anti-colitis capacity and the compatibility between hot-natured medicine and cold-natured medicine was main compatibility. However, the association between compatibility mechanism of HGD and its anti-colitis effect has not been fully illustrated yet. Aim of study: Here, we would explore whether cold-natured medicine Coptis chinensis Franch. plus Phellodendron chinense C.K.Schneid. (CP) and hot-natured medicine Angelica sinensis (Oliv.) Diels plus Zingiber officinale Roscoe (AZ) in HGD respectively produce different impacts on UC, and exert synergistic effect on UC together. Materials and methods: UPLC/MS-MS was used to qualitatively analyze chemical profiles of CP, AZ and CPAZ extracts. CPAZ-UC target network was constructed using network pharmacology. Colitis mice was induced by 3% DSS for 7 days and treated with CP, AZ and CPAZ for another 7 days. The levels of multiple cytokines and proportions of innate and adaptive immune cells were determined to assess inflammatory profiles. The leakage of FITC-dextran, expressions of tight junction proteins were detected for evaluation of gut barrier function. Results: CP, AZ and CPAZ could improve symptoms of colitis mice. CP showed superiority in reducing proportions of pro-inflammatory immune cells M1 cells, neutrophils, Th1 and Th17 cells, and levels of pro-inflammatory cytokines IFN-gamma, IL-6, IL-10, TNF-alpha. In the contrast, AZ had advantage of elevating ratios of anti-inflammatory immune cells M2 and Treg cells as well as the production of anti-inflammatory cytokines IL-10 and TGF-beta. In addition, CP and AZ synergistically regulated M1/M2 macrophage polarization and the following IL-6, IL-10, TNF-alpha, IFN-gamma production, thereby restoring intestinal mucosal barrier. Conclusion: Taken together, our study first demonstrated that cold-natured medicine CP and hot-natured medi-cine AZ took on different functions in treatment of colitis mice. Meanwhile, they exhibited synergistic effect on the alleviation of intestinal inflammation and reinforcement of gut barrier function and integrity. C1 [Li, Yan-Yang; He, Yue-Xian; Wu, Ye-Qun; Liu, Chang; Ren, Ling-Zhi; Lu, Xiang-Yi; Wang, Yu-Mei; Yu, Yang] Guangzhou Univ Chinese Med, Sch Pharmaceut Sci, Guangzhou 510006, Peoples R China. C3 Guangzhou University of Chinese Medicine RP Wang, YM; Yu, Y (corresponding author), Guangzhou Univ Chinese Med, Sch Pharmaceut Sci, Guangzhou 510006, Peoples R China. EM wangym@gzucm.edu.cn; yuyang@gzucm.edu.cn RI ; li, yanyang/IQR-7269-2023 OI Yu, Yang/0000-0002-4032-0522; FU National Natural Science Foundation of China; High-level University Discipline Collaborative Innovation Team Project of Guangzhou University of Chinese Medicine; [82074322]; [2021xk73] FX Acknowledgments This work was supported by the National Natural Science Foundation of China (Grant No. 82074322) , ?Double First-class? and High-level University Discipline Collaborative Innovation Team Project of Guangzhou University of Chinese Medicine (Grant No. 2021xk73) . The schematic representation in figure abstract was drawn by Figdrawplatform (https:// www.figdraw.com /) . 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PD MAR 1 PY 2023 VL 303 AR 115902 DI 10.1016/j.jep.2022.115902 EA NOV 2022 PG 14 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 7M8OC UT WOS:000906909800001 PM 36395977 DA 2026-03-26 ER PT J AU Li, ZH Pan, HT Yang, JH Chen, DJ Wang, Y Zhang, H Cheng, YY AF Li, Zhenhao Pan, Haitao Yang, Jihong Chen, Dongjie Wang, Yu Zhang, Han Cheng, Yiyu TI Xuanfei Baidu formula alleviates impaired mitochondrial dynamics and activated NLRP3 inflammasome by repressing NF-κB and MAPK pathways in LPS-induced ALI and inflammation models SO PHYTOMEDICINE LA English DT Article DE Xuanfei Baidu Formula; Mitochondrial dynamics; NLRP3 inflammasome; COVID-19; Inflammation ID MACROPHAGE POLARIZATION; RESPONSES; CELLS AB Background: Xuanfei Baidu Formula (XBF) is an effective traditional Chinese medicine (TCM) remedy for treating coronavirus disease 2019 (COVID-19) in China. This herbal medicine has shown effects in reducing clinical symptoms and shortening the average length of hospital stay for COVID-19 patients. Previous studies have demonstrated that XBF alleviates acute lung injury (ALI) by regulating macrophage-mediated immune inflammation, but the mechanisms of action remain elusive. Purpose: This study aimed to evaluate the lung-protective and anti-inflammatory effects of XBF and its underlying mechanisms. Methods: Here, XBF's effects were investigated in an ALI mouse model induced by inhalation of atomized lipopolysaccharide (LPS). Besides, the LPS-induced inflammation model in RAW264.7 cells was used to clarify the underlying mechanisms of XBF against ALI. Results: Our results showed that XBF treatment alleviated LPS-induced lung injury, as evidenced by reduced histopathological changes, pulmonary alveoli permeability, fibrosis, and apoptosis in the lung tissues. In addition, inflammation was alleviated as shown by decreased levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-1 beta in serum and bronchoalveolar lavage fluid (BALF), and reduced white blood cell (WBC) count in BALF. Furthermore, consistent with the in vivo assay, XBF inhibited LPS-induced inflammatory cytokines release and pro-inflammatory polarization in RAW264.7 cells. Mechanistically, XBF increased mitochondrial fusion by upregulating Mfn1 and attenuated NLRP3 inflammasome activation by repressing Casp11, respectively, to inhibit NF-kappa B and MAPK pathways, thus repressing pm-inflammatory macrophage polarization. Conclusion: In this study, we demonstrate that XBF exerts anti-ALI and-inflammatory effects by recovering mitochondrial dynamics and reducing inflammasome activation, providing a biological illustration of the clinical efficacy of XBF in treating COVID-19 patients. C1 [Li, Zhenhao; Yang, Jihong; Zhang, Han; Cheng, Yiyu] Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Peoples R China. [Li, Zhenhao; Pan, Haitao; Yang, Jihong; Chen, Dongjie] BoYu Intelligent Hlth Innovat Lab, Hangzhou 311121, Peoples R China. [Wang, Yu; Cheng, Yiyu] State Key Lab Component Based Chinese Med, Tianjin 301617, Peoples R China. [Zhang, Han] Tianjin Univ Tradit Chinese Med, Inst Tradit Chinese Med, Tianjin 301617, Peoples R China. C3 Zhejiang University; Tianjin University of Traditional Chinese Medicine RP Li, ZH; Zhang, H (corresponding author), Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Peoples R China.; Zhang, H (corresponding author), Tianjin Univ Tradit Chinese Med, Inst Tradit Chinese Med, Tianjin 301617, Peoples R China. EM zhenhao@zju.edu.cn; zhanghan@tjutcm.edu.cn RI Pan, Haitao/N-2529-2018; WANG, Yu/PHO-7146-2026; Yang, Jihong/NXB-9260-2025 OI Li, Zhenhao/0000-0001-8279-8981; Yang, Jihong/0000-0002-2753-0939; Chen, Dongjie/0009-0007-6480-7814 FU National Key Research andDevelopment Program of China; [2021YFE0200300]; [2020YFA0708000] FX Acknowledgments This work was supported by the National Key Research andDevelopment Program of China (No. 2021YFE0200300, No. 2020YFA0708000) . 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Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 6V9BV UT WOS:000895334500002 PM 36423572 OA Green Submitted, hybrid DA 2026-03-26 ER PT J AU Zhang, WL Li, SB Li, CT Li, TY Huang, YY AF Zhang, Wanlu Li, Shubo Li, Chunting Li, Tianye Huang, Yongye TI Remodeling tumor microenvironment with natural products to overcome drug resistance SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE tumor microenvironment; natural products; drug resistance; cancer stem cells; p53; traditional Chinese medicine ID CANCER-ASSOCIATED FIBROBLASTS; M2 MACROPHAGE POLARIZATION; BREAST-CANCER; MAST-CELLS; SUPPRESSOR-CELLS; PROSTATE-CANCER; C-MYC; ANTICANCER ACTIVITY; PANCREATIC-CANCER; DOWN-REGULATION AB With cancer incidence rates continuing to increase and occurrence of resistance in drug treatment, there is a pressing demand to find safer and more effective anticancer strategy for cancer patients. Natural products, have the advantage of low toxicity and multiple action targets, are always used in the treatment of cancer prevention in early stage and cancer supplement in late stage. Tumor microenvironment is necessary for cancer cells to survive and progression, and immune activation is a vital means for the tumor microenvironment to eliminate cancer cells. A number of studies have found that various natural products could target and regulate immune cells such as T cells, macrophages, mast cells as well as inflammatory cytokines in the tumor microenvironment. Natural products tuning the tumor microenvironment via various mechanisms to activate the immune response have immeasurable potential for cancer immunotherapy. In this review, it highlights the research findings related to natural products regulating immune responses against cancer, especially reveals the possibility of utilizing natural products to remodel the tumor microenvironment to overcome drug resistance. C1 [Zhang, Wanlu; Li, Chunting; Li, Tianye; Huang, Yongye] Northeastern Univ, Coll Life & Hlth Sci, Shenyang, Peoples R China. [Li, Shubo] Liaoning Ctr Anim Dis Control & Prevent, Liaoning Agr Dev Serv Ctr, Shenyang, Peoples R China. C3 Northeastern University - China RP Huang, YY (corresponding author), Northeastern Univ, Coll Life & Hlth Sci, Shenyang, Peoples R China. EM huangyongye88@163.com FU National Natural Science Foundation of China [81502582]; Fundamental Research Funds for the Central Universities [N182004002]; Natural Science Foundation of Liaoning Province [2021-MS-104, 2022-YGJC-39]; Fundamental Scientific Research Fund of Liaoning Provincial Education Department [LJKQZ2021002]; Liaoning Revitalization Talents Program, Key technologies research in major disease control and prevention [XLYC2007098] FX This study was funded by the National Natural Science Foundation of China (Nos.81502582). Funding was also provided by the Fundamental Research Funds for the Central Universities (N182004002), Natural Science Foundation of Liaoning Province (2021-MS-104, 2022-YGJC-39), Fundamental Scientific Research Fund of Liaoning Provincial Education Department (LJKQZ2021002), and Liaoning Revitalization Talents Program, Key technologies research in major disease control and prevention (XLYC2007098). 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Immunol. PD NOV 10 PY 2022 VL 13 AR 1051998 DI 10.3389/fimmu.2022.1051998 PG 22 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA 6O1JY UT WOS:000890003000001 PM 36439106 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Du, P Xu, JB Jiang, YF Zhao, J Gao, CQ Fang, YD Yang, XR Yang, YP Zhang, JA AF Du, Peng Xu, Jianbin Jiang, Yanfei Zhao, Jing Gao, Chaoqun Fang, Yudie Yang, Xiaorong Yang, Yan-ping Zhang, Jin-an TI Saikosaponin-d Attenuates Hashimoto's Thyroiditis by Regulating Macrophage Polarization SO JOURNAL OF IMMUNOLOGY RESEARCH LA English DT Article ID T-CELL; DISEASE; AUTOIMMUNE; PREVALENCE; EXPRESSION; INCREASES; CYTOKINES; BALANCE; RISK; TH17 AB Objective. Hashimoto's thyroiditis (HT) is one of the most common clinical autoimmune diseases. Recent studies have found that HT pathogenesis is associated with macrophage polarization. Saikosaponin-d (SSd) is an active component in the Chinese medicine Bupleurum, which has anti-inflammatory and immunomodulatory effects. The purpose of this study was to verify the therapeutic effect of SSd on HT and to investigate the regulatory effect of SSd on macrophage polarization in HT. Methods. Network pharmacology analysis was used to predict the relevant targets and signaling pathways of SSd for HT treatment. The therapeutic effect of SSd on HT model mice and the effect on macrophage polarization were detected by animal experiment. Results. Network pharmacological analysis showed that SSd can alleviate HT against multiple targets such as IL-6 and IL-10 and can act on macrophage polarization-related signaling pathways such as MAPK and JAK-STAT signaling pathways. Animal experiments showed that SSd intervention attenuated the lymphocytic infiltration in thyroid tissues of HT mice (P=0.044); SSd intervention reduced serum TPOAb antibody level in HT mice (P < 0.001); SSd adjusted M1/M2 imbalance towards M2-type macrophage polarization in the spleen of HT mice (P=0.003); SSd inhibited the expressions of Th1-type cytokine IFN-gamma and Th17-type cytokine IL-17 systemically and locally in the thyroid of HT mice (P < 0.05). Conclusion. SSd treatment can regulate Th1/Th2 and Th17/Treg imbalances and reduce the severity of HT in mice by promoting the polarization of M2 macrophages. C1 [Du, Peng; Jiang, Yanfei; Zhao, Jing; Gao, Chaoqun; Yang, Xiaorong; Yang, Yan-ping; Zhang, Jin-an] Shanghai Univ Med & Hlth Sci, Affiliated Zhoupu Hosp, Dept Endocrinol & Rheumatol, Shanghai 201318, Peoples R China. [Du, Peng; Xu, Jianbin; Fang, Yudie] Shanghai Univ Tradit Chinese Med, Grad Sch, Shanghai 201203, Peoples R China. [Zhang, Jin-an] Shanghai Univ Tradit Chinese Med, Shanghai 201203, Peoples R China. C3 Shanghai University of Medicine & Health Sciences; Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine RP Yang, YP; Zhang, JA (corresponding author), Shanghai Univ Med & Hlth Sci, Affiliated Zhoupu Hosp, Dept Endocrinol & Rheumatol, Shanghai 201318, Peoples R China.; Zhang, JA (corresponding author), Shanghai Univ Tradit Chinese Med, Shanghai 201203, Peoples R China. EM dupeng2020@hotmail.com; xujianbinwork@hotmail.com; jiangyanfeino.1@163.com; 65349380@qq.com; gaocq2020@outlook.com; fangyudiework@shutcm.edu.cn; sxwnpcszyxr@126.com; yyp3287@163.com; zhangjinan@hotmail.com RI ; jianbin, xu/IAM-4237-2023; Du, Peng/HMV-9570-2023 OI Zhang, Jin-an/0000-0002-1700-4695; Jiang, Yanfei/0000-0002-2753-5254; FU National Natural Science Foundation of China [81900710, 81873636]; Second Round of Medical Discipline Construction Project of Pudong New Area-Clinical Characteristic Discipline [PWYts2021-09]; Excellent Young Medical Talents Training Program of Pudong New Area [PWRq2020-46]; Clinical Research Center of Thyroid Diseases of Shanghai Health Medical College [20MC20200002] FX The present work was supported by grants from the National Natural Science Foundation of China (81900710 and 81873636); the Second Round of Medical Discipline Construction Project of Pudong New Area-Clinical Characteristic Discipline (PWYts2021-09); the Excellent Young Medical Talents Training Program of Pudong New Area (PWRq2020-46); and the Clinical Research Center of Thyroid Diseases of Shanghai Health Medical College (20MC20200002). 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Res. PD NOV 8 PY 2022 VL 2022 AR 7455494 DI 10.1155/2022/7455494 PG 12 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA 6P4UR UT WOS:000890925900001 PM 36398316 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhou, P Lai, J Li, YY Deng, JZ Zhao, CL Huang, QQ Yang, F Yang, S Wu, YS Tang, XQ Huang, FH Wang, L Huang, XW Zou, WJ Wu, JM AF Zhou, Ping Lai, Jia Li, Yueyue Deng, Junzhu Zhao, Chunling Huang, Qianqian Yang, Fei Yang, Shuo Wu, Yuesong Tang, Xiaoqin Huang, Feihong Wang, Long Huang, Xinwu Zou, Wenjun Wu, Jianming TI Methyl Gallate Alleviates Acute Ulcerative Colitis by Modulating Gut Microbiota and Inhibiting TLR4/NF-κB Pathway SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE ulcerative colitis; methyl gallate; gut microbiota; gut immunity; TLR4/NF-kappa B ID INFLAMMATORY-BOWEL-DISEASE; POPULATION AB Ulcerative colitis (UC) is a complex immune-mediated inflammatory disease. In recent years, the incidence of UC has increased rapidly, however, its exact etiology and mechanism are still unclear. Based on the definite anti-inflammatory and antibacterial activities of San guisorba officinalis L., we studied its monomer, methyl gallate (MG). In this study, we employed flow cytometry and detected nitric oxide production, finding MG regulated macrophage polarization and inhibited the expression of proinflammatory cytokines in vitro. MG also exhibited anti-inflammatory activity accompanying with ameliorating body weight loss, improving colon length and histological damage in dextran sulfate sodium-induced UC mice. Meanwhile, transcription sequencing and 16S rRNA sequencing analyzed the key signaling pathways and changes in the gut microbiota of MG for UC treatment, proving that MG could alleviate inflammation by regulating the TLR4/NF-kappa B pathway in vivo and in vitro. Additionally, MG altered the diversity and composition of the gut microbiota and changed the abundance of metabolic products. In conclusion, our results are the first to demonstrate that MG has obvious therapeutic effects against acute UC, which is related to macrophage polarization, improved intestinal flora dysbiosis and inhibition of TLR4/NF-kappa B signaling pathway, and MG may be a promising therapeutic agent for UC treatment. C1 [Zhou, Ping; Li, Yueyue; Deng, Junzhu; Zou, Wenjun] Chengdu Univ Tradit Chinese Med, Sch Pharm, Chengdu 611137, Peoples R China. [Zhou, Ping; Zhao, Chunling; Wu, Jianming] Southwest Med Univ, Sch Basic Med Sci, Luzhou 646000, Peoples R China. [Lai, Jia; Yang, Fei; Yang, Shuo; Wu, Yuesong; Tang, Xiaoqin; Huang, Feihong; Wang, Long; Huang, Xinwu; Wu, Jianming] Southwest Med Univ, Sch Pharm, Luzhou 646000, Peoples R China. [Huang, Qianqian; Huang, Feihong; Wang, Long; Huang, Xinwu] Southwest Med Univ, Luzhou Key Lab Act Screening & Druggabil Evaluat, Luzhou 646000, Peoples R China. [Wu, Jianming] Southwest Med Univ, Educ Minist Key Lab Med Electrophysiol, Luzhou 646000, Peoples R China. C3 Chengdu University of Traditional Chinese Medicine; Southwest Medical University; Southwest Medical University; Southwest Medical University; Southwest Medical University RP Zou, WJ (corresponding author), Chengdu Univ Tradit Chinese Med, Sch Pharm, Chengdu 611137, Peoples R China.; Wu, JM (corresponding author), Southwest Med Univ, Sch Basic Med Sci, Luzhou 646000, Peoples R China.; Wu, JM (corresponding author), Southwest Med Univ, Sch Pharm, Luzhou 646000, Peoples R China.; Wu, JM (corresponding author), Southwest Med Univ, Educ Minist Key Lab Med Electrophysiol, Luzhou 646000, Peoples R China. EM zouwenjun@cdutcm.edu.cn; jianmingwu@swmu.edu.cn RI Wu, Jianming/B-6839-2018; Tang, Xiaoqin/KIB-4359-2024; li, yueyue/IVH-9846-2023; wu, yuesong/NRX-9214-2025 OI Wu, Jianming/0000-0002-6136-7469; FU National Natural Science Foundation of China [82074129, 81804221, 82204666]; Science and Technology Planning Project of Sichuan Province, China [23NSFSC2155, 2022JDJQ0061, 2019YJ0484, 2019YFSY0014, 2019JDPT0010, 2019YJ0473]; Science and Technology Program of Luzhou, China [2019LZXNYD-J11, 2019LZXNYDJ05, 2020LZXNYDZ03, 2020LZXNYDP01] FX This research was funded by grants from the National Natural Science Foundation of China [Grant Nos. 82074129, 81804221 and 82204666], the Science and Technology Planning Project of Sichuan Province, China [Grant Nos. 23NSFSC2155, 2022JDJQ0061, 2019YJ0484, 2019YFSY0014, 2019JDPT0010, and 2019YJ0473], Science and Technology Program of Luzhou, China [Grant Nos. 2019LZXNYD-J11, 2019LZXNYDJ05, 2020LZXNYDZ03 and 2020LZXNYDP01]. 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PD NOV PY 2022 VL 23 IS 22 AR 14024 DI 10.3390/ijms232214024 PG 19 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry GA 6K4KN UT WOS:000887473300001 PM 36430509 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Liu, T Xu, M Shi, ZY Li, MY Wang, RY Shi, YA Xu, X Shao, TJ Sun, QH AF Liu, Ting Xu, Min Shi, Zhenyu Li, Meiya Wang, Rongyun Shi, Yanan Xu, Xiao Shao, Tiejuan Sun, Qiuhua TI Shenhuang plaster ameliorates the Inflammation of postoperative ileus through inhibiting PI3K/Akt/NF-?B pathway SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE Postoperative ileus; Shenhuang plaster; Anti-inflammation; PI3K; Akt; NF-?B pathway; Macrophage polarization ID MACROPHAGE ACTIVATION; SIGNALING PATHWAY; PATHOPHYSIOLOGY AB Background: Although Shenhuang plaster (SHP) from traditional Chinese medicine prescriptions, has the po-tential to promote the recovery progression of postoperative ileus (POI), the underlying mechanism remains elusive. Along these lines, in this work, both in vivo and in vitro studies were conducted to systematically explore the regulatory effect and mechanism of SHP on the inflammatory response of the intestinal basal layer in the POI model mice. Methods: Intestinal manipulation in mice was utilized for the POI model. The impact of SHP in response to POI was evaluated by carrying fluorescein-labeled dextran, histomorphology, immunohistochemistry, in combination with flow cytometry analysis and transcriptome RNA sequencing in vivo. Besides, the cytotoxicity of the SHP treatment on RAW264.7 cells was detected by cell counting kit-8 (CCK-8), the biological effects were assessed by polymerase chain reaction (PCR) and the potential influences on the PI3K/Akt/NF-Kappa B pathway were identified through detecting the expression levels of P85, AKT, IKK and P65 by western blot in vitro. Results: The implementation of the SHP treatment could significantly reduce the expressions of interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha in the intestine, whereas the recovery of gastrointestinal motility is pro-moted. In addition, SHP can regulate the polarization of macrophages, indicating that the proportion of the M2 type is increased after the application of the SHP treatment. In addition, SHP inhibited the activity of PI3K/AKT/ NF-Kappa B signaling pathway-related proteins.Conclusion: SHP can significantly ameliorate the inflammatory response of POI and at the same time promote the recovery of gastrointestinal motility. Its mechanism may be mediated by the polarization of macrophages through the PI3K/AKT/NF-Kappa B signaling pathway. C1 [Liu, Ting; Xu, Min; Wang, Rongyun; Shi, Yanan; Xu, Xiao; Sun, Qiuhua] Zhejiang Chinese Med Univ, Coll Nursing, Hangzhou, Peoples R China. [Xu, Min] Zhejiang Chinese Med Univ, Affiliated Hosp 1, Dept Adm, Hangzhou, Peoples R China. [Shi, Zhenyu] Zhejiang Chinese Med Univ, Affiliated Hosp 1, Dept Orthopaed Surg, Hangzhou, Peoples R China. [Li, Meiya] Zhejiang Chinese Med Univ, Acad Chinese Med Sci, Hangzhou, Peoples R China. [Wang, Rongyun; Shao, Tiejuan] Zhejiang Chinese Med Univ, Sch Basic Med Sci, Hangzhou, Peoples R China. C3 Zhejiang Chinese Medical University; Zhejiang Chinese Medical University; Zhejiang Chinese Medical University; Zhejiang Chinese Medical University; Zhejiang Chinese Medical University RP Sun, QH (corresponding author), Zhejiang Chinese Med Univ, Coll Nursing, Hangzhou, Peoples R China.; Shao, TJ (corresponding author), Zhejiang Chinese Med Univ, Sch Basic Med Sci, Hangzhou, Peoples R China. EM sunqiuhua@zcmu.edu.cn RI Xu, Xiao/K-5069-2019 OI Xu, Xiao/0000-0001-9272-6236 FU National Natural Science Foundation of China; China Postdoctoral Science Foun-dation; Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University; [8197152282]; [2022M712850] FX Acknowledgments This work was supported by the National Natural Science Foundation of China (No. 8197152282) and the China Postdoctoral Science Foun-dation (No. 2022M712850) . We thank for technical support from Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University. 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Pharmacother. PD DEC PY 2022 VL 156 AR 113922 DI 10.1016/j.biopha.2022.113922 EA OCT 2022 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 6G5FA UT WOS:000884780200001 PM 36411615 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Ma, XR Wang, S Li, CL Jia, XH Wang, TT Leng, Z Lu, R Kong, XW Zhang, JY Li, L AF Ma, Xiaoran Wang, Shuang Li, Chenglin Jia, Xihui Wang, Tiantian Leng, Zhe Lu, Ran Kong, Xiaowen Zhang, Jinyu Li, Ling TI Baicalein inhibits the polarization of microglia/macrophages to the M1 phenotype by targeting STAT1 in EAE mice SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Baicalein; EAE; MS; Microglia; macrophage; STAT1 ID ISCHEMIC BRAIN-INJURY; SIGNAL TRANSDUCERS; MICROGLIA; TRANSCRIPTION; INFLAMMATION; EXPRESSION; WOGONIN; BLOCKS AB Microglia/macrophage polarization modulation plays a key role in the pathogenesis of multiple sclerosis (MS)/ experimental autoimmune encephalomyelitis (EAE). M1 microglia/macrophages secrete a variety of cytokines that cause inflammation and facilitate demyelination in the central nervous system (CNS). Baicalein (5,6,7-tri-hydroxyflavone, C15H10O5, BAI), a natural flavonoid isolated from the roots of the traditional Chinese medicine Scutellaria baicalensis Georgi, has been suggested to have a wide range of biological effects, including antioxidant, anti-inflammatory, and neuroprotective properties. In this study, flow cytometry, Western blotting, immuno-fluorescence and other methods were used to investigate whether BAI could reduce the demyelination and in-flammatory response of the spinal cord in EAE mice induced by MOG35-55 and affect the polarization of spinal microglia/macrophages. Our results showed that BAI treatment delayed the onset of EAE and alleviated clinical symptoms, demyelination and inflammatory cell infiltration. Meanwhile, BAI inhibited the overactivation of M1 microglia/macrophages in vivo and in vitro, significantly decreased the expression of proinflammatory cytokines in M1 microglia/macrophages, and inhibited the activation of STAT1. Subsequently, molecular docking, pull -down and immunofluorescence experiments confirmed that BAI has the ability to bind to the SH2 domain of STAT1 and that BAI colocalizes with p-STAT1 in the cytoplasm rather than being transferred to the nucleus during inflammatory stimulation. This study showed that BAI might inhibit the polarization of microglia/mac-rophages to the M1 phenotype in EAE mice by targeting STAT1. This new discovery lays a theoretical and experimental foundation for the clinical application of BAI in the treatment of MS. C1 [Ma, Xiaoran] Qingdao Univ, Sch Basic Med, Dept Special Med, Qingdao, Peoples R China. [Wang, Shuang; Li, Chenglin; Jia, Xihui; Wang, Tiantian; Lu, Ran; Zhang, Jinyu; Li, Ling] Qingdao Univ, Sch Basic Med, Qingdao, Peoples R China. [Leng, Zhe] Qingdao Univ, Women & Childrens Hosp, Qingdao, Peoples R China. [Kong, Xiaowen] Qingdao Univ, Sch Stomatol, Qingdao, Peoples R China. [Li, Ling] Qingdao Univ, Sch Basic Med, Dept Human Anat Histol & Embryol, 308 Ningxia Rd, Qingdao 266071, Shandong, Peoples R China. C3 Qingdao University; Qingdao University; Qingdao University; Qingdao University; Qingdao University RP Li, L (corresponding author), Qingdao Univ, Sch Basic Med, Dept Human Anat Histol & Embryol, 308 Ningxia Rd, Qingdao 266071, Shandong, Peoples R China. EM liling743@126.com RI ; Ma, Xiaoran/PMR-0269-2026; LI, CHENGLIN/JUF-8254-2023 OI Li, Ling/0000-0001-5358-4968; FU National natural Science Foundation of China; Natural Science Foundation of Shandong Province; [82001754]; [ZR2020MH416] FX Acknowledgement This work was supported by the National natural Science Foundation of China (82001754) , Natural Science Foundation of Shandong Province (ZR2020MH416) . 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Immunopharmacol. PD DEC PY 2022 VL 113 AR 109373 DI 10.1016/j.intimp.2022.109373 EA OCT 2022 PN A PG 12 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA 5W1SG UT WOS:000877701000001 PM 36279665 DA 2026-03-26 ER PT J AU Al-Saedi, HF Ghanimi, HA Khoshnazar, SM Ghayour, MB Abdolmaleki, A AF Al-Saedi, Haider F. Ghanimi, Hussein A. Khoshnazar, Seyedeh Mahdieh Ghayour, Mohammad B. Abdolmaleki, Arash TI Neuroprotective effects of celastrol on sciatic nerve transection model in male Wistar rats SO IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES LA English DT Article DE Celastrol; Cytokine; Inflammation; Macrophage; Sciatic Nerve ID FUNCTIONAL RECOVERY; REGENERATION; MACROPHAGES; CELLS; INFLAMMATION; ACTIVATION; EXPRESSION; SURVIVAL; INJURY; BRAIN AB Objective(s): Celastrol is an herbal compound with neuroprotective properties. Our research aimed to assess the neuroprotective properties of celastrol on sciatic nerve transection in rats.Materials and Methods: The rats' left sciatic nerve was cut and sutured directly. The animals were then given 1 or 2 mg/kg celastrol intraperitoneally for two weeks. The sensory and locomotor behaviors of the animals were then evaluated for 16 weeks. Immunohistochemistry, ELISA, and real-time PCR were also utilized to evaluate macrophage polarization, cytokine secretion, and neurotrophin expression in injured nerves.Results: Results showed that both doses of celastrol significantly accelerated nerve regeneration and improved sensorimotor functional recovery when compared with controls. Nevertheless, administration of 2 mg/kg of celastrol significantly outperforms treatment with a dose of 1 mg/kg. Celastrol treatment-induced M2 polarization in macrophages decreased proinflammatory cytokines at the injury site. It also increased the expression of BDNF mRNA. Conclusion: These findings suggest that a two-week treatment with celastrol had neuroprotective effects in a rat sciatic nerve transection model, most likely by inducing macrophage M2 polarization and anti-inflammatory effects. C1 [Al-Saedi, Haider F.] Univ Al Ameed, Coll Pharm, Karbala, Iraq. [Ghanimi, Hussein A.] Univ Al Ameed, Coll Nursing, Karbala, Iraq. [Khoshnazar, Seyedeh Mahdieh] Kerman Univ Med Sci, Inst Neuropharmacol, Neurosci Res Ctr, Kerman, Iran. [Ghayour, Mohammad B.] Ferdowsi Univ Mashhad, Fac Sci, Dept Biol, Mashhad, Iran. [Abdolmaleki, Arash] Univ Mohaghegh Ardabili, Fac Adv Technol, Dept Biophys, Namin, Iran. C3 University of Al-Ameed; University of Al-Ameed; Kerman University of Medical Sciences; Ferdowsi University Mashhad; University of Mohaghegh Ardabili RP Abdolmaleki, A (corresponding author), Univ Mohaghegh Ardabili, Fac Adv Technol, Dept Biophys, Namin, Iran. 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J. Basic Med. Sci. PD OCT PY 2022 VL 25 IS 10 BP 1251 EP 1259 DI 10.22038/IJBMS.2022.66614.14617 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 5B7NQ UT WOS:000863758000013 PM 36311198 DA 2026-03-26 ER PT J AU Luo, JF Zhou, H Lio, CK AF Luo, Jin-Fang Zhou, Hua Lio, Chon-Kit TI Akebia Saponin D Inhibits the Inflammatory Reaction by Inhibiting the IL-6-STAT3-DNMT3b Axis and Activating the Nrf2 Pathway SO MOLECULES LA English DT Article DE Dipsacus asper Wall; ex Henry; Akbia saponin D; DNMT3b; p-STAT3; Nrf2 ID NF-KAPPA-B; MACROPHAGE POLARIZATION; METHYLATION; MONOXIDE AB Akebia saponin D (ASD) is derived from the Dipsacus asper Wall. ex Henry, which is a traditional Chinese medicine commonly used to treat rheumatic arthritis (RA). However, the in-depth mechanism of the anti-inflammatory effect of ASD is still unclear. This study aimed to preliminarily explore the anti-inflammatory effect of ASD and the underlying mechanisms from the perspective of DNA methylation and inflammation-related pathways. We found that ASD significantly reduced the production of multiple inflammatory mediators, including nitric oxide (NO) and prostaglandin E-2 (PGE(2)), in LPS-induced RAW264.7 cells. The expression of DNA methyltransferase (DNMT) 3b and inducible nitric oxide synthase (iNOS) was also obviously inhibited by the ASD treatment. The protein and mRNA levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were also significantly inhibited by ASD. ASD inhibited the macrophage M1 phenotype, inhibited the high level of DNMT3b, and downregulated the signal transducer and activator of the transcription 3 (STAT3) pathway to exert its anti-inflammatory activity. Furthermore, DNMT3b siRNA and Nrf2 siRNA significantly promoted the anti-inflammatory effect of ASD. Our study demonstrates for the first time that ASD inhibits the IL-6-STAT3-DNMT3b axis and activates the nuclear factor-E2-related factor 2 (Nrf2) signaling pathway to achieve its inhibitory effect on inflammatory reactions. C1 [Luo, Jin-Fang] Guizhou Univ Tradit Chinese Med, Basic Med Coll, Guiyang 550025, Peoples R China. [Zhou, Hua] Guangzhou Univ Chinese Med, Guangdong Prov Hosp Chinese Med, Guangdong Prov Acad Chinese Med Sci,Guangdong Hon, Affiliated Hosp 2,State Key Lab Dampness Syndrome, Guangzhou 510006, Peoples R China. [Lio, Chon-Kit] Macau Univ Sci & Technol, Fac Chinese Med, Taipa 999078, Macao, Peoples R China. [Lio, Chon-Kit] Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Taipa 999078, Macao, Peoples R China. C3 Guizhou University of Traditional Chinese Medicine; Guangzhou University of Chinese Medicine; Macau University of Science & Technology; Macau University of Science & Technology RP Zhou, H (corresponding author), Guangzhou Univ Chinese Med, Guangdong Prov Hosp Chinese Med, Guangdong Prov Acad Chinese Med Sci,Guangdong Hon, Affiliated Hosp 2,State Key Lab Dampness Syndrome, Guangzhou 510006, Peoples R China. EM gutcmzhs@hotmail.com RI ; Zhou, Hua/IQS-0555-2023 OI LIO, CHON KIT/0009-0007-9509-575X; Zhou, Hua/0000-0002-7025-3690 FU Young Scientific and Technological Talent Growth Project of Guizhou Provincial Department of Education [[2021]194]; Special Research Project on Science and Technology of Traditional Chinese Medicine and Ethnic Medicine in Guizhou Province [QZYY-2021-012] FX This paper was supported by the Young Scientific and Technological Talent Growth Project of Guizhou Provincial Department of Education ([2021]194) and the Special Research Project on Science and Technology of Traditional Chinese Medicine and Ethnic Medicine in Guizhou Province (QZYY-2021-012). 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Recent evidence suggests the participation of M2-type macrophages in the pathogenesis of PF. The present study aimed to investigate the effect of peimine on a bleomycin (BLM)-induced PF rat model and the underlying mechanism of this effect. After BLM administration, peimine was administered to rats from day 29 to day 42, with pirfenidone (PFD) as a positive control. H&E and Masson's trichrome stain were used to analyze histological changes. Q-PCR and western blotting were used to measure mRNA levels and protein levels, respectively. High-throughput RNA sequencing (RNA-seq) technology detected the differentially expressed genes (DEGs) regulated by peimine. Our results revealed that peimine treatment significantly ameliorated BLM-induced PF by suppressing histological changes and collagen deposition. In addition, peimine decreased the number of M2 macrophages and the expression of profibrotic factors. RNA-seq results showed that DEGs regulated by peimine in IL-4-induced macrophages were mainly associated with immune system processes, the PI3K/Akt pathway, and the MAPKs pathway. Then, immunofluorescence assay and western blot results demonstrated that peimine treatment suppressed the expression of p-p38 MAPK and p-Akt (s473) and also inhibited the nuclear translocation of p-STAT6. In conclusion, the present study demonstrated that peimine has a protective effect on PF through the suppression of M2 polarization of macrophages by inhibiting the STAT6, p38 MAPK, and Akt signals. C1 [Cai, Ze-hui; Tian, Yan-ge; Li, Jun-zi; Zhao, Peng; Li, Jian-sheng; Bai, Yun-ping] Henan Univ Chinese Med, Henan Key Lab Chinese Med Resp Dis, Zhengzhou 450046, Henan, Peoples R China. [Cai, Ze-hui; Tian, Yan-ge; Li, Jun-zi; Zhao, Peng; Li, Jian-sheng; Bai, Yun-ping] Collaborat Innovat Ctr Chinese Med & Resp Dis Co, Zhengzhou 450046, Henan, Peoples R China. [Cai, Ze-hui] Zhengzhou Tradit Chinese Med Hosp, Zhengzhou 450006, Henan, Peoples R China. [Tian, Yan-ge; Li, Jun-zi; Zhao, Peng; Li, Jian-sheng; Bai, Yun-ping] Henan Univ Chinese Med, Acad Chinese Med Sci, Zhengzhou 450000, Peoples R China. [Mei, Xue] Henan Univ Chinese Med, Sch Med, Dept Pathogen Immunobiol, Zhengzhou 450000, Peoples R China. C3 Henan University of Traditional Chinese Medicine; Henan University of Traditional Chinese Medicine; Henan University of Traditional Chinese Medicine RP Bai, YP (corresponding author), Henan Univ Chinese Med, Henan Key Lab Chinese Med Resp Dis, Zhengzhou 450046, Henan, Peoples R China.; Bai, YP (corresponding author), Collaborat Innovat Ctr Chinese Med & Resp Dis Co, Zhengzhou 450046, Henan, Peoples R China.; Bai, YP (corresponding author), Henan Univ Chinese Med, Acad Chinese Med Sci, Zhengzhou 450000, Peoples R China.; Mei, X (corresponding author), Henan Univ Chinese Med, Sch Med, Dept Pathogen Immunobiol, Zhengzhou 450000, Peoples R China. EM meixue0363@sina.com; baiyunping@126.com RI ; Zhao, Peng/LWK-6324-2024; Li, Junzi/NOF-2210-2025; Li, Jian-sheng/AGT-3370-2022 OI Cai, Zehui/0000-0001-8812-6502; FU National Natural Science Fund of China [81904170]; Foundation of Department of Science and Technology of HeNan Province [202102310496, 212102310356]; Young Elite Scientists Sponsorship Program by CACM [2019-QNRC2-B03] FX The research is supported by National Natural Science Fund of China [grant number 81904170], Foundation of Department of Science and Technology of HeNan Province [grant numbers 202102310496, 212102310356], and Young Elite Scientists Sponsorship Program by CACM (2019-QNRC2-B03). 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Rep. PD OCT PY 2022 VL 42 IS 10 AR BSR20220986 DI 10.1042/BSR20220986 PG 11 WC Biochemistry & Molecular Biology; Cell Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Cell Biology GA VN1WR UT WOS:001134156300001 PM 36111628 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Yang, ZH Lin, SS Feng, WY Liu, YX Song, ZH Pan, GY Zhang, YH Dai, XD Ding, XY Chen, L Wang, Y AF Yang, Zhihua Lin, Shanshan Feng, Wanying Liu, Yangxi Song, Zhihui Pan, Guiyun Zhang, Yuhang Dai, Xiangdong Ding, Xinya Chen, Lu Wang, Yi TI A potential therapeutic target in traditional Chinese medicine for ulcerative colitis: Macrophage polarization SO FRONTIERS IN PHARMACOLOGY LA English DT Review DE macrophage polarization; traditional Chinese medicine; ulcerative colitis; potential mechanisms; gut microbiota; signaling pathway ID NF-KAPPA-B; INFLAMMATORY-BOWEL-DISEASE; SIGNALING PATHWAY; ACTIVATED MACROPHAGES; M1 POLARIZATION; PROTEIN-KINASES; TISSUE-REPAIR; CELLS; MICROBIOTA; BERBERINE AB Intestinal macrophages are the main participants of intestinal immune homeostasis and intestinal inflammation. Under different environmental stimuli, intestinal macrophages can be polarized into classical activated pro-inflammatory phenotype (M1) and alternative activated anti-inflammatory phenotype (M2). Its different polarization state is the "guide " to promoting the development and regression of inflammation. Under normal circumstances, intestinal macrophages can protect the intestine from inflammatory damage. However, under the influence of some genetic and environmental factors, the polarization imbalance of intestinal M1/M2 macrophages will lead to the imbalance in the regulation of intestinal inflammation and transform the physiological inflammatory response into pathological intestinal injury. In UC patients, the disorder of intestinal inflammation is closely related to the imbalance of intestinal M1/M2 macrophage polarization. Therefore, restoring the balance of M1/M2 macrophage polarization may be a potentially valuable therapeutic strategy for UC. Evidence has shown that traditional Chinese medicine (TCM) has positive therapeutic effects on UC by restoring the balance of M1/M2 macrophage polarization. This review summarizes the clinical evidence of TCM for UC, the vital role of macrophage polarization in the pathophysiology of UC, and the potential mechanism of TCM regulating macrophage polarization in the treatment of UC. We hope this review may provide some new enlightenment for the clinical treatment, fundamental research, and research and development of new Chinese medicine of UC. C1 [Yang, Zhihua; Feng, Wanying; Song, Zhihui; Pan, Guiyun; Zhang, Yuhang; Dai, Xiangdong; Chen, Lu; Wang, Yi] Tianjin Univ Tradit Chinese Med, Inst Tradit Chinese Med, Tianjin, Peoples R China. [Yang, Zhihua; Feng, Wanying; Song, Zhihui; Pan, Guiyun; Zhang, Yuhang; Dai, Xiangdong; Chen, Lu; Wang, Yi] Tianjin Univ Tradit Chinese Med, State Key Lab Component Based Chinese Med, Tianjin, Peoples R China. [Lin, Shanshan; Liu, Yangxi; Ding, Xinya] Tianjin Univ Tradit Chinese Med, Teaching Hosp 1, Natl Clin Res Ctr Chinese Med Acupuncture & Moxibu, Tianjin, Peoples R China. C3 Tianjin University of Traditional Chinese Medicine; Tianjin University of Traditional Chinese Medicine; Tianjin University of Traditional Chinese Medicine RP Chen, L; Wang, Y (corresponding author), Tianjin Univ Tradit Chinese Med, Inst Tradit Chinese Med, Tianjin, Peoples R China.; Chen, L; Wang, Y (corresponding author), Tianjin Univ Tradit Chinese Med, State Key Lab Component Based Chinese Med, Tianjin, Peoples R China. EM chenlutjutcm@tjutcm.edu.cn; wangyi@tjutcm.edu.cn RI zhang, yuhang/ISS-5685-2023; Lin, Shanshan/JDD-9776-2023 FU Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine; [ZYYCXTD-C-202203] FX Funding The study was supported by the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No: ZYYCXTD-C-202203). 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Pharmacol. PD SEP 6 PY 2022 VL 13 AR 999179 DI 10.3389/fphar.2022.999179 PG 22 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 4Q3VX UT WOS:000856012800001 PM 36147340 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Sun, XW Ma, LS Li, X Wang, J Li, YB Huang, ZJ AF Sun, Xiaowei Ma, Lusheng Li, Xiao Wang, Jiao Li, Yuanbin Huang, Zijing TI Ferulic acid alleviates retinal neovascularization by modulating microglia/macrophage polarization through the ROS/NF-?B axis SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE retinal neovascularization; Ferulic acid; microglia/macrophage polarization; inflammation; NF-kappa B ID ISCHEMIA-INDUCED ANGIOGENESIS; CELLS; INHIBITION; INTERLEUKIN-10 AB Inflammation plays a pivotal role in ischemia-induced retinal neovascularization. Targeting microglia/macrophage-based neuroinflammation presents a promising therapeutic strategy. Ferulic acid (FA), a natural and active ingredient in plants, exerts favorable anti-oxidative and anti-inflammatory activities. In this study, we investigated the inhibitory effect of FA against hypoxia-induced retinal angiogenesis using cultured retinal vascular endothelial cells and an oxygen-induced retinopathy mouse (OIR) model. The immunoregulatory effect of FA on microglia/macrophage polarization was evaluated by detecting the expression of specific markers for both pro-inflammatory "M1 " and anti-inflammatory "M2 " phenotypes using co-immunostaining and polymerase chain reaction assays. The underlying molecular mechanism upon FA treatment was also explored. The results showed that FA supplement markedly inhibited retinal pathological angiogenesis both in vivo and in vitro. In addition, FA switched microglia/macrophage polarization from "M1 " towards "M2 " phenotype and alleviated the inflammatory response. Mechanically, the anti-angiogenic and anti-inflammatory properties of FA were mainly due to blockade of the ROS/NF-kappa B pathway. Our data demonstrated an anti-angiogenic effect of FA through regulating M1-to-M2 microglia/macrophage polarization, suggesting a potential therapeutic strategy for retinal neovascular diseases. C1 [Sun, Xiaowei; Ma, Lusheng; Wang, Jiao; Li, Yuanbin] Qingdao Univ, Affiliated Yantai Yuhuangding Hosp, Dept Ophthalmol, Yantai, Peoples R China. [Li, Xiao] Zhengzhou Univ, Affiliated Hosp 1, Dept Ophthalmol, Zhengzhou, Peoples R China. [Huang, Zijing] Shantou Univ, Chinese Univ Hong Kong, Joint Shantou Int Eye Ctr, Shantou, Peoples R China. C3 Qingdao University; Zhengzhou University; Shantou University RP Li, YB (corresponding author), Qingdao Univ, Affiliated Yantai Yuhuangding Hosp, Dept Ophthalmol, Yantai, Peoples R China.; Huang, ZJ (corresponding author), Shantou Univ, Chinese Univ Hong Kong, Joint Shantou Int Eye Ctr, Shantou, Peoples R China. EM huangzj@jsiec.org; yuanbinli@yeah.net RI ; Sun, xiaowei/ABE-2463-2021 OI Li, Yuanbin/0009-0008-8424-522X; FU National Natural Science Foundation of China; [82101112] FX Funding This work was supported by the National Natural Science Foundation of China (No. 82101112) to ZH. 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Immunol. PD SEP 2 PY 2022 VL 13 AR 976729 DI 10.3389/fimmu.2022.976729 PG 14 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA 5B0UO UT WOS:000863292300001 PM 36119027 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Lu, LW Gao, Y Quek, SY Foster, M Eason, CT Liu, M Wang, MF Chen, JH Chen, F AF Lu, Louise W. Gao, Yao Quek, Siew-Young Foster, Meika Eason, Charles T. Liu, Min Wang, Mingfu Chen, Jie-Hua Chen, Feng TI The landscape of potential health benefits of carotenoids as natural supportive therapeutics in protecting against Coronavirus infection SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Review DE Carotenoids; COVID-19; SARS-CoV-2; Anti -inflammation; Immunity; Natural supportive therapeutics ID INFLAMMATORY GENE-EXPRESSION; CARDIOVASCULAR-DISEASE RISK; ACTIVATED RECEPTOR-GAMMA; INDUCED OXIDATIVE STRESS; WHITE ADIPOSE-TISSUE; 3RD NATIONAL-HEALTH; ACUTE LUNG INJURY; BETA-CAROTENE; METABOLIC SYNDROME; LIPID-PEROXIDATION AB The Coronavirus Disease-2019 (COVID-19) pandemic urges researching possibilities for prevention and man-agement of the effects of the virus. Carotenoids are natural phytochemicals of anti-oxidant, anti-inflammatory and immunomodulatory properties and may exert potential in aiding in combatting the pandemic. This review presents the direct and indirect evidence of the health benefits of carotenoids and derivatives based on in vitro and in vivo studies, human clinical trials and epidemiological studies and proposes possible mechanisms of action via which carotenoids may have the capacity to protect against COVID-19 effects. The current evidence provides a rationale for considering carotenoids as natural supportive nutrients via antioxidant activities, including scavenging lipid-soluble radicals, reducing hypoxia-associated superoxide by activating antioxidant enzymes, or suppressing enzymes that produce reactive oxygen species (ROS). Carotenoids may regulate COVID-19 induced over-production of pro-inflammatory cytokines, chemokines, pro-inflammatory enzymes and adhe-sion molecules by nuclear factor kappa B (NF-kappa B), renin-angiotensin-aldosterone system (RAS) and interleukins- 6-Janus kinase-signal transducer and activator of transcription (IL-6-JAK/STAT) pathways and suppress the polarization of pro-inflammatory M1 macrophage. Moreover, carotenoids may modulate the peroxisome proliferator-activated receptors gamma by acting as agonists to alleviate COVID-19 symptoms. They also may poten-tially block the cellular receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human angiotensin-converting enzyme 2 (ACE2). These activities may reduce the severity of COVID-19 and flu-like diseases. Thus, carotenoid supplementation may aid in combatting the pandemic, as well as seasonal flu. However, further in vitro, in vivo and in particular long-term clinical trials in COVID-19 patients are needed to evaluate this hypothesis. C1 [Lu, Louise W.] Univ Auckland, Sch Biol Sci, Dept Med, Auckland, New Zealand. [Gao, Yao] Univ Macau, Fac Hlth Sci, Macau, Macao, Peoples R China. [Quek, Siew-Young] Univ Auckland, Sch Chem Sci, Food Sci, Auckland, New Zealand. [Quek, Siew-Young] New Zealand Ctr Res Excellence Food Res, Riddet Inst, Palmerston North, New Zealand. [Foster, Meika] Edible Res Ltd, Auckland, New Zealand. [Foster, Meika; Eason, Charles T.] Wakatu Inc, Nelson, New Zealand. [Eason, Charles T.] Lincoln Univ, Lincoln, New Zealand. [Liu, Min] Southern Med Univ, Sch Publ Hlth, Dept Pathogen Biol, Guangdong Prov Key Lab Trop Dis Res, Guangzhou 510515, Guangdong, Peoples R China. [Wang, Mingfu; Chen, Jie-Hua; Chen, Feng] Shenzhen Univ, Inst Innovat Dev Food Ind, Shenzhen, Peoples R China. [Wang, Mingfu; Chen, Jie-Hua; Chen, Feng] Shenzhen Univ, Inst Adv Study, Shenzhen Key Lab Marine Microbiome Engn, Shenzhen, Peoples R China. [Chen, Jie-Hua; Chen, Feng] Shenzhen Univ, 3688 Nanhai Ave, Shenzhen 518060, Guangdong, Peoples R China. C3 University of Auckland; University of Macau; University of Auckland; Southern Medical University - China; Shenzhen University; Shenzhen University; Shenzhen University RP Chen, JH; Chen, F (corresponding author), Shenzhen Univ, 3688 Nanhai Ave, Shenzhen 518060, Guangdong, Peoples R China. EM siyanpijiehua@gmail.com; sfchen@szu.edu.cn RI chen, jiehua/NAZ-5029-2025; Wang, Mingfu/AAT-3292-2021 FU National Natural Science Foundation of China [31601472]; Guangdong Province Zhujiang Talent Program [2019ZT08H476]; Shenzhen Science and Technology Program [KQTD20180412181334790] FX Funding This work was supported by the National Natural Science Foundation of China (grant number 31601472) ; Guangdong Province Zhujiang Talent Program (grant number 2019ZT08H476) ; and Shenzhen Science and Technology Program (grant number KQTD20180412181334790) . 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Pharmacother. PD OCT PY 2022 VL 154 AR 113625 DI 10.1016/j.biopha.2022.113625 EA SEP 2022 PG 21 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 4X1YI UT WOS:000860644900005 PM 36058151 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Lv, HY Zhao, M Li, YR Li, K Chen, SJ Zhao, WW Wu, SH Han, YT AF Lv, Hongyu Zhao, Meng Li, Yiran Li, Kun Chen, Shaojuan Zhao, Wenwen Wu, Shaohua Han, Yantao TI Electrospun Chitosan-Polyvinyl Alcohol Nanofiber Dressings Loaded with Bioactive Ursolic Acid Promoting Diabetic Wound Healing SO NANOMATERIALS LA English DT Article DE electrospinning; bioactive nanofibers; ursolic acid; wound dressing; diabetic wound ID MACROPHAGE POLARIZATION; INFLAMMATION AB The design and development of novel dressing materials are urgently required for the treatment of chronic wounds caused by diabetic ulcers in clinics. In this study, ursolic acid (UA) extracted from Chinese herbal plants was encapsulated into electrospun nanofibers made from a blend of chitosan (CS) and polyvinyl alcohol (PVA) to generate innovative CS-PVA-UA dressings for diabetic wound treatment. The as-prepared CS-PVA-UA nanofiber mats exhibited randomly aligned fiber morphology with the mean fiber diameters in the range of 100-200 nm, possessing great morphological resemblance to the collagen fibrils which exist in the native skin extracellular matrix (ECM). In addition, the CS-PVA-UA nanofiber mats were found to possess good surface hydrophilicity and wettability, and sustained UA release behavior. The in vitro biological tests showed that the high concentration of UA could lead to slight cytotoxicity. It was also found that the CS-PVA-UA nanofiber dressings could significantly reduce the M1 phenotypic transition of macrophages that was even stimulated by lipopolysaccharide (LPS) and could effectively restore the M2 polarization of macrophages to shorten the inflammatory period. Moreover, the appropriate introduction of UA into CS-PVA nanofibers decreased the release levels of TNF-alpha and IL-6 inflammatory factors, and suppressed oxidative stress responses by reducing the generation of reactive oxygen species (ROS) as well. The results from mouse hepatic hemorrhage displayed that CS-PVA-UA nanofiber dressing possessed excellent hemostatic performance. The in vivo animal experiments displayed that the CS-PVA-UA nanofiber dressing could improve the closure rate, and also promote the revascularization and re-epithelization, as well as the deposition and remodeling of collagen matrix and the regeneration of hair follicles for diabetic wounds. Specifically, the mean contraction rate of diabetic wounds using CS-PVA-UA nanofiber dressing could reach 99.8% after 18 days of treatment. In summary, our present study offers a promising nanofibrous dressing candidate with multiple biological functions, including anti-inflammation, antioxidation, pro-angiogenesis, and hemostasis functions, for the treatment of hard-to-heal diabetic wounds. C1 [Lv, Hongyu; Zhao, Wenwen; Han, Yantao] Qingdao Univ, Coll Basic Med, 308 Ningxia Rd, Qingdao 266071, Peoples R China. [Zhao, Meng] Qingdao Univ, Coll Nursing, 308 Ningxia Rd, Qingdao 266071, Peoples R China. [Li, Yiran; Li, Kun; Chen, Shaojuan; Wu, Shaohua] Qingdao Univ, Coll Text & Clothing, 308 Ningxia Rd, Qingdao 266071, Peoples R China. C3 Qingdao University; Qingdao University; Qingdao University RP Han, YT (corresponding author), Qingdao Univ, Coll Basic Med, 308 Ningxia Rd, Qingdao 266071, Peoples R China.; Wu, SH (corresponding author), Qingdao Univ, Coll Text & Clothing, 308 Ningxia Rd, Qingdao 266071, Peoples R China. EM shaohua.wu@qdu.edu.cn; 18254887323@163.com RI ; Lv, Hongyu/JXL-4470-2024 OI Wu, Shaohua/0000-0002-7099-857X; FU China Postdoctoral Science Foundation [2020T130334]; Shandong Traditional Chinese Medicine Science and Technology Project [2021M137] FX This research was supported by the China Postdoctoral Science Foundation (2020M673586XB), the Shandong Traditional Chinese Medicine Science and Technology Project (2021M137), and a special grant from the China Postdoctoral Science Foundation (2020T130334). 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Wight et Arn. is a traditional Chinese herbal medicine, and its water-soluble ingredient Marsdenia tenacissima extract (MTE), was widely used for cancer treatment. The multi-pharmacological efficacies and mechanisms of MTE in directly inhibiting tumor cells have been extensively studied. However, the anti-tumor effects of MTE in the tumor-associated macrophages (TAMs) microenvironment remain unclear.Aim of the study: To uncover the role of hepatoma-derived growth factor (HDGF) in the interaction between TAMs and non-small cell lung cancer (NSCLC) cells. To evaluate the anti-tumor effects of MTE on the vicious crosstalk between TAMs and NSCLC by targeting HDGF.Materials and methods: HDGF-overexpression PC-9 and H292 NSCLC cell lines were constructed and verified. RNA-sequencing (RNA-seq) was performed in HDGF-overexpression PC-9 cells to probe the differential expression of genes. THP-1-derived macrophages were characterized using specific markers after stimulation with phorbol-12-myristate 13-acetate (PMA) and rhIL-4 or rhHDGF. The role of HDGF both in NSCLC cells and TAMs was determined using approaches like Western blot, qRT-PCR, ELISA, and flow cytometry. The interaction between tumor cells and TAMs were assessed by indirect co-culture H1975, PC-9 cells with M2 type macrophages. The effects of MTE on anti-tumor and macrophage polarization were evaluated in vitro and in vivo.Results: RNA-seq results identified IL-4 as a critical response to HDGF in NSCLC. HDGF induced macrophages polarizing toward M2 type, and promoted NSCLC cells proliferation, migration and invasion in vitro. On the one hand, HDGF dose-dependently promoted IL-4 expression in NSCLC cells. On the other hand, HDGF induced M2 macrophage polarization through the IL-4/JAK1/STAT3 signaling pathway. MTE treatment significantly decreased the expression and secretion of HDGF in NSCLC cells. Meanwhile, MTE treatment led to M2 macrophage repolarization, as evidenced by decreased expression of M2 markers and increased levels of M1 markers. Importantly, MTE treatment significantly suppressed tumor development in C57BL/6 mice bearing Lewis lung cancer (LLC) cells in vivo, accompanied by decreased plasma HDGF levels, reduced M2 macrophages infiltration and increased M1 macrophages proportion in mice tumor tissues.Conclusions: HDGF upregulated IL-4 expression in NSCLC cells, and promoted M2 polarization by the IL-4/JAK1/STAT3 signaling pathway in macrophages. MTE disturbed the interaction between NSCLC and TAMs in vitro, and inhibited tumor growth in vivo, at least in part, by suppressing HDGF. Therefore, our present study revealed a novel anti-tumor mechanism of MTE through inhibiting HDGF expression and enhancing macrophage polarization from M2 to M1 phenotype. C1 [Fu, Jia-lei; Hao, Hui-feng; Wang, Shan; Jiao, Yan-na; Li, Ping -ping; Han, Shu-yan] Peking Univ, Canc Hosp & Inst, Dept Integrat Chinese & Western Med, Minist Educ,Key Lab Carcinogenesis & Translat Res, Beijing 100142, Peoples R China. [Li, Ping -ping; Han, Shu-yan] Peking Univ, Canc Hosp & Inst, Dept Integrat Chinese & Western Med, 52 Fucheng Rd, Beijing 100142, Peoples R China. C3 Peking University; Peking University RP Li, PP; Han, SY (corresponding author), Peking Univ, Canc Hosp & Inst, Dept Integrat Chinese & Western Med, 52 Fucheng Rd, Beijing 100142, Peoples R China. EM lppma123@sina.com; shuyanhan@bjmu.edu.cn RI Wang, Shan/JCE-9802-2023; Hao, Huifeng/HOC-3848-2023; Han, Shuyan/IYS-8544-2023; FU, JIALEI/LYO-3203-2024 OI Hao, Huifeng/0000-0003-3396-1759; FU National Natural Science Foundation of China [81673730] FX Acknowledgements This work was supported by the National Natural Science Foundation of China (No. 81673730) . The authors would like to acknowledge Xijuan Liu for her help with flow cytometry and Baojun Chen for his help with animal experiment at the Central Laboratory of Peking University Can-cer Hospital and Institute. 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Ethnopharmacol. PD NOV 15 PY 2022 VL 298 AR 115607 DI 10.1016/j.jep.2022.115607 EA AUG 2022 PG 13 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 4Y2RT UT WOS:000861378100004 PM 35973634 DA 2026-03-26 ER PT J AU Wen, H Lu, DS Chen, HJ Zhu, YK Xie, Q Zhang, Z Wu, ZY AF Wen, Heng Lu, Dongshi Chen, Hanjian Zhu, Yeke Xie, Qing Zhang, Zhao Wu, Zhouyang TI Tetrahydropalmatine induces the polarization of M1 macrophages to M2 to relieve limb ischemia-reperfusion-induced lung injury via inhibiting the TLR4/NF-κB/NLRP3 signaling pathway SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE acute lung injury; limb ischemia-reperfusion; macrophage; tetrahydropalmatine; toll-like receptor 4 ID ACTIVATION AB Tetrahydropalmatine (THP) is the main component of the Chinese medicine Corydalis yanhusuo, which has been reported to alleviate limb ischemia-reperfusion-induced acute lung injury (LIR-ALI). This study aimed to investigate the mechanism underlying the effect of THP on relieving LIR-ALI. LIR-ALI model was established in rats with the presence or absence of THP pretreatment. Then, BEAS-2B cells and THP-1 macrophages were cocultured with rat serum from the Sham group and the Model group in the presence or absence of THP pretreatment. Subsequently, lung/body weight and lung wet/dry ratio of rats were calculated. Histological changes of lung tissues were observed by hematoxylin-eosin staining. Expression of CD86 and CD163 in lung tissues of rats was assessed by quantitative reverse transcription polymerase chain reaction, immunohistochemistry staining, and flow cytometry analysis. Levels of inflammatory cytokines were measured by enzyme linked immunosorbent assay. The expression of proteins related to toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-kappa B)/NLRP3 signaling was detected by western blot analysis. Results revealed that THP significantly relieved LIR-ALI in rats. Moreover, THP also reduced CD86 expression but elevated CD163 expression in lung tissues of rats with LIR-ALI. Furthermore, THP inhibited inflammation in serum and bronchoalveolar lavage fluid of rats with LIR-ALI and inactivated the TLR4/NF-kappa B/NLRP3 signaling in vivo. Additionally, coculture of serum from rats in the Model group also reduced viability, promoted inflammation, inactivated TLR4/NF-kappa B/NLRP3 expression in BEAS-2B cells and inhibited macrophage polarization, while these effects were all reversed by THP treatment. Collectively, THP could induce the polarization of M1 macrophage to M2 to suppress inflammation via inhibiting TLR4/NF-kappa B/NLRP3 signaling, thereby attenuating LIR-ALI. C1 [Wen, Heng; Chen, Hanjian; Zhu, Yeke; Xie, Qing] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Anesthesiol, Hangzhou, Zhejiang, Peoples R China. [Lu, Dongshi; Zhang, Zhao; Wu, Zhouyang] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Anesthesiol, Wuhan, Hubei, Peoples R China. C3 Zhejiang University; Huazhong University of Science & Technology RP Zhang, Z; Wu, ZY (corresponding author), Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, 1277 Jiefang Ave, Wuhan 430022, Hubei, Peoples R China. EM zhangzhao77@hust.edu.cn; wzy6638@hust.edu.cn RI Wen, Heng/GVT-9869-2022 OI Wen, Heng/0000-0001-8925-7643 FU Zhejiang Provincial Natural Science Foundation of China; Youth Research Project Fund of Zhejiang Traditional Chinese Medicine Science and Technology Plan [2019ZQ028] FX This research was supported by Zhejiang Provincial Natural Science Foundation of China (No.LQ22H010003) and Youth Research Project Fund of Zhejiang Traditional Chinese Medicine Science and Technology Plan (No.2019ZQ028). 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Res. PD SEP PY 2022 VL 83 IS 6 BP 1362 EP 1372 DI 10.1002/ddr.21965 EA AUG 2022 PG 11 WC Chemistry, Medicinal; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 4M3SR UT WOS:000841325900001 PM 35976115 DA 2026-03-26 ER PT J AU Dong, X Jiang, JL Lin, ZJ Wen, RJ Zou, L Luo, T Guan, ZJ Li, X Wang, LH Lu, L Li, H Huang, YS Yang, Z Wang, JY Ye, XH Hong, XH Wang, LJ Xian, SX Chen, ZX AF Dong, Xin Jiang, Jialin Lin, Zhijun Wen, Ruijia Zou, Ling Luo, Tong Guan, Zhuoji Li, Xuan Wang, Linhai Lu, Lu Li, Huan Huang, Yusheng Yang, Zhongqi Wang, Junyan Ye, Xiaohan Hong, Xiaohua Wang, Lingjun Xian, Shaoxiang Chen, Zixin TI Nuanxinkang protects against ischemia/reperfusion-induced heart failure through regulating IKKβ/IκBα/NF-κB-mediated macrophage polarization SO PHYTOMEDICINE LA English DT Article DE Heart failure; Ischemia/reperfusion; Inflammatory response; Macrophage polarization; NF-kappa B ID GINSENOSIDE; ACTIVATION; INHIBITION; MECHANISMS; LIPOPOLYSACCHARIDE; PATHOGENESIS; RESPONSES; INJURY; CELLS AB Background: Heart failure (HF) is a leading cause of death worldwide. Nuanxinkang (NXK) is an effective Chinese herbal formula used in treating HF, but its underlying potential mechanisms have not been fully elucidated. Purpose: To explore the protective activities of NXK in ischemia/reperfusion (IR)-induced HF through modulating the ratio of proinflammatory (M1) and anti-inflammatory (M2) macrophage populations and leading to the alleviation of inflammation. Materials and methods: In vivo, mice were subjected to myocardial IR to generate HF mouse models. Mice in the NXK group were treated with NXK for 28 days. Cardiac function was detected by echocardiography. Major lesions on mouse hearts were determined by hematoxylin-eosin (HE) staining, Masson staining, and TUNEL staining. Inflammatory cytokines were determined by enzyme-linked immunosorbent assay (ELISA) and qPCR examination. Flow cytometric analyses and qPCR examination were utilized for monitoring the temporal dynamics of macrophage infiltration following IR. In vitro, two polarized models were established by stimulating RAW264.7 cells with 200 ng/ml lipopolysaccharide (LPS) or 20 ng/ml interleukin-4 (IL-4). The RAW264.7 cells with nuclear factor-kappa B (NF-kappa B) overexpression was generated by transient transfection of NF-kappa B plasmids, and NXK intervention was conducted on this cell model to further clarify the involvement of NF-kappa B signaling in the NXK-mediated HF process. Results: In the present study, NXK was found to significantly contribute the cardiac function and ameliorate cardiac fibrosis and apoptosis after myocardial IR injury in vivo, which may be partially due to a decrease in inflammation. We therefore hypothesized that NXK reduced inflammatory damage by modulating subtypes of macrophages. And the results demonstrated that the percentage of proinflammatory macrophages infiltrated in the post-IR period was reduced with NXK treatment, and thereby blunting the wave of proinflammatory response and shifting the peak of the anti-inflammatory macrophage-mediated wound healing process towards an earlier time point. The further investigation showed that macrophage polarization was mediated by NXK through inhibiting the phosphorylation and the nuclear translocation of NF-kappa B. Besides, the phosphorylated IKK beta and I kappa B alpha, upstream mediators of the NF-kappa B pathway, also decreased by NXK. Moreover, the overexpression of NF-kappa B partially reversed the NXK-induced favorable activities; and successfully compensated the suppressive effect on inflammation and the phosphorylation of NF-kappa B. Conclusion: In conclude, our results demonstrated that NXK induced the cardioprotective effects against IR injury through a regulatory axis of IKK beta/I kappa B alpha/NF-kappa B-mediated macrophage polarization. The information gained from this study provide a possible natural strategy for anti-inflammatory treatment of HF. C1 [Dong, Xin; Jiang, Jialin; Lin, Zhijun; Wen, Ruijia; Zou, Ling; Luo, Tong; Guan, Zhuoji; Li, Xuan; Wang, Linhai; Lu, Lu; Li, Huan; Huang, Yusheng; Yang, Zhongqi; Wang, Junyan; Ye, Xiaohan; Hong, Xiaohua; Wang, Lingjun; Xian, Shaoxiang; Chen, Zixin] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangzhou 510405, Peoples R China. [Dong, Xin; Jiang, Jialin; Lin, Zhijun; Wen, Ruijia; Zou, Ling; Luo, Tong; Guan, Zhuoji; Li, Xuan; Wang, Linhai; Lu, Lu; Li, Huan; Huang, Yusheng; Yang, Zhongqi; Wang, Junyan; Ye, Xiaohan; Hong, Xiaohua; Wang, Lingjun; Xian, Shaoxiang; Chen, Zixin] Guangzhou Univ Chinese Med, Lingnan Med Res Ctr, Guangzhou 510405, Peoples R China. [Dong, Xin; Jiang, Jialin; Lin, Zhijun; Wen, Ruijia; Zou, Ling; Luo, Tong; Guan, Zhuoji; Li, Xuan; Wang, Linhai; Lu, Lu; Li, Huan; Huang, Yusheng; Yang, Zhongqi; Wang, Junyan; Ye, Xiaohan; Hong, Xiaohua; Wang, Lingjun; Xian, Shaoxiang; Chen, Zixin] Guangzhou Key Lab Chinese Med Prevent & Treatment, Guangzhou 510405, Peoples R China. [Ye, Xiaohan] Guangzhou Univ Chinese Med, Dongguan Hosp, Guangzhou 510405, PR, Peoples R China. [Zou, Ling; Hong, Xiaohua] Guangzhou Univ Chinese Med, Huizhou Hosp, Guangzhou 510405, PR, Peoples R China. C3 Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine RP Hong, XH; Wang, LJ; Xian, SX; Chen, ZX (corresponding author), Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangzhou 510405, Peoples R China. EM xhong19880513@163.com; smu868@163.com; shaoxiangx@hotmail.com; zxchen@gzucm.edu.cn RI Dong, Xin/OZD-6372-2025; Chen, Zixin/IST-1669-2023 OI Lu, Lu/0000-0002-9457-0164; Chen, Zixin/0000-0002-7288-7830 FU National Natural Science Foundation of China [81973777, 82004293]; Traditional Chinese Medicine Bureau of Guangdong Province [20211145]; Guangdong Science and Technology Department [2019A1515110374]; Department of Education of Guangdong Province [2019KQNCX020] FX This work was supported by grants from the National Natural Science Foundation of China (grant numbers 81973777 and 82004293), the Traditional Chinese Medicine Bureau of Guangdong Province (grant number 20211145), the Guangdong Science and Technology Department (grant number 2019A1515110374), and the Department of Education of Guangdong Province (grant number 2019KQNCX020). 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This study investigated its main chemical components for macrophage polarization regulation activity. Compounds were separated and purified, and their structures were elucidated based on NMR and HR-ESI-MS analyses. After inducing the M1 and M2 phenotype macrophages, CII-3 and testing components were added and co-incubated to evaluate their effects on the relevant markers of macrophages. Then, gradient concentrations of CII-3 and active monomers were further investigated for their effects on M2 macrophages. The effects were detected by RT-PCR, ELISA, flow cytometry, and immunofluorescence. Twelve compounds were identified from CII-3. CII-3 and pericanaside (5) had no obvious effect on M1 macrophages, while they significantly reduced the expression levels of M2 macrophage markers. Specifically, they significantly reduced the levels of TGF-beta and IL-10 and the mRNA expression levels of ARG-1 and CD206 in the M2 phenotypes of RAW264.7 and Ana-1 macrophages. The conditioned medium of CII-3 and pericanaside (5) could inhibit the migration capacity of CT26.WT tumor cells. Macrophage M1/M2 polarization is a dynamic equilibrium, and the M2 phenotype, which can promote the growth of tumor cells, is relatively highly expressed in the tumor microenvironment. CII-3 and pericanaside could significantly reduce the phenotype of M2-type macrophages, indicating that the anti-tumor activity of CII-3 could be related to the inhibitory effect on M2 polarization, and pericanaside was one of the active components. C1 [Xu, Jinglei; Che, Yihao; Liu, Xinyue; Liu, Chaohe; Meng, Di; Pang, Xiuqin; He, Miao; Liu, Guangming; Zhang, Chenggui; Yang, Dasong; Xiao, Huai] Dali Univ, Yunnan Prov Key Lab Entomol Biopharmaceut R&D, Dali 671000, Peoples R China. [Che, Yihao] Chinese Acad Sci, South China Sea Inst Oceanol, CAS Key Lab Trop Marine Bioresources & Ecol, Guangzhou 510301, Peoples R China. [Che, Yihao] Univ Chinese Acad Sci, Beijing 101408, Peoples R China. [Liu, Xinyue] Shanxi Med Univ, Sch Pharm, Taiyuan 030001, Peoples R China. C3 Dali University; Chinese Academy of Sciences; South China Sea Institute of Oceanology, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Shanxi Medical University RP Yang, DS; Xiao, H (corresponding author), Dali Univ, Yunnan Prov Key Lab Entomol Biopharmaceut R&D, Dali 671000, Peoples R China. EM xjl15093105827@163.com; cheyihao1995@163.com; liuxyue1@163.com; lch412728@163.com; m18768891906@163.com; p18787230348@163.com; mio_h@163.com; lgm13330555378@126.com; chenggui_zcg@163.com; yangdasongyunnan@126.com; xiaohuai@dali.edu.cn RI ; Yang, Da-Song/A-5888-2016 OI Xu, JingLei/0000-0003-2101-4631; Yang, Da-Song/0000-0002-8759-7393; Zhang, chenggui/0000-0002-2691-5079; Che, Yi-Hao/0000-0002-5602-0268 FU National Natural Science Foundation of China [82160822, 81960755, 81860742, 81860765, 81903926]; Special Program of Science and Technology of Yunnan Province [202002AA100007]; Special Fund Project for the Development of TCM Decoction Pieces Industry of Yunnan Province [2019-YG-067] FX This work was financially supported by a grant from the National Natural Science Foundation of China (No. 82160822, 81960755, 81860742, 81860765, 81903926), the Special Program of Science and Technology of Yunnan Province (202002AA100007), and the Special Fund Project for the Development of TCM Decoction Pieces Industry of Yunnan Province (2019-YG-067). 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Med., V12, P48, DOI 10.11954/ytctyy.201623018 Wu JY, 2020, MOL CELL, V77, P213, DOI 10.1016/j.molcel.2019.10.023 Xue NN, 2020, ACTA CIR BRAS, V35, DOI 10.1590/s0102-865020200100000002 Xue NN, 2017, SCI REP-UK, V7, DOI 10.1038/srep39011 Yang YX, 2015, J ASIAN NAT PROD RES, V17, P988, DOI 10.1080/10286020.2015.1047771 Ye YB, 2018, J CELL BIOCHEM, V119, P2951, DOI 10.1002/jcb.26509 Yu T.T., 2018, CHIN J IMMUNOL, V34, P5, DOI [10.3969/j.issn.1000-484X.2018.07.030, DOI 10.3969/J.ISSN.1000-484X.2018.07.030] Yu Yang, 2015, Zhongguo Zhong Yao Za Zhi, V40, P3496, DOI 10.4268/cjcmm20151728 Yuan C, 2020, BRAZ J MED BIOL RES, V53, DOI [10.1590/1414-431X20209488, 10.1590/1414-431x20209488] Zeng CJ, 2019, J MED ENTOMOL, V56, P1522, DOI 10.1093/jme/tjz081 Zhang T., 2017, NAT PROD RES DEV, V29, P7, DOI [10.16333/j.1001-6880.2017.11.009, DOI 10.16333/J.1001-6880.2017.11.009] Zhang Y, 2021, FRONT IMMUNOL, V11, DOI 10.3389/fimmu.2020.609705 Zhao W., 2015, FUNCTION PERIPLANETA Zhao YN, 2017, CHIN MED-UK, V12, DOI 10.1186/s13020-017-0149-6 NR 43 TC 12 Z9 14 U1 2 U2 33 PU MDPI PI BASEL PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND EI 1420-3049 J9 MOLECULES JI Molecules PD JUL PY 2022 VL 27 IS 14 AR 4416 DI 10.3390/molecules27144416 PG 14 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry GA 3G9VO UT WOS:000831693900001 PM 35889289 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Ren, Y He, JY Zhao, WH Ma, YZ AF Ren, Yu He, Jinying Zhao, Wenhua Ma, Yuzhen TI The Anti-Tumor Efficacy of Verbascoside on Ovarian Cancer via Facilitating CCN1-AKT/NF-κB Pathway-Mediated M1 Macrophage Polarization SO FRONTIERS IN ONCOLOGY LA English DT Article DE verbascoside; ovarian cancer; M1 macrophage polarization; CCN1; Akt/NF-kappa B pathway ID CELL-PROLIFERATION; SIGNALING PATHWAY; CHEMOPREVENTION; SUPPRESSION; CARCINOMA; APOPTOSIS AB Background: Ovarian cancer (OC) is the leading cause of gynecological cancer-related mortality. Verbascoside (VB) is a phenylpropanoid glycoside from Chinese herbs, with anti-tumour activities. This study aimed to investigate the effects and mechanism of VB on OC. Methods: OC cell lines SKOV3 and A2780 were used in this study. Cell viability, proliferation, and migration were measured using CCK-8, clonogenic, and transwell assays, respectively. Apoptosis and M1/M2 macrophages were detected using flow cytometry. The interaction between VB and CCN1 was predicted by molecular docking. The mRNA expression of CCN1 was detected by RT-qPCR. The protein levels of CCN1, AKT, p-AKT, p65, and p-p65 were determined by western blotting. A xenograft mice model was established for in vivo validation. Results: VB inhibited OC cell proliferation and migration in a dose-dependent manner, and promoted apoptosis and M1 macrophage polarization. VB downregulated CCN1 and inhibited the AKT/NF-kappa B pathway. LY294002, an AKT inhibitor, potentiated the anti-tumour effects of VB. CCN1 overexpression weakened the anti-tumour effects of VB and VB + LY294002. In vivo experiments verified that VB inhibited tumour growth and promoted M1 polarization, which is regulated by the CCN1-mediated AKT/NF-kappa B pathway. Conclusion: VB triggers the CCN1-AKT/NF-kappa B pathway-mediated M1 macrophage polarization for protecting against OC. C1 [Ren, Yu] Inner Mongolia Peoples Hosp, Sci Res Dept, Hohhot, Peoples R China. [He, Jinying; Zhao, Wenhua; Ma, Yuzhen] Inner Mongolia Peoples Hosp, Reprod Med Ctr, Hohhot, Peoples R China. RP Ma, YZ (corresponding author), Inner Mongolia Peoples Hosp, Reprod Med Ctr, Hohhot, Peoples R China. EM mayz@imnu.edu.cn FU Natural Science Foundation of Inner Mongolia Autonomous Region [2020MS08154]; Health Science and Technology Foundation of Inner Mongolia Autonomous Region [202202005] FX Funding This work was supported by the Natural Science Foundation of Inner Mongolia Autonomous Region [No. 2020MS08154] and the Health Science and Technology Foundation of Inner Mongolia Autonomous Region [No.202202005]. 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Oncol. PD JUN 17 PY 2022 VL 12 AR 901922 DI 10.3389/fonc.2022.901922 PG 13 WC Oncology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology GA 5X8ZT UT WOS:000878885500001 PM 35785168 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zeng, HR Zhao, B Zhang, D Rui, X Hou, XD Chen, XX Zhang, BR Yuan, Y Deng, HP Ge, GB AF Zeng, Hairong Zhao, Bei Zhang, Die Rui, Xin Hou, Xudong Chen, Xingxing Zhang, Benrui Yuan, Yi Deng, Hongping Ge, Guangbo TI Viola yedoensis Makino formula alleviates DNCB-induced atopic dermatitis by activating JAK2/STAT3 signaling pathway and promoting M2 macrophages polarization SO PHYTOMEDICINE LA English DT Article DE Viola yedoensis Makino (VYAC); Atopic dermatitis; Anti-inflammatory; Macrophages polarization; JAK2/STAT3 signaling pathway; Traditional Chinese medicine ID NF-KAPPA-B; SKIN; INFLAMMATION; GUIDELINES; MANAGEMENT; FILAGGRIN; EFFICACY; CANCER; M1 AB Background: Atopic dermatitis (AD), a common inflammatory skin disorder, severely affects the life quality of patients and renders heavy financial burden on patient's family. The Chinese medicine Viola yedoensis Makino formula (VYAC) has been widely used for treating various skin disorders. Previous studies have reported that VYAC is effective in relieving DNCB-induced AD and inflammation. However, the anti-inflammatory mechanism of VYAC is still ill-defined and poorly understood. This study aims to investigate the therapeutic effects of VYAC on DNCB-induced AD and to elucidate the underlying anti-inflammatory mechanisms. Methodology: VYAC were extracted with 70% ethanol and lyophilized for use. AD mice were established by DNCB. The therapeutic effects of VYAC were evaluated by oral administration VYAC (150, 300 and 600 mg/kg) daily in vivo. The histopathological and immunohistochemistry were used to analyze skin lesion and macrophages infiltration, RT-qPCR and Elisa were used to analyze the inflammatory factors in skin tissues and serum. To explore the underlying mechanism of VYAC against AD in vitro. RAW264.7 cells and bone-marrow-derived macrophages (BMDMs) were employed for macrophage polarization analysis. Flow cytometer, immunofluorescence and western blot were used to analyze M2 macrophages markers. STAT3 siRNA were transfected into both cells to validate the effects of VYAC-induced macrophages M2 polarization via JAK2/STAT3 signaling pathway. Results: VYAC ameliorated skin lesion of DNCB-induced AD mice by decreased clinical scores and epidermal thickness, decreased the level of pro-inflammatory factors (IL-1 beta, TNF-alpha and IL-18) and enhanced IL-10 anti-inflammatory factor level, inhibited macrophages infiltration and promoted M2 macrophages polarization in vivo. VYAC significantly promoted M2 macrophages polarization in vitro. It is observed that VYAC not only inhibited the phosphorylation of JAK2 and STAT3 in RAW264.7 cells and BMDMs, but also accelerated the translocation to the nucleus. What's more, VYAC reduced the polarization of M2 macrophage by activating JAK2/STAT3 signaling pathway was observed in both cells. Conclusions: Our findings demonstrate that VYAC significantly ameliorates skin lesion of DNCB-induced AD mice and reduces the levels of inflammatory factors by activating JAK2/STAT3 signaling pathway and promoting M2 macrophages polarization. C1 [Zeng, Hairong; Zhang, Die; Chen, Xingxing; Yuan, Yi] Shanghai Univ Tradit Chinese Med, Putuo Hosp, Shanghai 200062, Peoples R China. [Zeng, Hairong; Zhao, Bei; Hou, Xudong; Deng, Hongping; Ge, Guangbo] Shanghai Univ Tradit Chinese Med, Shanghai Frontiers Sci Ctr TCM Chem Biol, Inst Interdisciplinary Integrat Med Res, Shanghai 201203, Peoples R China. [Rui, Xin] Shanghai Univ Tradit Chinese Med, Baoshan Branch, Shuguang Hosp, Shanghai, Peoples R China. [Zhang, Benrui] Shanghai Univ Tradit Chinese Med, Shanghai 200062, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine RP Yuan, Y (corresponding author), Shanghai Univ Tradit Chinese Med, Putuo Hosp, Shanghai 200062, Peoples R China.; Deng, HP; Ge, GB (corresponding author), Shanghai Univ Tradit Chinese Med, Shanghai Frontiers Sci Ctr TCM Chem Biol, Inst Interdisciplinary Integrat Med Res, Shanghai 201203, Peoples R China. EM yuanyi0625@163.com; hpdeng@shutcm.edu.cn; geguangbo@shutcm.edu.cn RI DENG, HONGPING/U-6734-2019; Xudong, Hou/KZU-6503-2024 FU National Natural Science Foundation of China [81,922,070, 81,973,286, 81,703,880]; Shanghai Science and Technology Innovation Action Plans - Shanghai Science and Technology Committee, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine [20S21901500, 20S21900900, ZYYCXTD-D-202,004]; Science and Technology Innovation Project of Putuo District Health System [ptkwws202204]; Research Foundation for the Shanghai Hospital Pharmacy [2019-YY-09] FX This research was funded by the National Natural Science Foundation of China (81,922,070, 81,973,286, 81,703,880), Shanghai Science and Technology Innovation Action Plans (20S21901500 & 20S21900900) supported by Shanghai Science and Technology Committee, Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202,004), Science and Technology Innovation Project of Putuo District Health System (ptkwws202204) and Research Foundation for the Shanghai Hospital Pharmacy (2019-YY-09). 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Leeches are used in traditional Chinese medicine to treat cardiovascular diseases. HE-D is an active peptide extracted and isolated from leeches, which can inhibit the migration of RAW264.7 macrophages. Aim: This study shows the effects of HE-D on macrophages in atherosclerosis and the mechanism of inhibition on the migration of macrophages based on transcriptome sequencing (RNA-Seq). Materials and methods: The transwell method was used to detect the activity of HE-D in inhibiting the migration of macrophages. Macrophages were divided into control group, lipopolysaccharide group, and HE-D group. Samples were collected and RNA-Seq performed. The DEseq2 method detected significantly differentially expressed genes (DEGs), GO and KEGG Pathway databases were used to analyze the functions and pathway enrichment of DEGs. Finally, qRT-PCR and Western blotting were used to verify the genes screened by RNA-Seq analyses.Results: Cell experiments showed that HE-D can inhibit the migration of RAW264.7 macrophages induced by LPS. DEseq2 analyses showed that there were 363 DEGs after HE-D administration in the result of RNA-Seq. The GO function of DEGs was significantly enriched in cell migration and inflammation, and the DEGs related to cell migration were significantly enriched in the NF-Kappa B signaling pathway. qRT-PCR and Western blot analyses, showed that when compared with the LPS group, the related genes IKK alpha, IKK gamma, TRAF6, TLR4, and TRAF5 in the NF-Kappa B pathway were significantly down-regulated in the HE-D group. In addition, it was found that the inflammatory factors iNOS and TNF-alpha were significantly down-regulated, and Arg-1 and IL-10 were up-regulated.Conclusion: HE-D can inhibit the migration of macrophages by inhibiting IKK alpha and IKK gamma in the NF-Kappa B signaling pathway, and promote the transformation of macrophages from M1to M2 subtypes. Therefore, HE-D can potentially be used as a drug for the treatment of atherosclerosis. C1 [Wang, Ke; Cao, Qi; Yang, Qiong; Wei, Qiang; Zhao, Jiarui; Wang, Yuan; Hou, Junfeng; Song, Shuliang] Shandong Univ, Marine Coll, Weihai 264209, Peoples R China. [Song, Shuliang] Shandong Univ Weihai Res Inst Ind Technol, Weihai 264209, Peoples R China. [Wang, Ke] Changzhi Med Coll, Heping Hosp, Changzhi 046000, Peoples R China. [Hou, Junfeng; Song, Shuliang] Shandong Univ, Dept Marine Coll, Weihai 264209, Peoples R China. C3 Shandong University; Changzhi Medical College; Shandong University RP Hou, JF; Song, SL (corresponding author), Shandong Univ, Marine Coll, Weihai 264209, Peoples R China.; Hou, JF; Song, SL (corresponding author), Shandong Univ, Dept Marine Coll, Weihai 264209, Peoples R China. EM wangyuan1126@mail.sdu.edu.cn; caoqi@mail.sdu.edu.cn; yangqiong1237@163.com; wq18086420598@163.com; 201936684@mail.sdu.edu.cn; wangyuan1126@mail.sdu.edu.cn; houjf@sdu.edu.cn; songshuliang@sdu.edu.cn RI song, sl/GRS-1884-2022 FU Shandong Provincial Natural Science Foundation, China [ZR2017MH040] FX Acknowledgments K.W. and Q.C conducted the literature research and drafted the entire manuscript. Q.W. and Q.Y. edited the manuscript with the assist of Y.W. and J.R. K.J. and S.S. carried out the supervision and contributed to the key parts of the text associated with it. This work was supported by the Shandong Provincial Natural Science Foundation, China (ZR2017MH040) . We would like to thank excellent collaboration and our participants for their valuable time and cooperation. 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PD AUG 10 PY 2022 VL 294 AR 115380 DI 10.1016/j.jep.2022.115380 EA MAY 2022 PG 11 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 1X6PM UT WOS:000807574300005 PM 35589020 DA 2026-03-26 ER PT J AU Pang, L Liao, Q Zou, L Zhang, C Nie, X Yi, ZW Fu, CM Zhang, JM AF Pang, Lan Liao, Qian Zou, Liang Zhang, Chen Nie, Xin Yi, Zhiwen Fu, Chaomei Zhang, Jinming TI Two glycoproteins from medicinal insect Periplaneta americana (L.) promote diabetic wound healing via macrophage polarization modulation SO INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES LA English DT Article DE Periplaneta americana (L; ); Glycoprotein; Monosaccharide; Diabetic wound; Macrophage polarization ID STRUCTURAL-CHARACTERIZATION; POLYSACCHARIDES; PURIFICATION; OPTIMIZATION; EXTRACTION AB Along with the increasing attempts to explore the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine, researchers' attention turned to the endogenetic macromolecules, such as polysaccharides and peptides. Herein, we innovatively isolated two glycoproteins from PA, named PAGP-1 and PAGP-2, which were obtained by Cellulose DE-52 chromatography and purified by Sephadex G-100 gel in succession. The structural characterization of the two PAGPs were performed, including molecular weight, amino acid and monosaccharide composition, morphology analysis, FT-IR and 1H NMR analysis, CD spectroscopy, and glycosides linkage. As a result, two PAGPs belonged to O-glycopeptide bonds linked glycoproteins. The content of carbohydrate and protein of PAGP-1 was approximately 25.23% and 65.92% respectively, which of PAGP-2 was approximately 25.71% and 71.23%. Based on the remarkable antiinflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. In short, this study provides clear evidence that the glycoproteins would be the potential wound healing bioactive substances in PA. C1 [Pang, Lan; Liao, Qian; Zhang, Chen; Nie, Xin; Yi, Zhiwen; Fu, Chaomei; Zhang, Jinming] Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, Chengdu 611137, Peoples R China. [Zou, Liang] Chengdu Univ, Sch Food & Biol Engn, Key Lab Coarse Cereal Proc, Minist Agr & Rural Affairs, Chengdu 610106, Peoples R China. C3 Chengdu University of Traditional Chinese Medicine; Chengdu University RP Fu, CM; Zhang, JM (corresponding author), Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, Chengdu 611137, Peoples R China. EM chaomeifu@126.com; cdutcmzjm@126.com FU National Natural Science Foundation of China [U21A20409]; Multi-Dimensional Evaluation of Traditional Chinese Medicine Resources with Southwest Characteristics Interdisciplinary Innovation Team [ZYYCXTD-D-202209] FX Acknowledgments This work was supported by the National Natural Science Foundation of China (no. U21A20409) and the Multi-Dimensional Evaluation of Traditional Chinese Medicine Resources with Southwest Characteristics Interdisciplinary Innovation Team (no. ZYYCXTD-D-202209) . 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J. Biol. Macromol. PD JUN 1 PY 2022 VL 209 BP 2130 EP 2141 DI 10.1016/j.ijbiomac.2022.04.193 EA MAY 2022 PN B PG 12 WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 1V2VP UT WOS:000805954000006 PM 35500775 DA 2026-03-26 ER PT J AU Zhao, JY Pu, J Fan, J Feng, XY Xu, JW Zhang, R Shang, Y AF Zhao, Jia-yi Pu, Jin Fan, Jian Feng, Xin-yu Xu, Jian-wen Zhang, Rong Shang, Yan TI Tanshinone IIA prevents acute lung injury by regulating macrophage polarization SO JOURNAL OF INTEGRATIVE MEDICINE-JIM LA English DT Article DE Acute lung injury; Inflammation Cytokine storm; Tanshinone IIA; Macrophages ID LYMPHOCYTE RATIO; MECHANISMS; COULD AB Objective: Acute lung injury (ALI) is a serious respiratory dysfunction caused by pathogen or physical invasion. The strong induced inflammation often causes death. Tanshinone IIA (Tan-IIA) is the major constituent of Salvia miltiorrhiza Bunge and has been shown to display anti-inflammatory effects. The aim of the current study was to investigate the effects of Tan-IIA on ALI. Methods: A murine model of lipopolysaccharide (LPS)-induced ALI was used. The lungs and serum samples of mice were extracted at 3 days after treatment. ALI-induced inflammatory damages were confirmed from cytokine detections and histomorphology observations. Effects of Tan-IIA were investigated using in vivo and in vitro ALI models. Tan-IIA mechanisms were investigated by performing Western blot and flow cytometry experiments. A wound-healing assay was performed to confirm the Tan-IIA function. Results: The cytokine storm induced by LPS treatment was detected at 3 days after LPS treatment, and alveolar epithelial damage and lymphocyte aggregation were observed. Tan-IIA treatment attenuated the LPS-induced inflammation and reduced the levels of inflammatory cytokines released not only by inhibiting neutrophils, but also by macrophage. Moreover, we found that macrophage activation and polarization after LPS treatment were abrogated after applying the Tan-IIA treatment. An in vitro assay also confirmed that including the Tan-IIA supplement increased the relative amount of the M2 subtype and decreased that of M1. Rebalanced macrophages and Tan-IIA inhibited activations of the nuclear factor-jB and hypoxia-inducible factor pathways. Including Tan-IIA and macrophages also improved alveolar epithelial repair by regulating macrophage polarization. Conclusion: This study found that while an LPS-induced cytokine storm exacerbated ALI, including TanIIA could prevent ALI-induced inflammation and improve the alveolar epithelial repair, and do so by regulating macrophage polarization. Please cite this article as: Zhao JY, Pu J, Fan J, Feng XY, Xu JW, Zhang R, Shang Y. Tanshinone IIA prevents acute lung injury by regulating macrophage polarization. J Integr Med. 2022; 20(3): 274-280. (c) 2022 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. C1 [Zhao, Jia-yi; Fan, Jian; Shang, Yan] Naval Med Univ, Changhai Hosp, Dept Gen Practice, Shanghai 200433, Peoples R China. [Zhao, Jia-yi] Changhai Hongkou Hosp, Dept Gen Practice, Shanghai 200081, Peoples R China. [Pu, Jin] Naval Med Univ, Changhai Hosp, Dept Special Clin, Shanghai 200433, Peoples R China. [Feng, Xin-yu] Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China. [Xu, Jian-wen] Univ Shanghai Sci & Technol, Shidong Hosp, Dept Nursing, Shanghai 200438, Peoples R China. [Zhang, Rong; Shang, Yan] Naval Med Univ, Changhai Hosp, Dept Resp & Crit Care Med, Shanghai 200433, Peoples R China. C3 Naval Medical University; Naval Medical University; Chinese Academy of Sciences; Center for Excellence in Molecular Cell Science, CAS; University of Shanghai for Science & Technology; Naval Medical University RP Shang, Y (corresponding author), Naval Med Univ, Changhai Hosp, Dept Gen Practice, Shanghai 200433, Peoples R China.; Zhang, R; Shang, Y (corresponding author), Naval Med Univ, Changhai Hosp, Dept Resp & Crit Care Med, Shanghai 200433, Peoples R China. EM 31955041@qq.com; shangyan751200@163.com FU National Natural Science Foundation of China [81570020, 82170033]; Natural Science Foundation of Shanghai [21ZR1479200]; Shanghai Changhai Hospital Scientific Research Fund [2019SLZ002, 2019YXK018, CHJG2019029, CHPY2021A05] FX The present study was supported by National Natural Science Foundation of China (No. 81570020 and 82170033), Natural Science Foundation of Shanghai (21ZR1479200) Shanghai Changhai Hospital Scientific Research Fund (2019SLZ002, 2019YXK018, CHJG2019029 and CHPY2021A05). 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This study aimed to investigate the pathogenesis and potential therapeutic targets of ALI and to define the target gene of Tanreqing (TRQ), which is a traditional Chinese medicine formula composed of five medicines, scutellaria baicalensis, bear bile powder, goat horn powder, honeysuckle and forsythia. Macrophage activation plays a critical role in many pathophysiological processes, such as inflammation. Although the regulation of macrophage activation has been extensively investigated, there is little knowledge of the role of long noncoding RNAs (lncRNAs) in this process. In this study, we found that lncRNA-SNHG1 expression is distinctly regulated in differently activated macrophages in that it is upregulated in LPS. LncRNA-SNHG1 knockdown attenuates LPS-induced M1 macrophage activation. The SNHG1 promoter was bound by NF-kappa B subunit p65, indicative of SNHG1 being a direct transcriptional target of LPS-induced NF-kappa B activation. SNHG1 acts as a proinflammatory driver that leads to the production of inflammatory cytokines and the activation of macrophages and cytokine storms by physically interacting with high-mobility group box 1 (HMGB1) in ALI. TRQ inhibited NF-kappa B signaling activation and binding of NF-kappa B to the SNHG1 promoter. In conclusion, this study defined TRQ target genes, which can be further elucidated as mechanism(s) of TRQ action, and provides insight into the molecular pathogenesis of ALI. The lncRNA-SNHG1/HMGB1 axis is an ideal therapeutic for ALI treatment. C1 [Hu, Chunling; Li, Junlu; Tan, Yingshuai; Liu, Yang; Gao, Jing; Zhao, Shilong; Yao, Mengying; Lu, Xiaoxiao; Xing, Lihua] Zhengzhou Univ, Dept Resp Intens Care Unit, Affiliated Hosp 1, Zhengzhou, Peoples R China. [Bai, Chen] Beijing Univ Chinese Med, Sch Tradit Chinese Med, Beijing, Peoples R China. [Qiu, Lingxiao] Zhengzhou Univ, Dept Resp Med, Affiliated Hosp 1, Zhengzhou, Peoples R China. C3 Zhengzhou University; Beijing University of Chinese Medicine; Zhengzhou University RP Xing, LH (corresponding author), Zhengzhou Univ, Dept Resp Intens Care Unit, Affiliated Hosp 1, Zhengzhou, Peoples R China. EM xinglihua95088@163.com RI Qiu, Lingxiao/AAX-5663-2021; Liu, Yang/HMP-2099-2023; Lu, Xiaoxiao/J-1014-2019; Bai, Chen/ACV-1145-2022 FU National Natural Science Foundation of China [82074212]; Science and Technology Department of Henan Province (CN) [SB201901036] FX This work was supported by the National Natural Science Foundation of China (Number 82074212) and the Science and Technology Department of Henan Province (CN) (Number SB201901036). 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Immunol. PD APR 25 PY 2022 VL 13 AR 820718 DI 10.3389/fimmu.2022.820718 PG 18 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA 1G4MJ UT WOS:000795822700001 PM 35547731 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Jing, F Chen, X Xue, JB Huang, K Xing, F Hu, XD Peng, Y Liu, CH AF Jing, Fei Chen, Xi Xue, Jingbo Huang, Kai Xing, Feng Hu, Xudong Peng, Yuan Liu, Chenghai TI An Herbal Product Alleviates Bleomycin-Induced Pulmonary Fibrosis in Mice via Regulating NF-κB/TNF-a Signaling in Macrophages SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE fuzheng huayu formula; pulmonary fibrosis; network pharmacology; macrophages; TNF-alpha signal pathway; NF-kappa B; lipopolysaccharide; methylprednisolone ID TRADITIONAL CHINESE MEDICINE; PHARMACOLOGY; INFLAMMATION; PIRFENIDONE; MECHANISMS; PREDICTION; ONTOLOGY; TOOL AB Background and aim: Pro-inflammatory macrophages aggravated progress of pulmonary fibrosis (PF) both in patients and animal models. Fuzheng Huayu (FZHY) formula, a Chinese herbal product, is effective in treating pulmonary fibrosis in our previous study. But its action mechanism against PF relating to macrophage activation was unclear. This study was designed to evaluate the anti-fibrotic and anti-inflammatory roles of FZHY in pulmonary fibrosis and to elucidate the potential mechanisms. Methods: Network pharmacology was employed to identify the interrelationships among compounds of FZHY, potential targets and putative pathways on anti-pulmonary fibrosis. According to the data of bioinformatics analysis, the key pharmacological target for FZHY against PF was screened. The network pharmacological prediction was validated by a series of experimental assays, including CCK8, western blot and immunofluorescence staining. Then molecular mechanism of FZHY on relating to the predictive target were studied in bleomycin induced pulmonary fibrosis in mice with methylprednisolone as a positive control, and in lipopolysaccharide (LPS) stimulated cultured macrophages in culture, respectively. Results: The network pharmacology analysis reveal that a total of 12 FZHY-PF crossover proteins were filtered into a protein-protein interaction network complex and designated as the potential targets of FZHY against pulmonary fibrosis, while TNF-alpha signal pathway ranked at the top. FZHY and methylprednisolone could attenuate the lung fibrosis and decrease pulmonary TNF-alpha expression in bleomycin induced fibrotic mice, without difference between two treatments. While TNF-alpha was mainly originated from macrophages identified by double fluorescent staining of TNF-alpha and F4/80. LPS stimulated cultured macrophage polarization and activation demonstrated by the enhance contents of TNF-alpha and iNOS but decreased level of Arg-1. FZHY could alleviate the LPS stimulated macrophage polarization and activation demonstrated by decreasing TNF-alpha and iNOS and increasing Arg-1. In particular, FZHY could significantly reduce the production of p65 and the nuclear translocation of phosphorylated p65. Conclusion: Fuzheng Huayu formula has a good effect against pulmonary fibrosis induced by bleomycin in mice, whose action mechanism was associated with down-regulation of NF-kappa B/TNF-alpha signaling pathway in pro-inflammatory macrophages. These findings provided an important strategy for developing new agents against lung fibrosis and accelerated FZHY product application on patients with lung fibrosis. C1 [Jing, Fei; Xue, Jingbo; Xing, Feng; Peng, Yuan; Liu, Chenghai] Shanghai Univ Tradit Chinese Med, Inst Liver Dis, Shuguang Hosp, Shanghai, Peoples R China. [Chen, Xi; Huang, Kai; Liu, Chenghai] Shanghai Key Lab Tradit Chinese Clin Med, Shanghai, Peoples R China. [Hu, Xudong] Shanghai Univ Tradit Chinese Med, Sch Basic Med Sci, Shanghai, Peoples R China. [Liu, Chenghai] Minist Educ, Key Lab Liver & Kidney Dis, Shanghai, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine RP Peng, Y; Liu, CH (corresponding author), Shanghai Univ Tradit Chinese Med, Inst Liver Dis, Shuguang Hosp, Shanghai, Peoples R China.; Liu, CH (corresponding author), Shanghai Key Lab Tradit Chinese Clin Med, Shanghai, Peoples R China.; Liu, CH (corresponding author), Minist Educ, Key Lab Liver & Kidney Dis, Shanghai, Peoples R China. EM chenghai.liu@outlook.com; pengyuan1026@shutcm.edu.cn FU National Key Research and Development Program of China [2020YFC0845000]; Shanghai Science and technology innovation action plan [21S21900300, SGXZ-201910]; National Key Research and Development Program of China [2020YFC0845000]; Shanghai Science and technology innovation action plan [21S21900300]; Shuguang Siming Scholar Plan [SGXZ-201910] FX This work was supported by the National Key Research and Development Program of China (2020YFC0845000), Shanghai Science and technology innovation action plan (21S21900300) and the Shuguang Siming Scholar Plan (SGXZ-201910). 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Pharmacol. PD APR 25 PY 2022 VL 13 AR 805432 DI 10.3389/fphar.2022.805432 PG 14 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 1E1IS UT WOS:000794250000001 PM 35548340 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Xue, MT Sheng, WJ Song, X Shi, YJ Geng, ZJ Shen, L Wang, R Lü, HZ Hu, JG AF Xue, Meng-Tong Sheng, Wen-Jie Song, Xue Shi, Yu-Jiao Geng, Zhi-Jun Shen, Lin Wang, Rui Lu, He-Zuo Hu, Jian-Guo TI Atractylenolide III ameliorates spinal cord injury in rats by modulating microglial/macrophage polarization SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Article DE atractylenolide III; microglia; neuroinflammation; spinal cord injury ID KAPPA-B; MICROGLIAL POLARIZATION; MACROPHAGE ACTIVATION; LOCOMOTOR RECOVERY; NEUROPROTECTION; INHIBITION; ASTROCYTES; PATHWAY AB Background Inflammatory reactions induced by spinal cord injury (SCI) are essential for recovery after SCI. Atractylenolide III (ATL-III) is a natural monomeric herbal bioactive compound that is mainly derived in Atractylodes macrocephala Koidz and has anti-inflammatory and neuroprotective effects. Objective Here, we speculated that ATL-III may ameliorate SCI by modulating microglial/macrophage polarization. In the present research, we focused on investigating the role of ATL-III on SCI in rats and explored the potential mechanism. Methods The protective and anti-inflammatory effects of ATL-III on neuronal cells were examined in a rat SCI model and lipopolysaccharide (LPS)-stimulated BV2 microglial line. The spinal cord lesion area, myelin integrity, and surviving neurons were assessed by specific staining. Locomotor function was evaluated by the Basso, Beattie, and Bresnahan (BBB) scale, grid walk test, and footprint test. The activation and polarization of microglia/macrophages were assessed by immunohistofluorescence and flow cytometry. The expression of corresponding inflammatory factors from M1/M2 and the activation of relevant signaling pathways were assessed by Western blotting. Results ATL-III effectively improved histological and functional recovery in SCI rats. Furthermore, ATL-III promoted the transformation of M1 into M2 and attenuated the activation of microglia/macrophages, further suppressing the expression of corresponding inflammatory mediators. This effect may be partly mediated by inhibition of neuroinflammation through the NF-kappa B, JNK MAPK, p38 MAPK, and Akt pathways. Conclusion This study reveals a novel effect of ATL-III in the regulation of microglial/macrophage polarization and provides initial evidence that ATL-III has potential therapeutic benefits in SCI rats. C1 [Xue, Meng-Tong; Sheng, Wen-Jie; Shi, Yu-Jiao; Lu, He-Zuo; Hu, Jian-Guo] Bengbu Med Coll, Dept Clin Lab, Affiliated Hosp 1, Bengbu, Peoples R China. [Xue, Meng-Tong; Sheng, Wen-Jie; Song, Xue; Shi, Yu-Jiao; Geng, Zhi-Jun; Shen, Lin; Wang, Rui; Lu, He-Zuo; Hu, Jian-Guo] Bengbu Med Coll, Anhui Key Lab Tissue Transplantat, 287 Chang Huai Rd, Bengbu 233004, Peoples R China. [Lu, He-Zuo] Bengbu Med Coll, Dept Immunol, Bengbu, Peoples R China. C3 Bengbu Medical University; Bengbu Medical University; Bengbu Medical University RP Hu, JG (corresponding author), Bengbu Med Coll, Anhui Key Lab Tissue Transplantat, 287 Chang Huai Rd, Bengbu 233004, Peoples R China.; Lü, HZ (corresponding author), Bengbu Med Coll, Affiliated Hosp 1, Anhui Key Lab Tissue Transplantat, 287 Chang Huai Rd, Bengbu 233004, Peoples R China. EM jghu9200@bbmc.edu.cn RI wang, rui/JAC-6240-2023 OI Hu, Jian-Guo/0000-0002-9055-874X FU National Natural Science Foundation of China [81771343, 82071360]; 512 Talent Cultivation Plan of Bengbu Medical College [51201106]; Graduate Research Innovation Project of Bengbu Medical College [Byycx20039] FX National Natural Science Foundation of China (nos. 81771343, 82071360), the 512 Talent Cultivation Plan of Bengbu Medical College (by51201106) and the Graduate Research Innovation Project of Bengbu Medical College (Byycx20039) CR Aceves M, 2019, BRAIN BEHAV IMMUN, V79, P125, DOI 10.1016/j.bbi.2019.01.023 Ahuja CS, 2017, NAT REV DIS PRIMERS, V3, DOI 10.1038/nrdp.2017.18 Alizadeh A, 2019, FRONT NEUROL, V10, DOI 10.3389/fneur.2019.00282 Cerqueira SR, 2018, BIOMATERIALS, V177, P176, DOI 10.1016/j.biomaterials.2018.05.049 Chen YQ, 2020, J NEUROINFLAMM, V17, DOI 10.1186/s12974-020-01937-8 Chen YJ, 2015, J NEUROSCI RES, V93, P1526, DOI 10.1002/jnr.23612 Coyoy-Salgado A, 2019, OXID MED CELL LONGEV, V2019, DOI 10.1155/2019/3642491 du Sert NP, 2020, J CEREBR BLOOD F MET, V40, P1769, DOI [10.1177/0271678X20943823, 10.1371/journal.pbio.3000410] Duan FX, 2021, NEUROCHEM INT, V148, DOI 10.1016/j.neuint.2021.105105 Fujie T, 2022, TOXICOL APPL PHARM, V434, DOI 10.1016/j.taap.2021.115802 Gensel JC, 2015, BRAIN RES, V1619, P1, DOI 10.1016/j.brainres.2014.12.045 Guo XY, 2020, NEUROPHARMACOLOGY, V181, DOI 10.1016/j.neuropharm.2020.108336 Haidar MK, 2020, EUR J PHARM BIOPHARM, V153, P1, DOI 10.1016/j.ejpb.2020.05.032 Hong MH, 2010, ARCH PHARM RES, V33, P843, DOI 10.1007/s12272-010-0606-6 Jarisarapurin W, 2021, ANTIOXIDANTS-BASEL, V10, DOI 10.3390/antiox10081158 Jeong YH, 2019, INT J MOL SCI, V20, DOI 10.3390/ijms20164015 Ji GQ, 2016, IMMUNOPHARM IMMUNOT, V38, P98, DOI 10.3109/08923973.2015.1122617 Khuyagbaatar B, 2015, J NEUROTRAUM, V32, P1987, DOI 10.1089/neu.2015.3875 Kigerl KA, 2009, J NEUROSCI, V29, P13435, DOI 10.1523/JNEUROSCI.3257-09.2009 Kisucká A, 2021, CELLS-BASEL, V10, DOI 10.3390/cells10081943 Lasola JJM, 2021, PHARMACEUTICS, V13, DOI 10.3390/pharmaceutics13111841 Li X, 2021, CLIN TRANSL ALLERGY, V11, DOI 10.1002/clt2.12003 Liu BP, 2021, MAR DRUGS, V19, DOI 10.3390/md19110587 Liu C, 2014, NEUROCHEM RES, V39, P1753, DOI 10.1007/s11064-014-1370-7 Luo YX, 2016, J ETHNOPHARMACOL, V178, P66, DOI 10.1016/j.jep.2015.12.011 Ma SF, 2015, BRAIN BEHAV IMMUN, V45, P157, DOI 10.1016/j.bbi.2014.11.007 Martin E, 2017, JOVE-J VIS EXP, DOI 10.3791/55781 Mouihate A, 2020, CNS NEUROSCI THER, V26, P240, DOI 10.1111/cns.13195 Orr MB, 2018, NEUROTHERAPEUTICS, V15, P541, DOI 10.1007/s13311-018-0631-6 Schubert M, 2022, FREE RADICAL BIO MED, V178, P83, DOI 10.1016/j.freeradbiomed.2021.11.032 Sun X, 2016, J NEUROINFLAMM, V13, DOI 10.1186/s12974-016-0736-y Vergadi E, 2017, J IMMUNOL, V198, P1006, DOI 10.4049/jimmunol.1601515 Wang KT, 2010, J PHARM PHARMACOL, V62, P381, DOI 10.1211/jpp.62.03.0014 Wang MQ, 2019, OXID MED CELL LONGEV, V2019, DOI 10.1155/2019/1875471 Wang XJ, 2019, NANO LETT, V19, P829, DOI 10.1021/acs.nanolett.8b04020 White N., 2014, The Lancet, V383 Wu Y, 2018, J NEUROSCI RES, V96, P1265, DOI 10.1002/jnr.24221 Xie LS, 2020, AGING-US, V12, P22538, DOI 10.18632/aging.103663 Xu S, 2018, J NEUROINFLAMM, V15, DOI 10.1186/s12974-018-1183-8 Yang XW, 2016, INT J IMMUNOPATH PH, V29, P54, DOI 10.1177/0394632015617065 Zhang B, 2019, FRONT CELL NEUROSCI, V12, DOI 10.3389/fncel.2018.00531 Zhao H, 2015, NEUROSCIENCE, V290, P485, DOI 10.1016/j.neuroscience.2015.01.060 Zhou L, 2020, FRONT PHARMACOL, V11, DOI 10.3389/fphar.2020.01126 NR 43 TC 65 Z9 74 U1 2 U2 47 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-5930 EI 1755-5949 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PD JUL PY 2022 VL 28 IS 7 BP 1059 EP 1071 DI 10.1111/cns.13839 EA APR 2022 PG 13 WC Neurosciences; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 1T2FU UT WOS:000779924400001 PM 35403332 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Yan, SG Wei, HL Jia, R Zhen, MJ Bao, SC Wang, WB Liu, FR Li, JT AF Yan, Shuguang Wei, Hailiang Jia, Rui Zhen, Meijia Bao, Shengchuan Wang, Wenba Liu, Fanrong Li, Jingtao TI Wu-Mei-Wan Ameliorates Murine Ulcerative Colitis by Regulating Macrophage Polarization SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE wumeiwan decoction; ulcerative colitis; MAPK signaling pathways; NF- kappa B signaling pathway; STAT6 signaling pathway ID INFLAMMATION; BERBERINE; CYTOKINES; PROTECTS; INJURY; MICE AB An increasing body of evidence shows that macrophages play an important role in the pathogenesis of ulcerative colitis (UC). Macrophage polarization and changes in related signaling pathways are reported to have a protective effect on intestinal inflammation. The well-known Chinese medicine Wumeiwan (WMW) has been used to treat diarrhea, one of the main symptoms of colitis, for more than 2,000 years. Increasing evidence shows that WMW can inhibit intestinal inflammation and repair damaged intestinal mucosa, but its effector mechanisms are unknown. Therefore, we studied the prophylactic effects of WMW in dextran sulfate sodium (DSS)-induced UC and its effects on macrophage mechanisms and polarization. The results show that colitis was significantly alleviated in mice in the WMW group, and the secretion and expression of pro-inflammatory factors TNF-alpha, IL-1, and IL-6 were inhibited in the serum and colonic tissues of mice with WMW-treated colitis, whereas anti-inflammatory factors IL-10, Arg(-1), and TGF-beta 1 were increased. Subsequent studies found that WMW could inhibit M1 polarization and promote M2 polarization in colonic macrophages in DSS-induced colitis mice. Network pharmacology was used to predict potential targets and pathways, and further studies confirmed the related targets The results showed that WMW gradually inhibits the activation of the P38MAPK and NF-kappa B signaling pathways and further activates the STAT6 signaling pathway. In summary, WMW interferes with the p38MAPK, NF-kappa B and STAT6 signaling pathways to regulate M1/M2 polarization in macrophages, thereby protecting mice against DSS-induced colitis. C1 [Yan, Shuguang; Jia, Rui; Zhen, Meijia; Bao, Shengchuan; Wang, Wenba] Shaanxi Univ Chinese Med, Coll Basic Med, Xianyang, Peoples R China. [Yan, Shuguang; Wei, Hailiang; Jia, Rui; Zhen, Meijia; Bao, Shengchuan; Wang, Wenba; Li, Jingtao] Shaanxi Univ Chinese Med, Key Lab Gastrointestinal Dis & Prescript Shaanxi, Xianyang, Peoples R China. [Wei, Hailiang] Shaanxi Univ Chinese Med, Affliated Hosp, Dept Gen Surg, Xianyang, Peoples R China. [Liu, Fanrong] Yulin Hosp Tradit Chinese Med Shaanxi Prov, Dept Gastroenterol, Yulin, Peoples R China. [Li, Jingtao] Shaanxi Univ Chinese Med, Affliated Hosp, Dept Infect Dis, Xianyang, Peoples R China. C3 Shaanxi University of Chinese Medicine; Shaanxi University of Chinese Medicine; Shaanxi University of Chinese Medicine; Shaanxi University of Chinese Medicine RP Li, JT (corresponding author), Shaanxi Univ Chinese Med, Key Lab Gastrointestinal Dis & Prescript Shaanxi, Xianyang, Peoples R China.; Liu, FR (corresponding author), Yulin Hosp Tradit Chinese Med Shaanxi Prov, Dept Gastroenterol, Yulin, Peoples R China.; Li, JT (corresponding author), Shaanxi Univ Chinese Med, Affliated Hosp, Dept Infect Dis, Xianyang, Peoples R China. EM lfr13669149300@163.com; dr_lijingtao@163.com RI Li(李), Jitao(继涛)/J-6677-2019; bao, shengchuan/JAZ-1511-2023 OI Jia, Rui/0000-0003-3334-6043; bao, shengchuan/0000-0003-3742-0220 FU National Natural Science Foundation of China (NSFC) [81403320, 81873233]; Shaanxi University of Chinese Medicine Discipline Innovation Team Construction Project [2019-YL-05] FX Funding This research was supported by the National Natural Science Foundation of China (NSFC) (Grant No. 81403320; 81873233); Shaanxi University of Chinese Medicine Discipline Innovation Team Construction Project (Grant No. 2019-YL-05). 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Pharmacol. PD MAR 21 PY 2022 VL 13 AR 859167 DI 10.3389/fphar.2022.859167 PG 18 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 0P6JF UT WOS:000784333300001 PM 35387334 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Shi, HJ Chen, XY Chen, XR Wu, ZB Li, JY Sun, YQ Shi, DX Li, J AF Shi, Hui-Juan Chen, Xuan-Yu Chen, Xin-Ran Wu, Zhong-Bing Li, Jian-Yong Sun, Ya-Qin Shi, Dong-Xuan Li, Jing TI Chinese Medicine Formula Siwu-Yin Inhibits Esophageal Precancerous Lesions by Improving Intestinal Flora and Macrophage Polarization SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE esophageal precancerous lesions; Siwu-Yin; synthesis and secretion of bile acids; macrophage polarization; metabolomics; traditional Chinese medicine ID BILE-ACID RECEPTORS; MOUSE; MODERNIZATION; MIGRATION; JUNCTION; MODEL; TGR5 AB Siwu-Yin (SWY), a traditional Chinese medicinal formula, can replenish blood and nourish Yin. It was recorded in ancient Chinese medicine books in treating esophageal dysphagia, which has similar symptoms and prognosis with esophageal precancerous lesions and esophageal cancer. However, its effect has not been established in vivo. This study explores the antiesophageal cancer effect of SWY on rats with esophageal precancerous lesions. By performing 16S rRNA gene sequencing and metabolomics, it was suggested that SWY may improve the composition of intestinal flora of rats by regulating the synthesis and secretion of bile acids. In addition, flow cytometry results showed that SWY treatment modified tumor microenvironment by improving macrophage polarization and therefore inhibiting the occurrence of esophageal precancerous lesions. C1 [Shi, Hui-Juan; Shi, Dong-Xuan; Li, Jing] Hebei Med Univ, Hebei Canc Hosp, Dept Tradit Chinese Med, Hosp 4, Shijiazhuang, Peoples R China. [Chen, Xuan-Yu] St Johns Univ, Inst Biotechnol, Queens, NY USA. [Chen, Xin-Ran] Hebei Med Univ, Hebei Canc Hosp, Pharm Dept, Hosp 4, Shijiazhuang, Peoples R China. [Wu, Zhong-Bing; Li, Jing] Hebei Med Univ, Coll Integrated Tradit Chinese & Western Med, Shijiazhuang, Peoples R China. [Li, Jian-Yong] Hebei Ping An Hlth Grp, Pharmaceut Res Inst, Shijiazhuang, Peoples R China. [Sun, Ya-Qin] Shijiazhuang Yiling Pharmaceut Co Ltd, Hlth Food Res Off, Shijiazhuang, Peoples R China. C3 Hebei Medical University; St. John's University; Hebei Medical University; Hebei Medical University RP Li, J (corresponding author), Hebei Med Univ, Hebei Canc Hosp, Dept Tradit Chinese Med, Hosp 4, Shijiazhuang, Peoples R China.; Li, J (corresponding author), Hebei Med Univ, Coll Integrated Tradit Chinese & Western Med, Shijiazhuang, Peoples R China. EM lijingtiger@163.com RI shi, hui/JNS-2378-2023 FU National Natural Science Foundation of China [81973761]; Natural Science Foundation of Hebei Province [H2021206010]; Key Research and Development Project of Hebei Province [192777115D] FX Funding This study was supported by the National Natural Science Foundation of China (No. 81973761), the Natural Science Foundation of Hebei Province (No. H2021206010) and the Key Research and Development Project of Hebei Province (No. 192777115D). 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Pharmacol. PD MAR 3 PY 2022 VL 13 AR 812386 DI 10.3389/fphar.2022.812386 PG 15 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA ZZ3BP UT WOS:000773149000001 PM 35308250 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Li, W Luo, L Zhu, JY Yan, H Yang, X Tang, WQ Li, DD He, DM Wang, J Dai, WH Ma, XY Ao, SX Ma, W Du, NN Mao, CY Diao, XY Yang, X Liu, DY Zhang, ZQ Liang, HP Wang, FJ AF Li, Wei Luo, Li Zhu, Junyu Yan, Huan Yang, Xue Tang, Wanqi Li, Dandan He, Dongmei Wang, Jin Dai, Weihong Ma, Xiaoyuan Ao, Shengxiang Ma, Wei Du, Nana Mao, Chengyi Diao, Xiaoyan Yang, Xia Liu, Daoyan Zhang, Zaiqi Liang, Huaping Wang, Fangjie TI Water extract of Cayratia albifolia CLLi root relieves zymosan A-induced inflammation by restraining M1 macrophage polarization SO PHYTOMEDICINE LA English DT Article DE Cayratia albifolia C; L; Li; Inflammation; Macrophages polarization ID NF-KAPPA-B; KYNURENIC ACID; PROTEIN; DEXAMETHASONE; METABOLISM; ACTIVATION; RELEASE; KINASE; MTOR AB Background: Cayratia albifolia C.L.Li (CAC) is a traditional Chinese herbal medicine used to treat inflammatory diseases. Our laboratory has firstly reported that the water extract from CAC relieved lipopolysaccharide (LPS)induced inflammation, however stronger evidence is still needed to prove its anti-inflammatory effects and the mechanisms involved are also ambiguous.Purpose: This study sought to provide more evidence for the application of CAC in alleviating infectious inflammation and disclose novel pharmacological mechanisms.Methods: Mice were injected with zymA into their paws or peritoneal cavities, and then treated with CAC. ELISA, immunofluorescence and flow cytometry were performed to detect the cytokines (IL-113, IL-6, TNF-alpha and IL-10) generation, the cell infiltration, and the CD86 or CD206 expression of macrophages. Then in vitro assays were performed on bone marrow-derived macrophages (BMDMs) and peritoneal macrophages (PMs) to detect their expression of iNOS, arg-1 and the cytokines above. On mechanisms, western blotting (WB), electrophoretic mobility shift assay (EMSA) and flow cytometry were carried out to measure NF-Kappa B transcriptional activity, mitochondrial bioactivity and the mTORC1 activation when BMDMs were stimulated by zymA and treated with CAC. Finally, the chemical components consisted in the extract were analyzed by LC-MS.Results: 200 mg/kg CAC clearly inhibited zymA induced mouse paw edema and reduced the contents of IL-113, IL 6 and TNF-alpha rather than IL-10 in local tissues. CAC also reduced CD86 but not CD206 in macrophages in situ. Through in vitro experiments, it was discovered that CAC reduced the protein and mRNA levels of IL-113, IL-6 and TNF-alpha, and also inhibited iNOS expression, but showed no influence on IL-10 and arg-1 in macrophages. We found CAC reduced NF-Kappa B transcriptional activity, down-regulated mitochondrial membrane potential and ROS levels, and inhibited mTORC1 activity. Finally, we identified 15 major compounds in the extract, among which 4guanidinobutyric acid and kynurenic acid were the most abundant. Conclusion: This study provides further evidence that CAC significantly reduces zymA induced infectious inflammation. In addition, this novel data revealed that CAC restrained M1 rather than promoting M2 macrophages polarization via multi-target inhibitory effects, based on its potentially active components. C1 [Li, Wei; Luo, Li; Yan, Huan; Yang, Xue; Tang, Wanqi; Li, Dandan; Ma, Xiaoyuan; Ao, Shengxiang; Ma, Wei; Du, Nana; Diao, Xiaoyan; Yang, Xia; Liu, Daoyan; Liang, Huaping; Wang, Fangjie] Army Med Univ, Army Med Ctr, State Key Lab Trauma Burns & Combined Injury, Daping Hosp, Chongqing 400042, Peoples R China. [Zhang, Zaiqi] Hunan Univ Med, Hunan Prov Key Lab Dong Med, Changsha 418000, Hunan, Peoples R China. [Mao, Chengyi] Army Med Univ, Daping Hosp, Dept Pathol, Chongqing 400042, Peoples R China. [Dai, Weihong] Hainan Med Univ, Affiliated Hosp 2, Haikou 570216, Hainan, Peoples R China. [He, Dongmei; Wang, Jin] Guangzhou Univ Chinese Med, Affiliated Hosp 2, Guangzhou 510006, Peoples R China. [Zhu, Junyu] Xinjiang Med Univ, Coll Publ Hlth, Urumqi 830011, Peoples R China. [Zhu, Junyu] Xinjiang Autonomous Acad Instrumental Anal, Xinjiang Engn Technol Res Ctr Green Proc Nat Prod, Urumqi 830011, Peoples R China. C3 Army Medical University; Hunan University of Medicine; Army Medical University; Hainan Medical University; Guangzhou University of Chinese Medicine; Xinjiang Medical University RP Liang, HP; Wang, FJ (corresponding author), Army Med Univ, Army Med Ctr, State Key Lab Trauma Burns & Combined Injury, Daping Hosp, Chongqing 400042, Peoples R China.; Zhang, ZQ (corresponding author), Hunan Univ Med, Hunan Prov Key Lab Dong Med, Changsha 418000, Hunan, Peoples R China. EM qizaizhang@126.com; 13638356728@163.COM; wangfj10086@163.com RI fangjie, wang/IXD-5140-2023; ao, shengxiang/GSD-6306-2022; Yang, Xia/GOG-8272-2022 FU Hunan Provincial Key Laboratory of Dong Medicine [2015TP1020, 2017CT5025]; Military Biosafety Program [19SWAQ18]; National Defense Science-and Technology Basic Enhancement Program [2021-JCJQ-JJ-1081]; 2020 Chongqing Talent Program [CQ2020TP09]; Natural Science Foundation of Chongqing [cstc2020jcyj-msxmX0510]; 2019 Army Medical Center Talent Innavation Program [2019CXJSC016]; National Natural Science Foundation of China [82104247] FX This study was supported by the Hunan Provincial Key Laboratory of Dong Medicine (2015TP1020 and 2017CT5025), Military Biosafety Program (19SWAQ18), National Defense Science-and Technology Basic Enhancement Program (2021-JCJQ-JJ-1081), 2020 Chongqing Talent Program (CQ2020TP09), the Natural Science Foundation of Chongqing (cstc2020jcyj-msxmX0510), 2019 Army Medical Center Talent Innavation Program (2019CXJSC016), National Natural Science Foundation of China (Nos. 82104247). The authors would like to express their gratitude to EditSprings (https:// www.editsp rings.cn/) for the expert linguistic services provided. 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This study aims to evaluate the anti-inflammatory effects of SMS on gouty arthritis and its potential mechanism of action. MethodsThe effects and mechanism of SMS were evaluated in monosodium urate (MSU)-treated mice or macrophages. The expression of cytokines and PI3K/Akt was analyzed using real-time PCR and Western blotting analyses. Macrophage polarization was assessed with immunofluorescence assays, real-time PCR, and Western blotting. Mass spectrometry was used to screen the active ingredients of SMS. ResultsPretreatment with SMS ameliorated MSU-induced acute gouty arthritis in mice with increased PI3K/Akt activation and M2 macrophage polarization in the joint tissues. In vitro, SMS treatment significantly inhibited MSU-triggered inflammatory response, increased p-Akt and Arg-1 expression in macrophages, and promoted M2 macrophage polarization. These effects of SMS were inhibited when PI3K/Akt activation was blocked by LY294002 in the macrophages. Moreover, SMS significantly reduced serum uric acid levels in the hyperuricemia mice. Using mass spectrometry, the plant hormones ecdysone and estrone were detected as the potentially effective ingredients of SMS. ConclusionSMS ameliorated MSU-induced gouty arthritis and inhibited hyperuricemia. The anti-inflammatory mechanism of SMS may exert anti-inflammatory effects by promoting M2 polarization via PI3K/Akt signaling. Ecdysone and estrone might be the potentially effective ingredients of SMS. This research may provide evidence for the application of SMS in the treatment of gout. C1 [Cao, Ling; Zhao, Tianyi; Xue, Yu; Wan, Weiguo; Zou, Hejian; Zhu, Xiaoxia] Fudan Univ, Huashan Hosp, Div Rheumatol, Shanghai, Peoples R China. [Cao, Ling; Zhao, Tianyi; Xue, Yu; Wan, Weiguo; Zou, Hejian; Zhu, Xiaoxia] Fudan Univ, Inst Rheumatol Immunol & Allergy, Shanghai, Peoples R China. [Xue, Luan; Chen, Yueying; Quan, Feng] Shanghai Univ Tradit Chinese Med, Yueyang Hosp, Integrated Tradit Chinese & Western Med, Dept Rheumatol, Shanghai, Peoples R China. [Xiao, Yu] Inst Spacecraft Equipment, Shanghai, Peoples R China. [Han, Man; Jiang, Quan] China Acad Chinese Med Sci, Guanganmen Hosp, Beijing, Peoples R China. [Lu, Liwei] Univ Hong Kong, Dept Pathol, Hong Kong, Peoples R China. [Lu, Liwei] Univ Hong Kong, Shenzhen Inst Res & Innovat, Hong Kong, Peoples R China. C3 Fudan University; Fudan University; Shanghai University of Traditional Chinese Medicine; Guang'anmen Hospital, CACMS; China Academy of Chinese Medical Sciences; University of Hong Kong; The University of Hong Kong Shenzhen Institute of Research & Innovation; University of Hong Kong RP Zou, HJ; Zhu, XX (corresponding author), Fudan Univ, Huashan Hosp, Div Rheumatol, Shanghai, Peoples R China.; Zou, HJ; Zhu, XX (corresponding author), Fudan Univ, Inst Rheumatol Immunol & Allergy, Shanghai, Peoples R China. EM hjzou@fudan.edu.cn; xxzhu@unirheuma.org OI Jiang, Quan/0000-0002-3031-7848 FU National Natural Science Foundation of China [82071830]; Shanghai Hospital Development Center [SHDC12016227]; Shanghai Municipal Health Commission [20204Y0428]; Young Elite Scientists Sponsorship Program by CACM [CACM-2020-QNRC2-05] FX & nbsp;This work was supported by the National Natural Science Foundation of China (82071830) and Research Funding from the Shanghai Hospital Development Center (SHDC12016227) and Shanghai Municipal Health Commission (20204Y0428) and Young Elite Scientists Sponsorship Program by CACM(CACM-2020-QNRC2-05). 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Immunol. PD JAN 5 PY 2022 VL 12 AR 777522 DI 10.3389/fimmu.2021.777522 PG 11 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA YL3WM UT WOS:000745824800001 PM 35069549 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Li, S Yang, P Ding, X Zhang, H Ding, Y Tan, Q AF Li, Shiyan Yang, Ping Ding, Xiaofeng Zhang, Hao Ding, Youjun Tan, Qian TI Puerarin improves diabetic wound healing via regulation of macrophage M2 polarization phenotype SO BURNS & TRAUMA LA English DT Article DE Macrophage; Puerarin; Wound healing; Diabetes; Skin; Streptozotocin; Traditional Chinese medicine; Nuclear factor kinase B; Mitogen-activated protein kinase ID ACTIVATION; PATHWAY; REPAIR; CELLS AB Background Skin wound healing depends on the progress of different but overlapping stages of healing, including hemostasis, inflammatory, proliferative and remodeling. Failure of these stages to occur in a timely and gradual manner may result in non-healing pathological wounds. Macrophages and neutrophils have been shown to play an essential role in the inflammatory responses of wound tissue, and their active plasticity allows them to modulate tissue damage and repair functions. The ability of macrophages and neutrophils to regulate the occurrence and resolution of inflammatory processes is essential for the treatment of pathological wound healing. Methods Mice were categorized into negative control, streptozotocin, streptozotocin + puerarin and puerarin groups. The traditional Chinese medicine extract puerarin was selected to treat different groups of mice with a full-thickness skin defect wound. Cells of the RAW264.7 cell line were stimulated under different puerarin conditions. Then, real time quantitative polymerase chain reaction (RT-qPCR), western blot, immunofluorescence and other assays were carried out to explore the effect of puerarin on wound healing and its molecular mechanism. Results Animal experiments found that the wound healing of diabetic mice treated with puerarin was significantly accelerated, and histological analysis found that puerarin treatment markedly decreased the infiltration of macrophages and neutrophils in wound tissue. Through western blot, RT-qPCR and immunofluorescence experiments, it was observed that puerarin treatment remarkably inhibited nuclear factor kinase B (NF-kappa B) and mitogen-activated protein kinase (MAPK) signaling pathways, downregulated the expression of inflammatory cytokines and induced the M2 polarization of macrophages. At the cellular level, we also observed that puerarin improved M2 macrophage polarization and inhibited inflammatory pathway activation in a high-glucose culture. Conclusion Puerarin has a significant therapeutic effect on wound healing in diabetic mice. The therapeutic effect is achieved by regulating macrophage polarization through suppressing NF-kappa B and MAPK signaling cascades. C1 [Li, Shiyan; Yang, Ping; Zhang, Hao; Tan, Qian] Nanjing Univ, Affiliated Hosp, Med Sch, Dept Burns & Plast Surg Nanjing Drum Tower Hosp C, 321 Zhongshan Rd, Nanjing 210008, Jiangsu, Peoples R China. [Ding, Xiaofeng] Jiangsu Unvi, Nanjing Drum Tower Hosp Clin Coll, Dept Burns & Plast Surg, 321 Zhongshan Rd, Nanjing 210008, Jiangsu, Peoples R China. [Tan, Qian] Anqing Shihua Hosp, Dept Burns & Plast Surg, Nanjing Drum Tower Hosp Grp, Anqing 246002, Peoples R China. C3 Nanjing University RP Tan, Q (corresponding author), Nanjing Univ, Affiliated Hosp, Med Sch, Dept Burns & Plast Surg Nanjing Drum Tower Hosp C, 321 Zhongshan Rd, Nanjing 210008, Jiangsu, Peoples R China.; Tan, Q (corresponding author), Anqing Shihua Hosp, Dept Burns & Plast Surg, Nanjing Drum Tower Hosp Grp, Anqing 246002, Peoples R China. EM vincentnju@163.com; yangping1356@qq.com; 814732113@qq.com; zhanghaoch@outlook.com; youjunding@126.com; smmutanqian@sina.com RI 丁, 丁友军/HSH-1839-2023; zhang, hao/AFS-1562-2022 FU National Natural Science Foundation of China [81974288] FX This study was financially supported by The National Natural Science Foundation of China (81974288). 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Guanmaitong granule (GMTG) is a TCM (Traditional Chinese medicine) prescribed to treat AS. However, its mechanism remains unclear. Methods: We obtained reliable ingredients and targets of GMTG using the HERB database. AS-related targets were obtained from HERB and GeneCards databases. The target database was constructed by intersecting the ingredients of GMTG with the AS-related targets. STRING and Cytoscape were used to create protein-protein interaction (PPI) network and screen core targets. GO enrichment analysis and KEGG pathway analyses were performed using R. Finally, the ApoE-/- mice AS model was induced by a high-fat diet (HFD) for in vivo validation of core pathways and targets. Results: A total of 124 ingredients and 418 potential targets of GMTG for treating AS were obtained. Numerous ingredients and targets were related to Panax notoginseng, Salvia miltiorrhiza, and Astragalus. Most core targets and pathways were involved in the inflammatory immune response. GMTG could decrease serum triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and oxidized low-density lipoprotein level and increase the serum high-density lipoprotein-cholesterol level. Furthermore, GMTG reduced the plaque burden and promoted plaque remodeling by reducing plaque area, lipid deposition, foam cell content, and collagen fiber content in the plaque in the aortic root of ApoE-/- mice. GMTG inhibited systemic and plaque inflammatory immune response and increased plaque stability by inhibiting the excessive release of the TLR4/MyD88/NF-Kappa B pathway-induced inflammatory cytokines, tumor necrosis factor, interleukin-6, and interleukin-1 beta. Conclusion: Radix notoginseng, Radix salviae liguliobae, and Radix astragali are the main ingredients of GMTG for treating AS. Further, GMTG could regulate the level of serum lipids and inhibit inflammatory immune response, which resulted in anti-AS effects such as plaque stabilization, reduction of plaque burden, and plaque remodeling. GMTG is a promising multi-target treatment for AS. C1 [Yang, Mengqi; Zhang, Lei; Zhong, Xia] Shandong Univ Tradit Chinese Med, Coll Clin Med 1, Jinan 250014, Peoples R China. [Jiao, Huachen; Li, Yan; Zhang, Juan; Xue, Yitao] Shandong Univ Tradit Chinese Med, Affiliated Hosp, Cardiol Dept, Jinan 250014, Peoples R China. [Xue, Yitao] Shandong Univ Tradit Chinese Med, Affiliated Hosp, Cardiol Dept, Jing Shi Rd, Jinan 250014, Peoples R China. C3 Shandong University of Traditional Chinese Medicine; Shandong University of Traditional Chinese Medicine; Shandong University of Traditional Chinese Medicine RP Xue, YT (corresponding author), Shandong Univ Tradit Chinese Med, Affiliated Hosp, Cardiol Dept, Jing Shi Rd, Jinan 250014, Peoples R China. 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PY 2022 VL 16 BP 3145 EP 3168 DI 10.2147/DDDT.S372143 PG 24 WC Chemistry, Medicinal; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA 4Z3QV UT WOS:000862128700001 PM 36148321 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Chen, Y Wu, H Jiao, AN Tong, JB Zhu, J Zhang, M Li, ZG Li, P AF Chen, Yang Wu, Huan Jiao, Annan Tong, Jiabing Zhu, Jie Zhang, Mei Li, Zegeng Li, Ping TI Chinese Herbal Prescription QYSL Prevents Progression of Lung Cancer by Targeting Tumor Microenvironment SO ONCOLOGIE LA English DT Article DE Lung cancer; TME; traditional Chinese medicine; QYSL ID CELL EXHAUSTION; DRUG-RESISTANCE; MACROPHAGES; MEDICINE; PHENOTYPE; APOPTOSIS; INSIGHTS; EXTRACT; A549; M2 AB Objectives: Lung cancer is a common and malignant tumor in adults and ranks first in the incidence and mortality of the top five malignant tumors in China. Our previous studies have shown that QYSL prescription can balance lung cancer mice Th1/Th2 and inhibit tumor cell immune escape. Here, we examined the effects of QYSL on lung cancer associated macrophage and the potential associated mechanism. Methods: C57BL/6 mice were injected with Lewis lung cancer cells and treated with QYSL. FACS, RT-PCR, and western blot were used to examined the effect of QYSL on tumor immune microenvironment. Results: We found QYSL inhibited tumor growth in mice with lung cancer. Further study indicated that QYSL inhibited growth of lung tumor by promoting T cell activation and promoting macrophage polarization to M1 type. We found QYSL could markedly inhibit M2 macrophage related protein expression and promote M1 macrophage related protein expression. Additionally, STAT6 and MTOR expression were reduced in QYSL group. Conclusions: Overall, this study indicated that QYSL potently inhibited the growth of lung cancer by promoting T cell activation and M2 macrophage polarization to M1, which was found to be associated with the STAT6 and MTOR signaling pathway. C1 [Chen, Yang; Zhang, Mei; Li, Ping] Anhui Med Univ, Oncol Dept Integrated Tradit Chinese & Western Me, Affiliated Hosp 1, Hefei 230022, Peoples R China. [Wu, Huan] Anhui Univ Chinese Med, Sci Res & Expt Ctr, Hefei 230038, Peoples R China. [Jiao, Annan] Anhui Med Univ, Affiliated Hosp 1, Hefei 230022, Peoples R China. [Tong, Jiabing; Li, Zegeng] Anhui Univ Chinese Med, Affiliated Hosp 1, Hefei 230601, Peoples R China. [Zhu, Jie] Anhui Univ Chinese Med, Coll Integrated Chinese & Western Med, Hefei 230038, Peoples R China. C3 Anhui Medical University; Anhui University of Chinese Medicine; Anhui Medical University; Anhui University of Chinese Medicine; Anhui University of Chinese Medicine RP Li, P (corresponding author), Anhui Med Univ, Oncol Dept Integrated Tradit Chinese & Western Me, Affiliated Hosp 1, Hefei 230022, Peoples R China.; Li, ZG (corresponding author), Anhui Univ Chinese Med, Affiliated Hosp 1, Hefei 230601, Peoples R China. EM li6609@126.com; liping64@sina.com RI Wu, Huan/AAW-9822-2020 OI Wu, Huan/0000-0003-2752-8035 FU National Natural Science Foundation of China [82004314, 81874431]; Clinical Research Initiation Plan of the First Affiliated Hospital of Anhui Medical University [LCYJ2021YB017]; Beijing Xisike Clinical Oncology Research Foundation FX This work was supported by the National Natural Science Foundation of China (Grants 82004314, 81874431), the Clinical Research Initiation Plan of the First Affiliated Hospital of Anhui Medical University (Grant LCYJ2021YB017), the Beijing Xisike Clinical Oncology Research Foundation. 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Werner, Markus Chen, Xinchun Werz, Oliver TI Modulation of Inflammation-Related Lipid Mediator Pathways by Celastrol During Human Macrophage Polarization SO JOURNAL OF INFLAMMATION RESEARCH LA English DT Article DE inflammation; macrophages; lipoxygenase; cyclooxygenase; lipid mediators; specialized pro-resolving mediators; celastrol ID ANTIINFLAMMATORY DRUGS; NATURAL-PRODUCTS; KAPPA-B; EXPRESSION; DISEASE; PHAGOCYTES AB Background and Purpose: Celastrol (CS) is a major active ingredient of the Chinese/Asian herb Tripterygium wilfordii that is frequently used as phytomedicine to treat inflammation and autoimmune diseases. We showed before that short-term exposure to CS (1 mu M) favorably impacts the biosynthesis of inflammation-related lipid mediators (LM) in human polarized macrophages by modulating the activities of different lipoxygenases (LOXs). However, whether CS regulates the expression of LOXs and other related LM-biosynthetic enzymes during macrophage polarization is unknown. Here, we investigated how CS affects LM-biosynthetic enzyme expression on the protein level and studied concomitant LM signature profiles during polarization of human monocyte-derived macrophages (MDM) towards M1- and M2-like phenotypes. Methods and Results: We used LM metabololipidomics to study the long-term effects of CS on LM profile signatures after manipulation of human monocyte-derived macrophages (MDM) during polarization. Exposure of MDM to low concentrations of CS (ie, 0.2 mu M) during polarization to an inflammatory M1 phenotype potently suppressed the formation of pro-inflammatory cycloox-ygenase (COX)- and 5-LOX-derived LM, especially prostaglandin (PG)E-2. Notably, gene and enzyme expression of COX-2 and microsomal PGE 2 synthase (mPGES)-1 as well as M1 markers were strongly decreased by CS during M1-MDM polarization, along with impaired activation of nuclear factor-kappa B and p38 mitogen-activated protein kinase. During IL-4-induced M2 polarization, CS decreased the capacity of the resulting M2-MDM to generate pro-inflammatory COX and 5-LOX products as well but it also reduced the formation of 12/15-LOX products and specialized pro-resolving mediators, without affecting the levels of liberated fatty acid substrates. Conclusion: Depending on the timing and concentration, CS not only favorably affects LOX activities in macrophages but also the expression of LM-biosynthetic enzymes during macrophage polarization connected to changes of inflammation-related LM which might be of relevance for potential application of CS to treat inflammatory disorders. C1 [Zhang, Kehong; Jordan, Paul Mike; Pace, Simona; Hofstetter, Robert K.; Werner, Markus; Werz, Oliver] Friedrich Schiller Univ Jena, Inst Pharm, Dept Pharmaceut Med Chem, D-07743 Jena, Germany. [Zhang, Kehong; Chen, Xinchun] Shenzhen Univ, Sch Med, Dept Pathogen Biol, Guangdong Prov Key Lab Reg Immun & Dis, Shenzhen 518000, Peoples R China. C3 Friedrich Schiller University of Jena; Shenzhen University RP Werz, O (corresponding author), Friedrich Schiller Univ Jena, Inst Pharm, Dept Pharmaceut Med Chem, D-07743 Jena, Germany. EM oliver.werz@uni-jena.de RI ; 张, 克宏/GRJ-9476-2022; Hofstetter, Robert K/GPX-7380-2022; Jordan, Paul/KAM-4478-2024 OI Pace, Simona/0000-0001-5110-481X; Werz, Oliver/0000-0002-5064-4379; Hofstetter, Robert K/0000-0002-1077-9703; Jordan, Paul/0000-0002-8364-4236 FU Free State of Thuringia; European Social Fund [2019 FGR 0095]; Deutsche Forschungsgemeinschaft (DFG) , Collaborative Research Center [SFB 1278, 316213987, A04, SFB 1127] FX This work was supported by the Free State of Thuringia and the European Social Fund (2019 FGR 0095) and by the Deutsche Forschungsgemeinschaft (DFG), Collaborative Research Center SFB 1278 "PolyTarget" (project number 316213987, project A04) and - SFB 1127 "ChemBioSys" (project number 239748522, project A04). 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Inflamm. Res. PY 2022 VL 15 BP 3285 EP 3304 DI 10.2147/JIR.S356964 PG 20 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA 2A1NG UT WOS:000809276300002 PM 35676971 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Wang, XX Du, HJ Li, XD AF Wang, Xiaoxu Du, Hongjiao Li, Xiaodong TI Artesunate attenuates atherosclerosis by inhibiting macrophage M1-like polarization and improving metabolism SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Atherosclerosis; Macrophages polarization; Artesunate; Inflammation; HIF-1 alpha ID HYPOXIA-INDUCIBLE FACTOR; ACTIVATION; MONOCYTE; SIGNAL AB Object: Atherosclerosis (AS) is caused by chronic inflammation. Artesunate (ART), a sesquiterpene lactone endoperoxide isolated from Chinese herbal medicine, displays excellent anti-inflammatory activity. In this study, we investigated the effects of artesunate on atherosclerosis in ApoE knock-out mice, and used untargeted metabolomics to determine metabolite changes in these mice following ART treatment. Methods: ApoE knock-out mice were fed a western diet and administered ART for eight weeks. Untargeted metabolomics was used to detect differential metabolites following the administration of ART. Oil Red O was used to assess plaque size, western blot and ELISA were used to detect inflammatory factors, and flow cytometry was used to detect the expression of markers on macrophages. Results: Results of the in vivo experiment suggested that ART reduced atherosclerotic plaques in murine aortic root. In addition both in vivo and vitro experiments suggested that ART reduced the expression levels of inflammating cytokines, but enhanced those of the anti-inflammatory cytokines in macrophages. Untargeted metabolomic analysis demonstrated that multiple metabolic pathways, which were blocked in AS mice, showed different degrees of improvement following ART treatment. Furthermore, bioinformatic analyses showed that the HIF-1 alpha pathway was altered in the AS mice and the ART treatment mice. In vitro experiments confirmed that LPS-induced upregulation of HIF-1 alpha expression and activation of the NF-kappa B signaling pathways was significantly inhibited by ART treatment. Conclusion: These results suggest that ART exerts anti-atherosclerosis effects by inhibiting M1 macrophage polarization. One of the molecular mechanisms is that ART inhibits M1-like macrophage polarization via regulating HIF-1 alpha and NF-kappa XB signaling pathways. C1 [Wang, Xiaoxu; Du, Hongjiao; Li, Xiaodong] China Med Univ, Shengjing Hosp, Dept Cardiol, Shenyang 110004, Peoples R China. C3 China Medical University RP Li, XD (corresponding author), China Med Univ, Shengjing Hosp, Dept Cardiol, Shenyang 110004, Peoples R China. EM licardio@163.com FU Scientific Research Project of Education Department of Liaoning Province [JCZR2020012] FX Funding This work was supported by a grant from the Scientific Research Project of Education Department of Liaoning Province (No. JCZR2020012) . 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PD JAN PY 2022 VL 102 AR 108413 DI 10.1016/j.intimp.2021.108413 PG 12 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA 0V1DB UT WOS:000788084700001 PM 34891003 OA hybrid DA 2026-03-26 ER PT J AU Ma, L Dai, XC Wu, CX Li, MS Sheng, HZ Mao, W AF Ma, Lan Dai, Xiaoce Wu, Chenxia Li, Mingshuang Sheng, Hongzhuan Mao, Wei TI Tanyu Tongzhi Formula Delays Atherosclerotic Plaque Progression by Promoting Alternative Macrophage Activation via PPARγ and AKT/ERK Signal Pathway in ApoE Knock-Out Mice SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE Tanyu Tongzhi formula; atherosclerosis; traditional Chinese medicine; alternative macrophage activation; PPAR gamma AB We previously demonstrated that the Tanyu Tongzhi Formula (TTF) significantly alleviated the clinical symptoms of patients with coronary heart disease and lowered serum lipid and inflammatory factor levels in patients with coronary heart disease and atherosclerosis model rats. However, the mechanism underlying TTF remains unknown. In this study, we examined the effect of TTF on atherosclerotic plaques in ApoE(-/-) mice and underlying mechanisms involved in macrophage polarization. Sixty male ApoE(-/-) mice were randomly divided into four groups. Mice in the control group were fed a regular diet, whereas experimental mice were fed a high-fat diet and received either saline (HFD group) or TTF at concentrations of 0.60 (TTF-L group) or 2.25 g/ml (TTF-H group) by daily oral gavage for 16 weeks. In the TTF-L and TTF-H groups, the levels of serum cholesterol, triglyceride, interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha were decreased, lipid content was significantly decreased, and percentage area of collagen/lipid increased in atherosclerotic plaque compared to in the HFD group. Moreover, we found TTF promoted the expression of alternative macrophage markers (Fizz1, Arg1, and Mrc) and suppressed the expression of M1 macrophage markers (TNF-alpha, IL-1 beta, and IL-6) by regulating peroxisome proliferator-activated receptor gamma (PPAR gamma) expression and AKT/extracellular signal-regulated kinase (ERK) activation. We further investigated whether alternative macrophage was reduced when PPAR gamma was inhibited or the AKT/ERK signaling pathway was activated. TTF delayed atherosclerotic plaque progression by promoting alternative macrophage activation through increasing PPAR gamma expression and inhibiting AKT/ERK phosphorylation, providing a theoretical basis for its clinical application. C1 [Ma, Lan; Sheng, Hongzhuan] Nantong Univ, Affiliated Hosp, Dept Cardiol, Nantong, Peoples R China. [Ma, Lan] Zhejiang Chinese Med Univ, Sch Clin Med 1, Hangzhou, Peoples R China. [Dai, Xiaoce] Jiaxing Univ, Affiliated Hosp 1, Dept Cardiol, Jiaxing, Peoples R China. [Wu, Chenxia; Li, Mingshuang; Mao, Wei] Zhejiang Chinese Med Univ, Affiliated Hosp 1, Dept Cardiol, Hangzhou, Peoples R China. [Mao, Wei] Key Lab Integrat Chinese & Western Med Diag & Tre, Hangzhou, Peoples R China. C3 Nantong University; Zhejiang Chinese Medical University; Jiaxing University; Zhejiang Chinese Medical University RP Sheng, HZ (corresponding author), Nantong Univ, Affiliated Hosp, Dept Cardiol, Nantong, Peoples R China.; Mao, W (corresponding author), Key Lab Integrat Chinese & Western Med Diag & Tre, Hangzhou, Peoples R China. EM maoweilw@163.com; yjshz@ntu.edu.cn FU National Natural Science Foundation [81973579]; Nantong Municipal Science and Technology Project [JCZ20196] FX Funding This work was supported by the National Natural Science Foundation to WM (grant numbers 81973579); Nantong Municipal Science and Technology Project (grant numbers JCZ20196). 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Pharmacol. PD DEC 13 PY 2021 VL 12 AR 734589 DI 10.3389/fphar.2021.734589 PG 14 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA YB3KK UT WOS:000738915300001 PM 34966274 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Liu, JL Zhang, YM Sheng, HQ Liang, CL Liu, HZ Guerrero, JAM Lu, ZY Mao, W Dai, ZH Liu, XS Zhang, L AF Liu, Jialing Zhang, Yanmei Sheng, Hongqin Liang, Chunling Liu, Huazhen Moran Guerrero, Jose Alberto Lu, Zhaoyu Mao, Wei Dai, Zhenhua Liu, Xusheng Zhang, Lei TI Hyperoside Suppresses Renal Inflammation by Regulating Macrophage Polarization in Mice With Type 2 Diabetes Mellitus SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE diabetic nephropathy; macrophage polarization; hyperoside; renal inflammation; Th1 cell; Treg cell ID KIDNEY-DISEASE; NEPHROPATHY; ACTIVATION; CELLS; MODELS; INJURY AB Accumulating evidence reveals that both inflammation and lymphocyte dysfunction play a vital role in the development of diabetic nephropathy (DN). Hyperoside (HPS) or quercetin-3-O-galactoside is an active flavonoid glycoside mainly found in the Chinese herbal medicine Tu-Si-Zi. Although HPS has a variety of pharmacological effects, including anti-oxidative and anti-apoptotic activities as well as podocyte-protective effects, its underlying anti-inflammatory mechanisms remain unclear. Herein, we investigated the therapeutic effects of HPS on murine DN and the potential mechanisms responsible for its efficacy. We used C57BLKS/6J (Lep) db/db mice and a high glucose (HG)-induced bone marrow-derived macrophage (BMDM) polarization system to investigate the potentially protective effects of HPS on DN. Our results showed that HPS markedly reduced diabetes-induced albuminuria and glomerular mesangial matrix expansion, accompanied with a significant improvement of fasting blood glucose level, hyperlipidaemia and body weight. Mechanistically, pretreatment with HPS effectively regulated macrophage polarization by shifting proinflammatory M1 macrophages (F4/80(+)CD11b(+)CD86(+)) to anti-inflammatory M2 ones (F4/80(+)CD11b(+)CD206(+)) in vivo and in bone marrow-derived macrophages (BMDMs) in vitro, resulting in the inhibition of renal proinflammatory macrophage infiltration and the reduction in expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF-alpha) and inducible nitric oxide synthase (iNOS) while increasing expression of anti-inflammatory cytokine Arg-1 and CD163/CD206 surface molecules. Unexpectedly, pretreatment with HPS suppressed CD4(+) T cell proliferation in a coculture model of IL-4-induced M2 macrophages and splenic CD4(+) T cells while promoting their differentiation into CD4(+)IL-4(+) Th2 and CD4(+)Foxp3(+) Treg cells. Taken together, we demonstrate that HPS ameliorates murine DN via promoting macrophage polarization from an M1 to M2 phenotype and CD4(+) T cell differentiation into Th2 and Treg populations. Our findings may be implicated for the treatment of DN in clinic. C1 [Liu, Jialing; Zhang, Yanmei; Sheng, Hongqin; Liang, Chunling; Liu, Huazhen; Lu, Zhaoyu; Mao, Wei; Dai, Zhenhua; Liu, Xusheng; Zhang, Lei] Guangzhou Univ Chinese Med, State Key Lab Dampness Syndrome Chinese Med, Clin Coll 2, Guangzhou, Peoples R China. [Liu, Jialing; Zhang, Yanmei; Sheng, Hongqin; Lu, Zhaoyu; Mao, Wei; Liu, Xusheng; Zhang, Lei] Guangzhou Univ Chinese Med, Dept Nephrol, Affiliated Hosp 2, Guangzhou, Peoples R China. [Liu, Jialing] Southern Univ Sci & Technol, Sch Med, Dept Biochem, Shenzhen, Peoples R China. [Liang, Chunling; Liu, Huazhen; Dai, Zhenhua; Zhang, Lei] Guangdong Prov Acad Chinese Med Sci, Sect Immunol & Joint Immunol Program, Guangzhou, Peoples R China. [Moran Guerrero, Jose Alberto] Tecnologico, Monterrey Inst Technol, Monterrey, Mexico. [Dai, Zhenhua; Zhang, Lei] Guangdong Prov Key Lab Clin Res Tradit Chinese Me, Guangzhou, Peoples R China. [Dai, Zhenhua] Guangzhou Univ Chinese Med, Guangdong Hong Kong Macau Joint Lab Chinese Med &, Guangzhou, Peoples R China. C3 Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine; Southern University of Science & Technology; Guangzhou University of Chinese Medicine; Tecnologico de Monterrey; Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine RP Dai, ZH; Liu, XS; Zhang, L (corresponding author), Guangzhou Univ Chinese Med, State Key Lab Dampness Syndrome Chinese Med, Clin Coll 2, Guangzhou, Peoples R China.; Liu, XS; Zhang, L (corresponding author), Guangzhou Univ Chinese Med, Dept Nephrol, Affiliated Hosp 2, Guangzhou, Peoples R China.; Dai, ZH; Zhang, L (corresponding author), Guangdong Prov Acad Chinese Med Sci, Sect Immunol & Joint Immunol Program, Guangzhou, Peoples R China.; Dai, ZH; Zhang, L (corresponding author), Guangdong Prov Key Lab Clin Res Tradit Chinese Me, Guangzhou, Peoples R China.; Dai, ZH (corresponding author), Guangzhou Univ Chinese Med, Guangdong Hong Kong Macau Joint Lab Chinese Med &, Guangzhou, Peoples R China. EM zdai2009@outlook.com; liuxusheng@gzucm.edu.cn; zhanglei@gzucm.edu.cn RI ; Zhang, Lei/JJD-8814-2023 OI MORAN GUERRERO, JOSE ALBERTO/0009-0004-7851-7808; FU State Key Laboratory of Dampness Syndrome of Chinese Medicine [SZ2021ZZ16, SZ2021ZZ43, SZ2021ZZ18]; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome [ZH2020KF02]; National Natural Science Foundation of China [81603717, 81873261]; Guangzhou University of Chinese Medicine [AFD018171Z11099]; Special Fund of Guangdong Provincial Science and Technology Innovation Strategy(Guangdong-Hong Kong-Macau Joint Lab) [2020B1212030006] FX This project was supported in part by grants from the State Key Laboratory of Dampness Syndrome of Chinese Medicine (SZ2021ZZ16, SZ2021ZZ43, and SZ2021ZZ18), Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome (ZH2020KF02), National Natural Science Foundation of China (81603717, 81873261), Guangzhou University of Chinese Medicine (Grant No: AFD018171Z11099), and Special Fund of Guangdong Provincial Science and Technology Innovation Strategy(Guangdong-Hong Kong-Macau Joint Lab, 2020B1212030006). 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Immunol. PD DEC 3 PY 2021 VL 12 AR 733808 DI 10.3389/fimmu.2021.733808 PG 17 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA ZH6VE UT WOS:000761073200001 PM 34925317 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Sawuer, G Ma, XK Zhang, YJ Zhang, XM Ainiwaer, Z An, DQ AF Sawuer, Guligena Ma, Xue-Kuan Zhang, Ya-Jie Zhang, Xuan-Ming Ainiwaer, Zulihumaer An, Dong-Qing TI Tianxiangdan Improves Coronary Microvascular Dysfunction in Rats by Inhibiting Microvascular Inflammation via Nrf2 Activation SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article ID MACROPHAGE POLARIZATION; PATHWAY; INJURY AB Background. Tianxiangdan (TXD) is used in traditional Chinese medicine because of its therapeutic and preventive effects in the treatment of coronary heart disease. However, the underlying mechanism of TXD in coronary microvascular disease (CMD) remains unclear. Methods. A rat model of CMD was developed to study the mechanism of TXD activity. Sodium laurate was injected into the left ventricle of Sprague-Dawley rats to induce CMD. The rats were divided into six groups: a sham-operated (sham) group, an untreated CMD group, a low-dose TXD group (0.81 g.kg(-1).d(-1)), a mid-dose TXD (TXD-M) group (1.62 g.kg(-1).d(-1)), a high-dose TXD (TXD-H) group (3.24 g.kg(-1).d(-1)), and a nicorandil (NCR) group (1.35 mg.kg(-1).d(-1)). The effect of TXD on rats with CMD was observed after four weeks, and the mechanism of TXD in lipopolysaccharide (LPS)-induced cardiac microvascular endothelial cells (CMECs) was explored through treatment with 50 mu g/mL TXD. Results. Compared with the rats in the untreated CMD group, rats in the TXD-M and TXD-H groups showed higher left ventricular ejection fraction values, improved pathological structures, decreased expressions of interleukin (IL)-1 beta, tumor necrosis factor-alpha (TNF-alpha), phosphorylated nuclear factor-kappa B inhibitor a (I kappa B alpha) and phosphorylated p65, and increased expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (P < 0.05). These effects were more pronounced in the TXD-H group than in the TXD-M group. In vitro experiments showed that TXD treatment increased the viability of LPS-induced CMECs and decreased the expression of IL-1 beta, TNF-alpha, phosphorylated I kappa B alpha, and phosphorylated p65 (P < 0.05). However, the effects of TXD on CMECs were markedly reversed upon treatment with ML385 (Nrf2 inhibitor). Conclusion. The results showed that TXD exerts a protective effect on rats with CMD and related inflammatory injuries, and its anti-inflammatory mechanism is related to the activation of Nrf2 signalling. C1 [Sawuer, Guligena; Zhang, Ya-Jie; Ainiwaer, Zulihumaer; An, Dong-Qing] Xinjiang Med Univ, Coll Tradit Chinese Med, Urumqi 830011, Peoples R China. [Ma, Xue-Kuan] Xinjiang Med Univ, Affiliated Hosp 4, Med Dept, Urumqi 830099, Peoples R China. [Zhang, Xuan-Ming] Shihezi Univ, Med Coll, Affiliated Hosp 1, Dept Tradit Chinese Med, Shihezi 832000, Peoples R China. [An, Dong-Qing] Xinjiang Med Univ, Xinjiang Key Lab Famous Prescript & Sci Formulas, Urumqi 830011, Peoples R China. C3 Xinjiang Medical University; Xinjiang Medical University; Shihezi University; Xinjiang Medical University RP An, DQ (corresponding author), Xinjiang Med Univ, Coll Tradit Chinese Med, Urumqi 830011, Peoples R China.; An, DQ (corresponding author), Xinjiang Med Univ, Xinjiang Key Lab Famous Prescript & Sci Formulas, Urumqi 830011, Peoples R China. EM guligenaa@outlook.com; snowywide@yandex.com; zhang.yj@yandex.com; open_xm@outlook.com; zulihumaerainiwaer@yandex.com; an_dongqing@yeah.net OI An, Dongqing/0000-0002-2350-0572; Ainiwaer, Zulihumaer/0009-0004-5211-9959 FU National Natural Science Foundation of China [81760843]; Autonomous Region Key Laboratory Open Project [2020D04006] FX This work was supported by the National Natural Science Foundation of China (81760843) and Autonomous Region Key Laboratory Open Project (2020D04006). The authors sincerely thank Prof. Lin Ren-Yong for providing technical assistance. 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Med. PD DEC 2 PY 2021 VL 2021 AR 4114784 DI 10.1155/2021/4114784 PG 11 WC Integrative & Complementary Medicine WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine GA 0V7RN UT WOS:000788538200003 PM 34899948 OA Green Submitted, hybrid DA 2026-03-26 ER PT J AU Xin, SL Yang, X Zhang, YP Xu, KS AF Xin, Sheng-liang Yang, Xia Zhang, Yu-ping Xu, Ke-shu TI Zhikang Capsule Ameliorates Inflammation, Drives Polarization to M2 Macrophages, and Inhibits Apoptosis in Lipopolysaccharide-induced RAW264.7 Cells SO CURRENT MEDICAL SCIENCE LA English DT Article DE Zhikang capsule; macrophage; RAW 264; 7; inflammation; apoptosis; nuclear factor kappa B ID NF-KAPPA-B; M1 MACROPHAGE; ACTIVATION; ALPHA; ATHEROSCLEROSIS; DYSFUNCTION; EXPRESSION; MONOCYTE; COLITIS; STRESS AB Objective To explore the anti-inflammatory effect of the traditional Chinese medicine Zhikang capsule (ZKC) on lipopolysaccharide (LPS)-induced RAW264.7 cells. Methods Safe concentrations of ZKC (0.175, 0.35, and 0.7 mg/mL) were used after the half-maximal inhibitory concentration (IC50) of RAW264.7 cells was calculated through the CCK-8 assay. In addition, the optimal intervention duration of ZKC (0.7 mg/mL) on RAW264.7 cells was determined to be 6 h, since all proinflammatory mediators [tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), inteleukin-6 (IL-6), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and monocyte chemotactic protein-1 (MCP-1)] had a decreasing tendency and relatively down-regulated mRNA expression levels as compared with other durations (4, 8, and 12 h). RAW264.7 cells were pretreated with ZKC at various concentrations (0.175, 0.35 and 0.7 mg/mL) for 6 h and then stimulated with LPS (1 mu g/mL) for an additional 12 h. Results In terms of inflammation, ZKC could reverse LPS-induced upregulation of TNF-alpha, IL-1 beta, IL-6, COX-2, iNOS, and MCP-1 at both the mRNA and protein levels in RAW264.7 cells in a dose-dependent manner. In terms of the NF-kappa B signaling pathway, ZKC could reduce phosphorylated p65 and promote M2 polarization of RAW264.7 cells under LPS stimulation in a dose-dependent manner. Moreover, ZKC exhibited a protective effect on macrophages from apoptosis. Conclusion ZKC exhibited obvious antiinflammatory and anti-apoptotic effects on LPS-induced RAW264.7 cells at the cellular level, and a weakened NF-kappa B signaling pathway may be a potential significant target. C1 [Xin, Sheng-liang] Peking Univ First Hosp, Dept Infect Dis, Beijing 100034, Peoples R China. [Yang, Xia] Wuhan Asia Gen Hosp, Dept Gastroenterol, Wuhan 430056, Peoples R China. [Zhang, Yu-ping; Xu, Ke-shu] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Gastroenterol, Wuhan 430022, Peoples R China. C3 Peking University; Huazhong University of Science & Technology RP Xu, KS (corresponding author), Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Gastroenterol, Wuhan 430022, Peoples R China. EM xsl0351@pku.edu.cn; 38243864@qq.com; xuzou2018@hust.edu.cn CR Afrin S, 2018, FOOD CHEM TOXICOL, V121, P203, DOI 10.1016/j.fct.2018.09.001 Barros MHM, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0080908 Boshtam M, 2017, INFLAMMATION, V40, P340, DOI 10.1007/s10753-016-0477-1 Cao SY, 2019, CHIN J NAT MEDICINES, V17, P81, DOI 10.1016/S1875-5364(19)30012-3 Che DH, 2017, MOL IMMUNOL, V90, P197, DOI 10.1016/j.molimm.2017.06.018 Chen Q, 2019, CHIN J NAT MEDICINES, V17, P461, DOI 10.1016/S1875-5364(19)30053-6 Chen YL, 2016, J ETHNOPHARMACOL, V185, P41, DOI 10.1016/j.jep.2016.03.028 Cheng C, 2015, GENET MOL RES, V14, P5127, DOI 10.4238/2015.May.18.2 Cheng CS, 2018, MOLECULES, V23, DOI 10.3390/molecules23081857 Cheng CW, 2018, INT J MOL MED, V41, P1877, DOI 10.3892/ijmm.2018.3389 Cho YC, 2015, J ETHNOPHARMACOL, V162, P140, DOI 10.1016/j.jep.2014.12.056 Chrobok NL, 2017, AMINO ACIDS, V49, P441, DOI 10.1007/s00726-016-2334-9 Conway EM, 2016, AM J RESP CRIT CARE, V193, P116, DOI 10.1164/rccm.201508-1545CI De Felice FG, 2014, DIABETES, V63, P2262, DOI 10.2337/db13-1954 Deng XL, 2017, BBA-MOL CELL BIOL L, V1862, P337, DOI 10.1016/j.bbalip.2016.12.007 Dou FF, 2019, AM J TRANSL RES, V11, P3825 Engin AB, 2017, ADV EXP MED BIOL, V960, P327, DOI 10.1007/978-3-319-48382-5_14 Fei L, 2016, J ETHNOPHARMACOL, V192, P236, DOI 10.1016/j.jep.2016.07.055 Fougère B, 2017, J GERONTOL A-BIOL, V72, P1218, DOI 10.1093/gerona/glw240 Ge H, 2017, DRUG DES DEV THER, V11, DOI 10.2147/DDDT.S133069 Geng J, 2019, ECOTOX ENVIRON SAFE, V176, P76, DOI 10.1016/j.ecoenv.2019.03.068 George L, 2019, IMMUNOL INVEST, V48, P451, DOI 10.1080/08820139.2019.1566355 Guo WX, 2012, INFLAMMATION, V35, P1764, DOI 10.1007/s10753-012-9495-9 Han C, 2010, INFLAMM RES, V59, P809, DOI 10.1007/s00011-010-0192-6 Hayden MS, 2008, CELL, V132, P344, DOI 10.1016/j.cell.2008.01.020 Hoesel B, 2013, MOL CANCER, V12, DOI 10.1186/1476-4598-12-86 Hokari R, 2001, FREE RADICAL BIO MED, V31, P153, DOI 10.1016/S0891-5849(01)00565-2 Hou JJ, 2017, SCI REP-UK, V7, DOI 10.1038/s41598-017-15074-5 Hu BY, 2014, J ETHNOPHARMACOL, V153, P846, DOI 10.1016/j.jep.2014.03.059 Huang C, 2020, LIFE SCI, V258, DOI 10.1016/j.lfs.2020.118146 Hung YL, 2017, SCI REP-UK, V7, DOI 10.1038/srep46299 Jablonski KA, 2015, PLOS ONE, V10, DOI 10.1371/journal.pone.0145342 Kao TC, 2010, J AGR FOOD CHEM, V58, P8623, DOI 10.1021/jf101841r Kaplan GG, 2015, NAT REV GASTRO HEPAT, V12, P720, DOI 10.1038/nrgastro.2015.150 Karpurapu M, 2011, BLOOD, V118, P5255, DOI 10.1182/blood-2011-03-341123 Kauppinen A, 2013, CELL SIGNAL, V25, P1939, DOI 10.1016/j.cellsig.2013.06.007 Lee HJ, 2012, INFLAMM RES, V61, P817, DOI 10.1007/s00011-012-0474-2 Lissner D, 2015, INFLAMM BOWEL DIS, V21, P1297, DOI 10.1097/MIB.0000000000000384 Liu JP, 2013, NEUROSCI LETT, V549, P63, DOI 10.1016/j.neulet.2013.06.002 Meng XM, 2019, ADV EXP MED BIOL, V1165, P285, DOI 10.1007/978-981-13-8871-2_13 Orecchioni M, 2019, FRONT IMMUNOL, V10, DOI 10.3389/fimmu.2019.01084 Seminara AR, 2007, CELL CYCLE, V6, P1772, DOI 10.4161/cc.6.14.4438 Shapouri-Moghaddam A, 2018, J CELL PHYSIOL, V233, P6425, DOI 10.1002/jcp.26429 Sigola LB, 2016, TISSUE CELL, V48, P389, DOI 10.1016/j.tice.2016.04.002 Somensi N, 2019, INT IMMUNOPHARMACOL, V75, DOI 10.1016/j.intimp.2019.105743 Steinbach EC, 2014, INFLAMM BOWEL DIS, V20, P166, DOI 10.1097/MIB.0b013e3182a69dca Tall AR, 2015, NAT REV IMMUNOL, V15, P104, DOI 10.1038/nri3793 Viola J, 2015, SEMIN IMMUNOL, V27, P184, DOI 10.1016/j.smim.2015.03.013 Vogel DYS, 2014, IMMUNOBIOLOGY, V219, P695, DOI 10.1016/j.imbio.2014.05.002 Wang HZ, 2016, FISH SHELLFISH IMMUN, V54, P564, DOI 10.1016/j.fsi.2016.04.132 Wang Yaqi, 2019, Zhejiang Da Xue Xue Bao Yi Xue Ban, V48, P204 Wen Q, 2018, INT IMMUNOPHARMACOL, V56, P90, DOI 10.1016/j.intimp.2018.01.023 Wu YX, 2007, LIFE SCI, V81, P1332, DOI 10.1016/j.lfs.2007.08.040 Wynn TA, 2013, NATURE, V496, P445, DOI 10.1038/nature12034 Zhang Jie, 2005, Zhongguo Zhong Xi Yi Jie He Za Zhi, V25, P839 Zhang Q, 2017, CELL, V168, P37, DOI 10.1016/j.cell.2016.12.012 Zong ZY, 2019, FRONT IMMUNOL, V10, DOI 10.3389/fimmu.2019.01643 NR 57 TC 2 Z9 3 U1 2 U2 41 PU SPRINGER PI NEW YORK PA ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES SN 2096-5230 EI 2523-899X J9 CURR MED SCI JI Curr. Med. Sci. PD DEC PY 2021 VL 41 IS 6 BP 1214 EP 1224 DI 10.1007/s11596-021-2441-z EA OCT 2021 PG 11 WC Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine GA XY1ZE UT WOS:000712477900001 PM 34705217 DA 2026-03-26 ER PT J AU Li, YJ Li, B Wang, P Wang, QH AF Li, Yujia Li, Bin Wang, Pan Wang, Qinghua TI Traditional Chinese Medicine, Qingfei Paidu Decoction and Xuanfei Baidu Decoction, Inhibited Cytokine Production via NF-κB Signaling Pathway in Macrophages: Implications for Coronavirus Disease 2019 (COVID-19) Therapy SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE COVID-19; traditional Chinese medicine; macrophage; NF-kappa B signaling pathway; cytokine storm ID IL-6 AB Background and Aims: Qingfei Paidu decoction (QPD) and Xuanfei Baidu decoction (XBD) are two typical traditional Chinese medicines with proven efficacy for the treatment of SARS-CoV-2, although the underlying mechanism is not well defined. Blunted immune response and enhanced production of pro-inflammatory cytokines (cytokine storm) are two main features observed in patients infected with SARS-CoV-2. Analysis based on network pharmacology has revealed that both QPD and XBD played an important role in the regulation of host immunity. We therefore investigated the role of QPD and XBD in the modulation of innate immunity in vitro, focusing on the type 1 interferon (IFN) signaling pathway in A549 cells and pro-inflammatory cytokine production in macrophages.& nbsp;Methods: A549 cells were treated with QPD or XBD and the production of endogenous IFN alpha and IFN beta as well as the expression levels of some interferon-stimulated genes (ISGs) were detected by reverse transcriptase-quantitative PCR (RT-qPCR). Macrophages derived from THP-1 cells were treated with QPD or XBD and their pro-inflammatory cytokine expression levels were measured by RT-qPCR, 6 h post LPS stimulation. In addition, the expression levels of some pro-inflammatory cytokines were further analyzed by ELISA. The effect of QPD and XBD on the NF-kappa B signaling pathway and the pinocytosis activity of THP-1-derived macrophages were evaluated by Western blot and neutral red uptake assay, respectively.& nbsp;Results: Although QPD and XBD showed very little effect on the type 1 IFN signaling pathway in A549 cells, either QPD or XBD markedly inhibited the production of pro-inflammatory markers including interleukin-6, tumor necrosis factor-alpha, monocyte chemotactic protein-1, and chemokine ligand 10 in THP-1-derived M1 macrophages. In addition, the phosphorylation of I kappa B alpha and NF-kappa B p65 during the process of macrophage polarization was significantly suppressed following QPD or XBD treatment. QPD and XBD also suppressed the pinocytosis activity of macrophages.& nbsp;Conclusion: QPD and XBD have been shown to have robust anti-inflammatory activities in vitro. Our study demonstrated that both QPD and XBD decreased pro-inflammatory cytokine expression, inhibited the activation of the NF-kappa B signaling pathway, and blunted pinocytosis activity in THP-1-derived macrophages. C1 [Li, Yujia] Chinese Acad Med Sci & Peking Union Med Coll, Inst Blood Transfus, Chengdu, Peoples R China. [Li, Yujia; Li, Bin] Chinese Acad Med Sci, Joint Lab Transfus Transmitted Dis TTD Inst Blood, Nanning, Peoples R China. [Li, Yujia; Li, Bin] Nanning Blood Ctr, Nanning, Peoples R China. [Wang, Pan; Wang, Qinghua] Tradit Chinese Med Hosp Wenjiang Dist, Chengdu, Peoples R China. C3 Chinese Academy of Medical Sciences - Peking Union Medical College; Institute of Blood Transfusion - CAMS; Peking Union Medical College; Chinese Academy of Medical Sciences - Peking Union Medical College RP Wang, P; Wang, QH (corresponding author), Tradit Chinese Med Hosp Wenjiang Dist, Chengdu, Peoples R China. EM wangpan761@163.com; qinghuawang2015@126.com RI Wang, Qinghua/GVT-3252-2022 OI Li, Bin/0000-0003-2945-4092 FU Chengdu Municipal Health Commission, Chengdu, China [2020179] FX Funding This work was supported by the Chengdu Municipal Health Commission, Chengdu, China (grant number 2020179) to QW. 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Pharmacol. PD OCT 26 PY 2021 VL 12 AR 722126 DI 10.3389/fphar.2021.722126 PG 10 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA XB4AY UT WOS:000721274100001 PM 34764867 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Yin, L Fan, ZP Liu, P Chen, LY Guan, ZY Liu, YH Luo, YY AF Yin, Li Fan, Zeping Liu, Peng Chen, Lanying Guan, Ziyi Liu, Yahui Luo, Yingying TI Anemoside A3 activates TLR4-dependent M1-phenotype macrophage polarization to represses breast tumor growth and angiogenesis SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Macrophage polarization; Toll-like receptor; Anemoside A3; Breast cancer; Angiogenesis ID PROGRESSION AB The polarization of macrophages has been previously demonstrated to be closely related to immune and in-flammatory processes in the tumorigenesis and progression of breast cancer. In the present study, Anemoside A3 (A3), an active compound from Pulsatilla saponins, was screened out and polarized M0 macrophages into the classically activated macrophages (M1-phenotype). We found that A3 is an activator of TLR4/NF-kappa B/MAPK signaling pathway. A3 increased the expression of CD86+ (a marker of M1 macrophage) in M0 macrophage, and increased the typical M1 macrophage pro-inflammatory cytokines TNF-alpha, and IL-12 expression in a TLR4-dependent manner. A macrophage-cancer cell co-culture system was established to evaluate whether A3 can could switch tumor-associated macrophages (TAMs) to the M1-phenotype. In the co-culture system, A3 increased the expression of IL-12 in macrophages, whereby suppressing MCF-7 breast cancer cell line proliferation and VEGF-mediated angiogenesis. Moreover, A3 induced M1 macrophage polarization in the 4 T1 murine breast cancer model and effectively inhibited tumor growth and tumor angiogenesis. Collectively, these findings indicated that A3 induced M1 macrophages polarization to repress breast tumorigenesis via targeting the TLR4/NF-kappa B/MAPK signaling pathway. This study provides a rationale for utilizing traditional Chinese medicine ex-tracts in the immunotherapy of breast cancer. C1 [Yin, Li; Fan, Zeping; Liu, Peng; Chen, Lanying; Guan, Ziyi; Liu, Yahui; Luo, Yingying] Jiangxi Univ Tradit Chinese Med, Natl Pharmaceut Engn Ctr Solid Preparat Chinese H, Yangming Rd, Nanchang 330006, Jiangxi, Peoples R China. [Yin, Li; Fan, Zeping; Liu, Peng; Chen, Lanying; Guan, Ziyi; Liu, Yahui; Luo, Yingying] Key Lab Evaluat Antitumor Effect Chinese Med Stre, Nanchang 330006, Jiangxi, Peoples R China. C3 Jiangxi University of Traditional Chinese Medicine RP Chen, LY (corresponding author), Jiangxi Univ Tradit Chinese Med, Natl Pharmaceut Engn Ctr Solid Preparat Chinese H, Yangming Rd, Nanchang 330006, Jiangxi, Peoples R China. EM cly5831@163.com FU National Natural Science Founda-tion of China [81860720, 81460618, 81660683]; Project of Key Laboratory of Traditional Chinese Medicine in Jiangxi Province FX This study was supported by the National Natural Science Founda-tion of China (Grant Nos. 81860720, 81460618 and 81660683) , and the Project of Key Laboratory of Traditional Chinese Medicine in Jiangxi Province. 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Appl. Pharmacol. PD DEC 1 PY 2021 VL 432 AR 115755 DI 10.1016/j.taap.2021.115755 EA OCT 2021 PG 15 WC Pharmacology & Pharmacy; Toxicology WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy; Toxicology GA WS3AJ UT WOS:000715057600001 PM 34673087 DA 2026-03-26 ER PT J AU Zhao, Y Ding, Z Ge, WH Liu, JH Xu, X Cheng, R Zhang, JF AF Zhao, Yang Ding, Zhao Ge, Wenhao Liu, Junhao Xu, Xi Cheng, Rui Zhang, Jianfa TI Riclinoctaose Attenuates Renal Ischemia-Reperfusion Injury by the Regulation of Macrophage Polarization SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE riclinoctaose; ischemia-reperfusion; immunomodulatory; macrophage polarization; DC-SIGN ID KIDNEY INJURY; DC-SIGN; ISCHEMIA/REPERFUSION INJURY; CHITOSAN OLIGOSACCHARIDE; INTERLEUKIN-10; DOXYCYCLINE; MECHANISM AB Renal ischemia-reperfusion injury is a major trigger of acute kidney injury and leads to permanent renal impairment, and effective therapies remain unresolved. Riclinoctaose is an immunomodulatory octasaccharide composed of glucose and galactose monomers. Here we investigated whether riclinoctaose protects against renal ischemia-reperfusion injury. In mice, pretreatment with riclinoctaose significantly improved renal function, structure, and the inflammatory response after renal ischemia-reperfusion. Flow cytometry analysis revealed that riclinoctaose inhibited ischemia-reperfusion-induced M1 macrophage polarization and facilitated M2 macrophage recruitment into the kidneys. In isolated mouse bone marrow-derived macrophages, pretreatment with riclinoctaose promoted the macrophage polarization toward M2-like phenotype. The inhibitor of Nrf-2/HO-1 brusatol diminished the effects of riclinoctaose on macrophage polarization. In mice, intravenous injection with riclinoctaose-pretreated bone marrow-derived macrophages also protected against renal ischemia-reperfusion injury. Fluorescence-labeled riclinoctaose specifically bound to the membrane of macrophages. Interfering with mDC-SIGN blocked the riclinoctaose function on M2 polarization of macrophages, consequently impairing the renoprotective effect of riclinoctaose. Our results revealed that riclinoctaose is a potential therapeutic agent in preventing renal ischemia-reperfusion injury. C1 [Zhao, Yang; Ding, Zhao; Ge, Wenhao; Liu, Junhao; Xu, Xi; Cheng, Rui; Zhang, Jianfa] Nanjing Univ Sci & Technol, Ctr Mol Metab, Nanjing, Peoples R China. C3 Nanjing University of Science & Technology RP Cheng, R; Zhang, JF (corresponding author), Nanjing Univ Sci & Technol, Ctr Mol Metab, Nanjing, Peoples R China. EM chengrui@njust.edu.cn RI ; Cheng, Rui/AAK-2637-2021; Ding, Zhao/AAB-7187-2019 OI Liu, Junhao/0000-0002-5797-4469; FU National Natural Science Foundation of China (NSFC) [31861163004, 31871178]; Fundamental Research Funds for the Central Universities [30920031102] FX Funding This work was supported by the National Natural Science Foundation of China (NSFC) (No. 31861163004, 31871178) and the Fundamental Research Funds for the Central Universities (No. 30920031102). 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Pharmacol. PD OCT 13 PY 2021 VL 12 AR 745425 DI 10.3389/fphar.2021.745425 PG 16 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA WP6PY UT WOS:000713252300001 PM 34721034 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Azadpour, M Farajollahi, MM Dariushnejad, H Varzi, AM Varezardi, A Barati, M AF Azadpour, Mojgan Farajollahi, Mohammad Morad Dariushnejad, Hassan Varzi, Ali Mohammad Varezardi, Amir Barati, Mitra TI Effects of synthetic silymarin-PLGA nanoparticles on M2 polarization and inflammatory cytokines in LPS-treated murine peritoneal macrophages SO IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES LA English DT Article DE Cytokines; Nanoparticles; Peritoneal macrophages; PLGA compound; Silymarin ID DENDRITIC CELL; SEPSIS; INFECTION; INHIBITION; EXPRESSION; RESISTANCE; MONOCYTES; DELIVERY; GAMMA AB Objective(s): Silymarin (SM) is a natural antioxidant compound with good anti-inflammatory effects, but its poor water solubility restricts its usage. Today, nanomaterial compounds (such as PLGA Poly D, L-lactic-co-glycolic acid) can provide a proper drug delivery system and help improve the accessibility of bioactive compounds to cells and tissues. Materials and Methods: In this study, PLGA nanoparticles (NPs) containing SM (SM-PLGA) were synthesized and characterized and their biological effects were evaluated on M2 macrophage polarization to regulate inflammation. SM-PLGA NPs were fabricated by the oil in water emulsion (O/W) method. Macrophages (MQs) were isolated from mouse peritoneum by the cold RPMI lavage protocol. Primary mouse MQ cells were treated by SM and SM-PLGA NPs and then stimulated with lipopolysaccharide (LPS). M2 polarization was evaluated by measurements of cytokine secretion levels (TNF-alpha, IL1-beta, and IL-10), flow cytometry markers (F4/80, CD11b, CD38, and CD206), and the expression of specific proteins (M2 Ym1 and Fizz1). Results: SM-PLGA characterization showed that NPs were fabricated in the desired form. SM and SM-PLGA decreased pro-inflammatory cytokines (TNF-alpha and IL1-beta) and increased IL10 as an antiinflammatory cytokine. On the other hand, the M2-associated markers and proteins increased following treatment with SM and SM-PLGA. Post-hoc analysis indicated that these changes were more pronounced in the SM-PLGA group. Conclusion: This study revealed that SM-PLGA could markedly promote M2 polarization, thereby providing a valuable medical approach against sepsis and septic shock. C1 [Azadpour, Mojgan; Barati, Mitra] Iran Univ Med Sci, Inst Immunol & Infect Dis, Res Ctr Pediat Infect Dis, Tehran, Iran. [Farajollahi, Mohammad Morad] Iran Univ Med Sci, Sch Allied Med Sci, Dept Med Biotechnol, Tehran, Iran. [Dariushnejad, Hassan] Lorestan Univ Med Sci, Fac Med, Dept Med Biotechnol, Khorramabad, Iran. [Dariushnejad, Hassan; Varzi, Ali Mohammad; Varezardi, Amir] Lorestan Univ Med Sci, Razi Herbal Med Res Ctr, Khorramabad, Iran. C3 Iran University of Medical Sciences; Iran University of Medical Sciences; Lorestan University of Medical Sciences; Lorestan University of Medical Sciences RP Barati, M (corresponding author), Iran Univ Med Sci, Tehran, Iran. EM Mojganazadpour@gmail.com RI barati, mitra/O-6955-2018; AZADPOUR, Mozhgan/AAJ-2416-2020; Dariushnejad, Hassan/AAE-1614-2019 FU Iran University of Medical Sciences [95-01-131-28128] FX The results presented in this paper were part of a PhD student thesis. This research project was supported by Iran University of Medical Sciences [Project ID: 95-01-131-28128]. 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J. Basic Med. Sci. PD OCT PY 2021 VL 24 IS 10 BP 1446 EP 1454 DI 10.22038/IJBMS.2021.59312.13161 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA WC0YN UT WOS:000703990500016 PM 35096304 DA 2026-03-26 ER PT J AU Xu, L Wang, H Yu, QQ Ge, JR Zhang, XZ Mei, D Liang, FQ Cai, XY Zhu, Y Shu, JL Tai, Y Wei, W Zhang, LL AF Xu, Li Wang, Han Yu, Qian-qian Ge, Jin-ru Zhang, Xian-zheng Mei, Dan Liang, Fa-qin Cai, Xiao-yu Zhu, Yue Shu, Jin-ling Tai, Yu Wei, Wei Zhang, Ling-ling TI The monomer derivative of paeoniflorin inhibits macrophage pyroptosis via regulating TLR4/NLRP3/GSDMD signaling pathway in adjuvant arthritis rats SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Rheumatoid arthritis; Macrophage pyroptosis; Adjuvant arthritis; Monomer derivative of paeoniflorin; TLR4; NLRP3; GSDMD signaling pathway ID RHEUMATOID-ARTHRITIS; TACI-IG; INFLAMMASOMES; LYMPHOCYTES; MANAGEMENT; RECEPTOR; NSAIDS; DRUGS AB Objective: This study was aimed to investigate the effect of monomer derivative of paeoniflorin (MDP) on macrophage pyroptosis mediated by TLR4/NLRP3/GSDMD signaling pathway in adjuvant arthritis (AA) rats. Method: Wistar rats were divided into normal group, AA model group, MDP (50 mg/kg) group and MTX (0.5 mg/ kg) group. The expression of TLR4, NLRP3 and GSDMD in macrophage were detected by immunofluorescence assay. The expression of TLR4 and the ratio of macrophage pyroptosis were analyzed by flow cytometry. Cell morphology was observed by scanning electron microscopy. The cytokine levels of IL-18 and IL-1I3 were detected by ELISA. The expressions of proteins related to macrophage pyroptosis were detected by western blot. Results: MDP has a therapeutic effect on rats AA by reducing the secondary inflammation and improving pathological changes. The results of X-ray imaging and ultrasound images showed that MDP could inhibit bone erosion, soft tissue swelling, and joint space narrowing. Macrophage pyroptosis was found in secondary inflammation of AA rats. The expressions of TLR4, MyD88, NLRP3, Caspase-1, ASC, and GSDMD-N in macrophage were increased, the levels of IL-18 and IL-1I3 were enhanced, and the morphology of pyroptosis could be observed. MDP could inhibit macrophage polarization and macrophage pyroptosis, and down-regulated the cytokine levels of IL-18 and IL-1I3 in AA rats. MDP could regulate the M1/M2 ratio, decreased the ratio of macrophage pyroptosis and down-regulated the expressions of TLR4, MyD88, NLRP3, Caspase-1, ASC, and GSDMD-N in vivo and in vitro. Conclusion: Abnormal activation of TLR4/NLRP3/GSDMD signaling pathway may be involved in macrophage pyroptosis in AA rats. The therapeutic effect of MDP on AA rats is related to the inhibition of macrophage pyroptosis by regulating the TLR4/NLRP3/GSDMD signaling pathway. C1 [Xu, Li; Wang, Han; Yu, Qian-qian; Ge, Jin-ru; Zhang, Xian-zheng; Mei, Dan; Liang, Fa-qin; Cai, Xiao-yu; Zhu, Yue; Shu, Jin-ling; Tai, Yu; Wei, Wei; Zhang, Ling-ling] Anhui Med Univ, Anhui Collaborat Innovat Ctr Antiinflammatory & I, Key Lab Antiinflammatory & Immune Med, Inst Clin Pharmacol,Minist Educ,Ctr Rheumatoid Ar, Hefei 230032, Peoples R China. C3 Anhui Medical University RP Wei, W; Zhang, LL (corresponding author), Anhui Med Univ, Anhui Collaborat Innovat Ctr Antiinflammatory & I, Key Lab Antiinflammatory & Immune Med, Inst Clin Pharmacol,Minist Educ,Ctr Rheumatoid Ar, Hefei 230032, Peoples R China. EM wwei@ahmu.edu.cn; ll-zhang@hotmail.com RI wei, wei/HHR-8613-2022; zhang, lingling/HDM-2189-2022 FU National Natural Science Foundation of China [U1803129, 81973332, 81803538]; Popu-lation Health Special Project of Key Research and Development Plan of Anhui Province [202104j07020032] FX The study was supported by the National Natural Science Foundation of China (grant numbers U1803129, 81973332, 81803538) , The Popu-lation Health Special Project of Key Research and Development Plan of Anhui Province in 2021 (Number: 202104j07020032) . 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PD DEC PY 2021 VL 101 AR 108169 DI 10.1016/j.intimp.2021.108169 EA OCT 2021 PN A PG 12 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA WE4GK UT WOS:000705586000002 PM 34607227 DA 2026-03-26 ER PT J AU Tian, LL Zhao, JL Kang, JQ Guo, SB Zhang, NN Shang, L Zhang, YL Zhang, J Jiang, X Lin, Y AF Tian, Lianlian Zhao, Jun-Long Kang, Jian-Qin Guo, Shi-bo Zhang, Nini Shang, Lei Zhang, Ya-Long Zhang, Jian Jiang, Xun Lin, Yan TI Astragaloside IV Alleviates the Experimental DSS-Induced Colitis by Remodeling Macrophage Polarization Through STAT Signaling SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE inflammatory bowel disease; astragaloside IV (AS-IV); macrophages polarization; STAT signaling; pro-resolving macrophage ID DISEASE; JAK; TRANSDUCER; ACTIVATION; NETWORK; MICE AB Inflammatory bowel disease (IBD) is characterized by chronic and relapsing intestinal inflammation, which currently lacks safe and effective medicine. Some previous studies indicated that Astragaloside IV (AS-IV), a natural saponin extracted from the traditional Chinese medicine herb Ligusticum chuanxiong, alleviates the experimental colitis symptoms in vitro and in vivo. However, the mechanism of AS-IV on IBD remains unclear. Accumulating evidence suggests that M2-polarized intestinal macrophages play a pivotal role in IBD progression. Here, we found that AS-IV attenuated clinical activity of DSS-induced colitis that mimics human IBD and resulted in the phenotypic transition of macrophages from immature pro-inflammatory macrophages to mature pro-resolving macrophages. In vitro, the phenotype changes of macrophages were observed by qRT-PCR after bone marrow-derived macrophages (BMDMs) were induced to M1/M2 and incubated with AS-IV, respectively. In addition, AS-IV was effective in inhibiting pro-inflammatory macrophages and promoting the pro-resolving macrophages to ameliorate experimental colitis via the regulation of the STAT signaling pathway. Hence, we propose that AS-IV can ameliorate experimental colitis partially by modulating macrophage phenotype by remodeling the STAT signaling, which seems to have an essential function in the ability of AS-IV to alleviate the pathological progress of IBD.

C1 [Tian, Lianlian; Kang, Jian-Qin; Guo, Shi-bo; Zhang, Nini; Zhang, Ya-Long; Jiang, Xun; Lin, Yan] Air Force Med Univ, Tangdu Hosp, Dept Pediat, Xian, Peoples R China. [Zhao, Jun-Long] Air Force Med Univ, Dept Med Genet & Dev Biol, State Key Lab Canc Biol, Xian, Peoples R China. [Shang, Lei] Air Force Med Univ, Dept Hlth Stat, Xian, Peoples R China. [Shang, Lei] Air Force Med Univ, Key Lab Hazard Assessment & Control Special Opera, Minist Educ, Xian, Peoples R China. [Zhang, Jian] Air Force Med Univ, Dept Biochem & Mol Biol, State Key Lab Canc Biol, Xian, Peoples R China. C3 Air Force Medical University; Air Force Medical University; Air Force Medical University; Air Force Medical University; Air Force Medical University RP Jiang, X; Lin, Y (corresponding author), Air Force Med Univ, Tangdu Hosp, Dept Pediat, Xian, Peoples R China.; Zhang, J (corresponding author), Air Force Med Univ, Dept Biochem & Mol Biol, State Key Lab Canc Biol, Xian, Peoples R China. EM biozhangj@fmmu.edu.cn; jiangx@fmmu.edu.cn; yiyilin19800823@126.com RI ; 林, 燕/IAO-0230-2023 OI Jiang, Xun/0000-0002-3344-4797; Zhao, Jun-Long/0000-0002-6148-5641; FU National Natural Science Foundation of China [82000522, 81802841]; China Postdoctoral Science Foundation [2021M693944] FX This work was supported by the National Natural Science Foundation of China (82000522, 81802841) and the China Postdoctoral Science Foundation (2021M693944). 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Immunol. PD SEP 13 PY 2021 VL 12 AR 740565 DI 10.3389/fimmu.2021.740565 PG 14 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA WB7UP UT WOS:000703774800001 PM 34589089 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Wu, YX Jiang, FJ Liu, G Wang, YY Gao, ZQ Jin, SH Nie, YJ Chen, D Chen, JL Pang, QF AF Wu, Ya-Xian Jiang, Feng-Juan Liu, Gang Wang, Ying-Ying Gao, Zhi-Qi Jin, Si-Hao Nie, Yun-Juan Chen, Dan Chen, Jun-Liang Pang, Qing-Feng TI Dehydrocostus Lactone Attenuates Methicillin-Resistant Staphylococcus aureus-Induced Inflammation and Acute Lung Injury via Modulating Macrophage Polarization SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE Dehydrocostus lactone; LTA; MRSA; acute lung injury; macrophage polarization ID MAPK/NF-KAPPA-B; LIPOTEICHOIC ACID; ACTIVATION; PROTECTS; RESOLUTION; PLASTICITY; CELLS; MICE; NRF2 AB Dehydrocostus lactone (DHL), a natural sesquiterpene lactone isolated from the traditional Chinese herbs Saussurea lappa and Inula helenium L., has important anti-inflammatory properties used for treating colitis, fibrosis, and Gram-negative bacteria-induced acute lung injury (ALI). However, the effects of DHL on Gram-positive bacteria-induced macrophage activation and ALI remains unclear. In this study, we found that DHL inhibited the phosphorylation of p38 MAPK, the degradation of I kappa B alpha, and the activation and nuclear translocation of NF-kappa B p65, but enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of Nrf2 and HO-1 in lipoteichoic acid (LTA)-stimulated RAW264.7 cells and primary bone-marrow-derived macrophages (BMDMs). Given the critical role of the p38 MAPK/NF-kappa B and AMPK/Nrf2 signaling pathways in the balance of M1/M2 macrophage polarization and inflammation, we speculated that DHL would also have an effect on macrophage polarization. Further studies verified that DHL promoted M2 macrophage polarization and reduced M1 polarization, then resulted in a decreased inflammatory response. An in vivo study also revealed that DHL exhibited anti-inflammatory effects and ameliorated methicillin-resistant Staphylococcus aureus (MRSA)-induced ALI. In addition, DHL treatment significantly inhibited the p38 MAPK/NF-kappa B pathway and activated AMPK/Nrf2 signaling, leading to accelerated switching of macrophages from M1 to M2 in the MRSA-induced murine ALI model. Collectively, these data demonstrated that DHL can promote macrophage polarization to an anti-inflammatory M2 phenotype via interfering in p38 MAPK/NF-kappa B signaling, as well as activating the AMPK/Nrf2 pathway in vitro and in vivo. Our results suggested that DHL might be a novel candidate for treating inflammatory diseases caused by Gram-positive bacteria. C1 [Wu, Ya-Xian; Jiang, Feng-Juan; Liu, Gang; Wang, Ying-Ying; Gao, Zhi-Qi; Jin, Si-Hao; Nie, Yun-Juan; Chen, Dan; Chen, Jun-Liang; Pang, Qing-Feng] Jiangnan Univ, Wuxi Sch Med, Wuxi 214122, Jiangsu, Peoples R China. [Wu, Ya-Xian] Jiangnan Univ, Sch Food Sci & Technol, Wuxi 214122, Jiangsu, Peoples R China. C3 Jiangnan University; Jiangnan University RP Pang, QF (corresponding author), Jiangnan Univ, Wuxi Sch Med, Wuxi 214122, Jiangsu, Peoples R China. EM yaxianwu@jiangnan.edu.cn; jiangfj2020@foxmail.com; weiruishang@foxmail.com; wangyingying2021@foxmail.com; gaozhiqi277@foxmail.com; jinsihao123@foxmail.com; nieyunjuan@jiangnan.edu.cn; danchen09@foxmail.com; chenjunliang572@foxmail.com; qfpang@jiangnan.edu.cn RI ; Jin, Sihao/JWP-0431-2024; Liu, Gang/KRQ-2480-2024 OI Pang, Qing-feng/0000-0003-0679-4780; Nie, Yunjuan/0000-0002-6167-4258; Liu, Gang/0000-0003-2492-4833 FU National Natural Science Foundation of China [81871518, 81901522, 82100018]; China Postdoctoral Science Foundation [2020M671347, 2021M691292]; Fundamental Research Funds for the Central Universities [JUSRP11955]; Natural Science Foundation of Jiangsu Province [BK20200602] FX This study was supported by the National Natural Science Foundation of China (81871518, 81901522, and 82100018); the China Postdoctoral Science Foundation (2020M671347 and 2021M691292); the Fundamental Research Funds for the Central Universities (JUSRP11955); and the Natural Science Foundation of Jiangsu Province (BK20200602). 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J. Mol. Sci. PD SEP PY 2021 VL 22 IS 18 AR 9754 DI 10.3390/ijms22189754 PG 18 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry GA UV5LO UT WOS:000699519900001 PM 34575918 OA Green Submitted, gold DA 2026-03-26 ER PT J AU He, S Wang, SS Liu, SQ Li, Z Liu, X Wu, JF AF He, Shan Wang, Shangshang Liu, Suqing Li, Zheng Liu, Xiao Wu, Jinfeng TI Baicalein Potentiated M1 Macrophage Polarization in Cancer Through Targeting PI3Kγ/ NF-κB Signaling SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE baicalein; tumor-associated macrophages; polarization; PI3K gamma; NF-k B ID TUMOR-ASSOCIATED MACROPHAGES; BREAST-CANCER; IN-VITRO; DIFFERENTIATION; RESISTANCE; ACTIVATION; APOPTOSIS; AUTOPHAGY; PATHWAY AB Baicalein is one of the bioactive compounds extracted from Scutellaria baicalensis. Recent studies indicated the antitumor effects of baicalein, however, the underlying mechanisms are needed to be further determined. In this study, we found that baicalein could inhibit the tumor growth in mice models of breast cancer and melanoma and worked as an immunomodulator to promote the infiltration of tumor-associated macrophages (TAMs) and skew the TAMs towards the M1-like phenotype. Baicalein also induced M1-like phenotype polarization in THP-1-derived macrophages. Meanwhile, the expression of pro-inflammatory factors associated with M1 macrophages, including TNF-alpha, IL-1 beta, CXCL9 and CXCL10, were increased after baicalein treatment. Mechanistically, the RNA-seq data suggested that baicalein potentiated the M1 macrophage polarization via the NF-kappa B/TNF-alpha signaling pathway. ELISA and confocal microscopy assay confirmed that baicalein significantly induced the production of TNF-alpha and the activation of NF-kappa B, while TNF-alpha neutralization inhibited baicalein-induced macrophage polarization toward M1, and NF-kappa B P65 knock-down suppressed baicalein-induced TNF-alpha production in THP-1-derived macrophages. Phosphoinositide 3-kinase (PI3k) gamma has been reported as a key molecule in macrophage polarization, and inhibition of PI3K gamma activates the NF-kappa B-related inflammatory signals. Our pharmacological network analysis predicted that PI3K gamma might be one of the major targets of baicalein. The results from the docking program and surface plasmon resonance (SPR) confirmed that baicalein displayed good binding activity to PI3K gamma. We further found that baicalein not only exhibited a direct inhibitory effect on the protein kinase activity of PI3K gamma, but also reduced the mRNA and protein expression of PI3K gamma, indicating that baicalein might be a novel PI3K gamma inhibitor. In summary, baicalein mediated the TAMs skewing to M1-TAMs, and then retarded tumor growth. These effects, at least in part, were linked to the PI3K gamma/NF-kappa B signaling. C1 [He, Shan; Wang, Shangshang; Liu, Suqing; Li, Zheng; Liu, Xiao; Wu, Jinfeng] Fudan Univ, Huashan Hosp, Dept Dermatol, Shanghai, Peoples R China. C3 Fudan University RP Liu, X; Wu, JF (corresponding author), Fudan Univ, Huashan Hosp, Dept Dermatol, Shanghai, Peoples R China. EM wujinfeng21@163.com; liuxiao19922010@163.com RI he, shan/JUV-4092-2023 FU National Natural Science Foundation of China [81973582, 82003357]; Shanghai Science and Technology Committee [21YF1404500] FX Funding The present study was supported by grants from the National Natural Science Foundation of China (81973582 and 82003357) and the Shanghai Science and Technology Committee (21YF1404500). 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Pharmacol. PD AUG 25 PY 2021 VL 12 AR 743837 DI 10.3389/fphar.2021.743837 PG 11 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA XG1IQ UT WOS:000724514000001 PM 34512367 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Ren, AQ Wang, HJ Zhu, HY Ye, G Li, K Chen, DF Zeng, T Li, H AF Ren, An-qi Wang, Hui-jun Zhu, Hai-yan Ye, Guan Li, Kun Chen, Dao-feng Zeng, Tao Li, Hong TI Glycoproteins From Rabdosia japonica var. glaucocalyx Regulate Macrophage Polarization and Alleviate Lipopolysaccharide-Induced Acute Lung Injury in Mice via TLR4/NF-κB Pathway SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE Rabdosia japonica var glaucocalyx; glycoproteins; acute lung injury; macrophage polarization; inflammation; TLR4/NF-kappa B signal pathway ID POLYSACCHARIDES AB Background and Aims: Rabdosia japonica var. glaucocalyx is a traditional Chinese medicine (TCM) for various inflammatory diseases. This present work aimed to investigate the protective effects of R. japonica var. glaucocalyx glycoproteins on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the potential mechanism. Methods: Glycoproteins (XPS) were isolated from R. japonica var. glaucocalyx, and homogeneous glycoprotein (XPS5-1) was purified from XPS. ANA-1 cells were used to observe the effect of glycoproteins on the secretion of inflammatory mediators by enzyme-linked immunosorbent assay (ELISA). Flow cytometry assay, immunofluorescence assay, and Western blot analysis were performed to detect macrophage polarization in vitro. The ALI model was induced by LPS via intratracheal instillation, and XPS (20, 40, and 80 mg/kg) was administered intragastrically 2 h later. The mechanisms of XPS against ALI were investigated by Western blot, ELISA, and immunohistochemistry. Results: In vitro, XPS and XPS5-1 downregulated LPS-induced proinflammatory mediators production including tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-6, and nitric oxide (NO) and upregulated LPS-induced IL-10 secretion. The LPS-stimulated macrophage polarization was also modulated from M1 to M2. In vivo, XPS maintained pulmonary histology with significantly reducing protein concentration and numbers of mononuclear cells in bronchoalveolar lavage fluid (BALF). The level of IL-10 in BALF was upregulated by XPS treatment. The level of cytokines including TNF-alpha, IL-1 beta, and IL-6 was downregulated. XPS also decreased infiltration of macrophages and polymorphonuclear leukocytes (PMNs) in lung. XPS suppressed the expression of key proteins in the TLR4/NF-kappa B signal pathway. Conclusion: XPS was demonstrated to be a potential agent for treating ALI. Our findings might provide evidence supporting the traditional application of R. japonica var. glaucocalyx in inflammation-linked diseases. C1 [Ren, An-qi; Li, Hong] Fudan Univ, Sch Pharm, Dept Pharmacol, Shanghai, Peoples R China. [Wang, Hui-jun] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, MOE Key Lab Standardizat Chinese Med, Shanghai, Peoples R China. [Wang, Hui-jun] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, SATCM Key Lab New Resources & Qual Evaluat Chines, Shanghai, Peoples R China. [Zhu, Hai-yan] Fudan Univ, Dept Biol Med, Sch Pharm, Shanghai, Peoples R China. [Zhu, Hai-yan] Fudan Univ, Shanghai Engn Res Ctr Immuno Therapeut, Sch Pharm, Shanghai, Peoples R China. [Ye, Guan; Li, Kun] Shanghai Pharmaceut Holding Co Ltd, Cent Res Inst, Shanghai, Peoples R China. [Chen, Dao-feng] Fudan Univ, Sch Pharm, Dept Pharmacognosy, Shanghai, Peoples R China. [Zeng, Tao] Fudan Univ, Clin Trial Inst, Obstet & Gynecol Hosp, Shanghai, Peoples R China. C3 Fudan University; Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine; Fudan University; Fudan University; Fudan University; Fudan University RP Li, H (corresponding author), Fudan Univ, Sch Pharm, Dept Pharmacol, Shanghai, Peoples R China.; Zeng, T (corresponding author), Fudan Univ, Clin Trial Inst, Obstet & Gynecol Hosp, Shanghai, Peoples R China. EM zengtao1283@163.com; lxzhang@shmu.edu.cn RI hong, li/T-6392-2019; Wang, Huijun/MTB-0279-2025 OI Wang, Huijun/0000-0001-6319-498X FU Ministry of Science and Technology of China [2019ZX09735001]; Natural Science Foundation of Shanghai [20ZR1458100]; Science and Technology Commission of Shanghai Municipality [15DZ1900104] FX This work was funded by the Ministry of Science and Technology of China (Grants Nos. 2019ZX09735001), Natural Science Foundation of Shanghai (No. 20ZR1458100), and Science and Technology Commission of Shanghai Municipality (No. 15DZ1900104). 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PD JUL 21 PY 2021 VL 12 AR 693298 DI 10.3389/fphar.2021.693298 PG 14 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA TU1FD UT WOS:000680784700001 PM 34366849 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Yang, R Xie, Y Li, Q Ye, YY Shi, YY Zhao, XD Wu, CY Xu, YY Wang, R Zhang, Y Yang, XJ Han, XH Liu, S AF Yang, Rui Xie, Ying Li, Qiong Ye, Yiyi Shi, Youyang Zhao, Xiangdong Wu, Chunyu Xu, Yiyun Wang, Rui Zhang, Yang Yang, Xiaojuan Han, Xianghui Liu, Sheng TI Ruyiping extract reduces lung metastasis in triple negative breast cancer by regulating macrophage polarization SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE Triple  negative breast cancer; Lung metastasis; Ruyiping extract; Macrophage  polarization ID TRADITIONAL CHINESE MEDICINE; ALTERNATIVE ACTIVATION; INTERVENTION; METABOLISM; SURVIVAL AB Lung metastasis of Triple-negative breast cancer (TNBC) causes severe breath-related events and poor prognosis. Ruyiping (RYP), a traditional Chinese medicine prescription, is used to treat breast cancer lung metastasis in clinical practice. This study was to explore the anti-lung-metastatic activities and mechanism of RYP extract by regulating macrophage polarization. The results showed that RYP can inhibit the viability and induce the apoptosis of TNBC cells. In in vitro experiments, RYP significantly inhibited the invasion and migration ability of TNBC cells promoted by M2, the subtype of macrophage which increased TNBC metastasis related genes. In in vivo experiments, RYP reduced the TNBC progression and lung metastasis. M2/M1 ration in the lung and M2 in the tumor was reduced by RYP, as well as M2 master regulator Stat6. Therefore, RYP extract may exhibit anti-lung metastasis function by reducing M2 in both tumor and lung through reducing Stat6. C1 [Yang, Rui; Xie, Ying; Ye, Yiyi; Shi, Youyang; Wu, Chunyu; Xu, Yiyun; Wang, Rui; Zhang, Yang; Yang, Xiaojuan; Han, Xianghui; Liu, Sheng] Shanghai Univ Tradit Chinese Med, Longhua Hosp, Inst Chinese Tradit Surg, Shanghai 200032, Peoples R China. [Li, Qiong] Shanghai Univ Tradit Chinese Med, Yueyang Hosp Tradit Chinese & Western Med, Dept Breast Surg, Shanghai 200000, Peoples R China. [Zhao, Xiangdong] Shenzhen Tradit Chinese Med Hosp, Dept Anus & Intestine Surg, Shenzhen 518000, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine; Shenzhen Traditional Chinese Medicine Hospital RP Han, XH; Liu, S (corresponding author), Shanghai Univ Tradit Chinese Med, Longhua Hosp, Inst Chinese Tradit Surg, Shanghai 200032, Peoples R China. EM hanxianghui1106@163.com; lshtcm@163.com RI ; Xie, Ying/PCT-1162-2025; wang, rui/JAC-6240-2023; Wu, Chunyu/LBI-5378-2024 OI Liu, Sheng/0000-0003-2090-6929; Wu, Chunyu/0009-0006-8834-3359 FU National Natural Science Foundation of China [81774308, 81573973]; Intelligent Medical Research Project of Shanghai Municipal Health and Family Planning Commission [2018ZHYL0206]; Longhua Hospital [LYTD-79] FX This work was supported by National Natural Science Foundation of China (No. 81774308, 81573973) . Intelligent Medical Research Project of Shanghai Municipal Health and Family Planning Commission (No. 2018ZHYL0206) . Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine (No. LYTD-79) . 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Pharmacother. PD SEP PY 2021 VL 141 AR 111883 DI 10.1016/j.biopha.2021.111883 EA JUL 2021 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA UR7IW UT WOS:000696919300006 PM 34246955 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Xian, HC Li, JY Zhang, YM Li, DT Zhu, YN Li, SY Tan, ZL Lin, ZB Li, XJ Pan, Y AF Xian, Haocheng Li, Jiayi Zhang, Yimeng Li, Ditian Zhu, Yinan Li, Siyan Tan, Zhelun Lin, Zhibin Li, Xuejun Pan, Yan TI Antimetastatic Effects of Ganoderma lucidum Polysaccharide Peptide on B16-F10-luc-G5 Melanoma Mice With Sleep Fragmentation SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE Ganoderma lucidum polysaccharide peptide; sleep fragmentation; tumor metastasis; proteomics; gut microbiota ID TUMOR-ASSOCIATED MACROPHAGES; NIGHT-SHIFT WORK; CANCER; ANTITUMOR; APNEA; ASSOCIATION; PROGRESSION; METASTASIS; INHIBITION; DISRUPTION AB Y Ganoderma lucidum (Lingzhi) polysaccharide peptide (GL-pp) is a component of the globally acknowledged traditional Chinese medicine Ganoderma lucidum; Ganoderma lucidum is known for its sedative, hypnotic, immune regulatory, antitumor, and other pharmacological effects. In recent years, sleep disorders have been linked to many diseases and human body disorders, including cancer. Some experimental studies in mice found that sleep fragmentation could promote tumor development and progression. However, effects on GL-pp on tumor metastasis under circumstances of sleep disorders have rarely been studied. Thus, in this study, we used mice with sleep fragmentation (SF) bearing B16-F10-luc-G5 melanoma tumors to investigate the effect of SF on melanoma metastasis. Furthermore, we investigated the antitumor and antimetastatic effects of GL-pp (80 mg/kg) in mice suffering from SF and bearing B16-F10-luc-G5. Then, whole proteomics was used to analyze the differences in protein expression in the lung tissue between SF mice bearing B16-F10-luc-G5 with and without GL-pp administration. High-throughput pyrosequencing of 16S rRNA was also used to analyze the impact of GL-pp on the gut microbiota composition in SF mice bearing B16-F10-luc-G5. Last, the effects of GL-pp on macrophage polarization and TNF-alpha serum levels were detected. Collectively, we found that SF significantly facilitated the B16-F10-luc-G5 melanoma tumor metastasis in mice, while GL-pp significantly reduced B16-F10-luc-G5 melanoma tumor metastasis under the condition of SF, in which proteomics and gut microbiota had been changed greatly. C1 [Pan, Yan] Peking Univ, Dept Pharmacol, Sch Basic Med Sci, Hlth Sci Ctr, Beijing, Peoples R China. Peking Univ, Beijing Key Lab Tumor Syst Biol, Beijing, Peoples R China. C3 Peking University; Peking University RP Pan, Y (corresponding author), Peking Univ, Dept Pharmacol, Sch Basic Med Sci, Hlth Sci Ctr, Beijing, Peoples R China. 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Pharmacol. PD JUL 8 PY 2021 VL 12 AR 650216 DI 10.3389/fphar.2021.650216 PG 16 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA TP3QA UT WOS:000677507100001 PM 34305583 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Chen, JB Wang, HJ Jia, LL He, J Li, Y Liu, H Wu, RX Qiu, YY Zhan, YP Yuan, ZT Cao, YJ Li, W Xu, K Yin, PH AF Chen, Jinbao Wang, Haijing Jia, Linlin He, Jing Li, Yue Liu, Huan Wu, Ruixin Qiu, Yanyan Zhan, Yueping Yuan, Zeting Cao, Yijun Li, Wei Xu, Ke Yin, Peihao TI Bufalin targets the SRC-3/MIF pathway in chemoresistant cells to regulate M2 macrophage polarization in colorectal cancer SO CANCER LETTERS LA English DT Article DE Colorectal cancer; Bufalin; Oxaliplatin resistance; SRC-3; MIF; Tumour microenvironment ID TUMOR-ASSOCIATED MACROPHAGES; MIGRATION INHIBITORY FACTOR; LUNG-CANCER; CINOBUFAGIN; SURVIVAL; AIB1 AB M2-polarized macrophages are one of critical factors in tumour chemoresistance. An increasing number of studies have shown that M2 macrophage polarization can be promoted by chemoresistance. A large number of evidences indicate that Bufalin has significant antitumour effect, previous studies have found that Bufalin can reduce the polarization of M2 macrophages to play an anti-tumour effect in vivo, but the mechanism remains unclear. In our study, we found that Bufalin reduced the polarization of M2 macrophages induced by chemoresistant cells both in vivo and in vitro; however, Bufalin had no obvious direct effect on M2 macrophage polarization. Furthermore, we demonstrated that Bufalin targeted the SRC-3 protein to reduce MIF release in chemoresistant cells in order to regulate the polarization of M2 macrophages.& nbsp; More interestingly, we also found that Cinobufacini, Bufalin is its main active monomer, which its could regulate the polarization of M2 macrophages to enhance the anti-tumour effect of oxaliplatin in vivo and in the clinic. Overall, this study provides a theoretical basis for the clinical application of drugs containing Bufalin as the main active ingredient in combination with established chemotherapy for the treatment of colorectal cancer. C1 [Chen, Jinbao; Wang, Haijing; Jia, Linlin; He, Jing; Li, Yue; Liu, Huan; Wu, Ruixin; Qiu, Yanyan; Zhan, Yueping; Yuan, Zeting; Li, Wei; Xu, Ke; Yin, Peihao] Shanghai Univ Tradit Chinese Med, Putuo Hosp, Intervent Canc Inst Chinese Integrat Med, Shanghai 200062, Peoples R China. [Xu, Ke; Yin, Peihao] Anhui Med Univ, Shanghai Putuo Cent Sch Clin Med, Hefei 230032, Anhui, Peoples R China. [Cao, Yijun; Li, Wei; Yin, Peihao] Shanghai Univ Tradit Chinese Med, Putuo Hosp, Dept Gen Surg, Shanghai 200062, Peoples R China. [Xu, Ke] Shanghai Univ, Inst Translat Med, Shanghai 200444, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine; Anhui Medical University; Shanghai University of Traditional Chinese Medicine; Shanghai University RP Yin, PH (corresponding author), Shanghai Univ Tradit Chinese Med, Putuo Hosp, Intervent Canc Inst Chinese Integrat Med, Shanghai 200062, Peoples R China.; Li, W (corresponding author), Shanghai Univ Tradit Chinese Med, Putuo Hosp, Dept Gen Surg, Shanghai 200062, Peoples R China.; Xu, K (corresponding author), Shanghai Univ, Inst Translat Med, Shanghai 200444, Peoples R China. EM cjb17317156680@163.com; wanghj0307@163.com; liwei1511972@163.com; cola519@163.com; yinpeihao@shutcm.edu.cn RI Schneider, Claus/H-7453-2012; jia, linlin/NIU-8117-2025; Wang, Haijing/ODJ-1350-2025; Xu, Ke/HGC-1204-2022; Xu, Ke/J-2781-2015 OI Zhan, Yueping/0000-0002-1282-0052; Xu, Ke/0000-0002-3942-2767; Yin, Peihao/0009-0001-1496-1107; Xu, Ke/0000-0002-3942-2767 FU National Natural Science Foundation of China [81873137]; Clinical Specialized Disease Construction Project of Shanghai Putuo District Municipal Health Commission [2020tszb03]; Natural Science Foundation of Shanghai [20ZR1450500]; Putuo District Health system [ptkwws201905]; Independent Innovation Project in Putuo District [ptkwws201701] FX This project was sponsored by the National Natural Science Foundation of China (81873137), Clinical Specialized Disease Construction Project of Shanghai Putuo District Municipal Health Commission (NO. 2020tszb03), Natural Science Foundation of Shanghai (20ZR1450500), Putuo District Health system (ptkwws201905) and Independent Innovation Project in Putuo District (ptkwws201701). 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PD AUG 10 PY 2021 VL 513 BP 63 EP 74 DI 10.1016/j.canlet.2021.05.008 EA MAY 2021 PG 12 WC Oncology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology GA SP7MO UT WOS:000659849200002 PM 34000344 DA 2026-03-26 ER PT J AU Li, JH Sun, ZY Luo, G Wang, S Cui, HM Yao, ZX Xiong, H He, YW Qian, Y Fan, CY AF Li, Juehong Sun, Ziyang Luo, Gang Wang, Shuo Cui, Haomin Yao, Zhixiao Xiong, Hao He, Yunwei Qian, Yun Fan, Cunyi TI Quercetin Attenuates Trauma-Induced Heterotopic Ossification by Tuning Immune Cell Infiltration and Related Inflammatory Insult SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE quercetin; heterotopic ossification; SIRT1; mast cells; macrophages AB Heterotopic ossification (HO) is one of the most intractable disorders following musculoskeletal injury and is characterized by the ectopic presence of bone tissue in the soft tissue leading to severe loss of function in the extremities. Recent studies have indicated that immune cell infiltration and inflammation are involved in aberrant bone formation. In this study, we found increased monocyte/macrophage and mast cell accumulation during early HO progression. Macrophage depletion by clodronate liposomes and mast cell stabilization by cromolyn sodium significantly impeded HO formation. Therefore, we proposed that the dietary phytochemical quercetin could also suppress immune cell recruitment and related inflammatory responses to prevent HO. As expected, quercetin inhibited the monocyte-to-macrophage transition, macrophage polarization, and mast cell activation in vitro in a dose-dependent manner. Using a murine burn/tenotomy model, we also demonstrated that quercetin attenuated inflammatory responses and HO in vivo. Furthermore, elevated SIRT1 and decreased acetylated NF kappa B p65 expression were responsible for the mechanism of quercetin, and the beneficial effects of quercetin were reversed by the SIRT1 antagonist EX527 and mimicked by the SIRT agonist SRT1720. The findings in this study suggest that targeting monocyte/macrophage and mast cell activities may represent an attractive approach for therapeutic intervention of HO and that quercetin may serve as a promising therapeutic candidate for the treatment of trauma-induced HO by modulating SIRT1/NF kappa B signaling. C1 [Li, Juehong; Sun, Ziyang; Luo, Gang; Wang, Shuo; Cui, Haomin; Yao, Zhixiao; Xiong, Hao; He, Yunwei; Qian, Yun; Fan, Cunyi] Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, Dept Orthopaed Surg, Shanghai, Peoples R China. [Li, Juehong; Sun, Ziyang; Luo, Gang; Wang, Shuo; Cui, Haomin; Yao, Zhixiao; Xiong, Hao; He, Yunwei; Qian, Yun; Fan, Cunyi] Shanghai Jiao Tong Univ, Sch Med, Youth Sci & Technol Innovat Studio, Shanghai, Peoples R China. C3 Shanghai Jiao Tong University; Shanghai Jiao Tong University RP Qian, Y; Fan, CY (corresponding author), Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, Dept Orthopaed Surg, Shanghai, Peoples R China.; Qian, Y; Fan, CY (corresponding author), Shanghai Jiao Tong Univ, Sch Med, Youth Sci & Technol Innovat Studio, Shanghai, Peoples R China. EM lollipopcloudland@foxmail.com; cyfan@sjtu.edu.cn RI Qian, Yun/U-9529-2019; fan, cunyi/ABI-7199-2020; Sun, Ziyang/M-1479-2019 OI Qian, Yun/0000-0003-1600-5693; fan, cunyi/0000-0002-7854-5233; Sun, Ziyang/0000-0002-8673-9521; wang, shuo/0000-0002-5151-6176 FU National Natural Science Foundation of China [81830076, 82002290, 81672146]; Shanghai Sailing Program [20YF1436000]; Science and Technology Development Fund of Shanghai Pudong New Area [PKJ2018Y55, PKJ2018-Y52]; Science Foundation of Shanghai Health and Family Planning Commission [20174Y0225] FX This work was supported by the National Natural Science Foundation of China (81830076, 82002290, 81672146), Shanghai Sailing Program (No. 20YF1436000), Science and Technology Development Fund of Shanghai Pudong New Area (PKJ2018Y55, PKJ2018-Y52) and a grant from Science Foundation of Shanghai Health and Family Planning Commission (20174Y0225). 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TRANSL RES, V12, P2062 Zhang X, 2016, CELL PHYSIOL BIOCHEM, V40, P104, DOI 10.1159/000452528 NR 72 TC 60 Z9 64 U1 2 U2 25 PU FRONTIERS MEDIA SA PI LAUSANNE PA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PD MAY 20 PY 2021 VL 12 AR 649285 DI 10.3389/fimmu.2021.649285 PG 22 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA SM0QR UT WOS:000657318100001 PM 34093537 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Chen, Q Qi, X Zhang, WW Zhang, YH Bi, YH Meng, QH Bian, HM Li, Y AF Chen, Qi Qi, Xu Zhang, Weiwei Zhang, Yuhan Bi, Yunhui Meng, Qinghai Bian, Huimin Li, Yu TI Catalpol Inhibits Macrophage Polarization and Prevents Postmenopausal Atherosclerosis Through Regulating Estrogen Receptor Alpha SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE catalpol; postmenopausal atherosclerosis; macrophage polarization; estrogen receptor; inflammation; oxidatie stress ID ENDOTHELIAL-CELL APOPTOSIS; OXIDATIVE STRESS; INFLAMMATION; HOMEOSTASIS; ACTIVATION; INJURY AB Lacking estrogen increases the risk of atherosclerosis (AS) in postmenopausal women. Inflammation plays a vital role in the pathological process of AS, and macrophages are closely related to inflammation. Catalpol is an iridoid glucoside extracted from the fresh roots of the traditional Chinese herb Rehmanniae radix preparata. In this study, we aimed to evaluate the effects of catalpol on macrophage polarization and postmenopausal AS. In addition, we investigated whether the mechanism of catalpol was dependent on regulating the expression of estrogen receptors (ERs). In vitro, lipopolysaccharides (LPS) and interferon-gamma (IFN-gamma) were applied to induce M1 macrophage polarization. In vivo, the ApoE(-/-) mice were fed with a high-fat diet to induce AS, and ovariectomy was operated to mimic the estrogen cessation. We demonstrated catalpol inhibited M1 macrophage polarization induced by LPS and INF-gamma, and eliminated lipid accumulation in postmenopausal AS mice. Catalpol not only suppressed the inflammatory response but also reduced the level of oxidative stress. Then, ERs (ER alpha and ER beta) inhibitors and ER alpha siRNA were also applied in confirming that the protective effect of catalpol was mediated by ER alpha, rather than ER beta. In conclusion, catalpol significantly inhibited macrophage polarization and prevented postmenopausal AS by increasing ER alpha expression. C1 [Chen, Qi; Zhang, Weiwei; Zhang, Yuhan; Bi, Yunhui; Meng, Qinghai; Bian, Huimin] Nanjing Univ Chinese Med, Sch Pharm, Nanjing, Peoples R China. [Li, Yu] Nanjing Med Univ, Affiliated Hosp 1, Dept Resp Med, Nanjing, Peoples R China. [Bian, Huimin] Nanjing Univ Chinese Med, Jiangsu Key Lab Pharmacol & Safety Evaluat Chines, Nanjing, Peoples R China. [Qi, Xu] Nanjing Univ Chinese Med, Sch Med & Life Sci, Nanjing, Peoples R China. C3 Nanjing University of Chinese Medicine; Nanjing Medical University; Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine RP Bian, HM (corresponding author), Nanjing Univ Chinese Med, Sch Pharm, Nanjing, Peoples R China.; Li, Y (corresponding author), Nanjing Med Univ, Affiliated Hosp 1, Dept Resp Med, Nanjing, Peoples R China.; Bian, HM (corresponding author), Nanjing Univ Chinese Med, Jiangsu Key Lab Pharmacol & Safety Evaluat Chines, Nanjing, Peoples R China. EM hmbian@sina.com; liyu@njucm.edu.cn RI zhang, yuhan/HLH-1222-2023; Chen, Qi/LXA-5480-2024 OI Meng, Qinghai/0000-0001-8039-4713; FU National Natural Science Foundation of China [81174029]; Open Project Program of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medicine [JKLPSE 201809]; Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD); Qing Lan Project; 14th "Six talent peaks" project in Jiangsu Province [WSN-015]; "Six One Project" of Jiangsu commission of health [LGY2018054] FX This work was supported by the National Natural Science Foundation of China (No. 81174029), the Open Project Program of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medicine (JKLPSE 201809), the Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), the Qing Lan Project, the 14th "Six talent peaks" project in Jiangsu Province (WSN-015) and "Six One Project" of Jiangsu commission of health (LGY2018054). 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Pharmacol. PD APR 30 PY 2021 VL 12 AR 655081 DI 10.3389/fphar.2021.655081 PG 16 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA SB5KX UT WOS:000650034000001 PM 33995075 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Yang, J Chen, G Guo, TW Qin, WY Jia, P AF Yang, Juan Chen, Gang Guo, Ting-Wang Qin, Wen-Yi Jia, Ping TI Simiao Wan attenuates monosodium urate crystal-induced arthritis in rats through contributing to macrophage M2 polarization SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Simiao Wan; Gouty arthritis; MSU-Induced arthritis; Macrophage polarization ID GOUTY-ARTHRITIS; IN-VIVO; MODEL; EXPRESSION; RESOLUTION AB Ethnopharmacological relevance: Simiao Wan (SMW) is a classical traditional Chinese medicine (TCM) prescription to empirically treat gouty arthritis (GA) in TCM clinical practice. However, the potential mechanisms of SMW on GA are not fully evaluated. Aim of study: The aim of this study is to investigate the role of macrophage polarization in the anti-GA activity of SMW. Materials and methods: Rats were intragastricly treated with SMW for consecutive 7 days. On day 6, monosodium urate (MSU) crystal-induced arthritis (MIA) in the ankle joint was prepared. Paw volume, gait score and histological score were measured. Levels of interleukin (IL)-1 beta and IL-10 in serum were detected by enzyme-linked immunosorbent assay. Expressions of inducible nitric oxide synthase (iNOS), arginase (Arg)-1, phosphorylated (p)-p65, inhibitor of nuclear factor (NF)-xB (IxB)alpha, p-signal transducer and transcription activator (STAT)3 and pJanus kinase (JAK)2 in synovial tissues were determined by Western blot. Results: The elevated paw volume, gait score and histological score in MIA rats were significantly decreased by SMW treatment. Meanwhile, SMW significantly decreased the IL-1 beta level and increased the IL-10 level in serum of MIA rats. Furthermore, SMW reduced the expressions of iNOS, p-p65 and enhanced the expressions of Arg-1, IxB alpha, p-STAT3 and p-JAK2 in synovial tissues of MIA rats. Conclusions: The results suggest that SMW attenuates the inflammation in MIA rats through promoting macrophage M2 polarization. C1 [Yang, Juan; Qin, Wen-Yi; Jia, Ping] Chongqing Med Univ, Dept Combinat Chinese & Western Med, Affiliated Hosp 1, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China. [Chen, Gang; Guo, Ting-Wang] Chongqing Technol & Business Univ, Coll Environm & Resources, Key Lab Nat Med Res, Chongqing Educ Commiss, Chongqing 400067, Peoples R China. C3 Chongqing Medical University; Chongqing Technology & Business University RP Jia, P (corresponding author), Chongqing Med Univ, Dept Combinat Chinese & Western Med, Affiliated Hosp 1, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China. EM jiaping008@163.com FU Key Program of Health Commission of Chongqing City [ZY201801008]; National Natural Science Foundation of China [81503420]; Key Laboratory of Natural Medicine Research of Chongqing Education Commission [KFJJ2018088] FX This work was supported by the Key Program of Health Commission of Chongqing City (ZY201801008), National Natural Science Foundation of China (81503420) and Key Laboratory of Natural Medicine Research of Chongqing Education Commission (KFJJ2018088). 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Ethnopharmacol. PD JUL 15 PY 2021 VL 275 AR 114123 DI 10.1016/j.jep.2021.114123 EA APR 2021 PG 7 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA SM5NR UT WOS:000657652500004 PM 33894285 DA 2026-03-26 ER PT J AU Deng, XX Jiao, YN Hao, HF Xue, D Bai, CC Han, SY AF Deng, Xin-Xin Jiao, Yan-Na Hao, Hui-Feng Xue, Dong Bai, Chang-Cai Han, Shu-Yan TI Taraxacum mongolicum extract inhibited malignant phenotype of triple-negative breast cancer cells in tumor-associated macrophages microenvironment through suppressing IL-10/STAT3/PD-L1 signaling pathways SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Triple-negative breast cancer; Taraxacum mongolicum; Tumor-associated macrophages; IL-10; STAT3; PD-L1 ID EXPRESSION; CHEMOTHERAPY AB Ethnopharmacological relevance: Triple-negative breast cancer (TNBC) is the most aggressive and the worst prognosis breast cancer with limited treatment options. Taraxacum mongolicum (also called dandelion) is a traditional Chinese medicine has been used to treat mastitis, breast abscess, and hyperplasia of mammary glands since ancient times. In modern pharmacological research, dandelion has been proven with anti-breast cancer activities. We previously reported that dandelion extract could induce apoptosis in TNBC cells. However, its antitumor effects and mechanisms in the tumor microenvironment have not yet been elucidated. Aim of the study: Tumor-associated macrophages (TAMs) play an important role in regulating the interaction between tumor cells and the immune system. The present study aimed to investigate the effects and mechanisms of dandelion extract on TNBC cells under the microenvironment of TAMs, as well as its influence on the polarization of M2 macrophages. Materials and methods: M2 macrophages were induced by phorbol-12-myristate 13-acetate (PMA) and interleukin 4 (IL-4), and verified by flow cytometry, quantitative RT-PCR (qRT-PCR), Western blotting, and ELISA. MDA-MB231 and MDA-MB-468 TNBC cells were co-cultured with the supernatant of M2 macrophage which providing the TAMs microenvironment. The antitumor activity of dandelion extract in TNBC cells was evaluated by MTT assay. The invasive and migratory capacity of TNBC cells was measured by transwell assays. The expression of protein and gene was assessed by Western blotting and qRT-PCR, respectively. Results: TAMs microenvironment promoted the proliferation, migration, and invasion of TNBC cells. However, dandelion extract inhibited the malignant property of MDA-MB-231 and MDA-MB-468 cells induced by TAMs. Both of TAMs and IL-10 caused STAT3 activation and PD-L1 higher expression, the immunosuppressive molecules in TNBC cells, and this effect can be attenuated by IL-10 neutralizing antibody. Dandelion extract exerted inhibition on STAT3 and PD-L1 in TNBC cells under TAMs microenvironment. Furthermore, in M2 macrophages, dandelion extract remarkably promoted the expression of M1-like marker TNF-alpha, IL-8, and iNOS, but reduced M2-like marker IL-10, CD206, Arginase-1, and TGF-beta. Conclusion: Dandelion extract inhibited the proliferation, migration and invasion of TNBC cells in TAMs microenvironment through suppressing IL-10/STAT3/PD-L1 immunosuppressive signaling pathway. Furthermore, dandelion extract promoted the polarization of macrophages from M2 to M1 phenotype. Thus, our results indicated that dandelion may serve as a promising therapeutic strategy for TNBC by modulating tumor immune microenvironment. C1 [Deng, Xin-Xin; Jiao, Yan-Na; Hao, Hui-Feng; Xue, Dong; Han, Shu-Yan] Peking Univ, Dept Integrat Chinese & Western Med, Key Lab Carcinogenesis & Translat Res, Minist Educ,Canc Hosp & Inst, Beijing 100142, Peoples R China. [Deng, Xin-Xin; Bai, Chang-Cai] Ningxia Med Univ, Ningxia Res Ctr Modern Hui Med Engn & Technol, Key Lab Hui Ethn Med Modernizat, Minist Educ,Pharm Coll, Yinchuan 750004, Ningxia, Peoples R China. C3 Peking University; Ningxia Medical University RP Xue, D; Han, SY (corresponding author), Peking Univ, Dept Integrat Chinese & Western Med, Canc Hosp & Inst, 52 Fucheng Rd, Beijing 100142, Peoples R China.; Bai, CC (corresponding author), Ningxia Med Univ, Pharm Coll, 1160 Shengli St, Yinchuan 750004, Ningxia, Peoples R China. EM xuedong123321@hotmail.com; changcaibai@163.com; shuyanhan@bjmu.edu.cn RI Han, Shuyan/IYS-8544-2023; Hao, Huifeng/HOC-3848-2023 OI Hao, Huifeng/0000-0003-3396-1759 FU National Natural Science Foundation of China [81873054, 82074062] FX This study was supported by the National Natural Science Foundation of China (Grant No. 81873054, 82074062) . 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Ethnopharmacol. PD JUN 28 PY 2021 VL 274 AR 113978 DI 10.1016/j.jep.2021.113978 EA MAR 2021 PG 11 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA RY2CH UT WOS:000647724700001 PM 33716082 OA hybrid DA 2026-03-26 ER PT J AU Song, M Li, ZH Gu, HS Tang, RY Zhang, R Zhu, YL Liu, JL Zhang, JJ Wang, LY AF Song, Ming Li, Zhen-hao Gu, Hong-shun Tang, Ru-ying Zhang, Rui Zhu, Ying-li Liu, Jin-lian Zhang, Jian-jun Wang, Lin-yuan TI Ganoderma lucidum Spore Polysaccharide Inhibits the Growth of Hepatocellular Carcinoma Cells by Altering Macrophage Polarity and Induction of Apoptosis SO JOURNAL OF IMMUNOLOGY RESEARCH LA English DT Article AB Background. Ganoderma lucidum has certain components with known pharmacological effects, including strengthening immunity and anti-inflammatory activity. G. lucidum seeds inherit all its biological characteristics. G. lucidum spore polysaccharide (GLSP) is the main active ingredient to enhance these effects. However, its specific biological mechanisms are not exact. Our research is aimed at revealing the specific biological mechanism of GLSP to enhance immunity and inhibit the growth of H22 hepatocellular carcinoma cells. Methods. We extracted primary macrophages (Mo) from BALB/c mice and treated them with GLSP (800 mu g/mL, 400 mu g/mL, and 200 mu g/mL) to observe its effects on macrophage polarization and cytokine secretion. We used GLSP and GLSP-intervened macrophage supernatant to treat H22 tumor cells and observed their effects using MTT and flow cytometry. Moreover, real-time fluorescent quantitative PCR and western blotting were used to observe the effect of GLSP-intervened macrophage supernatant on the PI3K/AKT and mitochondrial apoptosis pathways. Results. In this study, GLSP promoted the polarization of primary macrophages to M1 type and the upregulation of some cytokines such as TNF-alpha, IL-1 beta, IL-6, and TGF-beta 1. The MTT assay revealed that GLSP+Mo at 400 mu g/mL and 800 mu g/mL significantly inhibited H22 cell proliferation in a dose-dependent manner. Flow cytometry analysis revealed that GLSP+Mo induced apoptosis and cell cycle arrest at the G2/M phase, associated with the expression of critical genes and proteins (PI3K, p-AKT, BCL-2, BAX, and caspase-9) that regulate the PI3K/AKT pathway and apoptosis. GLSP reshapes the tumor microenvironment by activating macrophages, promotes the polarization of primary macrophages to M1 type, and promotes the secretion of various inflammatory factors and cytokines. Conclusion. Therefore, as a natural nutrient, GLSP is a potential agent in hepatocellular carcinoma cell treatment and induction of apoptosis. C1 [Song, Ming; Zhang, Rui; Liu, Jin-lian; Zhang, Jian-jun] Beijing Univ Chinese Med, Sch Tradit Chinese Med, Beijing 100029, Peoples R China. [Li, Zhen-hao] Zhejiang Shouxiangu Inst Rare Med Plant, Wuyi 321200, Peoples R China. [Gu, Hong-shun] Beijing Cairui Med Technol Inst, Beijing 100094, Peoples R China. [Tang, Ru-ying; Zhu, Ying-li; Wang, Lin-yuan] Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing 100029, Peoples R China. C3 Beijing University of Chinese Medicine; Beijing University of Chinese Medicine RP Zhang, JJ (corresponding author), Beijing Univ Chinese Med, Sch Tradit Chinese Med, Beijing 100029, Peoples R China.; Wang, LY (corresponding author), Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing 100029, Peoples R China. EM songming@bucm.edu.cn; zhenhao@zju.edu.cn; 20180941036@bucm.edu.cn; tangruying@bucm.edu.cn; zhangrui@bucm.edu.cn; zhuyingli1989@bucm.edu.cn; liujinlian@bucm.edu.cn; zhangjianjun@bucm.edu.cn; wangly@bucm.edu.cn RI ; ZHU, YINGLI/PIF-8285-2026 OI Lin-yuan, Wang/0000-0002-9048-2829; Song, Ming/0000-0002-6470-0968; Li, Zhenhao/0000-0001-8279-8981; Zhang, Rui/0000-0002-6500-6556; FU National Key R&D Program of China [2018YFC1706800] FX This work was supported by the National Key R&D Program of China (2018YFC1706800). 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Res. PD MAR 5 PY 2021 VL 2021 AR 6696606 DI 10.1155/2021/6696606 PG 14 WC Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology GA QX5NA UT WOS:000629392000001 PM 33748291 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Saeedifar, AM Mosayebi, G Ghazavi, A Bushehri, RH Ganji, A AF Saeedifar, Amir Mohammad Mosayebi, Ghasem Ghazavi, Ali Bushehri, Rouhollah Hemmati Ganji, Ali TI Macrophage polarization by phytotherapy in the tumor microenvironment SO PHYTOTHERAPY RESEARCH LA English DT Review DE macrophage polarization; phytotherapy; signaling pathways; tumor ID GLIOBLASTOMA CELL-PROLIFERATION; MOLECULAR-MECHANISMS; SIGNAL TRANSDUCER; CHLOROGENIC ACID; DENDRITIC CELLS; OVARIAN-CANCER; M2 PHENOTYPE; BETA-ELEMENE; IN-VITRO; KAPPA-B AB Several signaling pathways were involved in M1 (classic) and M2 (alternative) macrophage polarization. Disruption of M2-related signaling pathways and improvement of M1-related signaling pathways can be identified as one of the cancer therapeutic approaches. Prevention of macrophage differentiation into M2 by different herbal agents with antitumor properties can be considered as a promising therapeutic target for cancer patients. In the present review study, we investigated the effect of herbal compounds on M1 and M2 related signaling pathways to reduce M2 and increase M1 macrophage polarization for the treatment of different types of cancer. C1 [Saeedifar, Amir Mohammad; Mosayebi, Ghasem; Ghazavi, Ali; Bushehri, Rouhollah Hemmati; Ganji, Ali] Arak Univ Med Sci, Sch Med, Dept Immunol & Microbiol, Arak, Iran. [Mosayebi, Ghasem; Ganji, Ali] Arak Univ Med Sci, Mol & Med Res Ctr, Arak, Iran. [Ghazavi, Ali] Arak Univ Med Sci, Tradit & Complementary Med Res Ctr TCMRC, Arak, Iran. RP Ganji, A (corresponding author), Arak Univ Med Sci, Mol & Med Res Ctr, Arak, Iran. EM a.ganji@arakmu.ac.ir RI ghazavi, ali/A-8502-2013; Hemmati Bushehri, Rouhollah/PEV-1309-2025; Ganji, Ali/I-2345-2016 OI Hemmati Bushehri, Rouhollah/0000-0001-7680-3908; Ganji, Ali/0000-0002-2632-9889 FU Arak University of Medical Sciences FX The authors would like to thank the authorities of Arak University of Medical Sciences for their support. 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RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0951-418X EI 1099-1573 J9 PHYTOTHER RES JI Phytother. Res. PD JUL PY 2021 VL 35 IS 7 BP 3632 EP 3648 DI 10.1002/ptr.7058 EA FEB 2021 PG 17 WC Chemistry, Medicinal; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA TS8TH UT WOS:000621403100001 PM 33629797 DA 2026-03-26 ER PT J AU Huai, MX Zeng, JX Ge, WS AF Huai, Manxiu Zeng, Junxiang Ge, Wensong TI Artemisinin ameliorates intestinal inflammation by skewing macrophages to the M2 phenotype and inhibiting epithelial-mesenchymal transition SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Inflammatory bowel disease; Artemisinin macrophages; Epithelial-mesenchymal treatment AB Background: Inflammatory bowel disease (IBD) is a self-destructive intestinal disease whose etiology is unclear but complex and the effective treatment is deficient. Increasing evidences have indicated that immune dysfunction and epithelial-mesenchymal transition (EMT)-related intestinal mucosal barrier impaired hold critical position in the pathogenesis of IBD. Artemisinin (ART) is a sesquiterpenoid compound extracted from Chinese herbal medicine which has good immunomodulatory effects. Studies have shown that artemisinin and its analogues have therapeutic effects on a variety of tumors and immune-related disorders. The purpose of current study was to research the effect and mechanism about artemisinin-induced macrophage polarization to M2 phenotype and inhibiting the process of EMT. Methods: In vitro, the anti-inflammatory effect of artemisinin is mainly verified by RAW264.7 cells and tissue (colon tissue and PBMC) from CD patients with active intestinal inflammation. RAW264.7 cells stimulated with LPS to induce inflammatory state and ART were used as therapeutic treatment in different concentration. Then the expression levels of pro-inflammatory factors, macrophage polarization and ERK pathway were analyzed. Colon tissue and PBMC from CD patients were treated with ART in different concentrations and macrophage polarization, pro-inflammatory factors expression, EMT-related protein were analyzed. In vivo, DSS-induced colitis mice were treated by ART for seven days. The DAI score was calculated and the colons and spleens were harvested after the animals were sacrificed. The expression of macrophage markers and EMT-related markers in the intestines of mice in each group were monitored by qPCR and western blot. Result: ART treatment could decrease the levels of pro-inflammatory coefficient expressed in theRAW264.7 cells and human PBMC. Moreover, ART could ameliorate the intestinal inflammation in vivo through down-regulating the expression of pro-inflammatory factors, promoting macrophage polarization to M2 phenotype and inhibiting the process of EMT. Conclusion: Taken together, our findings demonstrated that artemisinin might ameliorate inflammation by inducing macrophage polarization to M2 phenotype and inhibiting the process of EMT, suggesting that ART may be applied to the rehabilitation of IBD in the future. C1 [Huai, Manxiu; Ge, Wensong] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Gastroenterol, Shanghai, Peoples R China. [Zeng, Junxiang] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Clin Lab, Shanghai, Peoples R China. C3 Shanghai Jiao Tong University; Shanghai Jiao Tong University RP Ge, WS (corresponding author), Shanghai Jiao Tong Univ, Sch Med, 1665 Kong Jiang Rd, Shanghai 200092, Peoples R China. EM gewensong@xinhuamed.com.cn OI Zeng, Junxiang/0000-0002-3042-1880 FU National Natural Science Foundation of ChinaGrants [81200279] FX This work was supported in part by the National Natural Science Foundation of ChinaGrants No. 81200279. 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Immunopharmacol. PD FEB PY 2021 VL 91 AR 107284 DI 10.1016/j.intimp.2020.107284 PG 9 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA QB1RM UT WOS:000613920500004 PM 33359851 DA 2026-03-26 ER PT J AU Wang, X Gao, SY Song, LY Liu, M Sun, ZQ Liu, JB AF Wang, Xue Gao, ShouYang Song, LiYou Liu, Ming Sun, ZiQian Liu, JunBao TI Astragaloside IV antagonizes M2 phenotype macrophage polarization-evoked ovarian cancer cell malignant progression by suppressing the HMGB1-TLR4 axis SO MOLECULAR IMMUNOLOGY LA English DT Article DE Ovarian cancer; Tumor microenvironment; Macrophages; Astragaloside IV; HMGB1 signaling ID TUMOR-ASSOCIATED MACROPHAGES; STATISTICS; TARGETS; RAGE AB Macrophages are the most abundant cells in tumor stroma and their polarization within tumor microenvironment exert the key roles in tumorigenesis. Astragaloside IV is a natural extract from traditional Chinese herbal Radix Astragali, and fulfills pleiotropic function in several cancers. Nevertheless, its function in ovarian cancer microenvironment remains elusive. In the present research, astragaloside IV exhibited little cytotoxicity within a certain dose range in THP-1 cells. Moreover, astragaloside IV suppressed the ratio of CD14(+)CD206(+) cells in IL-4/IL-13-treated THP-1 macrophages and transcripts of M2 macrophage markers (including CD206, CCL24, PPAR gamma, Arg-1, IL-10), indicating the inhibitory effects of astragaloside IV on IL-4/IL-13-induced macrophage M2 polarization. Intriguingly, astragaloside IV antagonized M2 macrophages coculture-evoked cell proliferation, invasion and migration in ovarian cancer cells. During this process, administration with astragaloside IV restrained the high expression of high-mobility group box1 (HMGB1) and TLR4 in macrophages co-cultured with ovarian cancer cells, concomitant with decreases in release of M2 marker TGF-beta, MMP-9 and IL-10. Moreover, targeting the HMGB1 signaling reversed M2 macrophages-induced ovarian cancer cell proliferation, invasion and migration. Noticeably, exogenous HMGB1 overturned the inhibitory efficacy of astragaloside IV against macrophage M2 polarization-evoked malignant potential in ovarian cancer cells. Together, these findings suggest that astragaloside IV may protect against M2 macrophages-evoked malignancy in ovarian cancer cells by suppressing the HMGB1-TLR4 signaling. Therefore, astragaloside may alleviate the progression of ovarian cancer by regulating macrophage M2 polarization within tumor microenvironment, implying a promising therapeutic strategy against ovarian cancer. C1 [Wang, Xue; Gao, ShouYang; Sun, ZiQian; Liu, JunBao] Jilin Univ, China Japan Union Hosp, Dept Obstet & Gynecol, Changchun 130033, Jilin, Peoples R China. [Song, LiYou] Jilin Canc Hosp, Dept Thyroid Surg, Changchun 130000, Jilin, Peoples R China. [Liu, Ming] Jilin Cent Hosp, Dept Obstet & Gynecol, Jilin 130011, Jilin, Peoples R China. C3 Jilin University RP Sun, ZQ; Liu, JB (corresponding author), Jilin Univ, China Japan Union Hosp, Dept Obstet & Gynecol, Changchun 130033, Jilin, Peoples R China. EM sunziqian@jlu.edu.cn; junbao@jlu.edu.cn CR Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI [10.3322/caac.21492, 10.3322/caac.21609] Carroll MJ, 2016, ONCOTARGET, V7, P86608, DOI 10.18632/oncotarget.13474 Cecchinato V, 2018, FRONT IMMUNOL, V9, DOI 10.3389/fimmu.2018.02118 Chen T, 2018, CANCER IMMUNOL IMMUN, V67, P1635, DOI 10.1007/s00262-018-2233-x Cheng HY, 2019, FRONT ONCOL, V9, DOI 10.3389/fonc.2019.00421 Dai PC, 2017, TUMOR BIOL, V39, DOI 10.1177/1010428317697555 Dion L, 2020, J CLIN MED, V9, DOI 10.3390/jcm9051339 Feng RM, 2019, CANCER COMMUN, V39, DOI 10.1186/s40880-019-0368-6 Guo ZS, 2013, AM J CANCER RES, V3, P1 Hao M, 2018, NEURAL REGEN RES, V13, P1081, DOI 10.4103/1673-5374.233452 Howlader N., 1975, SEER CANC STAT REV Huang CY, 2018, CELL DEATH DIS, V9, DOI 10.1038/s41419-018-1019-6 Jiang CX, 2018, MOL MED REP, V18, P3093, DOI 10.3892/mmr.2018.9271 Jiang K, 2017, INT IMMUNOPHARMACOL, V42, P195, DOI 10.1016/j.intimp.2016.10.001 Komohara Y, 2016, ADV DRUG DELIVER REV, V99, P180, DOI 10.1016/j.addr.2015.11.009 Li R, 2019, CELL DEATH DIFFER, V26, P2447, DOI 10.1038/s41418-019-0312-y Li Y, 2014, NEOPLASMA, V61, P579, DOI 10.4149/neo_2014_070 Lv W, 2016, CANCER LETT, V375, P245, DOI 10.1016/j.canlet.2016.02.005 Mantovani A, 2017, NAT REV CLIN ONCOL, V14, P399, DOI 10.1038/nrclinonc.2016.217 Miller KD, 2016, CA-CANCER J CLIN, V66, P271, DOI 10.3322/caac.21349 Najafi M, 2019, J CELL BIOCHEM, V120, P2756, DOI 10.1002/jcb.27646 Ngambenjawong C, 2017, ADV DRUG DELIVER REV, V114, P206, DOI 10.1016/j.addr.2017.04.010 Qi FH, 2015, BIOSCI TRENDS, V9, P16, DOI 10.5582/bst.2015.01019 Quail DF, 2013, NAT MED, V19, P1423, DOI 10.1038/nm.3394 Rahimi F, 2017, CANCER BIOMARK, V18, P61, DOI 10.3233/CBM-160674 Rojas A, 2016, TUMOR BIOL, V37, P3321, DOI 10.1007/s13277-015-3940-y Salmaninejad A, 2019, CELL ONCOL, V42, P591, DOI 10.1007/s13402-019-00453-z Siegel R, 2012, CA-CANCER J CLIN, V62, P10, DOI 10.3322/caac.20138 Tao FF, 2019, EVID-BASED COMPL ALT, V2019, DOI 10.1155/2019/3868354 Tariq M, 2017, J CELL BIOCHEM, V118, P2484, DOI 10.1002/jcb.25895 Torre LA, 2018, CA-CANCER J CLIN, V68, P284, DOI 10.3322/caac.21456 Wang EY, 2020, PHARMACOL RES, V157, DOI 10.1016/j.phrs.2020.104831 Wang MZ, 2020, FRONT PHARMACOL, V11, DOI 10.3389/fphar.2020.00957 Wang SX, 2018, BIOMED PHARMACOTHER, V102, P1037, DOI 10.1016/j.biopha.2018.03.127 Wang XB, 2015, INT J MOL SCI, V16, P22527, DOI 10.3390/ijms160922527 Wang ZF, 2017, WORLD J GASTROENTERO, V23, P8512, DOI 10.3748/wjg.v23.i48.8512 Xu F, 2018, J EXP CLIN CANC RES, V37, DOI 10.1186/s13046-018-0878-0 Zhang WQ, 2014, TUMOR BIOL, V35, P2175, DOI 10.1007/s13277-013-1288-8 Zhu ZS, 2017, WOUND REPAIR REGEN, V25, P377, DOI 10.1111/wrr.12532 NR 39 TC 51 Z9 55 U1 1 U2 53 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 EI 1872-9142 J9 MOL IMMUNOL JI Mol. Immunol. PD FEB PY 2021 VL 130 BP 113 EP 121 DI 10.1016/j.molimm.2020.11.014 EA JAN 2021 PG 9 WC Biochemistry & Molecular Biology; Immunology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Immunology GA PS6BL UT WOS:000608007700015 PM 33308900 DA 2026-03-26 ER PT J AU Li, L Gan, HY Jin, HQ Fang, Y Yang, Y Zhang, JP Hu, XW Chu, LS AF Li, Lin Gan, Haiyan Jin, Huaqian Fang, Yan Yang, Yan Zhang, Jianping Hu, Xiaowei Chu, Lisheng TI Astragaloside IV promotes microglia/macrophages M2 polarization and enhances neurogenesis and angiogenesis through PPARγ pathway after cerebral ischemia/reperfusion injury in rats SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Cerebral ischemia; reperfusion injury; Astragaloside IV; PPARγ Microglia; macrophage; Polarization ID ACTIVATED-RECEPTOR-GAMMA; ISCHEMIC-STROKE; ALTERNATIVE ACTIVATION; MICROGLIA POLARIZATION; FUNCTIONAL RECOVERY; BRAIN; CELLS; PHENOTYPE; NEUROINFLAMMATION; ROSIGLITAZONE AB Microglia/macrophages play a dual role in brain injury and repair following cerebral ischemia/reperfusion. Promoting microglia/macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype has been considered as a potential treatment for ischemic stroke. Astragaloside IV (AS-IV) is a primary active ingredient of Chinese herb Radix Astragali, which protects against acute cerebral ischemic/reperfusion injury through its antioxidant, anti-inflammatory, and anti-apoptotic properties. However, it remains unknown whether AS-IV improves ischemic brain tissue repair and its underlying mechanism. A transient middle cerebral artery occlusion (tMCAO) rat model was used in this study. The results showed that AS-IV significantly improved longterm brain injury, reduced the expression of M1 microglia/macrophage markers and increased the expression of M2 microglia/macrophage markers 14 days after cerebral ischemia/reperfusion. AS-IV also increased peroxisome proliferator-activated receptor gamma (PPAR gamma) mRNA and protein expression. Moreover, AS-IV promoted neurogenesis and angiogenesis, and increased the protein expression of brain-derived growth factor (BDNF), insulinlike growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF). However, these beneficial effects were greatly blocked by PPAR gamma antagonist T0070907. These results together suggest that AS-IV could enhance neurogenesis, angiogenesis and neurological functional recovery, which may be partially through transforming microglia/macrophage from M1 to M2 phenotype in a PPAR gamma-dependent manner after cerebral ischemia/ reperfusion injury. Therefore, AS-IV can be considered as a promising therapeutic agent for ischemic stroke. C1 [Li, Lin; Gan, Haiyan; Jin, Huaqian; Fang, Yan; Yang, Yan; Hu, Xiaowei; Chu, Lisheng] Zhejiang Chinese Med Univ, Dept Physiol, Hangzhou, Peoples R China. [Zhang, Jianping] Zhejiang Chinese Med Univ, Dept Anat, Hangzhou 310053, Peoples R China. C3 Zhejiang Chinese Medical University; Zhejiang Chinese Medical University RP Chu, LS (corresponding author), Zhejiang Chinese Med Univ, Dept Physiol, Hangzhou, Peoples R China. EM cls2004@zcmu.edu.cn FU National Natural Science Foundation of China [81073075, 81873028, 81903949]; Natural Science Foundation of Zhejiang Province [LQ19H290004] FX This work was supported by the National Natural Science Foundation of China (No. 81073075, 81873028, 81903949) and the Natural Science Foundation of Zhejiang Province (LQ19H290004) . 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Immunopharmacol. PD MAR PY 2021 VL 92 AR 107335 DI 10.1016/j.intimp.2020.107335 EA JAN 2021 PG 11 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA RZ4OM UT WOS:000648576500006 PM 33429332 DA 2026-03-26 ER PT J AU Wang, R Li, DF Hu, YF Liao, Q Jiang, TT Olatunji, OJ Yang, K Zuo, J AF Wang, Rui Li, Dan-Feng Hu, Yi-Fang Liao, Qiang Jiang, Tian-Tian Olatunji, Opeyemi Joshua Yang, Kui Zuo, Jian TI Qing-Luo-Yin Alleviated Monocytes/Macrophages-Mediated Inflammation in Rats with Adjuvant-Induced Arthritis by Disrupting Their Interaction with (Pre)-Adipocytes Through PPAR-γ Signaling SO DRUG DESIGN DEVELOPMENT AND THERAPY LA English DT Article DE fat metabolism; Qing-Luo-Yin; rheumatoid arthritis; macrophages polarization; adipokine; (pre)-adipocytes ID COLLAGEN-INDUCED ARTHRITIS; RHEUMATOID-ARTHRITIS; LIGANDS AB Background: The Chinese herbal formula Qing-Luo-Yin (QLY) has been successfully used in rheumatoid arthritis treatment for decades. It exhibits notable immune and metabolism regulatory properties. Thereby, we investigated its effects on the interplay between (pre)-adipocytes and monocytes/macrophages under adjuvant-induced arthritis (AIA) circumstances. Methods: Fat reservoir and histological characteristics of white fat tissues (WAT) in AIA rats receiving QLY treatment were examined upon sacrifice. Metabolic parameters, clinical indicators, and oxidative stress levels were determined using corresponding kits, while mRNA/protein expression was investigated by PCR and immunoblotting methods. M1 macrophage distribution in WAT was assessed by flow cytometry. The effects of QLY on (pre)-adipocytes were further validated by experiments in vitro. Results: Compared with normal healthy controls, body weight and circulating triglyceride were declined in AIA rats, but serological levels of free fatty acids and low-density lipoprotein cholesterol were increased. mRNA IL-1 beta and iNOS expression in white blood cells and rheumatoid factor, C-reactive protein, anti-cyclic citrullinated peptide antibody, MCP-1 and IL-1 beta production in serum/WAT were up-regulated. Obvious CD86(+)CD11b(+) macrophages were enriched in WAT. Meanwhile, expression of PPAR-gamma and SIRT1 and secretion of adiponectin and leptin in these AIA rats were impaired. QLY restored all these pathological changes. Of note, it significantly stimulated PPAR-gamma expression in the treated AIA rats. Accordingly, QLY-containing serum promoted SCD-1, PPAR-gamma, and SIRT1 expression in pre-adipocytes cultured in vitro. AIA rats-derived peripheral blood mononuclear cells suppressed PPAR-gamma and SCD-1 expression in co-cultured pre-adipocytes, but serum from AIA rats receiving QLY treatment did not exhibit this potential. The changes on PPAR-gamma expression eventually resulted in varied adipocyte differentiation statuses. PPAR-gamma selective inhibitor T0070907 abrogated QLY-induced MCP-1 production decline in LPS-primed pre-adipocytes and reduced adiponectin secretion. Conclusion: QLY was potent in promoting PPAR-gamma expression and consequently disrupted inflammatory feedback in WAT by altering monocytes/macrophages polarization and adipocytes differentiation. C1 [Wang, Rui; Li, Dan-Feng; Hu, Yi-Fang; Liao, Qiang; Jiang, Tian-Tian; Zuo, Jian] Yijishan Hosp, Affiliated Hosp 1, Wannan Med Coll, Dept Tradit Chinese Med, Wuhu 241000, Peoples R China. [Wang, Rui; Li, Dan-Feng; Hu, Yi-Fang; Liao, Qiang; Jiang, Tian-Tian; Yang, Kui; Zuo, Jian] Wannan Med Coll, Res Ctr Integrat Tradit Chinese & Western Med, Wuhu 241000, Peoples R China. [Olatunji, Opeyemi Joshua] Prince Songkla Univ, Fac Tradit Thai Med, Hat Yai 90112, Thailand. [Yang, Kui] Yijishan Hosp, Affiliated Hosp 1, Wannan Med Coll, Dept Pharm, Wuhu 241000, Peoples R China. [Zuo, Jian] Wannan Med Coll, Key Lab Noncoding RNA Transformat Res, Anhui Higher Educ Inst, Wuhu 241000, Peoples R China. C3 Wannan Medical College; Wannan Medical College; Prince of Songkla University; Wannan Medical College; Wannan Medical College RP Zuo, J (corresponding author), Yijishan Hosp, Affiliated Hosp 1, Wannan Med Coll, Dept Tradit Chinese Med, Wuhu 241000, Peoples R China. EM zuojian8178@163.com RI ; Olatunji, Opeyemi Joshua/L-2691-2018; Yang, Kui/HKN-9908-2023; LI, Danfeng/AAK-5163-2020 OI Zuo, Jian/0000-0003-4940-9408; Olatunji, Opeyemi Joshua/0000-0002-6800-4919; 廖, 强/0009-0002-7239-9340; FU National Natural Science Foundation of China [81973828, 81173596]; Major Project of Natural Science Foundation of the Department of Education of Anhui province [KJ2019A0416, KJ2020A0868]; Scientific Research Project of Health Commission of Anhui Province [AHWJ2021b061]; Funding of "Peak" Training Program for Scientific Research of Yijishan Hospital, Wannan Medical College [GF2019J01] FX This work was financially supported by National Natural Science Foundation of China (81973828 and 81173596), The Major Project of Natural Science Foundation of the Department of Education of Anhui province (KJ2019A0416 and KJ2020A0868), The Scientific Research Project of Health Commission of Anhui Province (AHWJ2021b061) and The Funding of "Peak" Training Program for Scientific Research of Yijishan Hospital, Wannan Medical College (GF2019J01). 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Dev. Ther. PY 2021 VL 15 BP 3105 EP 3118 DI 10.2147/DDDT.S320599 PG 14 WC Chemistry, Medicinal; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA TK4LO UT WOS:000674132000003 PM 34295151 OA Green Accepted, Green Submitted, gold DA 2026-03-26 ER PT J AU Fang, LY Chen, L Song, M He, J Zhang, LS Li, CX Wang, QY Yang, WJ Sun, W Leng, YZ Shi, H Wang, SX Gao, XM Wang, H AF Fang, Leyu Chen, Lu Song, Min He, Juan Zhang, Lusha Li, Chunxiao Wang, Qianyi Yang, Wenjie Sun, Wei Leng, Yuze Shi, Hong Wang, Shaoxia Gao, Xiumei Wang, Hong TI Naoxintong accelerates diabetic wound healing by attenuating inflammatory response SO PHARMACEUTICAL BIOLOGY LA English DT Article DE Efferocytosis; macrophage polarization; ECM remoulding ID EFFEROCYTOSIS; INJURY; AIRWAY AB Context Naoxintong (NXT), a prescribed traditional Chinese medicine, widely used in cerebrovascular and cardiovascular diseases, could be effective in diabetic wounds. Objective This study evaluates the wound healing activity of NXT by employing an excisional wound splinting model. Materials and methods NXT was dissolved in saline and given daily by gavage. Wounds were induced at the dorsum of non-diabetic (db/+) and diabetic (db/db) mice and treated with saline or 700 mg/kg/d NXT for 16 days. Wound closure was measured every four days. Extracellular matrix (ECM) remodelling, collagen deposition, leukocyte infiltration and expression of Col-3, CK14, CXCL1, CXCL2, MPO, Ly6G, CD68, CCR7, CD206, p-JAK1, p-STAT3 and p-STAT6 was analysed. Results NXT significantly accelerated rate of wound closure increased from 70% to 84%, accompanied by up-regulation of collagen deposition and ECM at days 16 post-injury. Moreover, NXT alleviated neutrophil infiltration, accompanied by down-regulation of CXCL1 and CXCL2 mRNA expression. In addition, NXT markedly augmented neutrophil efferocytosis. In diabetic wounds, the levels of M1 marker gene (CCR7) increased, while M2 marker gene (CD206) decreased, demonstrating a pro-inflammatory shift. Application of NXT increased M2 macrophage phenotype in db/db mice. Mechanistically, NXT treatment increased expression level of p-STAT3 and p-STAT6 at days 3 post-injury, indicating NXT mediated macrophages towards M2 phenotype and alleviated inflammation in diabetic wounds by activation of STAT3 and STAT6. Conclusions Our study provides evidence that NXT accelerates diabetic wound healing by attenuating inflammatory response, which provides an important basis for use of NXT in the treatment of chronic diabetic wound healing. C1 [Fang, Leyu; Chen, Lu; Song, Min; Zhang, Lusha; Li, Chunxiao; Wang, Qianyi; Yang, Wenjie; Sun, Wei; Leng, Yuze; Shi, Hong; Wang, Shaoxia; Gao, Xiumei; Wang, Hong] State Key Lab Component Based Chinese Med, Tianjin, Peoples R China. [Fang, Leyu; Chen, Lu; Song, Min; Zhang, Lusha; Li, Chunxiao; Wang, Qianyi; Yang, Wenjie; Sun, Wei; Leng, Yuze; Shi, Hong; Wang, Shaoxia; Gao, Xiumei; Wang, Hong] Tianjin Univ Tradit Chinese Med, Minist Educ, Key Lab Pharmacol Tradit Chinese Med Formulae, Tianjin, Peoples R China. [Fang, Leyu; Chen, Lu; Song, Min; Zhang, Lusha; Li, Chunxiao; Wang, Qianyi; Yang, Wenjie; Sun, Wei; Leng, Yuze; Shi, Hong; Wang, Shaoxia; Gao, Xiumei; Wang, Hong] Tianjin Univ Tradit Chinese Med, Tianjin Key Lab Chinese Med Pharmacol, Tianjin, Peoples R China. [Fang, Leyu; Song, Min; Zhang, Lusha; Li, Chunxiao; Wang, Qianyi; Yang, Wenjie; Sun, Wei; Leng, Yuze; Wang, Shaoxia; Wang, Hong] Tianjin Univ Tradit Chinese Med, Sch Integrat Med, 10 Poyanghu Rd, Tianjin 301617, Peoples R China. [Chen, Lu; Shi, Hong; Gao, Xiumei] Tianjin Univ Tradit Chinese Med, Inst Tradit Chinese Med, Tianjin, Peoples R China. [He, Juan] Buchang Pharmaceut Co Ltd, Xian, Peoples R China. C3 Tianjin University of Traditional Chinese Medicine; Tianjin University of Traditional Chinese Medicine; Tianjin University of Traditional Chinese Medicine; Tianjin University of Traditional Chinese Medicine RP Wang, H (corresponding author), Tianjin Univ Tradit Chinese Med, Sch Integrat Med, 10 Poyanghu Rd, Tianjin 301617, Peoples R China. EM wanghongsys@126.com RI GAO, Xiumei/IWD-8697-2023; Yang, Wen/AAM-8352-2020; Zhang, Lusha/PNF-9182-2026 FU National Natural Science Foundation of China [81603329]; Program of International S&T Cooperation Project of China [2015DFA30430]; Natural Science Foundation of Tianjin Municipal Government [16JCZDJC36300] FX This study was supported by the National Natural Science Foundation of China [Grant number: 81603329], Program of International S&T Cooperation Project of China [Grant number: 2015DFA30430] and Natural Science Foundation of Tianjin Municipal Government [Grant number: 16JCZDJC36300]. 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Biol. PD JAN 1 PY 2021 VL 59 IS 1 BP 252 EP 261 DI 10.1080/13880209.2021.1877735 PG 10 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA QT0OL UT WOS:000626292000001 PM 33684026 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Wu, H Chen, QY Wang, WZ Chu, S Liu, XX Liu, YJ Tan, C Zhu, F Deng, SJ Dong, YL Yu, T Gao, F He, HX Leng, XY Fan, H AF Wu, Hui Chen, Qian-Yun Wang, Wen-Zhu Chu, Si Liu, Xing-Xing Liu, Yu-Jin Tan, Chen Zhu, Feng Deng, Shuang-Jiao Dong, Ya-Lan Yu, Ting Gao, Fei He, Hong-Xia Leng, Xue-Yuan Fan, Heng TI Compound sophorae decoction enhances intestinal barrier function of dextran sodium sulfate induced colitis via regulating notch signaling pathway in mice SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE Ulcerative colitis; Compound sophorae decoction; Barrier function; Intestinal epithelial cells; Mucus; Notch ID INFLAMMATORY-BOWEL-DISEASE; INDUCED ULCERATIVE-COLITIS; DEPENDENT MUCUS LAYERS; GOBLET CELLS; PERMEABILITY; APOPTOSIS; INCREASE; COLON; CONTRIBUTES; ACTIVATION AB Background: Compound sophorae decoction (CSD), a Chinese Herbal decoction, is frequently clinically prescribed for patients suffered from ulcerative colitis (UC) characterized by bloody diarrhea. Yet, the underlying mechanism about how this formulae works is remain elusive. Methods: In the present study, the experimental colitis in C57BL/6 J mice was induced by oral administration of standard diets containing 3% dextran sodium sulfate (DSS), and CSD was given orally for treatment at the same time. The clinical symptoms including stool and body weight were recorded each day, and colon length and its histopathological changes were observed. Apoptosis of colonic epithelium was studied by detecting protein expression of cleaved caspase-3, and cell proliferation by Ki-67 immunohistochemistry. Tight junction complex like ZO-1 and occludin were also determined by transmission electron microscope and immunofluorescence. The concentration of FITC-dextran 4000 was measured to evaluate intestinal barrier permeability and possible signaling pathway was investigated. Mucin2 (MUC2) and notch pathway were tested through western blot. The M1/M2 ratio in spleen and mesenteric lymph nodes were detected by flow cytometry. And the mRNA levels of iNOS and Arg1 were examined by qRT-PCR. Results: CSD could significantly alleviate the clinical manifestations and pathological damage. Body weight loss and DAI score of mice with colitis were improved and shortening of colon was inhibited. The administration of CSD was able to reduce apoptotic epithelial cells and facilitate epithelial cell regeneration. Increased intestinal permeability was reduced in DSS-induced colitis mice. In addition, CSD treatment obviously up-regulated the expression of ZO-1 and occludin and the secretion of MUC2, regulated notch signaling, and decreased the ratio of M1/M2. Conclusions: These data together suggest that CSD can effectively mitigate intestinal inflammation, promote phenotypic change in macrophage phenotype and enhance colonic mucosal barrier function by, at least in part, regulating notch signaling in mice affected by DSS-induced colitis. C1 [Wu, Hui; Chen, Qian-Yun; Wang, Wen-Zhu; Chu, Si; Liu, Xing-Xing; Liu, Yu-Jin; Tan, Chen; Zhu, Feng; Deng, Shuang-Jiao; Dong, Ya-Lan; Yu, Ting; Gao, Fei; He, Hong-Xia; Leng, Xue-Yuan; Fan, Heng] Huazhong Univ Sci & Technol, Dept Integrated Tradit Chinese & Western Med, Union Hosp, Tongji Med Coll, Wuhan 430022, Peoples R China. C3 Huazhong University of Science & Technology RP Fan, H (corresponding author), 1277 Jiefang Ave, Wuhan 430022, Hubei, Peoples R China. EM fanheng009@aliyun.com FU National Natural Science Foundation of China [81774093] FX This work was supported by the National Natural Science Foundation of China (Nos. 81774093). 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PD JAN PY 2021 VL 133 AR 110937 DI 10.1016/j.biopha.2020.110937 PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA PN6SM UT WOS:000604606700005 PM 33217689 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhou, JB Ren, YL Tan, L Song, XMT Wang, M Li, YZ Cao, ZX Guo, CJ AF Zhou, Jianbo Ren, Yali Tan, Lu Song, Xiaominting Wang, Miao Li, Yuzhi Cao, Zhixing Guo, Chuanjie TI Norcantharidin: research advances in pharmaceutical activities and derivatives in recent years SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Review DE Biological activities; Norcantharidin; Derivatives; TCM ID EPITHELIAL-MESENCHYMAL TRANSITION; HEPATOCELLULAR-CARCINOMA CELLS; LUNG-CANCER CELLS; VASCULOGENIC MIMICRY; ANTICANCER ACTIVITY; INDUCED APOPTOSIS; CANTHARIDIN; TUMOR; METASTASIS; RESISTANCE AB Cantharidin (CTD) is the main bioactive component of Cantharides, which is called Banmao in Traditional Chinese Medicine (TCM). Norcantharidin (NCTD) is a structural modifier of CTD. To compare with CTD, NCTD has lighter side effects and stronger bioactivity in anti-cancer through inhibiting cell proliferation, causing apoptosis and autophagy, overwhelming migration and metastasis, affecting immunity as well as lymphangiogenesis. Examples of these effects include suppressing Protein Phosphatase 2A and modulating Wnt/beta catenin signal, with Caspase family proteins, AMPK pathway and c-Met/EGFR pathway involving respectively. Moreover, NCTD has the effects of immune enhancement, anti-platelet aggregation and inhibition of renal interstitial fibrosis with distinct signaling pathways. The immunological effects induced by NCTD are related to the regulation of macrophage polarization and LPS-mediated immune response. The antiplatelet activity that NCTD induced is relevant to the inhibition of platelet signaling and the downregulation of alpha 2 integrin. Furthermore, some of novel derivatives designed and synthesized artificially show stronger biological activities (e.g., anticancer effect, enzyme inhibition effect, antioxidant effect) and lower toxicity than NCTD itself. Plenty of literatures have reported various pharmacological effects of NCTD, particularly the anticancer effect, which has been widely concerned in clinical application and laboratory research. In this review, the pharmaceutical activities and derivatives of NCTD are discussed, which can be reference for further study. C1 [Zhou, Jianbo; Ren, Yali; Tan, Lu; Song, Xiaominting; Wang, Miao; Li, Yuzhi; Cao, Zhixing; Guo, Chuanjie] Chengdu Univ Tradit Chinese Med, Sch Pharm, Chengdu, Peoples R China. [Zhou, Jianbo; Ren, Yali; Tan, Lu; Song, Xiaominting; Wang, Miao; Li, Yuzhi; Cao, Zhixing; Guo, Chuanjie] Minist Educ, Key Lab Standardizat Chinese Herbal Med, Chengdu, Peoples R China. [Zhou, Jianbo; Ren, Yali; Tan, Lu; Song, Xiaominting; Wang, Miao; Li, Yuzhi; Cao, Zhixing; Guo, Chuanjie] Natl Key Lab Breeding Base Systemat Res Dev & Uti, Chengdu, Peoples R China. [Guo, Chuanjie] Chengdu Univ Tradit Chinese Med, Sch Basic Med, Chengdu, Peoples R China. C3 Chengdu University of Traditional Chinese Medicine; Chengdu University of Traditional Chinese Medicine RP Cao, ZX; Guo, CJ (corresponding author), 1166 Liu Tai Ave, Chengdu, Sichuan, Peoples R China. EM caozhixing@cdutcm.edu.cn; guochuanjie@stu.cdutcm.edu.cn RI Zhou, Jianbo/NES-5061-2025 OI Zhou, Jianbo/0000-0001-5781-5145 FU National Natural Science Foundation of China [81973189, 81300437, 81403149]; National Major Scientific and Technological Special Project of China [2017ZX09201001-008]; Sichuan Science and Technology Program [2018SZDZX0017]; Project of Sichuan Administration of Traditional Chinese Medicine [2018HJZX015]; Scientific Research Fund of CDUTCM [QNXZ2018007, QNXZ2018011, Ky-2020040] FX This study was supported by the National Natural Science Foundation of China (81973189, 81300437, 81403149), National Major Scientific and Technological Special Project of China (2017ZX09201001-008), Sichuan Science and Technology Program (2018SZDZX0017). Project of Sichuan Administration of Traditional Chinese Medicine [2018HJZX015]. Scientific Research Fund of CDUTCM [QNXZ2018007, QNXZ2018011 and Ky-2020040]. 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Pharmacother. PD NOV PY 2020 VL 131 AR 110755 DI 10.1016/j.biopha.2020.110755 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA OH6KI UT WOS:000582699600118 PM 33152920 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Li, J Cai, HW Sun, HH Qu, JB Zhao, B Hu, XF Li, WJ Qian, ZM Yu, X Kang, FH Wang, WX Zou, ZX Gu, BH Xu, KP AF Li, Jing Cai, Hongwei Sun, Huihui Qu, Jianbo Zhao, Bin Hu, Xuefeng Li, Wenjia Qian, Zhengming Yu, Xia Kang, Fenghua Wang, Wenxuan Zou, Zhenxin Gu, Baohua Xu, Kangping TI Extracts of Cordyceps sinensis inhibit breast cancer growth through promoting M1 macrophage polarization via NF-κB pathway activation SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Cordyceps sinensis; Breast cancer; Macrophage; 3D co-culture; NF-kappa B ID TUMOR-ASSOCIATED MACROPHAGES; METASTASIS; SURVIVAL; ENHANCE AB Ethnopharmacological relevance: Cordyceps sinensis is a traditional Chinese medicine. It is widely reported that Cordyceps sinensis has inhibitory effect on tumor growth and immunoregulation effect on macrophages. However, the exact mechanism of Cordyceps sinensis on macrophage polarization in tumor progression is not known. Aim of study: We aimed to investigate the role of extracts of Cordyceps sinensis on macrophage polarization and its underlying mechanism in antitumor activity. Materials and methods: The 4T1 orthotopic xenograft mouse model and immunohistochemical staining were used to investigate the effect of Cordyceps sinensis on breast tumor and the change of the macrophages phenotype in the tumor, respectively. A 3D co-culture assay was used to confirm the activity in vitro. Measurement of cytokines and NO, quantitative real-time PCR and flow cytometry assays were used to investigate the effect of Cordyceps sinensis on the macrophage polarization in vitro. The mechanism of the effect of Cordyceps sinensis on macrophages was investigated by using western blot assays. Results: In the orthotopic mouse tumor model, Cordyceps sinensis inhibited the 4T1 tumor growth in a dose dependent manner, and the immunohistochemical staining analysis showed that there is a positive correlation between tumor growth inhibition and macrophage M1-like polarized phenotype. The cytokines and NO measurement, quantitative real-time PCR assay and flow cytometry assays confirmed that Cordyceps sinensis could promote macrophage differentiation toward the M1 phenotype. The 3D co-culture assay and western blot assay showed that Cordyceps sinensis could inhibit tumor growth by promoting macrophage polarization and enhance its activity by activating the NF-kappa B signaling pathway. Conclusion: These findings suggest that Cordyceps sinensis could potently suppress TNBC progression by promoting M1 phenotypic differentiation of macrophages via activation NF-kappa B signaling pathway in tumor microenvironment. C1 [Li, Jing; Sun, Huihui; Yu, Xia; Kang, Fenghua; Wang, Wenxuan; Zou, Zhenxin; Xu, Kangping] Cent South Univ, Xiangya Sch Pharmaceut Sci, Changsha 410013, Peoples R China. [Cai, Hongwei; Zhao, Bin; Hu, Xuefeng; Li, Wenjia; Qian, Zhengming; Gu, Baohua] Sunshine Lake Pharma Co LTD, State Adm Tradit Chinese Med, Key Lab, Dongguan 523850, Peoples R China. [Qu, Jianbo] Natl Med Prod Adm, Ctr Drug Evaluat, Beijing 100022, Peoples R China. C3 Central South University RP Xu, KP (corresponding author), Cent South Univ, Xiangya Sch Pharmaceut Sci, Changsha 410013, Peoples R China.; Gu, BH (corresponding author), Sunshine Lake Pharma Co LTD, State Adm Tradit Chinese Med, Key Lab, Dongguan 523850, Peoples R China. EM baohua.gu@hec.cn; xukp395@csu.edu.cn RI ; Sun, Huihui/NFT-2916-2025; Wang, Wenxuan/NTQ-8441-2025 OI Kang, Fenghua/0000-0003-2323-3096; Qian, Zhengming/0000-0002-8467-2941; FU National Key R&D Program of China [2018YFC1706101]; Dongguan Academician Workstation Project [DGYSZ-2018-03]; Key Laboratory of State Administration of Traditional Chinese Medicine, Sunshine Lake Pharma Co., LTD. FX This work was funded by National Key R&D Program of China (2018YFC1706101)and Dongguan Academician Workstation Project (DGYSZ-2018-03), and supported by Key Laboratory of State Administration of Traditional Chinese Medicine, Sunshine Lake Pharma Co., LTD. 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Ethnopharmacol. PD OCT 5 PY 2020 VL 260 AR 112969 DI 10.1016/j.jep.2020.112969 PG 10 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA OC8CM UT WOS:000579384200043 PM 32422358 DA 2026-03-26 ER PT J AU Chen, MJ Hu, C Gao, Q Li, LQ Cheng, ZY Li, QR Li, ZH Wang, ZH Mao, ZJ Tian, WQ Zhang, X AF Chen, Meijuan Hu, Cheng Gao, Qian Li, Liqiu Cheng, Ziyu Li, Qirui Li, Zhihui Wang, Zhaohui Mao, Zejia Tian, Weiqian Zhang, Xu TI Study on metastasis inhibition of Kejinyan decoction on lung cancer by affecting tumor microenvironment SO CANCER CELL INTERNATIONAL LA English DT Article DE Lung cancer; Kejinyan decoction; Tumor microenvironment; Tumor-associated microphage (TAMs); Glycolysis; Metastasis ID MACROPHAGES; MECHANISMS; POLARIZATION; STATISTICS; METABOLISM; HALLMARKS; CELLS AB BackgroundKejinyan decoction, as an experienced formula of Zhou Zhongying (the Master of Traditional Chinese Medicine) has been widely used in clinic for lung cancer treatment in China, while the anti-lung cancer mechanism of it is still remained to be elucidated. Herein, our basic study found that the survival of lung cancer xenograft mice was significantly prolonged after intragastrically administered high dose of Kejinyan decoction (3.8 g per kg BW) for 15 days. More importantly, we found that Kejinyan decoction inhibited the metastasis of lung cancer cells in vivo. Thus in this study, we aim to elucidate the anti-metastasis effects of Kejinyan decoction.MethodsRNA-Seq was used to find out the gene regulation of Kejinyan decoction on the mice, flow cytometry assay was used to detect the immunocytes in the spleen, ELISA assay was used to detect the inflammatory factors in the serum and spleen, and immunofluorescence assay was used to detect the level of immune cells and the expression of glycol-metabolism related enzymes in situ. Also, we established a lung cancer orthotopic xenograft tumor model to assess the influence of Kejinyan decoction on the metastatic ability of lung cancer cells in vivo.ResultsGO analysis of gene sequencing of tumor tissue samples showed that Kejinyan decoction regulated immune response. Further flow cytometry analysis of splenic lymphocyte showed that Kejinyan decoction upregulated M1 macrophages and downregulated M2 macrophages, while the total level of macrophages changed little, which was verified by detection of CD68, F4/80, CD206, and CD86 in tumor tissue section. Moreover, detection of inflammatory cytokines showed that Kejinyan decoction downregulated TNF-alpha, IFN-gamma, IL-6, as well as IL-4, IL-13 in tumor microenvironment. Further studies also showed that Kejinyan decoction had little effect on tumor hypoxia, but downregulated glycolysis in tumor tissues. More importantly, we found that Kejinyan decoction inhibited the metastasis of lung cancer cells in vivo.ConclusionOur findings conclude that Kejinyan decoction inhibited lung cancer cell metastasis through affecting macrophage polarization and energy reprogramming. C1 [Chen, Meijuan; Gao, Qian; Li, Liqiu; Cheng, Ziyu; Li, Qirui; Li, Zhihui; Wang, Zhaohui; Mao, Zejia; Zhang, Xu] Nanjing Univ Chinese Med, Sch Med & Holist Integrat Med, Nanjing 210023, Peoples R China. [Hu, Cheng; Tian, Weiqian] Nanjing Univ Chinese Med, Jiangsu Prov Hosp Chinese Med, Affiliated Hosp, Nanjing 210029, Peoples R China. C3 Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine RP Zhang, X (corresponding author), Nanjing Univ Chinese Med, Sch Med & Holist Integrat Med, Nanjing 210023, Peoples R China. EM zhangxu@njucm.edu.cn RI Li, Liqiu/GXF-6749-2022 OI Zhang, Xu/0000-0002-1959-1758 FU Open Projects of the Discipline of Chinese Medicine of Nanjing University of Chinese Medicine; Subject of Academic priority discipline of Jiangsu Higher Education Institutions (PAPD) [ZYX03KF047]; Research Foundation of Education Bureau of Jiangsu Province [16KJA360001]; Postgraduate Research & Practice Innovation Program of Jiangsu Province [KYCX19_1239, KYCX19_1227] FX This study was supported by the Open Projects of the Discipline of Chinese Medicine of Nanjing University of Chinese Medicine Supported by the Subject of Academic priority discipline of Jiangsu Higher Education Institutions (PAPD) (Grant number: ZYX03KF047), the Research Foundation of Education Bureau of Jiangsu Province (Grant number: 16KJA360001). Postgraduate Research & Practice Innovation Program of Jiangsu Province (Grant number: KYCX19_1239, KYCX19_1227). 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It has long been acknowledged that the formation of foam cells is caused by excess lipid uptake and abnormal cholesterol metabolism function. And increasing evidence shows that inhibiting foam cell formation is a promising way to suppress the development of atherosclerotic lesions. In addition to excess foam cells accumulation, inflammation is another major contributor of atherosclerotic lesions. Recently, macrophage polarization has been demonstrated to play a vital role in the regulation of inflammatory response. Generally, macrophages mainly polarized into two phenotypes: either classically activated pro-inflammatory M1 or alternatively activated anti-inflammatory M2. And targeting macrophage polarization has been considered as a feasible approach to prevent the development of atherosclerosis. At present, the anti-atherosclerosis drugs mainly classified into two types: lipid-lowering drugs and anti-inflammatory drugs. A large part of those drugs belong to western medicine, and various side effects are unavoidable. Interestingly, in recent years, Traditional Chinese medicine has attracted growing attention because of its good efficacy and low negative effects. Rhubarb (called Da Huang in Chinese) is a famous folk medicine with a wide spectrum of pharmacological effects, such as lipid-lowering and anti-inflammatory effects. In this review, we summarized current findings about the regulatory effects of Rhubarb on foam cell formation and macrophage polarization, with emphasis on the molecular mechanisms of action that have been revealed during the past two decades, to better understand its pivotal role in the treatment and prevention of atherosclerosis. C1 [Liu, Xianfeng; Tian, Ruimin; Su, Siyu; Deng, Siang] Chengdu Univ Tradit Chinese Med, Coll Pharm, Chengdu 611137, Sichuan, Peoples R China. [Wu, Jiasi] Chengdu Univ Tradit Chinese Med, Acupuncture & Tuina Sch, Chengdu 611137, Peoples R China. [Meng, Xianli] Chengdu Univ Tradit Chinese Med, Innovat Inst Chinese Med & Pharm, Chengdu 611137, Sichuan, Peoples R China. C3 Chengdu University of Traditional Chinese Medicine; Chengdu University of Traditional Chinese Medicine; Chengdu University of Traditional Chinese Medicine RP Meng, XL (corresponding author), Chengdu Univ Tradit Chinese Med, Innovat Inst Chinese Med & Pharm, Chengdu 611137, Sichuan, Peoples R China. EM 1697339184@qq.com; jswoodr@aliyun.com; truimin@126.com; susiyu77@163.com; Dengsiang@qq.com; xlm999@cdutcm.edu.cn FU National Key Research and Development Program of China [2017YFC1703904]; National Natural Science Foundation of China [81773974] FX This work was supported by the National Key Research and Development Program of China (Nos. 2017YFC1703904) and the National Natural Science Foundation of China (Nos. 81773974). 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PD SEP PY 2020 VL 129 AR 110433 DI 10.1016/j.biopha.2020.110433 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA NJ9SF UT WOS:000566382800018 PM 32768936 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Guo, ZJ Li, SR Zhang, N Kang, QJ Zhai, HQ AF Guo, Zhaojuan Li, Siru Zhang, Nan Kang, Qianjun Zhai, Huaqiang TI Schisandra Inhibit Bleomycin-Induced Idiopathic Pulmonary Fibrosis in Rats via Suppressing M2 Macrophage Polarization SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID TGF-BETA/SMAD; MESENCHYMAL TRANSITION; LUNG MACROPHAGES; EPHEDRA-SINICA; GROWTH-FACTOR; PROMOTES; BETA; EXPRESSION; REGULATOR; CHINENSIS AB Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause and limited to the lungs.Schisandrae chinensis fructus(Wuweizi, Schisandra) is commonly used traditional Chinese medicines (TCM) for the treatment of pulmonary fibrosis, bronchitis, and other lung diseases in China. In this study, we investigated the therapeutic effect of Schisandra on IPF which is induced by bleomycin (BLM) in rats and the inhibition of alternatively activated macrophage (M2) polarization. Bleomycin-induced pulmonary fibrosis was used as a model for IPF, and rats were given drug interventions for 7 and 28 days to evaluate the role of Schisandra in the early oxidative phase and late fibrotic phases of BLM-induced pulmonary injury. The data showed that Schisandra exerted protective effects on BLM-induced pulmonary injury in two phases, which were improving inflammatory cell infiltration and severe damages of lung architectures and decreasing markers of M2 subtype. In order to prove the inhibitory effect of Schisandra on M2 polarization, in vitro experiments, we found that Schisandra downregulated the M2 ratio, which confirmed that the polarization of M2 was suppressed. Moreover, Schisandra blocked TGF-beta 1 signaling in AMs by reducing the levels of Smad3 and Smad4; meanwhile, the upregulation of Smad7 by Schisandra also promoted the effect of inhibition on the TGF-beta 1/Smad pathway. These results demonstrate that suppression of M2 polarization by Schisandra is associated with the development of IPF in rats. C1 [Guo, Zhaojuan; Kang, Qianjun] Beijing Univ Chinese Med, Beijing Inst Tradit Chinese Med, Beijing 100029, Peoples R China. [Li, Siru] New Jersey Inst Technol, Liberal & Art Coll, Newark, NJ 07102 USA. [Zhang, Nan; Zhai, Huaqiang] Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing 102488, Peoples R China. C3 Beijing University of Chinese Medicine; New Jersey Institute of Technology; Beijing University of Chinese Medicine RP Zhai, HQ (corresponding author), Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing 102488, Peoples R China. 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PD AUG 20 PY 2020 VL 2020 AR 5137349 DI 10.1155/2020/5137349 PG 11 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA NM1HO UT WOS:000567855300005 PM 32884941 OA Green Submitted, hybrid DA 2026-03-26 ER PT J AU Pan, L Lu, YH Li, ZH Tan, YP Yang, HM Ruan, P Li, RX AF Pan, Ling Lu, Yuehong Li, Zhanhua Tan, Yuping Yang, Hongmei Ruan, Ping Li, Ruixiang TI Ginkgo biloba Extract EGb761 Attenuates Bleomycin-Induced Experimental Pulmonary Fibrosis in Mice by Regulating the Balance of M1/M2 Macrophages and Nuclear Factor Kappa B (NF-κB)-Mediated Cellular Apoptosis SO MEDICAL SCIENCE MONITOR LA English DT Article DE Apoptosis; Ginkgo biloba; Idiopathic Pulmonary Fibrosis; Macrophages; Transcription Factor RelA ID INDUCED LUNG INJURY; ALTERNATIVE ACTIVATION; OXIDATIVE STRESS; EXPRESSION; MECHANISMS; PREVENTION; RECEPTORS; RESPONSES; EGB-761 AB Background: The aim of this study was to show whether the standardized Ginkgo biloba extract EGb761, a traditional Chinese medicine, has a therapeutic effect on pulmonary fibrosis (PF). Material/Methods: Bleomycin (BLM) was used for establishing the PF mouse model. The mice were treated with a gradient of EGb761 for 28 days to determine an appropriate drug dose. On day 28, the effect of EGb761 on lung injury and inflammation was confirmed by hematoxylin and eosin and Masson staining and evaluated by pulmonary alveolitis and Ashcroft score. The balance of M1/M2 macrophages was evaluated with the respective markers inducible nitric oxide synthase and and interleukin-10 by real-time polymerase chain reaction. Furthermore, the expressions of fibrosis-associated protein a-smooth muscle actin (SMA), related inflammatory protein transforming growth factor (TGF)-beta 1, the apoptosis-related proteins B-cell lymphoma-associated X protein (Bax), B-cell lymphoma (Bcl)-2, caspase-3, caspase-9, and phosphorylated nuclear factor (NF)-kappa B (p65) were assessed by western blot. Results: On day 28, PF was induced by treating with BLM, whereas EGb761 suppressed the PF of lung tissue. The BLM induced imbalance of M1/M2 macrophages was reduced by EGb761. Furthermore, the increasing amounts of alpha-SMA and TGF-beta 1 induced by BLM were suppressed by EGb761. In addition, the protein or messenger ribonucleic acid expression levels of phosphorylated NF-kappa B (p65), caspase-3, and caspase-9 were upregulated, whereas Bax and Bcl-2 were downregulated. Treatment with EGb761 restored the levels of these proteins except for caspase-9. Conclusions: This study illustrated the protective effect of EGb761 on BLM-induced PF by regulating the balance of M1/M2 macrophages and NF-kappa B (p65)-mediated apoptosis. The results demonstrated the potential clinical therapeutic effect of EGb761, providing a novel possibility for curing PF. C1 [Pan, Ling; Lu, Yuehong; Li, Zhanhua; Tan, Yuping; Yang, Hongmei; Ruan, Ping; Li, Ruixiang] Guangxi Tradit Chinese Med Univ, Ruikang Hosp, Resp Med Dept, Nanning, Guangxi, Peoples R China. C3 Guangxi University of Chinese Medicine RP Pan, L (corresponding author), Guangxi Tradit Chinese Med Univ, Ruikang Hosp, Resp Med Dept, Nanning, Guangxi, Peoples R China. 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Sci. Monitor PD AUG 16 PY 2020 VL 26 AR e922634 DI 10.12659/MSM.922634 PG 9 WC Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine GA NA3VM UT WOS:000559742400001 PM 32799214 OA Green Submitted, hybrid DA 2026-03-26 ER PT J AU Chung, HY Kim, JH Han, IH Ryu, JS AF Chung, Hyo-Yeoung Kim, Jung-Hyun Han, Ik-Hwan Ryu, Jae-Sook TI Polarization of M2 Macrophages by Interaction between Prostate Cancer Cells Treated with Trichomonas vaginalis and Adipocytes SO KOREAN JOURNAL OF PARASITOLOGY LA English DT Article DE Tichomonas vaginalis; prostate cancer; adipocyte; macrophage; M2 polarization ID ADIPOSE-TISSUE; ALTERNATIVE ACTIVATION; INFLAMMATORY RESPONSE; LOCAL PROLIFERATION; TUMOR PROGRESSION; EPITHELIAL-CELLS; OBESITY; MICROENVIRONMENT; POPULATION; INDUCTION AB Trichomonas vaginalis causes inflammation of the prostate and has been detected in tissues of prostate cancers (PCa), prostatitis and benign prostatic hyperplasia. Obesity is a risk factor for PCa and causes a chronic subclinical inflammation. This chronic inflammation further exacerbates adipose tissue inflammation as results of migration and activation of macrophages. Macrophages are the most abundant immune cells in the PCa microenvironment. M2 macrophages, known as Tumor-Associated Macrophages, are involved in increasing cancer malignancy. In this study, conditioned medium (TCM) of PCa cells infected with live trichomonads contained chemokines that stimulated migration of the mouse preadipocytes (3T3-L1 cells). Conditioned medium of adipocytes incubated with TCM (ATCM) contained Th2 cytokines (IL-4, IL-13). Macrophage migration was stimulated by ATCM. In macrophages treated with ATCM, expression of M2 markers increased, while M1 markers decreased. Therefore, it is suggested that ATCM induces polarization of M0 to M2 macrophages. In addition, conditioned medium from the macrophages incubated with ATCM stimulates the proliferation and invasiveness of PCa. Our findings suggest that interaction between inflamed PCa treated with T. vaginas and adipocytes causes M2 macrophage polarization, so contributing to the progression of PCa. C1 [Chung, Hyo-Yeoung; Kim, Jung-Hyun; Han, Ik-Hwan; Ryu, Jae-Sook] Hanyang Univ, Dept Environm Biol & Med Parasitol, Coll Med, Seoul 04763, South Korea. [Chung, Hyo-Yeoung; Kim, Jung-Hyun; Han, Ik-Hwan; Ryu, Jae-Sook] Hanyang Univ, Dept Biomed Sci, Grad Sch Biomed Sci & Engn, Seoul 04763, South Korea. C3 Hanyang University; Hanyang University RP Ryu, JS (corresponding author), Hanyang Univ, Dept Environm Biol & Med Parasitol, Coll Med, Seoul 04763, South Korea.; Ryu, JS (corresponding author), Hanyang Univ, Dept Biomed Sci, Grad Sch Biomed Sci & Engn, Seoul 04763, South Korea. EM jsryu@hanyang.ac.kr RI Han, Ik-Hwan/P-5516-2017 OI Han, Ik-Hwan/0000-0002-8145-6645 FU Basic Science Program through the National Research Foundation of Korea (NRF) - Ministry of Science and ICT [NRF-2017R1A2B 4002072] FX This research was supported by the Basic Science Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2017R1A2B 4002072). 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Parasitol. PD JUN PY 2020 VL 58 IS 3 BP 217 EP 227 DI 10.3347/kjp.2020.58.3.217 PG 11 WC Parasitology WE Science Citation Index Expanded (SCI-EXPANDED) SC Parasitology GA ME6DL UT WOS:000544744000001 PM 32615735 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Diao, H Tan, RZ Li, JC Zhong, X Wen, D Fan, JM Wang, L AF Diao Hui Tan Rui-Zhi Li Jian-Chun Zhong Xia Wen Dan Fan Jun-Ming Wang Li TI Astragalus propinquus Schischkin and Panax notoginseng (A&P) compound relieved cisplatin-induced acute kidney injury through inhibiting the mincle maintained macrophage inflammation SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Astragalus propinquus schischkin and panax notoginseng compound; AKI; Mincle; BMDM; NF-kappa B ID RESVERATROL; EXPRESSION; SECRETION; PROTECTS; RECEPTOR; RD AB Ethnopharmacological relevance: Acute kidney injury (AM) is a common disease in hospitalized patients, especially in critically ill patients. It is characterised with high morbidity and mortality, and is also an important cause of chronic kidney disease and chronic renal failure. Astragalus propinquus Schischkin and Panax notoginseng (A&P) compound, a famous traditional Chinese medicine, consists of Astragalus propinquus Schischkin, Panax notoginseng, Angelica sinensis, Achyranthes bidentata, and Ecklonia kurome, has been widely used for the treatment of various kidney diseases in the southwest of China. However, the effects of A&P on treatment of AKI and its underlying mechanism are needed to be uncovered. Aim of the study: Recent researches reported that Mincle (Macrophage-inducible C-type lectin) plays a key role in renal injury of AM by regulating the expression and secretion of inflammatory cytokines on macrophage through modulating NF-kappa B signaling pathway. Here, we aimed to investigate the renoprotective effect of A&P on AKI and whether by inhibiting Mincle. Materials and methods: We established a lipopolysaccharide (LPS)-induced Bone Marrow-Derived Macrophage (BMDM) inflammatory cell model and a cisplatin-induced mouse AKI model in vitro and in vivo. Renal histopathology staining was performed to observe kidney morphology. The expression and secretion of inflammatory cytokines were detected by real-time PCR and Enzyme-linked immunosorbent assay. Western blotting was used to detect the protein levels and Flow cytometry performed to detect polarization of macrophage. Results: The results showed that A&P significantly reduced the mRNA expression of IL-1 beta, IL-6, TNF alpha and MCP-1 in LPS-stimulated BMDM cells, and secretion of IL-1 beta and IL-6 in supernatant. The same results were found in Cisplatin-induced AM kidney and serum after treatment with A&P. The data also showed that A&P strongly reduced the mRNA and protein levels of Mincle in vitro and vivo, and also inhibited the activation of Syk and NF-kappa B. Notably, A&P down-regulated the M1 macrophage marker iNOS, which may relate to the inhibition of Mincle. Interestingly, both overexpression of Mincle by transfection of pcDNA3.1-Mincle plasmid and administration of TDB (a ligand of Mincle) can significantly abolished the A&P-inhibited inflammation in BMDM, suggesting Mincle pathway play a key role in macrophage inflammation in AKI. Conclusion: Our findings indicated that A&P protected kidney from inhibiting inflammation through downregulating of Mincle pathway in macrophage in AKI. It provides a potential medicine compound for the treatment of AKI. C1 [Diao Hui; Tan Rui-Zhi; Li Jian-Chun; Zhong Xia; Wen Dan; Fan Jun-Ming; Wang Li] Southwest Med Univ, Affiliated Tradit Med Hosp, Res Ctr Combine Tradit Chinese & Western Med, Luzhou 646000, Sichuan, Peoples R China. [Diao Hui; Wen Dan] Southwest Med Univ, Affiliated Hosp, Dept Nephrol, Luzhou 646000, Sichuan, Peoples R China. [Fan Jun-Ming] Chengdu Med Coll, Chengdu 610000, Sichuan, Peoples R China. C3 Southwest Medical University; Southwest Medical University; Chengdu Medical College RP Wang, L (corresponding author), 319 Zhongshan Rd, Luzhou 646000, Sichuan, Peoples R China. EM wangli120@swmu.edu.cn RI Fan, Junming/JVD-6973-2023; Zhong, Xia/ACJ-8622-2022 FU Luzhou - Southwest Medical Joint Platform Project [2017LZXNYD-Z03, 2018LZXNYD-PT03]; Southwest Medical University and Affiliated Traditional Medicine Hospital Joint program [2018XYLH-002, 2018XYLH-013, 2018XYLH-029]; Luzhou Science and Technology Project [2016-S-68(4/8)]; Luzhou Municipal - Southwest Medical University Joint Special Grant for the Introduction of High-level Talents (Lan Hui-Yao Team); Construction Project of Sichuan Provincial Key Laboratory of Medicine [53] FX This work is supported by Luzhou - Southwest Medical Joint Platform Project (2017LZXNYD-Z03 and 2018LZXNYD-PT03), the Southwest Medical University and Affiliated Traditional Medicine Hospital Joint program (2018XYLH-002, 2018XYLH-013 and 2018XYLH-029), the Luzhou Science and Technology Project (2016-S-68(4/8)), the Luzhou Municipal - Southwest Medical University Joint Special Grant for the Introduction of High-level Talents (Lan Hui-Yao Team), the Construction Project of Sichuan Provincial Key Laboratory of Medicine (2018#53). 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PD APR 24 PY 2020 VL 252 AR 112637 DI 10.1016/j.jep.2020.112637 PG 11 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA KT2UJ UT WOS:000518870800034 PM 32004631 DA 2026-03-26 ER PT J AU Liu, P Wang, LY Wang, YQ Wang, RL Li, FF Zhang, SJ Tao, Z Zhao, HP Han, ZP Chen, ZG Luo, YM AF Liu, Ping Wang, Li-ye Wang, Yu-qing Wang, Rong-liang Li, Fang-fang Zhang, Sijia Tao, Zhen Zhao, Hai-ping Han, Zi-ping Chen, Zhi-gang Luo, Yu-min TI The Chinese herb Fructus Broussonetiae aids learning and memory in chronic cerebral hypoperfusion by reducing proinflammatory microglia activation in rats SO JOURNAL OF INTEGRATIVE NEUROSCIENCE LA English DT Article DE Fructus Broussonetiae; chronic cerebral hypoperfusion; macrophages/microglia polarization; inducible nitric oxide synthase; arginase-1; neuroprotective effect; rats ID WHITE-MATTER DAMAGE; COGNITIVE IMPAIRMENT; DEMENTIA AB The neuroprotective role of Fructus Broussonetiae in a model of chronic cerebral hypoperfusion with cognitive decline was focused on neural plasticity and microglia/macrophage polarization. Chronic cerebral hypoperfusion was induced by bilateral common carotid artery ligation. Fructus Broussonetiae shortened escape latency and added the number of platform crossings of rats, up-regulated the expression of synaptophysin in the gray matter and increased myelin basic protein expression in the white matter. Further mechanistic experiments were conducted to examine microglia activation and M1/M2 polarization. It was shown that Fructus Broussonetiae reduced the activation of microglia revealed by decreased expression of ionized calcium-binding adapter molecule-1, inhibited M1 polarization of microglia and improved microglial M2 polarization shown by down-regulated the expression of inducible nitric oxide synthase and Fc fragment of IgG receptor Illa and up-regulated the expression of arginase-1. In conclusion, the Chinese herb Fructus Broussonetiae can improve cognitive function following chronic cerebral hypoperfusion by down-regulating the activation of microglia, inhibiting microglial M1 polarization, and improving neural plasticity. C1 [Liu, Ping; Wang, Rong-liang; Li, Fang-fang; Zhang, Sijia; Tao, Zhen; Zhao, Hai-ping; Han, Zi-ping; Luo, Yu-min] Capital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, Beijing 10053, Peoples R China. [Liu, Ping; Wang, Rong-liang; Li, Fang-fang; Zhang, Sijia; Tao, Zhen; Zhao, Hai-ping; Han, Zi-ping; Luo, Yu-min] Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 10053, Peoples R China. [Wang, Li-ye; Wang, Yu-qing; Chen, Zhi-gang] Beijing Univ Chinese Med, Dongfang Hosp, Beijing 10078, Peoples R China. [Luo, Yu-min] Beijing Geriatr Med Res Ctr, Beijing 10053, Peoples R China. [Luo, Yu-min] Beijing Key Lab Translat Med Cerebrovasc Dis, Beijing 10053, Peoples R China. [Luo, Yu-min] Beijing Inst Brain Disorders, Beijing 10053, Peoples R China. C3 Capital Medical University; Capital Medical University; Beijing University of Chinese Medicine RP Luo, YM (corresponding author), Capital Med Univ, Xuanwu Hosp, Inst Cerebrovasc Dis Res, Beijing 10053, Peoples R China.; Luo, YM (corresponding author), Capital Med Univ, Xuanwu Hosp, Dept Neurol, Beijing 10053, Peoples R China.; Chen, ZG (corresponding author), Beijing Univ Chinese Med, Dongfang Hosp, Beijing 10078, Peoples R China.; Luo, YM (corresponding author), Beijing Geriatr Med Res Ctr, Beijing 10053, Peoples R China.; Luo, YM (corresponding author), Beijing Key Lab Translat Med Cerebrovasc Dis, Beijing 10053, Peoples R China.; Luo, YM (corresponding author), Beijing Inst Brain Disorders, Beijing 10053, Peoples R China. EM chenzhigang64@126.com; yumin111@ccmu.edu.cn RI Wang, Rongliang/LSI-7188-2024; Wang, Li-ye/OMK-6485-2025; Zhang, Sijia/ISS-6609-2023; zhao, Haiping/I-1306-2014 OI zhao, Haiping/0000-0002-3244-1527 FU National Natural Science Foundation of China [81601157, 81801299, 81801149] FX This project was supported by the National Natural Science Foundation of China (81601157, 81801299, and 81801149). 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PD MAR 30 PY 2020 VL 19 IS 1 BP 21 EP 29 DI 10.31083/j.jin.2020.01.1213 PG 9 WC Neurosciences WE Science Citation Index Expanded (SCI-EXPANDED) SC Neurosciences & Neurology GA KZ3TV UT WOS:000523189000003 PM 32259883 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhao, MN Li, F Jian, YF Wang, XP Yang, HY Wang, J Su, J Lu, XM Xi, MM Wen, AD Li, J AF Zhao, Meina Li, Fei Jian, Yufan Wang, Xinpei Yang, Hongyan Wang, Jun Su, Jing Lu, Xinming Xi, Miaomiao Wen, Aidong Li, Jia TI Salvianolic acid B regulates macrophage polarization in ischemic/reperfused hearts by inhibiting mTORC1-induced glycolysis SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE Macrophage polarization; Myocardial ischemia/reperfusion injury; Salvianolic acid B; MTORC1 ID MYOCARDIAL-INFARCTION; NLRP3 INFLAMMASOME; M2 POLARIZATION; ACTIVATION; REPAIR; MILTIORRHIZA; MONOCYTE; HIF-1-ALPHA; PLASTICITY; IL-1-BETA AB Macrophages play important roles in the healing and remodeling of cardiac tissues after myocardial ischemia/ reperfusion (MI/R) injury. Here we investigated the potential effects of salvianolic acid B (SalB), one of the abundant and bioactive compounds extracted from Chinese herb Salvia Miltiorrhiza (Danshen), on macrophage-mediated inflammation after MI/R and the underlying mechanisms. In primary cultured bone marrow-derived macrophages (BMDMs), SalB attenuated lipopolysaccharide (LPS)-induced M1 biomarkers (IL-6, iNOS, CCL2 and TNF-alpha) mRNA expression in a concentration-dependent manner. In contrast, M2 biomarkers (Arg1, Clec10a and Mrc) mRNA levels following interleukinin-4 (IL-4) stimulation were significantly upregulated by SalB. In addition, LPS stimulation potently induced transcriptional upregulation of RagD, an important activation factor of mammalian target of rapamycin complex 1 (mTORC1). Interestingly, SalB inhibited RagD upregulation and mTORC1 activation, decreased glycolysis, and reduced inflammatory cytokine production in LPS-stimulated macrophages, all of which were blunted in RagD knockdown macrophages. In mice subjected to MI/R, SalB treatment decreased cardiac Ml-macrophages and increased M2-macrophages at 3 days post-MI/R, followed by decreased collagen deposition and ameliorated cardiac dysfunction at 7 days post-MI/R. Collectively, our data have shown that SalB decreases Ml-polarized macrophages in MI/R hearts via inhibiting mTORC1-dependent glycolysis, which might contribute to alleviated inflammation and improved cardiac dysfunction afforded by SalB after MI/R. C1 [Zhao, Meina; Li, Fei; Jian, Yufan; Wang, Jun; Su, Jing; Xi, Miaomiao; Wen, Aidong] Fourth Mil Med Univ, Xijing Hosp, Dept Pharm, Xian 710032, Shaanxi, Peoples R China. [Zhao, Meina] Shaanxi Univ Chinese Med, Coll Pharm, Xianyang 712046, Shaanxi, Peoples R China. [Wang, Xinpei; Yang, Hongyan; Li, Jia] Fourth Mil Med Univ, Sch Aerosp Med, Xian 710032, Peoples R China. [Wang, Jun] Shaanxi Armed Police Corps Hosp, Dept Anesthesiol, Xian 710054, Shaanxi, Peoples R China. [Lu, Xinming] YouYi Clin Labs Shaanxi, Xian 710065, Shaanxi, Peoples R China. [Xi, Miaomiao] TANK Med Biol Inst Xian, Xian 710032, Shaanxi, Peoples R China. C3 Air Force Medical University; Shaanxi University of Chinese Medicine; Air Force Medical University RP Xi, MM; Wen, AD (corresponding author), Fourth Mil Med Univ, Xijing Hosp, Dept Pharm, Xian 710032, Shaanxi, Peoples R China.; Li, J (corresponding author), Fourth Mil Med Univ, Sch Aerosp Med, Xian 710032, Peoples R China. EM miaomiaoxi2014@163.com; adwen-2004@hotmail.com; jiali816@fmmu.edu.cn RI ; Zhao, Meina/KBP-8496-2024; Wen, Aidong/I-5009-2017; Yang, Hongyan/AAQ-6670-2021 OI Wang, Xinpei/0000-0002-8480-0990; Li, Fei/0000-0002-7679-1641; Zhao, Meina/0009-0000-1645-6684; Wen, Aidong/0000-0002-4535-0501; FU National Natural Science Foundation of China [31771265, 31371150, 81470174]; National High Technology Research and Development Program of China [2014AA020542]; Shaanxi Outstanding Youth Fellowship; Younth Innovation Team of Shaanxi Universites; Talent Programme of Fourth Military Medical University [2019XC089] FX Supported by the National Natural Science Foundation of China (31771265, 31371150, 81470174), National High Technology Research and Development Program of China (2014AA020542). Shaanxi Outstanding Youth Fellowship, the Younth Innovation Team of Shaanxi Universites and the Talent Programme of Fourth Military Medical University (2019XC089). 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J. Pharmacol. PD MAR 15 PY 2020 VL 871 AR 172916 DI 10.1016/j.ejphar.2020.172916 PG 10 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA KM1HR UT WOS:000513869500004 PM 31930970 OA Green Submitted DA 2026-03-26 ER PT J AU Xu, B Zhang, HT Wang, YC Huang, SR Xu, L AF Xu, Bin Zhang, Haitao Wang, Yuchao Huang, Shuran Xu, Li TI Mechanism of Xu Li's Experiential Prescription for the Treatment of EGFR-Positive NSCLC SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article ID TRADITIONAL CHINESE MEDICINE; TUMOR; CANCER; MACROPHAGES; ACTIVATION; AUTOPHAGY; POLARIZATION; INHIBITION; ERLOTINIB AB The non-small-cell lung cancer (NSCLC) is the most common lung cancer which seriously threatens the human health. Xu Li's experiential prescription (XLEP) can treat the NSCLC. However, whether XLEP can regulate the autophagy in the EGFR-positive NSCLC still remains unknown. We found that the cellular activity of drug-resistant cells and sensitive cells were all decreased in the TCM group and TCM + Gef group. The expression of autophagy-associated proteins (mTOR and Beclin1-Vps34) in drug-resistant cells was decreased in the TCM group, while the expression of autophagy-associated proteins in sensitive cells was all decreased in the TCM + Gef group. The ratio of M1/M2 macrophages was increased when IL-4-induced RAW264.7 was treated with TCM. TCM treatment promoted the expression of CCL2 and CCL3 while it downregulated the CCL22 level among A549, H1975, and PC9 cells. The expression of TNF-alpha and IL-6 was increased, and the expression of IL-10 and TGF-beta was decreased in IL-4-induced RAW264.7 cells treated with TCM. And, TCM treatment also decreased the expression of Fizz1 and TGM2. In conclusion, this study indicated that XLEP could suppress the proliferation of EGFR-TKI-resistant cancer cells and increase the ratio of M1/M2 macrophages by inhibiting autophagy to treat the drug-resistant EGFR-positive NSCLC. C1 [Xu, Bin; Wang, Yuchao; Huang, Shuran] Nanjing Univ Chinese Med, Nanjing 210023, Peoples R China. [Xu, Bin; Zhang, Haitao] Nanjing Med Univ, Dept Resp Med, Affiliated Brain Hosp, Chest Hosp Dist, Nanjing 210029, Peoples R China. [Wang, Yuchao] Nanjing Med Univ, Dept Endoscop Ctr, Affiliated Brain Hosp, Chest Hosp Dist, Nanjing 210029, Peoples R China. [Huang, Shuran] Nanjing Univ Chinese Med, Affiliated Hosp 3, Nanjing 210022, Peoples R China. [Xu, Li] Nanjing Univ Chinese Med, Clin Med Coll 1, Nanjing 210023, Peoples R China. C3 Nanjing University of Chinese Medicine; Nanjing Medical University; Nanjing Medical University; Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine RP Xu, L (corresponding author), Nanjing Univ Chinese Med, Clin Med Coll 1, Nanjing 210023, Peoples R China. EM lxu7528@163.com RI Zhang, Jihui/U-7562-2017 FU project "Study on Community Management Model and Effect Evaluation of Lung Cancer" [BE2015691] FX This work was supported by the project "Study on Community Management Model and Effect Evaluation of Lung Cancer" (BE2015691). 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PD MAR 12 PY 2020 VL 2020 AR 8787153 DI 10.1155/2020/8787153 PG 9 WC Integrative & Complementary Medicine WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine GA KY4GS UT WOS:000522528400003 PM 32256661 OA Green Submitted, hybrid DA 2026-03-26 ER PT J AU Jin, ZC Shen, CF Zhang, HD Qi, RZ Guo, QJ Liu, R Hua, BJ Shi, Z AF Jin, Zhichao Shen, Chunfeng Zhang, Haidong Qi, Runzhi Guo, Qiujun Liu, Rui Hua, Baojin Shi, Zhan TI Chinese medicine Xiaoshui decoction inhibits malignant pleural effusion in mice and mediates tumor-associated macrophage polarization by activating autophagy SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article DE Xiaoshui decoction; Malignant pleural effusion; Macrophage; Autophagy; Traditional Chinese medicine ID EFFICACY; MODELS AB Ethnopharmacological relevance: Xiaoshui decoction (XSD) is a traditional Chinese medicine compound prescription that has been shown to reinforce the spleen and remove the fluid retention, while being widely used in the treatment of malignant pleural effusion (MPE). We previously reported that XSD alleviates symptoms and improves the quality of life in patients with MPE; however, the mechanism employed by XSD on MPE has not yet been elucidated. Aim of the study: To investigate the role and mechanism of XSD in inhibiting the development of MPE, and in regulating macrophage polarization in vitro and in vivo. Materials and methods: A murine MPE model was used to study the effect of XSD on MPE. Mice with MPE were randomly allocated to a control group and XSD-low-dose (1.144 g/mL), XSD-middle-dose (2.288 g/mL), XSD-high-dose (4.576 g/mL), or cisplatin groups. RAW264.7 cells were induced to form tumor-associated macrophages (TAMs) as well as M1 and M2 macrophages using different conditioned media in vitro. Results: XSD effectively inhibited MPE formation, reduced pleural permeability and angiogenesis, and prolonged mice survival. Particularly, XSD treatment induced the polarization of TAMs to the M1 phenotype in MPE. Moreover, in-vitro XSD remarkably promoted the expansion of M1 macrophages and reduced M2 macrophages by enhancing autophagy. Conclusions: XSD inhibits MPE development and regulates macrophage polarization by activating autophagy, indicating that XSD may serve as a novel option for integrative MPE therapies. C1 [Jin, Zhichao; Shi, Zhan] China Acad Chinese Med Sci, Inst Basic Res Clin Med, 16 Nanxiaojie, Beijing 100700, Peoples R China. [Jin, Zhichao; Zhang, Haidong] Nanjing Univ Chinese Med, Affiliated Hosp, Jiangsu Prov Hosp Chinese Med, Nanjing 210029, Jiangsu, Peoples R China. [Shen, Chunfeng] Nanjing Univ Chinese Med, Changzhou TCM Hosp, Changzhou 213003, Jiangsu, Peoples R China. [Qi, Runzhi; Guo, Qiujun; Liu, Rui; Hua, Baojin] China Acad Chinese Med Sci, Guanganmen Hosp, 5 Beixiange Rd, Beijing 100053, Peoples R China. C3 China Academy of Chinese Medical Sciences; Institute of Basic Research In Clinical Medicine, CACMS; Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine; Guang'anmen Hospital, CACMS; China Academy of Chinese Medical Sciences RP Shi, Z (corresponding author), China Acad Chinese Med Sci, Inst Basic Res Clin Med, 16 Nanxiaojie, Beijing 100700, Peoples R China. EM jzc0702@126.com; 18961191985@189.com; zhdrk@163.com; qrz1211@126.com; m2928@126.com; drliur@126.com; huabaojin@souhu.com; shizhan209@163.com RI Shi, Z/ISB-4324-2023 FU National Natural Science Foundation of China [81603610, 81904110]; Science and Technology Planning Project of Jiangsu Province, China [BK20191086] FX We acknowledge the National Natural Science Foundation of China [grant number 81603610, 81904110] and Science and Technology Planning Project of Jiangsu Province, China [grant number BK20191086] for founding support, and Guang'anmen Hospital, China Academy of Chinese Medical Sciences for animal handling and sample collection. We sincerely appreciate technical assistance for experiments from Yingxia Pei, Xin Qi, Yun Zhang, and Qi Zheng, Guang'anmen Hospital, China Academy of Chinese Medical Sciences. 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PD MAR 1 PY 2020 VL 249 AR 112412 DI 10.1016/j.jep.2019.112412 PG 11 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA KO2XO UT WOS:000515412700045 PM 31751649 DA 2026-03-26 ER PT J AU Xu, M Li, X Song, LC AF Xu, Ming Li, XiaoYong Song, Laichun TI Baicalin regulates macrophages polarization and alleviates myocardial ischaemia/reperfusion injury via inhibiting JAK/STAT pathway SO PHARMACEUTICAL BIOLOGY LA English DT Article DE Chinese herb extracts; inflammation; myocardial injury; cardiac apoptosis ID ISCHEMIA-REPERFUSION INJURY; JAK-STAT PATHWAY; ISCHEMIA/REPERFUSION INJURY; TISSUE-REPAIR; RAT HEARTS; DAMAGE; HYPOXIA/REOXYGENATION; INFLAMMATION; MECHANISMS; PROTECTION AB Context Baicalin is an active compound which demonstrates cardioprotection effects against myocardial ischaemia/reperfusion injury (MI/RI). Objective To investigate how baicalin protects against myocardial injury and to explore its potential mechanism. We hypothesized that baicalin-modulated macrophages change from M1 (pro-inflammatory subset) to M2 (anti-inflammatory subset) under I/R stress. Materials and methods We established an ischaemia/reperfusion (I/R) model using Sprague Dawley (SD) rat, then baicalin was intragastric administration (20, 60 or 120 mg/kg) for 24 h. The rats were randomly divided into five groups (n = 10): control, I/R, I/R + baicalin (20 mg/kg), I/R + baicalin (60 mg/kg) and I/R + baicalin (120 mg/kg). Cardiac function was detected by echocardiography, HE staining and ELISA, respectively. Macrophage phenotype was examined by flow cytometry. Furthermore, IHC, qRT-PCR and WB were employed to analyse the related mechanisms. Results The study showed that baicalin (20, 60 or 120 mg/kg) significantly improved cardiac function and impeded cardiac apoptosis in rats. In addition, the repair of myocardial morphology (reduced neutrophil infiltration) further confirmed its cardiacprotective effect. Moreover, baicalin effectively decreased iNOS, IL-1 beta and IL-6, and up-regulated Arg-1, IL-10 and TGF-beta via changing the macrophage phenotype (from M1 towards M2). Notably, treatment with baicalin also inhibited the phosphorylation levels of JAK2 and STAT3. Discussion and conclusions:It was confirmed that baicalin alleviated post-I/R myocardial injury and reduced inflammation via JAK/STAT pathway, and baicalin treatment might be recommended as a new approach for myocardial ischaemic complications. C1 [Xu, Ming; Li, XiaoYong; Song, Laichun] Wuhan Asia Heart Hosp, Dept Cardiac Surg, 753 Jinghan Rd, Wuhan, Peoples R China. RP Song, LC (corresponding author), Wuhan Asia Heart Hosp, Dept Cardiac Surg, 753 Jinghan Rd, Wuhan, Peoples R China. 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PD JAN 1 PY 2020 VL 58 IS 1 BP 655 EP 663 DI 10.1080/13880209.2020.1779318 PG 9 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA MI8AL UT WOS:000547623300001 PM 32649845 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Chen, R Lu, XY Li, Z Sun, Y He, ZX Li, XM AF Chen, Ran Lu, Xiuying Li, Zhen Sun, Yajing He, Zhengxin Li, Xiaoming TI Dihydroartemisinin Prevents Progression and Metastasis of Head and Neck Squamous Cell Carcinoma by Inhibiting Polarization of Macrophages in Tumor Microenvironment SO ONCOTARGETS AND THERAPY LA English DT Article DE dihydroartemisinin; tumor-associated macrophages; HNSCC; STAT3; macrophage polarization ID IN-VITRO; T-CELLS; CANCER; EXPRESSION; ACTIVATION; RECEPTOR; STAT3; LIPOPOLYSACCHARIDE; CYCLOOXYGENASE-2; DIFFERENTIATION AB Background: Polarized M2 macrophages are an important type of tumor-associated macrophage (TAM), with roles in the growth, invasion, and migration of cancer cells in the tumor microenvironment. Dihydroartemisinin (DHA), a traditional Chinese medicine extract, has been shown to inhibit the progression and metastasis of head and neck squamous cell carcinoma (HNSCC); however, the effect of DHA on cancer prevention, and the associated mechanism, has not been investigated in the tumor microenvironment. Materials and Methods: First, human Thp-1 monocytes were induced and differentiated into M2 macrophages using phorbol 12-myristate 13-acetate (PMA), interleukin-6 (IL-6), and interleukin-4 (IL-4). Induction success was confirmed by cell morphology evaluation, flow cytometry, and quantitative real-time polymerase chain reaction (qRT-PCR). Then, DHA was applied to interfere with M2 macrophage polarization, and conditioned medium (CM), including conditioned medium from M2 macrophages (M2-CM) and conditioned medium from M2 macrophages with DHA (M2-DHA-CM), was obtained. CM was applied to Fadu or Cal-27 cells, and its effects on cancer invasion, migration, and angiogenesis were evaluated using transwell, wound-healing, and tube formation assays, respectively. Finally, Western blotting was used to evaluate the relationship between signal transducer and activator of transcription 3 (STAT3) signaling pathway activation and M2 macrophage polarization. Results: Human Thp-1 monocytes were successfully polarized into M2-like TAMs using PMA, IL-6, and IL-4. We found that M2-like TAMs promoted the invasion, migration, and angiogenesis of HNSCC cells; however, DHA significantly inhibited IL-4/IL-6-induced M2 macrophage polarization. Additionally, as DHA induced a decrease in the number of M2-like TAMs, M2-DHA-CM inhibited the induction of invasion, migration, and angiogenesis of Fadu and Cal-27 cells. Finally, DHA inhibited M2 macrophage polarization by blocking STAT3 pathway activation in macrophages. Conclusion: DHA inhibits the invasion, migration, and angiogenesis of HNSCC by preventing M2 macrophage polarization via blocking STAT3 phosphorylation. C1 [Chen, Ran; Li, Xiaoming] Hebei Med Univ, Grad Sch, Shijiazhuang, Hebei, Peoples R China. [Chen, Ran; Lu, Xiuying; Li, Zhen; Sun, Yajing; Li, Xiaoming] 980th Hosp PLA Joint Logist Support Force, Dept Otolaryngol Head & Neck Surg, Shijiazhuang, Hebei, Peoples R China. [He, Zhengxin] 980th Hosp PLA Joint Logist Support Force, Dept Lab Med, Shijiazhuang, Hebei, Peoples R China. C3 Hebei Medical University RP Li, XM (corresponding author), Hebei Medicial Univ, Dept Otolaryngol Head & Neck Surg, Shijiazhuang 050017, Hebei, Peoples R China.; Li, XM (corresponding author), 980th Hosp PLA Joint Logist Support Force, Shijiazhuang 050082, Hebei, Peoples R China. EM xmlmo@126.com RI chen, ran/KZU-2340-2024; He, Zhengxin/HKX-3448-2023 FU Key Research and Development Project Plan of Hebei Province Science and Technology Department [18277736D]; Key Subject of Medical Science Research in Hebei Province of China [20170201] FX This study was supported by the Key Research and Development Project Plan of Hebei Province Science and Technology Department (No. 18277736D), and Key Subject of Medical Science Research in Hebei Province of China (No. 20170201). 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PY 2020 VL 13 BP 3375 EP 3387 DI 10.2147/OTT.S249046 PG 13 WC Biotechnology & Applied Microbiology; Oncology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biotechnology & Applied Microbiology; Oncology GA LF0XK UT WOS:000527150300001 PM 32425545 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Wang, Q Zhou, X Yang, L Luo, MC Han, L Lu, Y Shi, Q Wang, YJ Liang, QQ AF Wang, Qiong Zhou, Xin Yang, Long Luo, Maocai Han, Lei Lu, Yao Shi, Qi Wang, Yongjun Liang, Qianqian TI Gentiopicroside (GENT) protects against sepsis induced by lipopolysaccharide (LPS) through the NF-κB signaling pathway SO ANNALS OF TRANSLATIONAL MEDICINE LA English DT Article DE Gentiopicroside (GENT); lipopolysaccharide shock (LPS shock); primary macrophages; NF-kappa B ID MONONUCLEAR PHAGOCYTE SYSTEM; IMMUNOHISTOCHEMICAL LOCALIZATION; MACROPHAGES; INFLAMMATION; INTERLEUKIN-1-BETA; IDENTIFICATION; SUPPRESSION AB Background: Sepsis is a high-mortality disease without effective therapeutic options. The hyperactivation of the monocyte-macrophage system, especially M1 macrophages, triggers the onset of septic shock. Gentiopicroside (GENT), the main active component in the traditional Chinese medicinal herb Radix Gentianae, has been shown to have anti-inflammatory properties. Nevertheless, this anti-inflammatory effect has not been fully elucidated. Methods: In vitro, we stimulated primary bone marrow-derived macrophages ( BMMs) or peritoneal elucidated macrophages (PEMs) by lipopolysaccharide (LPS) and interferon (IFN)-gamma and pre-treated with GENT and we tested the cytokines such as interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF) alpha production by enzyme linked immunosorbent assay (ELISA) or real-time quantitative PCR (qPCR). Further, we determined the NF-kappa B-mediated inflammatory pathway such as IKK alpha/beta and p65 phosphorylation by Western blot. Then we detected the p65 nuclear localization by immunofluorescent staining. Moreover, NF-kappa B inhibitor and p65-targeted siRNAs were further used to validate the anti-inflammatory mechanism of GENT. In vivo, GENT (50 mg/kg) was administered intragastrically before and after LPS (40 mg/kg) injection. The death time were recorded and the serum levels of IL-1 beta, IL-6 and TNF alpha were tested by ELISA, and the IL-1 beta, IL-6 and TNF alpha mRNA expression in the lung were test by qPCR and the M1 infiltration in the lung were determined by F4/80 and INOS immunofluorescent staining Results: In vitro, we observed that GENT reduced the inflammatory cytokine production of BMMs stimulated by ( LPS)/IFN-gamma and ameliorated the phosphorylation of IKK alpha/beta and p65, the degradation of I kappa B alpha, and the translocation of p65 into the nucleus. We did not find GENT has any effect on MAPK signaling under LPS/IFN-gamma stimulation. NF-kappa B inhibitor and p65 siRNAs eliminated the inhibition effect of GENT. In vivo, we observed GENT prevented mice from dying in the LPS-induced shock model and decreased the serum levels of IL-1 beta and IL-6, the mRNA expression of IL-1 beta, IL-6 and TNFa in lung tissue, and the amount of M1 macrophage infiltration in the lung. Conclusions: GENT prevented LPS/IFN-gamma-induced inflammatory cytokine production by macrophages through the NF-kappa B signaling pathway in vitro and protected against the endotoxin shock induced by LPS in vivo. C1 [Wang, Qiong; Shi, Qi; Wang, Yongjun; Liang, Qianqian] Shanghai Univ Tradit Chinese Med, Longhua Hosp, Inst Spine, 725 Wan Ping South Rd, Shanghai 200032, Peoples R China. [Wang, Qiong; Shi, Qi; Wang, Yongjun; Liang, Qianqian] Shanghai Univ Tradit Chinese Med, Key Lab Theory & Theory & Therapy Muscles & Bones, Minist Educ, Shanghai 200032, Peoples R China. [Zhou, Xin; Han, Lei; Lu, Yao] Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China. [Zhou, Xin; Han, Lei; Lu, Yao] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China. [Yang, Long] Shanghai Eighth Peoples Hosp, Dept Rehabil Med, Shanghai 200235, Peoples R China. [Luo, Maocai] Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Pediat, Shanghai 200025, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine; Chinese Academy of Sciences; Center for Excellence in Molecular Cell Science, CAS; Chinese Academy of Sciences; Center for Excellence in Molecular Cell Science, CAS; Shanghai Jiao Tong University RP Wang, YJ; Liang, QQ (corresponding author), Shanghai Univ Tradit Chinese Med, Longhua Hosp, Inst Spine, 725 Wan Ping South Rd, Shanghai 200032, Peoples R China. EM yjwang88@hotmail.com; liangqianqiantcm@126.com RI Luo, Maocai/HZJ-9817-2023; 卢, 遥/KCJ-5425-2024; Zhou, Xin/AAY-4100-2021 OI Zhou, Xin/0000-0001-9281-3612 FU National Natural Science Foundation of China [81822050, 81673990, 81730107, 81330085]; Leading medical talents in Shanghai [2019LJ02]; Dawn plan of Shanghai Municipal Education Commission [19SG39]; Shanghai TCM Medical Center of Chronic Disease [2017ZZ01010]; Program for the Innovative Research Team of the Ministry of Science and Technology of China [2015RA4002]; "Innovation Team" Development Projects [IRT1270]; Research Project of Shanghai Science and Technology Commission [17401971100]; Three year action plan of Shanghai to further speed up the development of traditional Chinese Medicine [ZY(2018-2020)-CCCX-3003] FX This work was supported by research grants from the National Natural Science Foundation of China (81822050 and 81673990 to Q Liang, 81730107 to Y Wang, 81330085 to Q Shi), Leading medical talents in Shanghai (2019LJ02 to Q Liang), Dawn plan of Shanghai Municipal Education Commission (19SG39 to Q Liang), the Shanghai TCM Medical Center of Chronic Disease (2017ZZ01010 to Y Wang), the Program for the Innovative Research Team of the Ministry of Science and Technology of China (2015RA4002 to Y Wang), the "Innovation Team" Development Projects (IRT1270 to Y Wang), and the Research Project of Shanghai Science and Technology Commission (17401971100 to Q Liang), Three year action plan of Shanghai to further speed up the development of traditional Chinese Medicine [ZY(2018-2020)-CCCX-3003 to Y Wang]. 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TRANSL. MED. PD DEC PY 2019 VL 7 IS 23 AR 731 DI 10.21037/atm.2019.11.126 PG 15 WC Oncology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Research & Experimental Medicine GA JW7WF UT WOS:000503257700020 PM 32042747 OA Green Published, gold DA 2026-03-26 ER PT J AU Lu, WJ Wang, QY Sun, XQ He, H Wang, QX Wu, Y Liu, Y Wang, Y Li, C AF Lu, Wenji Wang, Qiyan Sun, Xiaoqian He, Hao Wang, Qixin Wu, Yan Liu, Yue Wang, Yong Li, Chun TI Qishen Granule Improved Cardiac Remodeling via Balancing M1 and M2 Macrophages SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE Qishen Granule; myocardial fibrosis; splenic monocytes; macrophages; angiogenesis ID MYOCARDIAL FIBROSIS; SPLENIC RESERVOIR; MONOCYTES; RESIDENT; ROLES; MODEL; MICE AB Macrophages play a pivotal role in myocardial remodeling (MR) process which could eventually lead to heart failure. Splenic monocytes could be mobilized and recruited under inflammatory conditions and differentiated into different types of macrophages in heart tissues. Inflammatory M1 macrophages could aggravate tissue damage whereas M2 macrophages could promote angiogenesis and tissue repair process. Unbalanced ratio of M1/M2 macrophages may eventually lead to adverse remodeling. Therefore, regulating differentiation and activities of macrophages are potential strategies for the management of myocardial remodeling. Qishen Granule (QSG) is an effective Chinese medicine for treating heart failure. Our previous studies demonstrated that QSG could inhibit myocardial fibrosis through regulating secretion of cytokines and activation of macrophages. However, the detailed effects of QSG on had not been elucidated yet. In this study, we aimed to explore the effect of QSG on the release of splenic monocytes, the recruitment of monocytes into heart tissues and the differentiation of macrophages under ischemic conditions. Our results showed that QSG could suppress the release of monocytes from the spleen and recruitment of monocytes to heart tissues via inhibiting splenic angiotensin (Ang) II/AT1-cardiac monocyte chemotactic protein (MCP)-1/CC chemokine receptor 2 (CCR2) pathway. The anti-fibrotic effect of QSG was exerted by inhibiting M1 macrophage-activated transforming growth factor (TGF)-beta 1/Smad3 pathway. Meanwhile, QSG could promote angiogenesis by promoting differentiation of M1 macrophages into M2 macrophages. Our results suggest that compounds of Chinese medicine have synergistic effects on cardiac and splenic organs through regulating differentiation of monocytes/macrophages in inhibiting myocardial remodeling. C1 [Lu, Wenji; Sun, Xiaoqian; Wang, Yong] Beijing Univ Chinese Med, Coll Chinese Med, Beijing, Peoples R China. [Wang, Qiyan; He, Hao] Beijing Univ Chinese Med, Sch Life Sci, Beijing, Peoples R China. [Wang, Qixin; Li, Chun] Beijing Univ Chinese Med, Modern Res Ctr Tradit Chinese Med, Sch Chinese Mat Med, Beijing, Peoples R China. [Wu, Yan] Beijing Univ Chinese Med, Ctr Sci Expt, Beijing, Peoples R China. [Liu, Yue] China Acad Chinese Med Sci, Xiyuan Hosp, Cardiovasc Dis Ctr, Beijing, Peoples R China. C3 Beijing University of Chinese Medicine; Beijing University of Chinese Medicine; Beijing University of Chinese Medicine; Beijing University of Chinese Medicine; Xiyuan Hospital, CACMS; China Academy of Chinese Medical Sciences RP Wang, Y (corresponding author), Beijing Univ Chinese Med, Coll Chinese Med, Beijing, Peoples R China.; Li, C (corresponding author), Beijing Univ Chinese Med, Modern Res Ctr Tradit Chinese Med, Sch Chinese Mat Med, Beijing, Peoples R China.; Liu, Y (corresponding author), China Acad Chinese Med Sci, Xiyuan Hosp, Cardiovasc Dis Ctr, Beijing, Peoples R China. EM liuyueheart@hotmail.com; doctor_wangyong@163.com; lichun19850204@163.com RI Liu, Yue/U-8022-2017; Li, Chun/MTD-8257-2025 OI Li, Chun/0000-0001-8643-9679 FU National Natural Science Foundation of China [81673802, 81530100, 81673712, 81822049]; Fok Ying Tung Education Foundation [151044]; Beijing Nova program [Z171100001117028]; Talent Young Scientist of China Association for Science and Technology [CACM-2017-QNRC2-C13, CACM-2018-QNRC2-C07]; Fundamental Research Funds for the Central Universities [2017-JYB-JS-020] FX This work was supported by the Grants from the National Natural Science Foundation of China (Nos. 81673802, 81530100, 81673712, and 81822049), Fok Ying Tung Education Foundation (No. 151044), Beijing Nova program (No. Z171100001117028), Talent Young Scientist of China Association for Science and Technology (No. CACM-2017-QNRC2-C13, No. CACM-2018-QNRC2-C07), the Fundamental Research Funds for the Central Universities (2017-JYB-JS-020). 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PD NOV 25 PY 2019 VL 10 AR 1399 DI 10.3389/fphar.2019.01399 PG 10 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA JU6JH UT WOS:000501780300001 PM 31824322 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Wang, LX Wu, WB Zhu, XW Ng, WY Gong, CY Yao, C Ni, ZY Yan, XW Fang, C Zhu, SG AF Wang, Lixin Wu, Wenbin Zhu, Xiaowen Ng, Wanyi Gong, Chenyuan Yao, Chao Ni, Zhongya Yan, Xuewei Fang, Cheng Zhu, Shiguo TI The Ancient Chinese Decoction Yu-Ping-Feng Suppresses Orthotopic Lewis Lung Cancer Tumor Growth Through Increasing M1 Macrophage Polarization and CD4+ T Cell Cytotoxicity SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE non-small cell lung cancer; Yu-Ping-Feng; Macrophages; CD4(+) T cells; tumor microenvironment ID TRANSPORTERS; RECRUITMENT; STATISTICS; PLASTICITY; RESISTANCE; PATHWAYS AB Background: The tumor microenvironment (TME) has a deep influence on cancer progression and has become into a new target for cancer treatment. In our previous study, we found that Yu-Ping-Feng (YPF), an ancient Chinese herbal decoction, significantly inhibited the Lewis lung cancer (LLC) tumor growth in a subcutaneous xenograft tumor model, and prolonged the survival of tumor-bearing mice. But the regulation of Yu-Ping-Feng on tumor microenvironment is unknown. Methods: To access the effect of Yu-Ping-Feng on non-small cell lung cancer, an orthotopic luciferase stably expressed Lewis lung cancer tumor model was established on C57BL/6 mice, and then the survival and the tumor growth were evaluated. To address the tumor microenvironment immune regulation, the percentages of CD4(+) T cells, CD8(+) T cells, natural killer cells (NK), regulatory T cells (Treg), macrophages, and myeloid-derived suppressor cells (MDSC) in spleens and tumor tissues, the macrophage polarization and CD4(+) T cell cytotocixity were analyzed by flow cytometry, biophotonic cell killing activity assay, real-time PCR and western-blot. Results: Yu-Ping-Feng significantly prolonged orthotopic lung tumor-bearing mouse survival, and increased the percentages of CD4(+) T cell and M1 macrophages and the cytotoxicity of CD4(+) T cells. Yu-Ping-Feng significantly enhanced macrophage-mediated lysis of LLC in a concentration-dependent manner, and had no effect on CD4(+) T cell-mediated lysis of LLC, but significantly increased CD4(+) T cell-mediated lysis after co-incubated with macrophages. In addition, Yu-Ping-Feng induced M1 macrophage polarization through promoting the phosphorylation of STAT1. Conclusion: Yu-Ping-Feng induced M1 macrophages polarization, and then activated CD4(+) T lymphocytes, resulting in killing of LLC cells. Yu-Ping-Feng was a potent regulator of M1 macrophage polarization and might have a promising application in tumor immunotherapy. C1 [Wang, Lixin; Yao, Chao; Zhu, Shiguo] Shanghai Univ Tradit Chinese Med, Sch Basic Med Sci, Dept Immunol & Pathogen Biol, Shanghai, Peoples R China. [Wu, Wenbin] Shanghai Univ Tradit Chinese Med, Expt Anim Ctr, Expt Ctr Sci & Technol, Shanghai, Peoples R China. [Zhu, Xiaowen; Ng, Wanyi; Gong, Chenyuan; Ni, Zhongya; Yan, Xuewei; Fang, Cheng; Zhu, Shiguo] Shanghai Univ Tradit Chinese Med, Sch Basic Med Sci, Lab Integrat Med, Shanghai, Peoples R China. C3 Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine; Shanghai University of Traditional Chinese Medicine RP Zhu, SG (corresponding author), Shanghai Univ Tradit Chinese Med, Sch Basic Med Sci, Dept Immunol & Pathogen Biol, Shanghai, Peoples R China.; Zhu, SG (corresponding author), Shanghai Univ Tradit Chinese Med, Sch Basic Med Sci, Lab Integrat Med, Shanghai, Peoples R China. EM zhushiguo@shutcm.edu.cn RI GONG, CHEN/JDW-5727-2023 OI Fang, Cheng/0000-0002-7978-4420 FU National Natural Science Foundation of China [81803933, 81903848, 81903932]; Natural Science Foundation of Shanghai [19ZR1457500]; Xinglin Young Talent Program of Shanghai University of Traditional Chinese Medicine [30304113598] FX This study was supported by National Natural Science Foundation of China (81803933, 81903848, 81903932), Natural Science Foundation of Shanghai (19ZR1457500), Xinglin Young Talent Program of Shanghai University of Traditional Chinese Medicine, and the interdisciplinary project of Clinical Immunology of Traditional Chinese Medicine in Shanghai (30304113598). The funding body had no role in the design of the study, collection, analysis, interpretation of data, and writing the manuscript. 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PD NOV 8 PY 2019 VL 10 AR 1333 DI 10.3389/fphar.2019.01333 PG 16 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA JQ5FL UT WOS:000498971200001 PM 31780946 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Leong, W Huang, GX Khan, I Xia, WR Li, YC Liu, YH Li, XA Han, RX Su, ZR Hsiao, WLW AF Leong, Waikit Huang, Guoxin Khan, Imran Xia, Wenrui Li, Yucui Liu, Yuhong Li, Xiaoang Han, Ruixuan Su, Ziren Hsiao, W. L. Wendy TI Patchouli Essential Oil and Its Derived Compounds Revealed Prebiotic-Like Effects in C57BL/6J Mice SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE patchouli essential oil; patchouli alcohol; pogostone; beta-patchoulene; gut microbiota ID CHAIN FATTY-ACIDS; GUT MICROBIOTA; POGOSTEMON-CABLIN; (-)-PATCHOULI ALCOHOL; HELICOBACTER-PYLORI; POGOSTONE; HERBA; DIET; INFLAMMATION; PROTECTS AB Pogostemon cablin (Blanco) Benth (PC) is a Chinese medicinal plant traditionally used for the treatment of gastrointestinal symptoms. To investigate the prebiotic effect of patchouli essential oil (PEO) and its derived compounds through the modulation of gut microbiota (GM). C57BL/6J mice were treated with the PEO and three active components of PEO, i.e. patchouli alcohol (PA), pogostone (PO) and beta-patchoulene (beta-PAE) for 15 consecutive days. Fecal samples and mucosa were collected for GM biomarkers studies. PEO, PA, PO, and beta-PAE improve the gut epithelial barrier by altering the status of E-cadherin vs. N-cadherin expressions, and increasing the mucosal p-lysozyme and Muc 2. Moreover, the treatments also facilitate the polarization of M1 to M2 macrophage phenotypes, meanwhile, suppress the pro-inflammatory cytokines. Fecal microbial DNAs were analyzed and evaluated for GM composition by ERIC-PCR and 16S rRNA amplicon sequencing. The GM diversity was increased with the treated groups compared to the control. Further analysis showed that some known short chain fatty acids (SCFAs)-producing bacteria, e.g. Anaerostipes butyraticus, Butytivibrio fibrisolvens, Clostridium jejuense, Eubacterium uniforme, and Lactobacillus lactis were significantly enriched in the treated groups. In addition, the key SCFAs receptors, GPR 41, 43 and 109a, were significantly stimulated in the gut epithelial layer of the treated mice. By contract, the relative abundance of pathogens Sutterlla spp., Fusobacterium mortiferum, and Helicobacter spp. were distinctly reduced by the treatments with PEO and beta-PAE. Our findings provide insightful information that the microbiota/host dynamic interaction may play a key role for the pharmacological activities of PEO, PA, PO, and beta-PAE. C1 [Leong, Waikit; Huang, Guoxin; Khan, Imran; Xia, Wenrui; Li, Xiaoang; Han, Ruixuan; Hsiao, W. L. Wendy] Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Taipa, Macao, Peoples R China. [Li, Yucui; Liu, Yuhong; Su, Ziren] Guangzhou Univ Chinese Med, Guangdong Prov Key Lab New Chinese Med Dev & Res, Math Engn Acad Chinese Med, Guangzhou, Guangdong, Peoples R China. C3 Macau University of Science & Technology; Guangzhou University of Chinese Medicine RP Hsiao, WLW (corresponding author), Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Taipa, Macao, Peoples R China. EM wlhsiao@must.edu.mo RI Khan, Imran/J-2843-2019; Huang, Guoxin/AAB-5329-2022; Liu, Yuhong/Y-4597-2019; Su, Zi-Ren/O-5014-2019 OI Khan, Imran/0000-0002-9114-4434; Li, Xiaoang/0009-0005-1930-2476; Huang, Guoxin/0000-0001-8128-7135; XIA, Wenrui/0009-0001-8865-2614 FU Science and Technology Development Fund, Macau SAR [FDCT130-2016-A3, 0054-2018-A2] FX This study was funded by The Science and Technology Development Fund, Macau SAR (File No. FDCT130-2016-A3 & 0054-2018-A2) to WH. 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Pharmacol. PD OCT 17 PY 2019 VL 10 AR 1229 DI 10.3389/fphar.2019.01229 PG 11 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA JO4KM UT WOS:000497548500001 PM 31680986 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Xu, J Liu, YT Zhao, Z Zhao, LY Wang, DW Liu, Q AF Xu, Jian Liu, Yuntao Zhao, Zhen Zhao, Liyun Wang, Dawei Liu, Qing TI The role of traditional Chinese medicine in the treatment of atherosclerosis through the regulation of macrophage activity SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Review DE Atherosclerosis; Macrophage; Chinese herbal medicine ID FOAM-CELL-FORMATION; LOW-DENSITY-LIPOPROTEIN; E-KNOCKOUT MICE; NLRP3 INFLAMMASOME ACTIVATION; PROMOTES CHOLESTEROL EFFLUX; LDL-STIMULATED MACROPHAGES; APOE NULL MICE; ATTENUATES ATHEROSCLEROSIS; PLAQUE STABILITY; SALVIANOLIC ACID AB Atherosclerosis (AS) is the main cause of ischemic cardiovascular, cerebrovascular and peripheral vascular diseases. Macrophage activity has been proven to play a critical role during the AS pathological process, which involves the adhesion, aggregation of mononuclear-macrophages, cell differentiation of M1/M2 macrophages as part of complex mechanisms occurring during lipid metabolism, apoptosis, autophagy, inflammation and immune reaction. Therefore, the development of effective AS treatments is likely to target macrophage activity. Certain herbal extracts (such as Salvia miltiorrhiza) have exhibited enormous potential for AS treatment in the past. Here, we aim to provide a summary on the current understanding of the type of action and the underlying target/pathway in macrophage regulation of certain herbal extracts used in Traditional Chinese Medicine for treatment of AS. C1 [Xu, Jian; Liu, Yuntao; Zhao, Zhen; Wang, Dawei; Liu, Qing] Guangzhou Univ Chinese Med, Guangdong Prov Hosp Chinese Med, Zhuhai Hosp, Sch Clin Med 2, Guangzhou, Guangdong, Peoples R China. [Liu, Yuntao] Guangdong Prov Hosp Chinese Med, Guangdong Prov Key Lab Res Emergency Tradit Chine, Guangzhou, Guangdong, Peoples R China. [Wang, Dawei] Guangzhou Univ Chinese Med, Shunde Hosp, Foshan, Peoples R China. [Liu, Qing] Fudan Univ, Sch Basic Med Sci, Dept Immunol, Shanghai, Peoples R China. [Zhao, Liyun] Guangdong Second Prov Hosp Chinese Med, Intens Care Unit, Guangzhou, Guangdong, Peoples R China. C3 Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine; Southern Medical University - China; Fudan University RP Liu, Q (corresponding author), Guangzhou Univ Chinese Med, Sch Clin Med 2, Guangzhou, Guangdong, Peoples R China. EM davidwang33@139.com; 851757626@qq.com RI Liu, Qing/AGK-1980-2022 FU National Natural Science Foundation of China [81603460]; Postdoctoral Science Foundation of China [2015 M581533]; Administration of Traditional Chinese Medicine of Guangdong Province [2018401981115]; Guangzhou Science Technology and Innovation Committee [201607010337]; Guangzhou University of Traditional Chinese Medicine High-level University Construction Project [A1-AFD018171Z11089] FX This research was supported by National Natural Science Foundation of China (No. 81603460, to Q.L.), Postdoctoral Science Foundation of China (No. 2015 M581533, to Q.L.); Administration of Traditional Chinese Medicine of Guangdong Province (No. 2018401981115), Guangzhou Science Technology and Innovation Committee (No. 201607010337) and Guangzhou University of Traditional Chinese Medicine High-level University Construction Project (No. A1-AFD018171Z11089). Thanks for the participation of Zhihao Luo, Guofu Zhong and Yu Lai in reading and correcting the manuscript. 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Pharmacother. PD OCT PY 2019 VL 118 AR 109375 DI 10.1016/j.biopha.2019.109375 PG 17 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA IY4WZ UT WOS:000486395000022 PM 31548175 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Yang, SL Wang, HG Yang, YL Wang, R Wang, YH Wu, CF Du, GH AF Yang, Shilun Wang, Haigang Yang, Yinglin Wang, Rui Wang, Yuehua Wu, Chunfu Du, Guanhua TI Baicalein administered in the subacute phase ameliorates ischemia-reperfusion-induced brain injury by reducing neuroinflammation and neuronal damage SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE Ischemic stroke; Cerebral ischemia-reperfusion injury; Baicalein; NF-kappa B signaling; Neuroinflammation ID NF-KAPPA-B; CHRONIC CEREBRAL HYPOPERFUSION; MACROPHAGE POLARIZATION; INDUCED INFLAMMATION; INDUCED APOPTOSIS; STROKE; INHIBITION; AUTOPHAGY; PATHWAY; DEATH AB Ischemic stroke is a cerebrovascular disease with high morbidity, high mortality, and high disability, representing a serious threat to human life and health. Clinically, the extensive injury caused by ischemic stroke results from ischemia-reperfusion (I/R) injury thrombolytic treatment. However, there are few reports on the use of medications in the subacute stage of cerebral I/R. Baicalein (5,6,7-trihydroxyflavone) is a biologically active ingredient extracted from the root of Scutellaria baicalensis Georgi. In the present study, we investigated the therapeutic effect of baicalein administered in the subacute phase of cerebral I/R injury in a rat model of ischemia induced by occlusion of the middle cerebral artery (MCA). Rats were treated daily with baicalein (200 mg/kg, i.g.) in the subacute phase (24 h after reperfusion) for 7 days. The results showed that baicalein significantly reduced neurobehavioral deficits and decreased brain infarct volume from 18.99% to 7.41%. Immunofluorescence analysis of the ischemic penumbra showed that baicalein significantly reduced expression of the M1 marker, cluster of differentiation (CD) 16 and CD86, and increased expression of the M2 marker, CD 163 and CD206, indicating that baicalein inhibited M1 transformation and promoted M2 transformation of microglia/macrophage to inhibit neuroinflammation. Moreover, baicalein suppressed NF-kappa B signaling by reducing I kappa B alpha phosphorylation and nuclear translocation of NF-kappa B/p65, which decreased the release of the pro-inflammatory factors IL-6, IL-18, and TNF-alpha. In addition, baicalein reduced phosphorylation of JNK, ERK and p38, which are involved modulation of microglia/macrophage M1/M2 polarization. Western blot analysis of apoptosis- and autophagy-related proteins showed that baicalein increased the Bcl-2/Bax ratio and reduced caspase-3 expression to decrease neuronal apoptosis and ameliorate neuronal loss. Baicalein also decreased the LC3-II/LC3-I ratio and promoted phosphorylation of the PI3K/Akt/mTOR signaling pathway which implied inhibition of autophagy. These observations suggest that baicalein exerts neuroprotective effects by reducing neuroinflammation, apoptosis and autophagy, and protects against cerebral I/R injury in the subacute phase in vivo. C1 [Yang, Shilun; Wu, Chunfu; Du, Guanhua] Shenyang Pharmaceut Univ, Sch Life Sci & Biopharmaceut, 103 Wenhua Rd, Shenyang 110016, Liaoning, Peoples R China. [Yang, Shilun; Wang, Haigang; Yang, Yinglin; Wang, Yuehua; Du, Guanhua] Chinese Acad Med Sci, Inst Mat Med, Beijing Key Lab Drug Targets Identificat & Drug S, 2 Nanwei Rd, Beijing 100050, Peoples R China. [Yang, Shilun; Wang, Haigang; Yang, Yinglin; Wang, Yuehua; Du, Guanhua] Peking Union Med Coll, 2 Nanwei Rd, Beijing 100050, Peoples R China. [Wang, Rui] Guangdong Pharmaceut Univ, Sch Tradit Chinese Med, 280 Waihuan East Rd, Guangzhou 510006, Guangdong, Peoples R China. C3 Shenyang Pharmaceutical University; Chinese Academy of Medical Sciences - Peking Union Medical College; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Guangdong Pharmaceutical University RP Wu, CF; Du, GH (corresponding author), Shenyang Pharmaceut Univ, Sch Life Sci & Biopharmaceut, 103 Wenhua Rd, Shenyang 110016, Liaoning, Peoples R China. EM wucf@syphu.edu.cn; dugh@imm.ac.cn RI ; 王, 瑞/HPC-9690-2023; Wang, Yue-Hua/HJG-4859-2022 OI Yang, Shilun/0000-0003-2734-3698; FU CAMS Innovation Fund for Medical Sciences [2017-I2M-1-010, 2016-I2M-3-007]; National Major Scientific and Technological Special Project for "Significant New Drugs Development" [2017ZX09101003-003-019] FX This project was supported by the CAMS Innovation Fund for Medical Sciences (2017-I2M-1-010 and 2016-I2M-3-007) and the National Major Scientific and Technological Special Project for "Significant New Drugs Development" (2017ZX09101003-003-019). 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PD SEP PY 2019 VL 117 AR 109102 DI 10.1016/j.biopha.2019.109102 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA IM2EA UT WOS:000477804500016 PM 31228802 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zheng, QN Wei, XH Pan, CS Li, Q Liu, YY Fan, JY Han, JY AF Zheng, Qian-Ning Wei, Xiao-Hong Pan, Chun-Shui Li, Quan Liu, Yu-Ying Fan, Jing-Yu Han, Jing-Yan TI QiShenYiQi Pills® ameliorates ischemia/reperfusion-induced myocardial fibrosis involving RP S19-mediated TGFβ1/Smads signaling pathway SO PHARMACOLOGICAL RESEARCH LA English DT Article DE Myocardial fibrosis; M2 macrophage; MMPs; Chemokine; Myocardial blood flow ID MONOCYTE CHEMOTACTIC FACTOR; RIBOSOMAL-PROTEIN DIMER; MICROCIRCULATORY DISTURBANCE; INFLAMMATION; MEDICINE; DISEASE; INJURY AB QiShenYiQi Pills (QSYQ) is a compound Chinese medicine widely used in China for treatment of cardiovascular disease. However, limited data are available regarding the anti-fibrotic role of QSYQ after ischemia/reperfusion (I/R) injury. This study aimed to investigate the effect of post-treatment with QSYQ on myocardial fibrosis after I/R-induced myocardium injury, and the role of different compounds of QSYQ, focusing especially on the involvement of chemokine ribosomal protein S19 (RP S19) dimer and monocyte migration. Male Sprague-Dawley rats were subjected to left anterior descending coronary artery occlusion for 30 min followed by reperfusion with or without administration of QSYQ (0.6, 1.2, or 1.8 g/kg) once daily by gavage for 6 days. Post-treatment with QSYQ diminished I/R-induced infarct size, alleviated myocardium injury, attenuated myocardial fibrosis after 6 days of reperfusion, and restored heart function and myocardial blood flow after I/R. In addition, the drug significantly inhibited monocyte infiltration and macrophage polarization towards M2, which was attributable to chemokine RP S19 dimer. Moreover, Western blots revealed that QSYQ blocked I/R-induced increase in TGF beta 1 and TGF beta RII and reversed its relevant gene expression, such as Smad3,4,6,7, and inhibited the increase of MMP 2,9 expression. As the major components of QSYQ, astragaloside IV (AsIV), 3,4-dihydroxy-phenyl lactic acid (DLA), and notoginsenoside R1 (R1) were assessed as to the contribution of each of them to the expression of the proteins concerned. The results showed that the effect of AsIV was similar to QSYQ, while DLA and R1 only partly simulated the effect of QSYQ. The results provide evidence for the potential role of QSYQ in treating myocardial fibrosis following I/R injury. This effect may be associated with QSYQ's inhibition effect on monocyte chemotaxis and TGF beta 1/Smads signaling pathway with different component targeting distinct link (s) of the signaling. C1 [Zheng, Qian-Ning; Wei, Xiao-Hong; Han, Jing-Yan] Peking Univ, Sch Basic Med Sci, Dept Integrat Chinese & Western Med, 38 Xueyuan Rd, Beijing 100191, Peoples R China. [Zheng, Qian-Ning; Wei, Xiao-Hong; Pan, Chun-Shui; Li, Quan; Liu, Yu-Ying; Fan, Jing-Yu; Han, Jing-Yan] Peking Univ, Hlth Sci Ctr, Tasly Microcirculat Res Ctr, Beijing 100191, Peoples R China. [Zheng, Qian-Ning; Wei, Xiao-Hong; Pan, Chun-Shui; Li, Quan; Liu, Yu-Ying; Han, Jing-Yan] State Adm Tradit Chinese Med Peoples Republ China, Key Lab Stasis & Phlegm, Beijing 100191, Peoples R China. [Zheng, Qian-Ning; Wei, Xiao-Hong; Pan, Chun-Shui; Li, Quan; Liu, Yu-Ying; Han, Jing-Yan] Beijing Lab Integrat Microangiopathy, Beijing 100191, Peoples R China. [Zheng, Qian-Ning; Wei, Xiao-Hong; Pan, Chun-Shui; Li, Quan; Liu, Yu-Ying; Fan, Jing-Yu; Han, Jing-Yan] State Key Lab Core Technol Innovat Chinese Med, Beijing 100191, Peoples R China. C3 Peking University; Tasly Holding Group Co Ltd; Peking University RP Han, JY (corresponding author), Peking Univ, Sch Basic Med Sci, Dept Integrat Chinese & Western Med, 38 Xueyuan Rd, Beijing 100191, Peoples R China. EM hanjingyan@bjmu.edu.cn RI han, jingyan/HJG-6568-2022 FU State Key Laboratory of Core Technology in Innovative Chinese Medicine [20170034] FX This study was supported by the State Key Laboratory of Core Technology in Innovative Chinese Medicine (20170034). 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PD AUG PY 2019 VL 146 AR 104272 DI 10.1016/j.phrs.2019.104272 PG 14 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA IS6FS UT WOS:000482248300039 PM 31085230 DA 2026-03-26 ER PT J AU Jang, HM Park, KT Noh, HD Lee, SH Kim, DH AF Jang, Hyo-Min Park, Keon-Tae Noh, Hyun-Deok Lee, So-Hyeon Kim, Dong-Hyun TI Kakkalide and irisolidone alleviate 2,4,6-trinitrobenzenesulfonic acid-induced colitis in mice by inhibiting lipopolysaccharide binding to toll-like receptor-4 and proteobacteria population SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Pueraria lobata; Kakkalide; Irisolidone; Colitis; Macrophages; Gut microbiota ID NF-KAPPA-B; INFLAMMATION; ACTIVATION; RESVERATROL; METABOLITES; PUERARIAE; ARTHRITIS; FLOS; M1 AB The flower of Pueraria lobata (family Fabaceae) has been clinically used in traditional Chinese medicine to counteract symptoms associated with drinking alcohol and liver injury and to alleviate inflammatory diseases. Its major constituent kakkalide is metabolized to irisolidone by gut microbiota. This research study was undertaken to understand the anti-colitis mechanism of kakkalide and irisolidone in vitro and in vivo. Kakkalide and its metabolite irisolidone inhibited lipopolysaccharide (LPS)-stimulated NF-kappa B activation and TNF-alpha expression in macrophages. They also inhibited LPS-induced phosphorylation of IRAK1 and TAK1 and activation of NF-kappa B by inhibiting the binding of Alexa Fluor 488-conjugated LPS in vitro. Orally administered irisolidone or kakkalide alleviated colon shortening and myeloperoxidase activity in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. Their treatments also protected epithelial cell disruption and infiltration of CD11b(+)/CD11c(+) cells in the colon. Furthermore, they suppressed TNBS-induced expression of M1 macrophage markers TNF-alpha, CD80, CD86, and Arg2 expression while the expression of M2 macrophage markers Arg1, CD163, CD206, and IL-10 was induced. They also suppressed the fecal Proteobacteria population. Overall, the anti-colitic effects of irisolidone were superior to those of kakkalide. Kakkalide and its metabolite irisolidone inhibited inflammation in vitro and in vivo by inhibiting LPS binding to toll-like receptor 4 and gut proteobacteria population. C1 [Jang, Hyo-Min; Kim, Dong-Hyun] Kyung Hee Univ, Neurobiota Res Ctr, Coll Pharm, 26 Kyungheedae Ro, Seoul 02447, South Korea. [Jang, Hyo-Min; Kim, Dong-Hyun] Kyung Hee Univ, Dept Life & Nanopharmaceut Sci, Coll Pharm, 26 Kyungheedae Ro, Seoul 02447, South Korea. [Park, Keon-Tae; Noh, Hyun-Deok; Lee, So-Hyeon] Kyung Hee Univ, Dept Korean Pharm, Coll Pharm, 26 Kyungheedae Ro, Seoul 02447, South Korea. C3 Kyung Hee University; Kyung Hee University; Kyung Hee University RP Kim, DH (corresponding author), Kyung Hee Univ, Coll Pharm, 26 Kyungheedae Ro, Seoul 02447, South Korea. EM dhkim@khu.ac.kr RI Lee, Seungwoo/E-9350-2012; Kim, Dong-Hyun/AAJ-8795-2020 FU Medical Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT and Future Planning [NRF-2017R1A5A2014768] FX The present study was supported by the Medical Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT and Future Planning (NRF-2017R1A5A2014768). 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Immunopharmacol. PD AUG PY 2019 VL 73 BP 246 EP 253 DI 10.1016/j.intimp.2019.05.008 PG 8 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA IL1WD UT WOS:000477092100027 PM 31112869 DA 2026-03-26 ER PT J AU Gnanaprakasam, JNR Estrada-Muñiz, E Vega, L AF Rashida Gnanaprakasam, J. N. Estrada-Muniz, Elizabet Vega, Libia TI The antineoplastic agent anacardic 6-pentadecyl salicylic acid produces immunomodulation in vivo via the activation of MAPKs SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE 6-Pentadecyl salicylic acid; Amphipterygium adstringens; MAP kinases; Macrophages; Immune modulation ID AMPHYPTERYGIUM-ADSTRINGENS; AMPHIPTERYGIUM-ADSTRINGENS; MACROPHAGE POLARIZATION; AQUEOUS EXTRACT; ACETYLTRANSFERASE; PROLIFERATION; INHIBITION; KINASES; BARK; JNK AB Anacardic 6-pentadecyl salicylic acid (6SA) is the active component of Amphipterygium adstringens, a plant used in traditional medicine for the treatment of malaria and vascular diseases and as an anti-bacterial and immune-modulatory agent. However, the effect of 6SA on the immune system remains unclear. In this study, we examined the immune-stimulatory activity of 6SA in 6-8-week-old female BALB/c mice. We found that treatment with 2 mg/kg of 6SA increased the proportions of macrophages after 7 and 14 days of treatment and of natural killer (NK) cells after 14 days of treatment in circulating blood. In lymph nodes, treatment with 6SA for 14 days increased the number of macrophages. In addition, 6SA increases in the systemic levels of pro-inflammatory cytokines such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-12, IL-6 and IL-1 beta and of nitric oxide (NO). We observed an increase in the secretion of Granulocyte/Macrophage Colony Stimulation Factor (GMCSF) that could explain the increase in the proportion of macrophages. Moreover, 6SA induced the classical activation of macrophages by increasing their expression of MHC-II and their production of TNF-alpha. These M1-polarised macrophages presented enhanced phagocytosis and NO secretion. This activation was due to induction of the phosphorylation of MAPKs such as ERK, JNK and p38 because specific inhibitors of the phosphorylation of these MAPKs reduced the 6SA-induced phagocytosis and NO and particularly, the secretion of GM-CSF in macrophages by inhibition of ERK. Despite these effects on macrophages, 6SA does not have any direct effect on the proportion of lymphocytes. C1 [Rashida Gnanaprakasam, J. N.; Estrada-Muniz, Elizabet; Vega, Libia] Natl Polytech Inst, Ctr Res & Adv Studies, Dept Toxicol, Av IPN,2508 San Pedro Zacatenco, Mexico City 07360, DF, Mexico. C3 Instituto Politecnico Nacional - Mexico RP Vega, L (corresponding author), Natl Polytech Inst, Ctr Res & Adv Studies, Lab Genet Toxicol & Immunol, Dept Toxicol, Av IPN,2508 San Pedro Zacatenco, Mexico City 07360, DF, Mexico. EM lvega@cinvestav.mx RI GNANAPRAKASAM, JN RASHIDA/ABI-1671-2020; Vega, Libia/C-3391-2013 OI GNANAPRAKASAM, JN RASHIDA/0000-0002-9086-0949; Vega, Libia/0000-0002-4993-5267 FU National Council of Science and Technology of Mexico (Conacyt) [283159] FX JNRG received a scholarship from the National Council of Science and Technology of Mexico (Conacyt) (283159). We thank Dr. Luis Donis and M.Sc. Victor Hugo Rosales-Garcia for their technical assistance in flow cytometry. 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Appl. Pharmacol. PD AUG 1 PY 2019 VL 376 BP 82 EP 92 DI 10.1016/j.taap.2019.05.017 PG 11 WC Pharmacology & Pharmacy; Toxicology WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy; Toxicology GA IF3NF UT WOS:000472986800008 PM 31129177 DA 2026-03-26 ER PT J AU Zhang, L Zhou, ZJZ Zhai, W Pang, J Mo, YY Yang, G Qu, ZW Hu, YL AF Zhang, Lu Zhou, Zhangjiuzhi Zhai, Wei Pang, Jie Mo, Yuyan Yang, Guang Qu, Zuwei Hu, Yanli TI Safflower yellow attenuates learning and memory deficits in amyloid -induced Alzheimer's disease rats by inhibiting neuroglia cell activation and inflammatory signaling pathways SO METABOLIC BRAIN DISEASE LA English DT Article DE Alzheimer's disease; Safflower yellow; Inflammatory; Neuroglia cells ID MICROGLIA/MACROPHAGE POLARIZATION DYNAMICS; TAU PHOSPHORYLATION; NITRIC-OXIDE; MOUSE MODEL; MICROGLIA AB Safflower yellow (SY) is an aqueous extract of natural safflower. Our laboratory has reported protective effects of alleviating memory impairment with SY in a transgentic mouse model of Alzheimer's disease. The possible beneficial effects of SY on amyloid--induced neuroinflammation in dementia remain unclarified. This study we hypothesize that astrocytes and microglia may cause amyloid- deposition and produce a neuroinflammatory response, aims to explain the role and mechanism of SY in regulating glial activation and reducing A deposition in A(1-42) induced rat model. Wistar rats were treated with SY for one month after bilateral hippocampal injection of aggregated A(1-42); behavioral tests were performed to demonstrate the amelioration of cognitive function. After that, the contents of iNOS, IL-1, IL-6, and TNF- in AD brain was detected. Western blot and real-time PCR were used to detect the M1 and M2-associated markers to demonstrate the activation of microglia. The conducted experiments have revealed that SY could strengthen spatial learning and memory ability of dementia rats, decrease the contents of iNOS, IL-1, IL-6, and TNF- and depress the activation of glial cells. Moreover, the SY treatment inhibited the M1 release of pro-inflammatory cytokines (iNOS and CD86), increased the expression of arginase-1, CD206, and YM-1 thereby reduced inflammation in model rats. Thus our results indicated that SY has very important theoretical and clinical value for the research and development of Chinese medicine for the treatment of AD. C1 [Zhang, Lu; Zhou, Zhangjiuzhi; Zhai, Wei; Pang, Jie; Mo, Yuyan; Yang, Guang; Qu, Zuwei; Hu, Yanli] Shihezi Univ, Dept Pharmacol, Minist Educ, Key Lab Xinjiang Phytomed Resource & Utilizat, Shihezi 832000, Xinjiang, Peoples R China. C3 Shihezi University RP Hu, YL (corresponding author), Shihezi Univ, Dept Pharmacol, Minist Educ, Key Lab Xinjiang Phytomed Resource & Utilizat, Shihezi 832000, Xinjiang, Peoples R China. EM wzx330@163.com FU Project of Social Development of the Corps [2016 AD001]; Natural Science Foundation of China [81660603] FX This research was supported by the Project of Social Development of the Corps (No. 2016 AD001), Natural Science Foundation of China (No. 81660603). CR Bal-Price A, 2001, J NEUROSCI, V21, P6480 Boche D, 2013, NEUROPATH APPL NEURO, V39, P3, DOI 10.1111/nan.12011 Couturier J, 2016, J NEUROINFLAMM, V13, DOI 10.1186/s12974-016-0477-y Cuadros MA, 2006, J HISTOCHEM CYTOCHEM, V54, P727, DOI 10.1369/jhc.5A6832.2006 Ding S, 2014, NEURAL REGEN RES, V9, P2048, DOI 10.4103/1673-5374.147929 Dodel R, 2011, J NEUROSCI, V31, P5847, DOI 10.1523/JNEUROSCI.4401-10.2011 Finch CE, 2007, CURR ALZHEIMER RES, V4, P185, DOI 10.2174/156720507780362254 Ghosh S, 2013, J NEUROSCI, V33, P5053, DOI 10.1523/JNEUROSCI.4361-12.2013 Griffin WST, 2013, NEW ENGL J MED, V368, P770, DOI 10.1056/NEJMcibr1214546 Halle A, 2008, NAT IMMUNOL, V9, P857, DOI 10.1038/ni.1636 Han XH, 2010, BRAIN INJURY, V24, P773, DOI 10.3109/02699051003610482 Hardas SS, 2013, REDOX BIOL, V1, P80, DOI 10.1016/j.redox.2013.01.002 Hu XM, 2012, STROKE, V43, P3063, DOI 10.1161/STROKEAHA.112.659656 Jeon YC, 2013, J VET SCI, V14, P21, DOI 10.4142/jvs.2013.14.1.21 Kasza A, 2017, MOLECULES, V22, DOI 10.3390/molecules22112007 Li JZ, 2018, FRONT AGING NEUROSCI, V10, DOI 10.3389/fnagi.2018.00085 Li R, 2007, AM J PHYSIOL-ENDOC M, V293, pE1703, DOI 10.1152/ajpendo.00462.2007 Liu CY, 2013, PLOS ONE, V8, DOI 10.1371/journal.pone.0054841 Liu Z, 2014, EUR J PHARMACOL, V738, P206, DOI 10.1016/j.ejphar.2014.05.041 Ma Q, 2015, BIOMED PHARMACOTHER, V76, P153, DOI 10.1016/j.biopha.2015.10.004 Mawuenyega KG, 2010, SCIENCE, V330, P1774, DOI 10.1126/science.1197623 MURPHY S, 1993, TRENDS NEUROSCI, V16, P323, DOI 10.1016/0166-2236(93)90109-Y Ohsawa K, 2000, J CELL SCI, V113, P3073 Pisanu A, 2014, NEUROBIOL DIS, V71, P280, DOI 10.1016/j.nbd.2014.08.011 Ramirez AI, 2017, FRONT AGING NEUROSCI, V9, DOI 10.3389/fnagi.2017.00214 Ruan YY, 2016, METAB BRAIN DIS, V31, P1133, DOI 10.1007/s11011-016-9857-3 Sastre M, 2006, P NATL ACAD SCI USA, V103, P443, DOI 10.1073/pnas.0503839103 Shi XM, 2018, BIOMED PHARMACOTHER, V98, P553, DOI 10.1016/j.biopha.2017.12.099 Tweedie D, 2012, J NEUROINFLAMM, V9, DOI 10.1186/1742-2094-9-106 Wang GH, 2013, J CEREBR BLOOD F MET, V33, P1864, DOI 10.1038/jcbfm.2013.146 Wang XH, 2015, BRAIN RES, V1627, P101, DOI 10.1016/j.brainres.2015.09.015 Zheng Z, 2004, NEUROL RES, V26, P884, DOI 10.1179/016164104X2357 NR 32 TC 32 Z9 38 U1 0 U2 21 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 EI 1573-7365 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD JUN PY 2019 VL 34 IS 3 BP 927 EP 939 DI 10.1007/s11011-019-00398-0 PG 13 WC Endocrinology & Metabolism; Neurosciences WE Science Citation Index Expanded (SCI-EXPANDED) SC Endocrinology & Metabolism; Neurosciences & Neurology GA HY4AX UT WOS:000468070600020 PM 30830599 DA 2026-03-26 ER PT J AU Liu, LW Xing, QQ Zhao, X Tan, M Lu, Y Dong, YM Dai, C Zhang, Y AF Liut, Li-wei Xing, Qiong-qiong Zhao, Xia Tan, Min Lu, Yuan Dong, Ying-mei Dai, Chen Zhang, Yang TI Proteomic Analysis Provides Insights Into the Therapeutic Effect of GU-BEN-FANG-XIAO Decoction on a Persistent Asthmatic Mouse Model SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE GU-BEN-FANG-XIAO decoction; iTRAQ; chronic persistent asthma; macrophage; IPA ID AIRWAY EPITHELIAL-CELLS; GENETIC POLYMORPHISMS; MACROPHAGES; CHILDREN; INFLAMMATION; STRESS; TISSUE; FIZZ1; RISK; LUNG AB Gubenfangxiao decoction (GBFXD) is a traditional Chinese medicine based on a combination of Yu-Ping-Feng-San and Erchen decoctions. GBFXD has been widely used for decades in treating asthma at the Affiliated Hospital of Nanjing University of Chinese Medicine. Previously, GBFXD was found to reduce lung inflammation and airway remodeling; however, the underlying mechanism remains unknown. In this study, the effects of GBFXD on asthmatic mice were evaluated based on pathology and lung function; airway hyperresponsiveness (AHR) and pathology were compared among the two different mouse models utilized. Furthermore, the mechanism of action of GBFXD on asthmatic mice was analyzed using iTRAQ labeling technology combined with ingenuity pathway analysis (IPA). Modeling analysis of pre- and post-treatment proteins identified 75 differentially expressed proteins. These proteins were related to B-cell development, calcium-induced lymphocyte apoptosis, antigen presentation, and Th1 and Th2 activation pathways. Moreover, 68 differentially expressed proteins were identified in the GBFXD treatment group compared with the model group. Upstream regulatory factors predicted that interleukin (IL)-4 (necessary for inducing polarization of type 2 [M2] macrophages), cyclooxygenase, and prostaglandin E2 are significantly elevated in the model group. Based on IPA analysis, it was concluded that several pathways, including mitochondrial dysfunction and oxidative phosphorylation, are closely associated with the therapeutic effects of GBFXD in asthma. Moreover, the differential expression of several proteins, including the M2 markers, MRC1, ARG1, Retnla, Chil3, and CHIA, were validated by western blotting, confirming that GBFXD can reduce airway inflammation, which fits the pattern of an alternative M2 activation state, and attenuate AHR. Overall, our findings indicate that GBFXD significantly suppresses M2 macrophage polarization, providing further insights into the mechanism underlying the protective effects of GBFXD. C1 [Liut, Li-wei; Xing, Qiong-qiong; Zhao, Xia; Tan, Min; Dong, Ying-mei] Nanjing Univ Chinese Med, Affiliated Hosp, Nanjing, Jiangsu, Peoples R China. [Liut, Li-wei; Xing, Qiong-qiong; Zhao, Xia; Tan, Min; Dong, Ying-mei] Nanjing Univ Chinese Med, Inst Pediat, Jiangsu Key Lab Pediat Resp Dis, Nanjing, Jiangsu, Peoples R China. [Lu, Yuan] Soochow Univ, Childrens Hosp, Suzhou, Peoples R China. [Dai, Chen] Nanjing Agr Univ, Coll Life Sci, Nanjing, Jiangsu, Peoples R China. [Zhang, Yang] Fudan Univ, Shanghai Med Sch, Dept Chem, Shanghai, Peoples R China. [Zhang, Yang] Fudan Univ, Shanghai Med Sch, Inst Biomed Sci, Shanghai, Peoples R China. C3 Nanjing University of Chinese Medicine; Nanjing University of Chinese Medicine; Soochow University - China; Nanjing Agricultural University; Fudan University; Fudan University RP Zhao, X (corresponding author), Nanjing Univ Chinese Med, Affiliated Hosp, Nanjing, Jiangsu, Peoples R China.; Zhao, X (corresponding author), Nanjing Univ Chinese Med, Inst Pediat, Jiangsu Key Lab Pediat Resp Dis, Nanjing, Jiangsu, Peoples R China. EM zhaoxiahy@hotmail.com OI Liu, Liwei/0009-0009-7300-1956; Dai, Chen/0000-0002-4613-6945 FU Major Research Plan of Natural Science Foundation of the Jiangsu Higher Education Institutions of China [15KJA360003]; Natural Science Foundation of China [81774367]; Innovation Program for Graduate Students of Jiangsu Province, China [KYCX18_1553, KYCX18_1555]; leading academics training program of Chinese Medicine in Jiangsu Province, China [SLJ0224]; Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) FX This work was supported by the Major Research Plan of Natural Science Foundation of the Jiangsu Higher Education Institutions of China (Grant No. 15KJA360003), the Natural Science Foundation of China (Grant No. 81774367), the Innovation Program for Graduate Students of Jiangsu Province, China (Grant Nos. KYCX18_1553 and KYCX18_1555), the leading academics training program of Chinese Medicine in Jiangsu Province, China (Grant No. SLJ0224) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). 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Pharmacol. PD MAY 7 PY 2019 VL 10 AR 441 DI 10.3389/fphar.2019.00441 PG 16 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA HX3TP UT WOS:000467316100001 PM 31133848 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Xu, L Li, L Zhang, CY Schluesener, H Zhang, ZY AF Xu, Lu Li, Lei Zhang, Chen-Yang Schluesener, Hermann Zhang, Zhi-Yuan TI Natural Diterpenoid Oridonin Ameliorates Experimental Autoimmune Neuritis by Promoting Anti-inflammatory Macrophages Through Blocking Notch Pathway SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE Guillain-Barre syndrome; experimental autoimmune neuritis; Oridonin; anti-inflammatory macrophage; Notch pathway ID RABDOSIA-RUBESCENS; M2 MACROPHAGES; NITRIC-OXIDE; RAT; CELLS; IMMUNE; INHIBITION; PROLIFERATION; INFLAMMATION; DISORDERS AB The diterpenoid compound, Oridonin, extracted from the Chinese herb, Rabdosia rubescens, possesses multiple biological activities and properties. Oridonin exhibited efficient anti-inflammatory activity by inducing a switch in macrophage polarization to the anti-inflammatory phenotype through inhibition of the Notch pathway in our in vitro study; therefore, its potential therapeutic effects were further investigated in the animal model of human Guillain-Barre syndrome (GBS) and other polyneuropathies - experimental autoimmune neuritis (EAN). Either preventive or therapeutic treatments with Oridonin greatly attenuated disease peak severity, suppressed paraparesis, shortened disease duration, and even delayed EAN onset. Progression of neuropathic pain, demyelination, inflammatory cellular accumulations, and inflammatory cytokines in peripheral nerves were significantly attenuated. Meanwhile, accumulation of immune cells in the spinal roots and microglial activation in the lumbar spinal cord were also reduced. Interestingly, Oridonin treatment significantly increased the proportion of anti-inflammatory macrophages and made them locally dominant among all infiltrated macrophages in the peripheral nerves. The down-regulation of local Notch pathway proteins, together with our in vitro results indicated their possible involvement. Taken together, our results demonstrated that Oridonin effectively suppressed EAN by attenuating local inflammatory reaction and increasing the proportion of immune regulating macrophages in the peripheral nerves, possibly through blockage of the Notch pathway, which suggests Oridonin as a potential therapeutic candidate for human GBS and neuropathies. C1 [Xu, Lu; Li, Lei; Zhang, Chen-Yang; Zhang, Zhi-Yuan] Nanjing Med Univ, Dept Pathol, Nanjing, Jiangsu, Peoples R China. [Schluesener, Hermann; Zhang, Zhi-Yuan] Univ Tubingen, Inst Pathol & Neuropathol, Div Immunopathol Nervous Syst, Tubingen, Germany. [Zhang, Zhi-Yuan] Nanjing Med Univ, Sir Run Run Hosp, Dept Neurol, Nanjing, Jiangsu, Peoples R China. C3 Nanjing Medical University; Eberhard Karls University of Tubingen; Eberhard Karls University Hospital; Nanjing Medical University RP Zhang, ZY (corresponding author), Nanjing Med Univ, Dept Pathol, Nanjing, Jiangsu, Peoples R China.; Zhang, ZY (corresponding author), Univ Tubingen, Inst Pathol & Neuropathol, Div Immunopathol Nervous Syst, Tubingen, Germany.; Zhang, ZY (corresponding author), Nanjing Med Univ, Sir Run Run Hosp, Dept Neurol, Nanjing, Jiangsu, Peoples R China. EM zzy@njmu.edu.cn RI Zhang, Zhi-Yuan/L-1001-2017; LEI, LI/AGB-6335-2022 OI Zhang, Zhi-Yuan/0000-0001-9067-0670; FU National Natural Science Foundation of China [81571240, 81771171]; Jiangsu Provincial Innovation Team Program Foundation FX This work was supported by the National Natural Science Foundation of China (Grant Nos. 81571240 and 81771171) and the Jiangsu Provincial Innovation Team Program Foundation. 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Neurosci. PD APR 2 PY 2019 VL 13 AR 272 DI 10.3389/fnins.2019.00272 PG 14 WC Neurosciences WE Science Citation Index Expanded (SCI-EXPANDED) SC Neurosciences & Neurology GA HR4DO UT WOS:000463095100001 PM 31001070 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Wang, SW Bai, YF Weng, YY Fan, XY Huang, H Zheng, F Xu, Y Zhang, F AF Wang, Si-wei Bai, Yong-feng Weng, Yuan-yuan Fan, Xue-yu Huang, Hui Zheng, Fang Xu, Yi Zhang, Feng TI Cinobufacini Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice through Inhibiting M1 Macrophage Polarization SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DSS-INDUCED COLITIS; TUMOR-ASSOCIATED MACROPHAGES; NF-KAPPA-B; ATHEROSCLEROSIS; PROTECTS; EFFICACY; ALPHA AB Cinobufacini is a traditional Chinese medicine used clinically that has antitumor and anti-inflammatory effects. It improves colitis outcomes in the clinical setting, but the mechanism underlying its function yet to be uncovered. We investigated the protective effects and mechanisms of cinobufacini on colitis using a dextran sulfate sodium (DSS)-induced colitis mouse model, mainly focusing on the impact of macrophage polarization. Our results showed that cinobufacini dramatically ameliorated DSS-induced colitis in mice. Cinobufacini treatment reduced the infiltration of activated F4/80(+) and/or CD68(+) macrophages into the colon in DSS-induced colitis mice. More importantly, cinobufacini significantly decreased the quantity of M1 macrophages and the expression of proinflammatory cytokines such as interleukin-6, tumor necrosis factor alpha, and inducible nitric oxide synthase. Cinobufacini also increased the population of M2 macrophages and the expression of anti-inflammatory factors such as interleukin-10 and arginase-1 in DSS-induced colitis mice. Furthermore, our study demonstrated that cinobufacini inhibited M1 macrophage polarization in lipopolysaccharide-induced RAW 264.7 cells. Mechanistically, our in vivo and in vitro results showed that cinobufacini inhibition of M1 macrophage polarization may be associated with the suppression of nuclear factor KB activation. Our study suggests that cinobufacini could ameliorate DSS-induced colitis in mice by inhibiting M1 macrophage polarization. C1 [Wang, Si-wei; Zheng, Fang; Zhang, Feng] Peoples Hosp Quzhou, Dept Core Facil, Quzhou, Peoples R China. [Bai, Yong-feng; Weng, Yuan-yuan; Fan, Xue-yu; Huang, Hui; Zhang, Feng] Peoples Hosp Quzhou, Clin Lab, Quzhou, Peoples R China. [Xu, Yi] Peoples Hosp Quzhou, Dept Urol, 2 Zhongloudi Rd, Quzhou 324000, Peoples R China. RP Xu, Y (corresponding author), Peoples Hosp Quzhou, Dept Urol, 2 Zhongloudi Rd, Quzhou 324000, Peoples R China.; Zhang, F (corresponding author), Peoples Hosp Quzhou, Dept Cent Lab, 2 Zhongloudi Rd, Quzhou 324000, Peoples R China. EM yixumd@126.com; felix.f.zhang@outlook.com RI ; Zhang, Feng/NGR-7510-2025 OI Wang, Siwei/0000-0001-8813-6647; Zhang, Feng/0000-0002-6751-0377 FU Zhejiang Provincial Natural Science Foundation [LYY18H280001]; Chinese Medicine Science Foundation of Zhejiang Province [2018ZB134]; Quzhou Technology Projects [2016J016, 20172004] FX This work was supported by Zhejiang Provincial Natural Science Foundation [LYY18H280001]; The Chinese Medicine Science Foundation of Zhejiang Province [2018ZB134] and Quzhou Technology Projects [2016J016, 20172004]. 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Pharmacol. Exp. Ther. PD MAR 1 PY 2019 VL 368 IS 3 BP 391 EP 400 DI 10.1124/jpet.118.254516 PG 10 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA HM1AI UT WOS:000459179300006 PM 30606760 OA Bronze DA 2026-03-26 ER PT J AU Kong, LN Lin, X Huang, C Ma, TT Meng, XM Hu, CJ Wang, QQ Liu, YH Shi, QP Li, J AF Kong Ling-Na Lin Xiang Huang Cheng Ma Tao-Tao Meng Xiao-Ming Hu Chao-Jie Wang Qian-Qian Liu Yan-Hui Shi Qing-Ping Li Jun TI Hesperetin derivative-12 (HDND-12) regulates macrophage polarization by modulating JAK2/STAT3 signaling pathway SO CHINESE JOURNAL OF NATURAL MEDICINES LA English DT Article DE Hesperetin Derivative-12; Macrophage Polarization; JAK2/STAT3; RAW264.7 cells ID TUMOR-ASSOCIATED MACROPHAGES; ACTIVATION; HESPERIDIN; CELLS; INJURY; GAMMA AB Macrophages show significant heterogeneity in function and phenotype, which could shift into different populations of cells in response to exposure to various micro-environmental signals. These changes, also termed as macrophage polarization, of which play an important role in the pathogenesis of many diseases. Numerous studies have proved that Hesperidin (HDN), a traditional Chinese medicine, extracted from fruit peels of the genus citrus, play key roles in anti-inflammation, anti-tumor, anti-oxidant and so on. However, the role of HDN in macrophage polarization has never been reported. Additional, because of its poor water solubility and bioavailability. Our laboratory had synthesized many hesperidin derivatives. Among them, hesperidin derivatives-12 (HDND-12) has better water solubility and bioavailability. So, we evaluated the role of HDND-12 in macrophage polarization in the present study. The results showed that the expression of Arginase-1 (Arg-1), interleukin-10 (IL-10), transforming growth factor beta (TGF-beta) were up-regulated by HDND-12, whereas the expression of inducible Nitric Oxide Synthase (iNOS) was down-regulated in LPS- and IFN-gamma-treated (MD RAW264.7 cells. Moreover, the expression of p-JAK2 and p-STAT3 were significantly decreased after stimulation with HDND-12 in MI-like macrophages. More importantly, when we taken AG490 (inhibitor of JAK2/STAT3 signaling), the protein levels of iNOS were significantly reduced in AG490 stimulation group compare with control in LPS, IFN-gamma and HDND-12 stimulation cells. Taken together, these findings indicated that HDND-12 could prevent polarization toward MI-like macrophages, at least in part, through modulating JAK2/STAT3 pathway. C1 [Kong Ling-Na; Shi Qing-Ping] Bengbu Med Coll, Affiliated Hosp 1, Bengbu 233000, Peoples R China. [Lin Xiang] Bengbu Med Coll, Affiliated Hosp 2, Bengbu 233000, Peoples R China. [Kong Ling-Na; Huang Cheng; Ma Tao-Tao; Meng Xiao-Ming; Hu Chao-Jie; Wang Qian-Qian; Liu Yan-Hui; Li Jun] Minist Educ, Key Lab Antiinflammatory & Immune Med, Hefei 230032, Anhui, Peoples R China. [Kong Ling-Na; Lin Xiang; Huang Cheng; Ma Tao-Tao; Meng Xiao-Ming; Wang Qian-Qian; Liu Yan-Hui; Li Jun] Anhui Med Univ, Inst Liver Dis, Hefei 230032, Anhui, Peoples R China. [Hu Chao-Jie] Anhui Prov Hosp, Hefei 230001, Anhui, Peoples R China. [Kong Ling-Na; Huang Cheng; Ma Tao-Tao; Meng Xiao-Ming; Li Jun] Anhui Med Univ, Anhui Inst Innovat Drugs, Key Lab Major Autoimmune Dis, Sch Pharm, Hefei 230032, Anhui, Peoples R China. C3 Bengbu Medical University; Bengbu Medical University; Anhui Medical University; Anhui Medical University RP Li, J (corresponding author), Minist Educ, Key Lab Antiinflammatory & Immune Med, Hefei 230032, Anhui, Peoples R China.; Li, J (corresponding author), Anhui Med Univ, Inst Liver Dis, Hefei 230032, Anhui, Peoples R China.; Li, J (corresponding author), Anhui Med Univ, Anhui Inst Innovat Drugs, Key Lab Major Autoimmune Dis, Sch Pharm, Hefei 230032, Anhui, Peoples R China. EM lj@ahmu.edu.cn RI Liu, Yanhui/O-4367-2018 FU Key Fund Project of Anhui Education Department [KJ2016A364]; National Natural Science Foundation of China [81473268] FX This work was supported by the Key Fund Project of Anhui Education Department (No. KJ2016A364) and National Natural Science Foundation of China (No. 81473268). 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J. Nat. Med. PD FEB PY 2019 VL 17 IS 2 BP 122 EP 130 DI 10.1016/S1875-5364(19)30014-7 PG 9 WC Integrative & Complementary Medicine; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Integrative & Complementary Medicine; Pharmacology & Pharmacy GA HM0KS UT WOS:000459137100003 PM 30797418 DA 2026-03-26 ER PT J AU Lin, JY Cai, QY Liang, B Wu, LZ Zhuang, Y He, YF Lin, WR AF Lin, Jiayu Cai, Qingyan Liang, Bo Wu, Lizhen Zhuang, Yong He, Yuanfang Lin, Wanrong TI Berberine, a Traditional Chinese Medicine, Reduces Inflammation in Adipose Tissue, Polarizes M2 Macrophages, and Increases Energy Expenditure in Mice Fed a High-Fat Diet SO MEDICAL SCIENCE MONITOR LA English DT Article DE Berberine; Inflammation; Macrophages ID INSULIN-RESISTANCE; LIVER-DISEASE; ER STRESS; METAANALYSIS; ACTIVATION; MECHANISMS; OBESITY; CELLS AB Background: The uncoupling protein 1 (UCP1) gene has a role in mitochondrial energy expenditure in brown adipose tissue. This study aimed to investigate the effects of berberine, a benzylisoquinoline alkaloid used in traditional Chinese medicine, on energy expenditure, expression of the UCP1 gene, the cell stress protein inositol-requiring enzyme la (IRE1 alpha), apoptosis genes, and macrophage phenotype (M1 and M2) in white and brown adipose tissue in an obese mouse model fed a high-fat diet. Material/Methods: Four-week-old C57BL/6J male mice (n=20) were divided into a high-fat diet group, a normal diet group, a group treated with berberine at 100 mg/kg/d in 0.9% normal saline, and a non-treated group. Whole-body fat mass, blood glucose, insulin resistance, and oxygen expenditure during physical activity were measured. After 16 weeks, the mice were euthanized for examination of liver and adipose tissue. The expression of pro-inflammatory cytokines, apoptosis genes, thermogenic genes (including UCP1), and IRE1 alpha, were investigated using immunohistochemistry, Western blot, and quantitative reverse transcription polymerase chain reaction (qRT-PCR), in white and brown adipose tissue. Magnetic cell sorting harvested M1 and M2 macrophages in adipose tissue. Clodronate liposomes were used to inhibit macrophage recruitment. Results: Berberine treatment in mice fed a high-fat diet increased energy metabolism, glucose tolerance, and expression of UCP1, and reduced expression of pro-inflammatory cytokines, macrophage recruitment, and resulted in M2 macrophage polarization in white adipose tissue. Polarized M2 macrophages showed reduced expression of apoptotic genes and IRE1 alpha. Conclusions: Berberine improved metabolic function in a mouse model fed a high-fat diet. C1 [Lin, Jiayu; Cai, Qingyan; Liang, Bo; Wu, Lizhen; Zhuang, Yong] Fujian Med Univ, Affiliated Hosp 2, Dept Endocrinol, Quanzhou, Fujian, Peoples R China. [He, Yuanfang] Fujian Med Univ, Affiliated Hosp 2, Dept Nephrol, Quanzhou, Fujian, Peoples R China. [Lin, Wanrong] Shishi Overseas Chinese Hosp, Dept Endocrinol, Quanzhou, Fujian, Peoples R China. C3 Fujian Medical University; Fujian Medical University RP Lin, JY (corresponding author), Fujian Med Univ, Affiliated Hosp 2, Dept Endocrinol, Quanzhou, Fujian, Peoples R China. 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Monitor PD JAN 4 PY 2019 VL 25 BP 87 EP 97 DI 10.12659/MSM.911849 PG 11 WC Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine GA HG6HW UT WOS:000455082800001 PM 30606998 OA Green Submitted DA 2026-03-26 ER PT J AU Wang, MY Hua, XS Niu, HM Sun, ZY Zhang, L Li, YL Zhang, L Li, L AF Wang, Mingyang Hua, Xuesi Niu, Hongmei Sun, Zhengyu Zhang, Li Li, Yali Zhang, Lan Li, Lin TI Cornel Iridoid Glycoside Protects Against White Matter Lesions Induced by Cerebral lschemia in Rats via Activation of the Brain-Derived Neurotrophic Factor/Neuregulin-1 Pathway SO NEUROPSYCHIATRIC DISEASE AND TREATMENT LA English DT Article DE cornel iridoid glycoside; white matter lesion; cerebral ischemia; brain-derived neurotrophic factor; neuregulin-1 pathway ID MICROGLIA/MACROPHAGE POLARIZATION; NERVOUS-SYSTEM; ISCHEMIA; DAMAGE; NEUREGULIN-1; INJURY; DIFFERENTIATION; HYPOPERFUSION; IMPAIRMENT; RECOVERY AB Background: Ischemic stroke often induces profound white matter lesions, resulting in poor neurological outcomes and impaired post-stroke recovery. The present study aimed to investigate the effects of cornel iridoid glycoside (CIG), a major active component extracted from Cornus officinalis, on the white matter injury induced by ischemic stroke and further investigate its neuroprotective mechanisms. Methods: Adult male Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO) surgery for 2 h, followed by reperfusion. Rats were intragastrically administered CIG (60 mg/kg and 120 mg/kg) beginning 6 h afters reperfusion, once daily for seven days. A series of behavioral tests (modified neurological severity scores test, object recognition test, adhesive removal test, and beam walking test) were performed to evaluate the neurological functioning in MCAO rats. Histology of the white matter was studied using luxol fast blue staining and transmission electron microscopy. Immunohistochemical staining was performed to assess myelin loss, oligodendrocyte maturation, and glial activation. Activation of the brain-derived neurotrophic factor (BDNF)/neuregulin-1 (NRG1) pathway was evaluated by Western blotting. Results: CIG treatment remarkably decreased the neurological deficit score, accelerated the recovery of somatosensory and motor functions, and ameliorated the memory deficit in MCAO rats. Furthermore, CIG alleviated white matter lesions and demyelination, increased myelin basic protein expression and the number of mature oligodendrocytes, and decreased the number of activated microglia and astrocytes in the corpus callosum of MCAO rats. In addition, Western blot analysis indicated that CIG increased the expression of BDNF/p-TrkB, NRG1/ErbB4 proteins, which further elevated PI3K p110 alpha/p-Akt/p-mTOR signaling in the corpus callosum of MCAO rats. Conclusion: We demonstrated that CIG protects against white matter lesions induced by cerebral ischemia partially by decreasing the number of activated microglia and astrocytes, increasing BDNF level, and activating NRG1/ErbB4 and its downstream PI3K/Akt/mTOR pathways in the white matter. CIG might be used as a potential neuroprotective agent for the treatment of ischemic stroke. C1 [Wang, Mingyang; Niu, Hongmei; Sun, Zhengyu; Zhang, Li; Li, Yali; Zhang, Lan; Li, Lin] Capital Med Univ, Xuanwu Hosp,Beijing Engn Res Ctr Nerve Syst Drugs, Dept Pharm,Minist Educ,Beijing Inst Brain Disorde, Natl Clin Res Ctr Geriatr Dis,Key Lab Neurodegene, Beijing, Peoples R China. [Hua, Xuesi] Univ Michigan, Ann Arbor, MI 48109 USA. C3 Capital Medical University; University of Michigan System; University of Michigan RP Zhang, L; Li, L (corresponding author), Capital Med Univ, Dept Pharm, Xuanwu Hosp, 45 Changchun St, Beijing 100053, Peoples R China. EM lanizhg@126.com; linlixw@126.com RI ; Wang, Mingyang/OFO-4025-2025 OI Hua, Xuesi/0000-0001-5036-007X; FU National Natural Science Foundation of China [81473373, 81874351, 81673406]; National Science and Technology Major Project of China [2015ZX09101-016]; Beijing Postdoctoral Research Foundation [2018-ZZ-112] FX This work was supported by National Natural Science Foundation of China (81473373, 81874351, 81673406), National Science and Technology Major Project of China (2015ZX09101-016), and Beijing Postdoctoral Research Foundation (2018-ZZ-112). 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Dis. Treat. PY 2019 VL 15 BP 3327 EP 3340 DI 10.2147/NDT.S228417 PG 14 WC Clinical Neurology; Psychiatry WE Science Citation Index Expanded (SCI-EXPANDED) SC Neurosciences & Neurology; Psychiatry GA JT4VV UT WOS:000500989900001 PM 31819458 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Davoodvandi, A Sahebnasagh, R Mardanshah, O Asemi, Z Nejati, M Shahrzad, MK Mirzaei, HR Mirzaei, H AF Davoodvandi, Amirhossein Sahebnasagh, Roxana Mardanshah, Omid Asemi, Zatollah Nejati, Majid Shahrzad, Mohammad K. Mirzaei, Hamid R. Mirzaei, Hamed TI Medicinal Plants As Natural Polarizers of Macrophages: Phytochemicals and Pharmacological Effects SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE Medicinal plant; phytochemicals; macrophage polarization; therapy; natural polarizers; pharmacological effects ID MATRIX METALLOPROTEINASES; GLUCOCORTICOID-RECEPTOR; INFLAMMATORY RESPONSES; MOLECULAR-MECHANISMS; IN-VITRO; ANTIINFLAMMATORY ACTIVITY; SIGNALING PATHWAY; OXIDATIVE STRESS; INTERFERON-GAMMA; SOCS PROTEINS AB Macrophages are one of the crucial mediators of the immune response in different physiological and pathological conditions. These cells have critical functions in the inflammation mechanisms that are involved in the inhibition or progression of a wide range of diseases including cancer, autoimmune diseases, etc. It has been shown that macrophages are generally divided into two subtypes, M1 and M2, which are distinguished on the basis of their different gene expression patterns and phenotype. M1 macrophages are known as pro-inflammatory cells and are involved in inflammatory mechanisms, whereas M2 macrophages are known as anti-inflammatory cells that are involved in the inhibition of the inflammatory pathways. M2 macrophages help in tissue healing via producing anti-inflammatory cytokines. Increasing evidence indicated that the appearance of different macrophage subtypes is associated with the fate of diseases (progression versus suppression). Hence, polarization of macrophages can be introduced as an important venue in finding, designing and developing novel therapeutic approaches. Albeit, there are different pharmacological agents that are used for the treatment of various disorders, it has been shown that several natural compounds have the potential to regulate M1 to M2 macrophage polarization and vice versa. Herein, for the first time, we summarized new insights into the pharmacological effects of natural compounds on macrophage polarization. C1 [Davoodvandi, Amirhossein] Kashan Univ Med Sci, Student Res Comm, Kashan, Iran. [Davoodvandi, Amirhossein; Asemi, Zatollah; Mirzaei, Hamed] Kashan Univ Med Sci, Res Ctr Biochem & Nutr Metab Dis, Kashan, Iran. [Sahebnasagh, Roxana] Univ Tehran Med Sci, Sch Adv Technol Med, Dept Mol Med, Tehran, Iran. [Mardanshah, Omid] Sirjan Fac Med Sci, Dept Lab Sci, Sirjan, Iran. [Nejati, Majid] Kashan Univ Med Sci, Anat Sci Res Ctr, Kashan, Iran. [Shahrzad, Mohammad K.] Shahid Beheshti Univ Med Sci, Shohadae Tajrish Hosp, Dept Internal Med & Endocrinol, Tehran, Iran. [Mirzaei, Hamid R.] Univ Tehran Med Sci, Sch Med, Dept Med Immunol, Tehran, Iran. C3 Tehran University of Medical Sciences; Shahid Beheshti University Medical Sciences; Tehran University of Medical Sciences RP Mirzaei, H (corresponding author), Kashan Univ Med Sci, Res Ctr Biochem & Nutr Metab Dis, Kashan, Iran.; Shahrzad, MK (corresponding author), Shahid Beheshti Univ Med Sci, Shohadae Tajrish Hosp, Dept Internal Med & Endocrinol, Tehran, Iran.; Mirzaei, HR (corresponding author), Univ Tehran Med Sci, Sch Med, Dept Med Immunol, Tehran, Iran. EM mk_shahrzad@yahoo.com; h-mirzaei@tums.ac.ir; mirzaei-h@kaums.ac.ir RI Shahrzad, Mohammad Karim/AAU-7371-2021; asemi, zatollah/J-2677-2018; Davoodvandi, Amirhossein/JVO-6631-2024; Mardanshah, Omid/D-1328-2018; Nejati, Majid/AAE-9002-2020; Mirzaei, Hamid Reza/I-4673-2019 OI Shahrzad, Mohammad Karim/0000-0002-8872-0859; Davoodvandi, Amirhossein/0000-0001-9649-7071; Mardanshah, Omid/0000-0001-9692-5750; FU Kashan University of Medical Sciences (KAUMS) [97202] FX The research grant was provided by the Research Deputy of Kashan University of Medical Sciences (KAUMS), Grant No. 97202. 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ETHNOPHARMACOL, V198, P194, DOI 10.1016/j.jep.2016.11.052 NR 154 TC 23 Z9 24 U1 0 U2 13 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2019 VL 25 IS 30 BP 3225 EP 3238 DI 10.2174/1381612825666190829154934 PG 14 WC Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Pharmacology & Pharmacy GA JN5BU UT WOS:000496914600006 PM 31465276 DA 2026-03-26 ER PT J AU Lu, JD Yang, YL Peng, JT Xiang, M Wang, DC Xiong, GL Li, SM AF Lu, Jiandong Yang, Yilong Peng, Jinting Xiang, Min Wang, Dongcai Xiong, Guoliang Li, Shunmin TI Trichosanthes kirilowii lectin ameliorates streptozocin-induced kidney injury via modulation of the balance between M1/M2 phenotype macrophage SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE Diabetic nephropathy; Macrophage polarization; Notch; Podocyte; Trichosanthes kirilowii lectin ID CISPLATIN-INDUCED NEPHROTOXICITY; DIABETIC-NEPHROPATHY; RENAL INJURY; POLARIZATION; M1 AB Background: Macrophage polarization has been reported to induce podocyte injury, which is a typical characteristic of diabetic nephropathy (DN). Trichosanthes kirilowii is an herb showing renal protective effect as well as immune-regulating effect. Therefore, it was hypothesized that the renal protective effect of Trichosanthes kirilowii was associated with its modulation on macrophage polarization. In the current study, we tested the hypothesis by subjecting DN rats to treatment of Trichosanthes kirilowii lectin (TKL), an active component of Trichosanthes kirilowii. Method: DN was induced using streptozocin (STZ) method, and after 3 days, treatments were performed with different doses of TKL for eight weeks. The effect of TKL on the renal function, structure, and inflammation was assessed. To explain the pathway mediating the effect of TKL on renal tissues, the expressions of markers involved in macrophage polarization, podocyte proliferation, and Notch signaling were determined. Moreover, the DN rats were further administrated with Notch signaling inhibitor, Dibenzazepine (DIB), to verify the key role of Notch signaling in the renal protective effect of TKL. Results: STZ induced damages in renal function and structure, which was attenuated by TKL of different doses. Moreover, STZ also increased the production of TNF-alpha and iNOS while suppressed the production of IL-10 and arginase-1 (Arg-1). The induced inflammation by STZ was inhibited by TKL. The polarization of macrophage into M1 type during the development of DN was blocked by TKL, contributing to the increased proliferation potential of podocytes. Regarding Notch signaling, TKL administration inhibited the activation of the pathway by suppressing the expression of Notch1, NICD1, and Hes1. The administration of DIB had similar effect to that of TKL administration on renal function and structure. Conclusions: The study for the first time showed that TKL attenuated deterioration in renal structure and function by increasing M2 macrophage proportion via inhibition of Notch signaling. C1 [Lu, Jiandong; Peng, Jinting; Xiang, Min; Xiong, Guoliang; Li, Shunmin] Guangzhou Univ Chinese Med, Shenzhen Tradit Chinese Med Hosp, Dept Nephrol, Shenzhen, Guangdong, Peoples R China. [Yang, Yilong] Guangzhou Univ Chinese Med, Shenzhen Affiliated Hosp, Geriatr Dept Tradit Chinese Med, Shenzhen, Guangdong, Peoples R China. [Wang, Dongcai] Guangzhou Univ Chinese Med, Shenzhen Tradit Chinese Med Hosp, Ctr Dis Early Treatment, Shenzhen, Guangdong, Peoples R China. C3 Shenzhen Traditional Chinese Medicine Hospital; Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine; Guangzhou University of Chinese Medicine; Shenzhen Traditional Chinese Medicine Hospital RP Xiong, GL; Li, SM (corresponding author), Guangzhou Univ Chinese Med, Shenzhen Tradit Chinese Med Hosp, Dept Nephrol, Shenzhen, Guangdong, Peoples R China. EM szxiongguoliang@126.com; zyylishumnin@163.com RI Yang, Yilong/HTL-4828-2023 FU Shenzhen Science and Technology Project [JCYJ20140408152909279]; Development and Reform Commission of Shenzhen Municipality Special funds for future industrial development; Research Project of Health Planning System in Shenzhen [SZFZ2017097] FX This work was supported by Shenzhen Science and Technology Project (Project number: JCYJ20140408152909279) and Development and Reform Commission of Shenzhen Municipality Special funds for future industrial development (2015) and Research Project of Health Planning System in Shenzhen (SZFZ2017097). 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Pharmacother. PD JAN PY 2019 VL 109 BP 93 EP 102 DI 10.1016/j.biopha.2018.10.060 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Research & Experimental Medicine; Pharmacology & Pharmacy GA HD5AE UT WOS:000452539100010 PM 30396096 OA Green Submitted, hybrid DA 2026-03-26 ER PT J AU Koh, YC Yang, GL Lai, CS Weerawatanakorn, M Pan, MH AF Koh, Yen-Chun Yang, Guliang Lai, Ching-Shu Weerawatanakorn, Monthana Pan, Min-Hsiung TI Chemopreventive Effects of Phytochemicals and Medicines on M1/M2 Polarized Macrophage Role in Inflammation-Related Diseases SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Review DE chemoprevention; phytochemicals; M1/M2 macrophage; inflammation ID NF-KAPPA-B; M1 MACROPHAGE; M2 POLARIZATION; MICROGLIAL POLARIZATION; AMELIORATES OBESITY; INSULIN-RESISTANCE; TISSUE-REPAIR; ACTIVATION; PHENOTYPE; HOMEOSTASIS AB Macrophages can polarize into two different states (M1 and M2), which play contrasting roles during pathogenesis or tissue damage. M1 polarized macrophages produce pro-inflammatory cytokines and mediators resulting in inflammation, while M2 macrophages have an anti-inflammatory effect. Secretion of appropriate cytokines and chemokines from macrophages can lead to the modification of the microenvironment for bridging innate and adaptive immune responses. Increasing evidence suggests that polarized macrophages are pivotal for disease progression, and the regulation of macrophage polarization may provide a new approach in therapeutic treatment of inflammation-related diseases, including cancer, obesity and metabolic diseases, fibrosis in organs, brain damage and neuron injuries, and colorectal disease. Polarized macrophages affect the microenvironment by secreting cytokines and chemokines while cytokines or mediators that are produced by resident cells or tissues may also influence macrophages behavior. The interplay of macrophages and other cells can affect disease progression, and therefore, understanding the activation of macrophages and the interaction between polarized macrophages and disease progression is imperative prior to taking therapeutic or preventive actions. Manipulation of macrophages can be an entry point for disease improvement, but the mechanism and potential must be understood. In this review, some advanced studies regarding the role of macrophages in different diseases, potential mechanisms involved, and intervention of drugs or phytochemicals, which are effective on macrophage polarization, will be discussed. C1 [Koh, Yen-Chun; Pan, Min-Hsiung] Natl Taiwan Univ, Inst Food Sci & Technol, Taipei 10617, Taiwan. [Yang, Guliang; Pan, Min-Hsiung] Huanggang Normal Univ, Hubei Collaborat Innovat Ctr Characterist Resourc, Hubei Key Lab Econ Forest Germplasm Improvement &, Huanggang 410083, Peoples R China. [Lai, Ching-Shu] Natl Kaohsiung Marine Univ, Dept Seafood Sci, Kaohsiung 811, Taiwan. [Weerawatanakorn, Monthana] Naresuan Univ, Fac Agr Nat Resources & Environm, Phitsanulok 65000, Thailand. [Pan, Min-Hsiung] China Med Univ, China Med Univ Hosp, Dept Med Res, Taichung 40402, Taiwan. [Pan, Min-Hsiung] Asia Univ, Dept Hlth & Nutr Biotechnol, Taichung 41354, Taiwan. C3 National Taiwan University; Huanggang Normal University; National Kaohsiung University of Science & Technology; Naresuan University; China Medical University Taiwan; China Medical University Hospital - Taiwan; Asia University Taiwan RP Pan, MH (corresponding author), Natl Taiwan Univ, Inst Food Sci & Technol, Taipei 10617, Taiwan.; Pan, MH (corresponding author), Huanggang Normal Univ, Hubei Collaborat Innovat Ctr Characterist Resourc, Hubei Key Lab Econ Forest Germplasm Improvement &, Huanggang 410083, Peoples R China.; Pan, MH (corresponding author), China Med Univ, China Med Univ Hosp, Dept Med Res, Taichung 40402, Taiwan.; Pan, MH (corresponding author), Asia Univ, Dept Hlth & Nutr Biotechnol, Taichung 41354, Taiwan. EM yenkoh0123@gmail.com; guliangyang@163.com; chlai@mail.nkmu.edu.tw; monthanac@nu.ac.th; mhpan@ntu.edu.tw RI KOH, YEN CHUN/LFT-5555-2024; Pan, Min-Hsiung/AAT-8865-2021; Weerawatanakorn, Monthana/AAS-3236-2020 OI KOH, YEN CHUN/0000-0001-7683-873X; Pan, Min-Hsiung/0000-0002-5188-7030; FU Ministry of Science and Technology [105-2320-B-002-031-MY3, 105-2628-B-002-003-MY3] FX This study was supported by the Ministry of Science and Technology (105-2320-B-002-031-MY3, 105-2628-B-002-003-MY3). 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J. Mol. Sci. PD AUG PY 2018 VL 19 IS 8 AR 2208 DI 10.3390/ijms19082208 PG 30 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Chemistry GA GR7LE UT WOS:000442869800060 PM 30060570 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Hu, QH Du, HJ Ma, GX Pei, F Ma, N Yuan, B Nakata, PA Yang, WJ AF Hu, Qiuhui Du, Hengjun Ma, Gaoxing Pei, Fei Ma, Ning Yuan, Biao Nakata, Paul A. Yang, Wenjian TI Purification, identification and functional characterization of an immunomodulatory protein from Pleurotus eryngii SO FOOD & FUNCTION LA English DT Article ID TOLL-LIKE RECEPTORS; MACROPHAGE POLARIZATION; INNATE IMMUNITY; RAW264.7 CELLS; MUSHROOM; POLYSACCHARIDES; ACTIVATION; MICE; ANTIOXIDANT; EXTRACT AB Pleurotus eryngii contains bioactive compounds that can activate the immune system. Here we report the identification, purification, and functional characterization of the bioactive P. eryngii protein (PEP) 1b. PEP 1b was discovered to be a 21.9 kDa protein with the ability to induce the M1-polarization of the macrophage cell line RAW 264.7 cells. Biochemical measurements showed that PEP 1b stimulated nitric oxide (NO), IL-1, IL-6 and TNF- production and regulated inducible NO synthase. Phosphorylation and inhibitor studies revealed that PEP 1b promoted the translocation of NF-kB from the cytosol to the nucleus allowing the induction of target gene expression and NO production. The phosphorylation of JNK and ERK1/2 was found to be necessary for NO production. Each phosphorylation pathway was found to require a Toll-like receptor (TLR) 4 as a prerequisite for PEP 1b-induced NO production. This study suggests that PEP 1b is an immunomodulatory protein that can boost cellular immune responses through the activation of the TLR4-NF-B and MAPK signaling pathways. C1 [Hu, Qiuhui; Du, Hengjun; Pei, Fei; Ma, Ning; Yang, Wenjian] Nanjing Univ Finance & Econ, Coll Food Sci & Engn, Collaborat Innovat Ctr Modern Grain Circulat & Sa, Key Lab Grains & Oils Qual Control & Proc, Nanjing 210023, Jiangsu, Peoples R China. [Ma, Gaoxing; Yuan, Biao] Nanjing Agr Univ, Coll Food Sci & Technol, Nanjing 210095, Jiangsu, Peoples R China. [Nakata, Paul A.] Baylor Coll Med, Dept Pediat, USDA ARS, Childrens Nutr Res Ctr, Houston, TX 77030 USA. C3 Nanjing University of Finance & Economics; Nanjing Agricultural University; Baylor College of Medicine; United States Department of Agriculture (USDA) RP Yang, WJ (corresponding author), Nanjing Univ Finance & Econ, Coll Food Sci & Engn, Collaborat Innovat Ctr Modern Grain Circulat & Sa, Key Lab Grains & Oils Qual Control & Proc, Nanjing 210023, Jiangsu, Peoples R China. EM lingwentt@163.com RI ; Pei, Fei/KYQ-2303-2024; YUAN, BIAO/O-9471-2019; Du, Hengjun/L-5817-2018 OI , wenjian/0000-0002-7527-8491; Ma, Gaoxing/0000-0002-5549-1367; Nakata, Paul/0000-0002-6331-9700; YUAN, BIAO/0000-0001-9482-7612; Du, Hengjun/0000-0001-9571-1670 FU National Natural Science Foundation of China [31471927]; Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD); U.S. Department of Agriculture, Agricultural Research Service [58-3092-5-001] FX This work is financially supported by the National Natural Science Foundation of China (No. 31471927), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). P. A. N. is supported by the U.S. Department of Agriculture, Agricultural Research Service, under Cooperative agreement number 58-3092-5-001. 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Crocin is an active ingredient of Crocus sativus L. This study established a rat coronary atherosclerosis model induced by vitamin D3 (VD3), to explore the effect of Crocin on lipid metabolism, macrophage polarization and the activity of inflammatory proteins. The results revealed that Crocin decreased blood lipid levels by decreasing the levels of endothelin (ET), total cholesterol (TC), trigly-ceridelow (TG) and low-density lipoprotein cholesterol (LDL-c), elevating the level of high-density lipoprotein cholesterin (HDL-c). Crocin also inhibited lipogenesis by suppressing the expression of lipogenesis-related proteins and elevating lipid catabolism-related proteins. Moreover, Crocin effectively alleviated inflammation by suppressing the expression of pro-inflammatory cytokines and increasing levels of anti-inflammatory cytokines. We further found that Crocin promoted macrophage polarization to the M2 phenotype by reducing M1 markers (CD40(+) and CD11c(+)) and elevating M2 markers (CD613(+) and CD206(+)). Finally, Crocin strongly inhibited the expression of NF-kappa B p65 and its translocation into the nucleus. Crocin partially counteracted nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) p65 expression and the nuclei accumulation caused by NF-kappa B p65 overexpression. Taken together, our research indicated that Crocin inhibited lipogenesis and alleviated the inflammation in a VD3-induced rat coronary atherosclerosis model by promoting M2 macrophage polarization and maybe by inhibiting NF-kappa B p65 nuclear translocation. This study implicates Crocin as a potential therapeutic strategy for coronary atherosclerosis. 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PD FEB PY 2018 VL 55 BP 120 EP 127 DI 10.1016/j.intimp.2017.11.037 PG 8 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA GC4LH UT WOS:000429755500015 PM 29248792 DA 2026-03-26 ER PT J AU Yang, Z He, CM He, JY Chu, J Liu, HP Deng, XY AF Yang, Zhi He, Chengmin He, Jinyang Chu, Jing Liu, Hanping Deng, Xiaoyuan TI Curcumin-mediated bone marrow mesenchymal stem cell sheets create a favorable immune microenvironment for adult full-thickness cutaneous wound healing SO STEM CELL RESEARCH & THERAPY LA English DT Article DE Curcumin; Bone marrow mesenchymal stem cell; Cell sheet; Immune response; Cutaneous wound healing ID EXTRACELLULAR-MATRIX; TISSUE REGENERATION; GENE-EXPRESSION; GROWTH-FACTORS; TGF-BETA; MACROPHAGES; REPAIR; FIBROSIS; DELIVERY; INJURY AB Background: Adult full-thickness cutaneous wound repair suffers from an imbalanced immune response, leading to nonfunctional reconstructed tissue and fibrosis. Although various treatments have been reported, the immune-mediated tissue regeneration driven by biomaterial offers an attractive regenerative strategy for damaged tissue repair. Methods: In this research, we investigated a specific bone marrow-derived mesenchymal stem cell (BMSC) sheet that was induced by the Traditional Chinese Medicine curcumin (CS-C) and its immunomodulatory effects on wound repair. Comparisons were made with the BMSC sheet induced without curcumin (CS-N) and control (saline). Results: In vitro cultured BMSC sheets (CS-C) showed that curcumin promoted the proliferation of BMSCs and modified the features of produced extracellular matrix (ECM) secreted by BMSCs, especially the contents of ECM structural proteins such as fibronectin (FN) and collagen I and III, as well as the ratio of collagen III/I. Two-photon fluorescence (TPF) and second-harmonic generation (SHG) imaging of mouse implantation revealed superior engraftment of BMSCs, maintained for 35 days in the CS-C group. Most importantly, CS-C created a favorable immune microenvironment. The chemokine stromal cell-derived factor 1 (SDF1) was abundantly produced by CS-C, thus facilitating a mass migration of leukocytes from which significantly increased expression of signature T(H)1 cells (interferon gamma) and M1 macrophages (tumor necrosis factor alpha) genes were confirmed at 7 days postoperation. The number of T(H)1 cells and associated pro-inflammatory M1 macrophages subsequently decreased sharply after 14 days post-operation, suggesting a rapid type I immune regression. Furthermore, the CS-C group showed an increased trend towards M2 macrophage polarization in the early phase. CS-C led to an epidermal thickness and collagen deposition that was closer to that of normal skin. Conclusions: Curcumin has a good regulatory effect on BMSCs and this promising CS-C biomaterial creates a proregenerative immune microenvironment for cutaneous wound healing. C1 [Yang, Zhi; He, Chengmin; Chu, Jing; Liu, Hanping; Deng, Xiaoyuan] South China Normal Univ, Coll Biophoton, MOE Key Lab Laser Life Sci, 55 Zhongshan Ave West, Guangzhou 510631, Guangdong, Peoples R China. [He, Jinyang] Guangzhou Univ Chinese Med, Trop Med Inst, Guangzhou, Guangdong, Peoples R China. C3 South China Normal University; Guangzhou University of Chinese Medicine RP Liu, HP; Deng, XY (corresponding author), South China Normal Univ, Coll Biophoton, MOE Key Lab Laser Life Sci, 55 Zhongshan Ave West, Guangzhou 510631, Guangdong, Peoples R China. EM liuhp@scnu.edu.cn; xydeng12@126.com FU National Natural Science Foundation of China [81671729, 81171379] FX This work was supported by the National Natural Science Foundation of China (no. 81671729) and (no. 81171379). 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Ther. PD JAN 31 PY 2018 VL 9 AR 21 DI 10.1186/s13287-018-0768-6 PG 18 WC Cell & Tissue Engineering; Cell Biology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology; Research & Experimental Medicine GA FU2NG UT WOS:000423686300004 PM 29386050 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Lai, YS Putra, RBDS Aui, SP Chang, KT AF Lai, Yin-Siew Putra, Renanda Baghaz Dzulhamdhani Surya Aui, Shin-Peir Chang, Ko-Tung TI M2C Polarization by Baicalin Enhances Efferocytosis via Upregulation of MERTK Receptor SO AMERICAN JOURNAL OF CHINESE MEDICINE LA English DT Article DE Baicalin; Bone Marrow; Macrophage; M2; Phagocytosis; Efferocytosis ID MACROPHAGE POLARIZATION; CELLS; GAMMA; PHAGOCYTOSIS; NEUTROPHILS; ACTIVATION; CLEARANCE; AUTOPHAGY; INJURY; IL-10 AB Baicalin is the main active ingredient primary isolated from the Chinese herb, Scutellaria baicalensis Georgi. Although baicalin can induce M2 macrophage polarization, we still do not know the subtype of macrophages polarized by baicalin. In this study, we characterized that murine bone marrow derived macrophages induced by M-CSF can be further polarized into M2(C) phenotype by baicalin. The signatures of M2(C) macrophages for mRNA expression like interferon regulatory factor 4 (IRF4), interleukin-10 (IL-10), MERTK and PTX3 were up-regulated. Moreover, we observed the concomitantly decreasing of tumor necrosis factor alpha (TNF-alpha), interferon regulatory factor 5 (IRF5), IL-6. In contrast, M2 macrophages polarized by IL-4 increased gene transcript of arginase-1 (Arg-1) and surface marker of CD206 indicates that their identity as M2(A) rather than M2(C) subtypes. Interestingly, the phagocytosis as well as efferocytosis activity were significantly enhanced in M2(C) macrophage polarized by baicalin and these capacities were associated with the expression of MERTK receptor. Finally, we conclude that baicalin induced M2(C) macrophages polarization with both elevations of efferocytosis and anti-inflammatory activity. C1 [Lai, Yin-Siew; Putra, Renanda Baghaz Dzulhamdhani Surya; Aui, Shin-Peir; Chang, Ko-Tung] Natl Pingtung Univ Sci & Technol, Dept Biol Sci & Technol, 1 Shuefu Rd, Pingtung 91201, Taiwan. [Lai, Yin-Siew; Chang, Ko-Tung] Natl Pingtung Univ Sci & Technol, Precis Instruments Ctr, Flow Cytometry Ctr, 1 Shuefu Rd, Pingtung 91201, Taiwan. C3 National Pingtung University Science & Technology; National Pingtung University Science & Technology RP Chang, KT (corresponding author), Natl Pingtung Univ Sci & Technol, Dept Biol Sci & Technol, 1 Shuefu Rd, Pingtung 91201, Taiwan. EM kotungc@mail.npust.edu.tw OI Baghaz, Renanda/0000-0002-3556-0759; Lai, Yin Siew/0000-0003-2963-9038; Chang, Ko-Tung/0000-0001-9383-831X FU Ministry of Science and Technology in Taiwan [MOST 104-2314-B-020-MY3, MOST 106-2314-B-020-001, MOST 106-2731-M-020-001] FX This study was supported by the Ministry of Science and Technology in Taiwan (grant MOST 104-2314-B-020-MY3, MOST 106-2314-B-020-001 and MOST 106-2731-M-020-001). We thank them for their assistance from Core Facilities-Flow Cytometry Unit at National Pingtung University of Science and Technology in Taiwan. 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Huiyang Shengji Extract (HSE) is a Traditional Chinese Medicine prescription for treating chronic wounds. Little is known about the underlying molecular mechanism of HSE. This study aim to investigate the effect of HSE on macrophage phenotype transition in chronic skin wound of mice and macrophages in vitro. Balb/c mice were randomly divided into four groups: control (normal wound-NS treated), model (delayed wound-NS treated), HSE-treated groups, and bFGF-treated groups. The immunosuppressive mice were operated by full-thickness excision. Macrophage phenotype markers on the wound were analyzed by immunohistochemistry, real-time PCR, and Western blot. The in vitro cytotoxicity and phagocytosis of macrophages was assessed by CCK-8 and neutral red assays. Macrophage 1/2 (M1/M2) markers were analyzed using ELISA, flow cytometry, and real-time PCR. The results showed delayed wound healing in immunosuppressed mice. HSE promoted macrophage recruitment to the wounded tissue, decreased the expression of iNOS and IL-6, and increased the level of CD206, VEGF, and TGF-beta during granulation tissue formation. In vitro, HSE inhibited the inflammatory activated macrophages secreting M1 cytokines, promoted secretion of M2 cytokines, increased Arg-1 mRNA, and decreased iNOS mRNA significantly. In conclusion, an imbalance of macrophage phenotype contributed to impaired wound healing in immunosuppressed mice. HSE promoted impaired wound healing by regulating the macrophage phenotype transition: a potential therapeutic mechanism of HSE for the chronic non-healing wound. C1 [He, Xiujuan; Lin, Yan; Meng, Yujiao; Xue, Yan; Han, Xuyang; Li, Ping] Capital Med Univ, Beijing Inst TCM, Beijing Hosp Tradit Chinese Med, Beijing, Peoples R China. C3 Capital Medical University RP Li, P (corresponding author), Capital Med Univ, Beijing Inst TCM, Beijing Hosp Tradit Chinese Med, Beijing, Peoples R China. 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The results showed that 0.02% phlorizin dietary treatment in high fat diet fed mice for 6 weeks significantly reduced concentration of serum and adipose tissue pro-inflammation cytokines, including MCP-1, TNF-, IL-1, IL-6, and IL-1 without altering body fat and serum lipid levels. Phlorizin inhibited inflammation related pathways: c-Jun N-terminal kinase and nuclear factor B (NFB) pathways, down-regulated the protein expression of macrophage maker F4/80 and M1 macrophage marker CD11c, up-regulated the protein expression of M2 macrophage marker CD206 in adipose tissue. This research provides novel insight into the treatment effect of phlorizin in obesity related inflammation. Practical applicationsPhlorizin, a member of the chalcone class of organic compounds especially abundant in apples has been used in human medicine for long because of its extensive bioactivities, such as anti-diabetes and antioxidation. This study demonstrated that phlorizin inhibited adipose tissue inflammatory response in HFD-fed obese mice via inhibition of c-Jun N-terminal kinase and IKK-/NFB pathways, reduction of macrophage infiltration and regulation of M1/M2 macrophage polarization. Phlorizin can be a practical bioactive compound on attenuating obesity related inflammation and metabolic disorders. C1 [Tian, Yuan; Xu, Yancheng] Wuhan Univ, Dept Endocrinol, Zhongnan Hosp, Wuhan, Hubei, Peoples R China. [Tian, Yuan; Gao, Ling; Guo, Yan] Hubei Univ Arts & Sci, Dept Endocrinol, Xiangyang Cent Hosp, Xiangyang, Hubei, Peoples R China. C3 Wuhan University; Hubei University of Arts & Science RP Xu, YC (corresponding author), Wuhan Univ, Dept Endocrinol, Zhongnan Hosp, Wuhan, Hubei, Peoples R China. EM oxyc@163.com FU National Natural Science Foundation of China [81370872] FX National Natural Science Foundation of China, Grant/Award Number: 81370872 CR [Anonymous], OB PREV MAN GLOB EP [Anonymous], P NUTR SOC Barreca D, 2014, FOOD CHEM, V160, P292, DOI 10.1016/j.foodchem.2014.03.118 BARTLETT GR, 1959, THE JOURNAL OF BIOLO, V234, P466 Bartsch H, 2006, LANGENBECK ARCH SURG, V391, P499, DOI 10.1007/s00423-006-0073-1 Bastard JP, 2006, EUR CYTOKINE NETW, V17, P4 Bhuvaneswari S, 2014, CELL STRESS CHAPERON, V19, P183, DOI 10.1007/s12192-013-0443-x Bondia-Pons I, 2012, J PHYSIOL BIOCHEM, V68, P701, DOI 10.1007/s13105-012-0154-2 Bouloumié A, 2005, CURR OPIN CLIN NUTR, V8, P347, DOI 10.1097/01.mco.0000172571.41149.52 Chang WT, 2012, FOOD CHEM, V134, P972, DOI 10.1016/j.foodchem.2012.03.002 Chawla A, 2011, NAT REV IMMUNOL, V11, P738, DOI 10.1038/nri3071 Ehrenkranz JRL, 2005, DIABETES-METAB RES, V21, P31, DOI 10.1002/dmrr.532 FOLCH J, 1957, J BIOL CHEM, V226, P497 Fuentes E, 2013, MEDIAT INFLAMM, V2013, DOI 10.1155/2013/136584 Fujisaka S, 2009, DIABETES, V58, P2574, DOI 10.2337/db08-1475 Gosch C, 2010, PHYTOCHEMISTRY, V71, P838, DOI 10.1016/j.phytochem.2010.03.003 Huang WC, 2013, MOL NUTR FOOD RES, V57, P1803, DOI 10.1002/mnfr.201300001 James WPT, 2006, ANN NY ACAD SCI, V1083, P1, DOI 10.1196/annals.1367.002 Lumeng CN, 2007, J CLIN INVEST, V117, P175, DOI 10.1172/JCI29881 Lumeng CN, 2011, J CLIN INVEST, V121, P2111, DOI 10.1172/JCI57132 Martinez FO, 2008, FRONT BIOSCI-LANDMRK, V13, P453, DOI 10.2741/2692 Mei XR, 2016, J AGR FOOD CHEM, V64, P7502, DOI 10.1021/acs.jafc.6b03474 Mills CD, 2012, CRIT REV IMMUNOL, V32, P463, DOI 10.1615/CritRevImmunol.v32.i6.10 Monteiro R, 2010, MEDIAT INFLAMM, V2010, DOI 10.1155/2010/289645 MUZIO M, 1998, THE JOURNAL OF EXPER, V187, P2097 Qin XX, 2015, MOLECULES, V20, P21193, DOI 10.3390/molecules201219754 Rezk BM, 2002, BIOCHEM BIOPH RES CO, V295, P9, DOI 10.1016/S0006-291X(02)00618-6 ROSSETTI L, 1987, J CLIN INVEST, V79, P1510, DOI 10.1172/JCI112981 Shin SK, 2016, NUTRIENTS, V8, DOI 10.3390/nu8020092 Shoelson SE, 2007, GASTROENTEROLOGY, V132, P2169, DOI 10.1053/j.gastro.2007.03.059 Suganami T, 2010, J LEUKOCYTE BIOL, V88, P33, DOI 10.1189/jlb.0210072 Wang N., 2015, M1/M2 Macrophages: The Arginine Fork in the Road to Health and Disease, P230 Wellen KE, 2003, J CLIN INVEST, V112, P1785, DOI 10.1172/JCI20514 Wensveen FM, 2015, EUR J IMMUNOL, V45, P2446, DOI 10.1002/eji.201545502 Wisse BE, 2004, J AM SOC NEPHROL, V15, P2792, DOI 10.1097/01.ASN.0000141966.69934.21 Xu HY, 2003, J CLIN INVEST, V112, P1821, DOI 10.1172/JCI200319451 NR 36 TC 14 Z9 16 U1 2 U2 48 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-8884 EI 1745-4514 J9 J FOOD BIOCHEM JI J. Food Biochem. PD DEC PY 2017 VL 41 IS 6 AR e12407 DI 10.1111/jfbc.12407 PG 6 WC Biochemistry & Molecular Biology; Food Science & Technology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Food Science & Technology GA FO8FS UT WOS:000417120500006 DA 2026-03-26 ER PT J AU Liang, YB Tang, H Chen, ZB Zeng, LJ Wu, JG Yang, W Li, ZY Ma, ZF AF Liang, Yan-Bing Tang, Hao Chen, Zhi-Bin Zeng, Li-Jin Wu, Jing-Guo Yang, Wen Li, Zhen-Yu Ma, Zhong-Fu TI Downregulated SOCS1 expression activates the JAK1/STAT1 pathway and promotes polarization of macrophages into M1 type SO MOLECULAR MEDICINE REPORTS LA English DT Article DE suppressor of cytokine signaling-1; Janus kinase 1; signal transducer and activator of transcription 1; macrophage ID CYTOKINE SIGNALING 3; NEGATIVE REGULATORS; HUMAN MONOCYTES; IN-VITRO; JAK-STAT; SUPPRESSOR; PROTEINS; IFN AB Macrophage polarization is flexible, and involves in different signaling pathways and various transcription factors. Suppressor of cytokine signaling (SOCS) is an important inhibitor of cytokine signaling pathways and also a key physiological regulator for natural and acquired immunity systems. Following transfection of SOCS1 short hairpin (sh) RNA into mouse macrophage cells, reverse transcription-quantitative polymerase chain reaction demonstrated that the mRNA levels of Janus kinase (JAK) 1 and signal transducer and activator of transcription (STAT) 1 increased significantly. In addition, western blotting indicated that JAK1, STAT1 and p-STAT1 expression was significantly enhanced. Fludarabine can inhibit phosphorylation of STAT1 and SOCS1 expression. When fludarabine was added and SOCS1 shRNA was transfected, the inhibition of fludarabine was weakened, and p-STAT1 expression was upregulated. Flow cytometry detection indicated that, following the downregulation of SOCS1 expression, M1-type cells significantly increased, but the proportion of M2-type cells did not change significantly. Fludarabine can reduce the effect of SOCS1 shRNA on promoting M1-type cell polarization, and macrophages can polarize into both M1 and M2 phenotypes. Further ELISA results presented that, when downregulating SOCS1 expression, interleukin (IL)-4 and IL-10 expression was both downregulated, and tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma expression was significantly upregulated. When adding fludarabine or injecting with the traditional Chinese medicine Xuebijing, IL-4 and IL-10 expression was both significantly upregulated, and TNF-alpha and IFN-gamma expression was significantly downregulated. When adding fludarabine and downregulating SOCS1, IL-4, IL-10, TNF-alpha and IFN-gamma expression presented no significant changes. The above results indicated that, when SOCS1 expression is downregulated, it will activate the JAK1/STAT1 pathway, and thereby promote the polarization of macrophages into M1 type. The findings are of great importance for understanding occurrence, development and treatment of various immune-related diseases. C1 [Liang, Yan-Bing; Tang, Hao; Chen, Zhi-Bin; Zeng, Li-Jin; Wu, Jing-Guo; Yang, Wen; Li, Zhen-Yu; Ma, Zhong-Fu] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Gen Internal Med, 58 Zhongshan Second Rd, Guangzhou 510080, Guangdong, Peoples R China. C3 Sun Yat Sen University RP Ma, ZF (corresponding author), Sun Yat Sen Univ, Affiliated Hosp 1, Dept Gen Internal Med, 58 Zhongshan Second Rd, Guangzhou 510080, Guangdong, Peoples R China. EM 1362670488@qq.com RI Yang, Wen/ABE-7541-2021; Chen, Zhibin/LOS-5137-2024 FU Science and Technology Planning Project of Guangdong Province [2012B031800291]; Science and Technology Planning Project of Guangzhou City [201300000160]; Tianjin Chase Sun Pharmaceutical Co., Ltd. FX The present study was supported by grants from Science and Technology Planning Project of Guangdong Province (grant no. 2012B031800291), the Science and Technology Planning Project of Guangzhou City (grant no. 201300000160). This study was supported by funding from Tianjin Chase Sun Pharmaceutical Co., Ltd. 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PD NOV PY 2017 VL 16 IS 5 BP 6405 EP 6411 DI 10.3892/mmr.2017.7384 PG 7 WC Oncology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Research & Experimental Medicine GA FM0ZU UT WOS:000414698900090 PM 28901399 OA Bronze DA 2026-03-26 ER PT J AU Xu, XL Guo, YH Zhao, JX He, SS Wang, Y Lin, Y Wang, N Liu, QQ AF Xu, Xiaolong Guo, Yuhong Zhao, Jingxia He, Shasha Wang, Yan Lin, Yan Wang, Ning Liu, Qingquan TI Punicalagin, a PTP1B inhibitor, induces M2c phenotype polarization via up-regulation of HO-1 in murine macrophages SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Punicalagin; M2 polarization; PTP1B; HO-1; Murine ID HIGH-FAT-DIET; HEME OXYGENASE-1; POMEGRANATE JUICE; ACTIVE COMPONENT; OXIDATIVE STRESS; IN-VITRO; GM-CSF; ACTIVATION; INFLAMMATION; CELLS AB Current data have shown that punicalagin (PUN), an ellagitannin isolated from pomegranate, possesses antiinflammatory and anti-oxidant properties; however, its direct targets have not yet been reported. This is the first report that PTP1B serves as a direct target of PUN, with IC50 value of 1.04 mu M. Results from NPOI further showed that the K-on and K-off of PUN-PTP1B complex were 3.38e2 M-1 s(-1) and 4.13e-3 s(-1), respectively. The active site Arg24 of PTP1B was identified as a key binding site of PUN by computation simulation and point mutation. Moreover, inhibition of PTP1B by PUN promoted an M2c-like macrophage polarization and enhanced antiinflammatory cytokines expression, including IL-10 and M-CSF. Based on gene expression profile, we elucidated that PUN treatment significantly up-regulated 275 genes and down-regulated 1059 genes. M1-like macrophage marker genes, such as Tlr4, Irf1/2, Hmgb1, and Stat1 were down-regulated, while M2 marker genes, including Tmem171, Gpr35, Csf1, Il1rn, Cebpb, Fos, Vegfa, Slc11a1, and Bhlhe40 were up-regulated in PUN-treated macrophages. Hmox-1, a gene encoding HO-1 protein, was preferentially expressed with 16-fold change. Inhibition of HO-1 obviously restored PUN-induced M2 polarization and IL-10 secretion. In addition, phosphorylation of both Akt and STAT3 contributed to PUN-induced HO-1 expression. This study provided new insights into the mechanisms of PUN-mediated anti-inflammatory and anti-oxidant activities and provided new therapeutic strategies for inflammatory diseases. C1 [Xu, Xiaolong; Guo, Yuhong; Zhao, Jingxia; He, Shasha; Wang, Yan; Lin, Yan; Wang, Ning; Liu, Qingquan] Capital Med Univ, Beijing Hosp Tradit Chinese Med, Beijing 100010, Peoples R China. [Xu, Xiaolong; Guo, Yuhong; Zhao, Jingxia; He, Shasha; Wang, Yan; Lin, Yan; Wang, Ning; Liu, Qingquan] Beijing Inst Tradit Chinese Med, Beijing 100010, Peoples R China. [Xu, Xiaolong; Guo, Yuhong; Zhao, Jingxia; He, Shasha; Wang, Yan; Lin, Yan; Liu, Qingquan] Beijing Key Lab Basic Res Tradit Chinese Med Infe, Beijing 100010, Peoples R China. C3 Capital Medical University RP Liu, QQ (corresponding author), Capital Med Univ, Beijing Hosp Tradit Chinese Med, Beijing 100010, Peoples R China. EM Liuqingquan2003@126.com RI Liu, Qingquan/AEH-9465-2022 OI xu, xiaolong/0000-0003-3333-0906 FU National Natural Science Foundation of China [81603364, 81673934]; Beijing Natural Science Foundation [7174290]; Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support [ZYLX201611] FX This work was supported by grants from the National Natural Science Foundation of China (Nos. 81603364 and 81673934), Beijing Natural Science Foundation (7174290), and Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (No. ZYLX201611). 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Biol. Med. PD SEP PY 2017 VL 110 BP 408 EP 420 DI 10.1016/j.freeradbiomed.2017.06.014 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA FB3NK UT WOS:000406049200037 PM 28690198 DA 2026-03-26 ER PT J AU Liu, ZJ Ran, YY Huang, S Wen, SH Zhang, WX Liu, XR Ji, ZL Geng, XK Ji, XM Du, HS Leak, RK Hu, XM AF Liu, Zongjian Ran, Yuanyuan Huang, Shuo Wen, Shaohong Zhang, Wenxiu Liu, Xiangrong Ji, Zhili Geng, Xiaokun Ji, Xunming Du, Huishan Leak, Rehana K. Hu, Xiaoming TI Curcumin Protects against Ischemic Stroke by Titrating Microglia/Macrophage Polarization SO FRONTIERS IN AGING NEUROSCIENCE LA English DT Article DE curcumin; microglial polarization; ischemic stroke; inflammation; neuroprotection ID FOCAL CEREBRAL-ISCHEMIA; M2 MACROPHAGE POLARIZATION; BRAIN-INJURY; MICROGLIA POLARIZATION; INFLAMMATION; RATS; MICE; M1; MICRORNA-155; DYSFUNCTION AB Stroke is the most common type of cerebrovascular disease and is a leading cause of disability and death. Ischemic stroke accounts for approximately 80% of all strokes. The remaining 20% of strokes are hemorrhagic in nature. To date, therapeutic options for acute ischemic stroke are very limited. Recent research suggests that shifting microglial phenotype from the pro-inflammatory M1 state toward the anti-inflammatory and tissue-reparative M2 phenotype may be an effective therapeutic strategy for ischemic stroke. The dietary phytochemical curcumin has shown promise in experimental stroke models, but its effects on microglial polarization and long-term recovery after stroke are unknown. Here we address these gaps by subjecting mice to distal middle cerebral artery occlusion (dMCAO) and administering curcumin intraperitoneally (150 mg/kg) immediately after ischemia and 24 h later. Histological studies revealed that curcumin post-treatment significantly reduced cerebral ischemic damage 3 days after dMCAO. Sensorimotor functions-as measured by the adhesive removal test and modified Garcia scores-were superior in curcumin-treated mice at 3, 5, 7 and 10 days after stroke. RT-PCR measurements revealed an elevation of M2 microglia/macrophage phenotypic markers and a reduction in M1 markers in curcumin-treated brains 3 days after dMCAO. Immunofluorescent staining further showed that curcumin treatment significantly increased the number of CD206(+)Iba1(+) M2 microglia/ macrophages and reduced the number of CD16 (+)Iba1(+) M1 cells 10 days after stroke. In vitro studies using the BV2 microglial cell line confirmed that curcumin inhibited lipopolysaccharide (LPS) and interferon-g (IFN-gamma)-induced M1 polarization. Curcumin treatment concentration-dependently reduced the expression of pro-inflammatory cytokines, including TNF-alpha, IL-6 and IL-12p70, in the absence of any toxic effect on microglial cell survival. In conclusion, we demonstrate that curcumin has a profound regulatory effect on microglial responses, promoting M2 microglial polarization and inhibiting microgliamediated pro-inflammatory responses. Curcumin post-treatment reduces ischemic stroke-induced brain damage and improves functional outcomes, providing new evidence that curcumin might be a promising therapeutic strategy for stroke. C1 [Liu, Zongjian; Ran, Yuanyuan; Huang, Shuo; Geng, Xiaokun; Ji, Xunming; Du, Huishan; Hu, Xiaoming] Capital Med Univ, Beijing Luhe Hosp, China Amer Inst Neurosci, Beijing, Peoples R China. [Liu, Zongjian; Ran, Yuanyuan; Huang, Shuo; Wen, Shaohong; Zhang, Wenxiu; Ji, Zhili] Capital Med Univ, Beijing Luhe Hosp, Cent Lab, Beijing, Peoples R China. [Liu, Xiangrong; Ji, Xunming] Capital Med Univ, Xuan Wu Hosp, Inst Hypoxia Med, Beijing, Peoples R China. [Leak, Rehana K.] Duquesne Univ, Div Pharmaceut Sci, Pittsburgh, PA 15219 USA. [Hu, Xiaoming] Univ Pittsburgh, Sch Med, Pittsburgh Inst Brain Disorders & Recovery, Pittsburgh, PA 15260 USA. [Hu, Xiaoming] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. C3 Capital Medical University; Capital Medical University; Capital Medical University; Duquesne University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh RP Hu, XM (corresponding author), Capital Med Univ, Beijing Luhe Hosp, China Amer Inst Neurosci, Beijing, Peoples R China.; Hu, XM (corresponding author), Univ Pittsburgh, Sch Med, Pittsburgh Inst Brain Disorders & Recovery, Pittsburgh, PA 15260 USA.; Hu, XM (corresponding author), Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. EM hux2@upmc.edu RI geng, xiaokun/MKF-4374-2025; Leak, Rehana/I-2607-2019; Ji, Xunming/AAN-3370-2021; Hu, Xiaoming/AFD-8346-2022 OI Leak, Rehana/0000-0003-2817-7417; Ran, Yuanyuan/0000-0002-6760-5173; 刘, 宗建/0000-0002-8528-8992; FU National Natural Science Foundation of China [81571152, 81671161]; Natural Science Foundation of Beijing Municipality [7163219] FX This work was supported by the National Natural Science Foundation of China, 81571152 (to XH) and 81671161 (to ZL), and the Natural Science Foundation of Beijing Municipality, 7163219 (to ZL). 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PD JUL 21 PY 2017 VL 9 AR 233 DI 10.3389/fnagi.2017.00233 PG 10 WC Geriatrics & Gerontology; Neurosciences WE Science Citation Index Expanded (SCI-EXPANDED) SC Geriatrics & Gerontology; Neurosciences & Neurology GA FB5NL UT WOS:000406188500002 PM 28785217 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Jia, J Shi, XJ Jing, XQ Li, JG Gao, J Liu, MY Lin, CI Guo, XZ Hua, Q AF Jia, Jing Shi, Xiaojie Jing, Xiaoqian Li, Jianguo Gao, Jie Liu, Mengya Lin, Chi-Iou Guo, Xinzhi Hua, Qian TI BCL6 mediates the effects of Gastrodin on promoting M2-like macrophage polarization and protecting against oxidative stress-induced apoptosis and cell death in macrophages SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Gastrodin; BCL6; Cerebral palsy; Macrophage polarization ID CEREBRAL-PALSY; INFLAMMATION; FUTURE; INJURY; EXPRESSION; PATHWAY; BRAIN; BLOOD AB Cerebral palsy (CP) is the most common childhood disability worldwide, yet biomarkers for predicting CP are lacking. By subjecting peripheral blood samples from 62 CP patients and 30 healthy controls to Affymetrix GeneChip (R) PrimeView (TM) HumanGene Expression Microarray analysis, we identified the novel biomarker B-cell lymphoma 6 (BCL6) as the most upregulated gene in the CP samples. Gastrodin is a traditional Chinese medicine and bioactive compound that promotes adductor angle release, as well as gross and fine motor performance by increasing Gross Motor Function Measure-66 and Fine Motor Function Measure-45 scores. Gastrodin upregulates the mRNA expression of Mgl2 and Mrc1, M2 macrophage markers, and arginase activity, an M2 polarization indicator, in murine RAW264.7 macrophages. Moreover, these effects were blocked by BCL6 siRNA, which also abrogated the protective effects of Gastrodin against hydrogen peroxide-induced apoptosis and death in RAW264.7 cells. Our work identified BCL6 as a novel biomarker for early prediction of CP. Moreover, we demonstrated that Gastrodin not only stimulated polarization toward M2-like macrophages, which promote tissue repair, but also rescued macrophages from oxidative stress, apoptosis and death by inducing BCL6 expression. BCL6-targeted therapeutic strategies have promise for improving motor performance in CP patients. (C) 2017 Elsevier Inc. All rights reserved. C1 [Jia, Jing; Hua, Qian] Beijing Univ Chinese Med, Sch Preclin Med, 11 N 3rd Ring Rd E, Beijing 100029, Peoples R China. [Shi, Xiaojie; Jing, Xiaoqian; Lin, Chi-Iou; Guo, Xinzhi] Shanxi Cerebral Palsy Rehabil Hosp, Dept Rehabil, Taiyuan 030006, Peoples R China. [Li, Jianguo; Gao, Jie; Liu, Mengya] China Inst Radiat Protect, Drug Safety Evaluat Ctr, Taiyuan 030006, Peoples R China. C3 Beijing University of Chinese Medicine RP Hua, Q (corresponding author), Beijing Univ Chinese Med, Sch Preclin Med, 11 N 3rd Ring Rd E, Beijing 100029, Peoples R China. EM q.hua07@gmail.com RI Hua, qian/F-2760-2012; Gao, Jie/KMY-7382-2024 OI Hua, qian/0000-0003-4238-4594; FU Special Fund for Health Research in the Public Welfare of China [201302001] FX We thank Drs. Zhuoyu Li and Peng Yang (Shanxi University, Taiyuan, China) for their technical assistance. This work was supported by a grant from the Special Fund for Health Research in the Public Welfare of China (#201302001). 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PD APR 29 PY 2017 VL 486 IS 2 BP 458 EP 464 DI 10.1016/j.bbrc.2017.03.062 PG 7 WC Biochemistry & Molecular Biology; Biophysics WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology; Biophysics GA ES1AV UT WOS:000399261200036 PM 28315684 DA 2026-03-26 ER PT J AU Huang, YJ Yang, CK Wei, PL Huynh, TT Whang-Peng, J Meng, TC Hsiao, M Tzeng, YM Wu, AT Yen, Y AF Huang, Yan-Jiun Yang, Ching-Kuo Wei, Po-Li Huynh, Thanh-Tuan Whang-Peng, Jacqueline Meng, Tzu-Ching Hsiao, Michael Tzeng, Yew-Ming Wu, Alexander Th Yen, Yun TI Ovatodiolide suppresses colon tumorigenesis and prevents polarization of M2 tumor-associated macrophages through YAP oncogenic pathways SO JOURNAL OF HEMATOLOGY & ONCOLOGY LA English DT Article DE M2 tumor-associated macrophages; Colon tumorigenesis; Stemness; YAP1; Ovatodiolide ID BREAST-CANCER CELLS; COLORECTAL-CANCER; BETA-CATENIN; ANISOMELES-INDICA; STEM; ACTIVATION; RESISTANCE; HEPATOBLASTOMA; ANGIOGENESIS; PROGRESSION AB Background: An increased expression of Yes-associated protein (YAP1) has been shown to promote tumorigenesis in many cancer types including colon. However, the role of YAP1 in promoting colon tumorigenesis remains unclear. Here, we demonstrate that YAP1 expression is associated with M2 tumor-associated macrophage polarization and the generation of colon cancer stem-like cells. YAP1 downregulation by gene silencing or a phytochemical, ovatodiolide, not only suppresses colon cancer tumorigenesis but also prevents M2 TAM polarization. Methods: Human monocytic cells, THP-1, and colon cancer cell lines, HCT116 and DLD-1, were co-cultured to mimic the interactions between tumor and its microenvironment. M2 polarization of the THP-1 cells were examined using both flow cytometry and q-PCR technique. The inhibition of YAP1 signaling was achieved by gene-silencing technique or ovatodiolide. The molecular consequences of YAP1 inhibition was demonstrated via colony formation, migration, and colon-sphere formation assays. 5-FU and ovatodiolide were used in drug combination studies. Xenograft and syngeneic mouse models were used to investigate the role of YAP1 in colon tumorigenesis and TAM generation. Results: An increased YAP1 expression was found to be associated with a poor prognosis in patients with colon cancer using bioinformatics approach. We showed an increased YAP1 expression in the colon spheres, and colon cancer cells co-cultured with M2 TAMs. YAP1-silencing led to the concomitant decreased expression of major oncogenic pathways including Kras, mTOR, beta-catenin, and M2-promoting IL-4 and tumor-promoting IL-6 cytokines. TAM co-cultured colon spheres showed a significantly higher tumor-initiating ability in vivo. Ovatodiolide treatment alone and in combination with 5-FU significantly suppressed in vivo tumorigenesis and less TAM infiltration in CT26 syngeneic mouse model. Conclusions: We have identified the dual function of YAP1 where its suppression not only inhibited tumorigenesis but also prevented the generation of cancer stem-like cells and M2 TAM polarization. Ovatodiolide treatment suppressed YAP1 oncogenic pathways to inhibit colon tumorigenesis and M2 TAM generation both in vitro and in vivo. Ovatodiolide should be considered for its potential for adjuvant therapeutic development. C1 [Huang, Yan-Jiun; Wu, Alexander Th; Yen, Yun] Taipei Med Univ, Coll Med Sci & Technol, PhD Program Translat Med, Taipei, Taiwan. [Huang, Yan-Jiun; Wei, Po-Li] Taipei Med Univ, Taipei Med Univ Hosp, Dept Surg, Div Colorectal Surg, Taipei, Taiwan. [Huang, Yan-Jiun; Wei, Po-Li] Taipei Med Univ, Coll Med, Dept Surg, Taipei, Taiwan. [Yang, Ching-Kuo] Mackay Mem Hosp, Dept Surg, Div Colorectal Surg, Taipei, Taiwan. [Huynh, Thanh-Tuan] Univ Med & Pharm, Ctr Mol Biomed, Ho Chi Minh City, Vietnam. [Whang-Peng, Jacqueline] Taipei Med Univ, Wan Fang Hosp, Div Canc Ctr, Taipei, Taiwan. [Meng, Tzu-Ching] Acad Sinica, Inst Biol Chem, Taipei, Taiwan. [Hsiao, Michael] Acad Sinica, Genom Res Ctr, Taipei, Taiwan. [Tzeng, Yew-Ming] Natl Taitung Univ, Ctr Gen Educ, Taitung 95092, Taiwan. [Yen, Yun] Taipei Med Univ, Coll Med Sci & Technol, PhD Program Canc Biol & Drug Discovery, Taipei, Taiwan. [Whang-Peng, Jacqueline] Taipei Med Univ, Ctr Excellence Canc Res, Taipei, Taiwan. [Tzeng, Yew-Ming] Taitung Univ, Dept Life Sci, Taitung, Taiwan. C3 Taipei Medical University; Taipei Medical University; Taipei Medical University Hospital; Taipei Medical University; Mackay Memorial Hospital; Hochiminh City University of Medicine & Pharmacy; Taipei Medical University; Taipei Municipal WanFang Hospital; Academia Sinica - Taiwan; Academia Sinica - Taiwan; Taipei Medical University; Taipei Medical University RP Yen, Y (corresponding author), Taipei Med Univ, Coll Med Sci & Technol, PhD Program Translat Med, Taipei, Taiwan.; Yen, Y (corresponding author), Taipei Med Univ, Coll Med Sci & Technol, PhD Program Canc Biol & Drug Discovery, Taipei, Taiwan. EM yyen@tmu.edu.tw RI Hsiao, Michael/U-6238-2019; Meng, Tzu-Ching/G-5426-2019 OI Hsiao, Michael/0000-0001-8529-9213; Meng, Tzu-Ching/0000-0001-7693-2021 FU Taipei Medical University [TMUTOP103003-8]; Top University Project, the Ministry of Education, Taiwan; Health and welfare surcharge of tobacco products, Ministry of Health and Welfare, Taiwan [MOST1042314-B-038-077-MY3, MOHW105-TDU-B-212-134001] FX This study was funded by the following agencies. (1) TMUTOP103003-8 from Taipei Medical University, The Aim for the Top University Project, the Ministry of Education, Taiwan, to Alexander TH Wu and Yan-Jun Huang. (2) MOST1042314-B-038-077-MY3 and MOHW105-TDU-B-212-134001 (Health and welfare surcharge of tobacco products, Ministry of Health and Welfare, Taiwan) to Dr. Whang-Peng Jacqueline and Excellence for Cancer Research (TMU-CECR). 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Hematol. Oncol. PD FEB 28 PY 2017 VL 10 AR 60 DI 10.1186/s13045-017-0421-3 PG 17 WC Oncology; Hematology WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Hematology GA EO6GE UT WOS:000396789300003 PM 28241877 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Wei, ZQ Yan, L Chen, YX Bao, CH Deng, J Deng, JG AF Wei, Zhiquan Yan, Li Chen, Yixin Bao, Chuanhong Deng, Jing Deng, Jiagang TI Mangiferin inhibits macrophage classical activation via downregulating interferon regulatory factor 5 expression SO MOLECULAR MEDICINE REPORTS LA English DT Article DE mangiferin; macrophage classical activation; interferon regulatory factor 5; anti-inflammation; M1 macrophage; THP-1 cells ID NF-KAPPA-B; CHRONIC-BRONCHITIS; AIRWAY INFLAMMATION; IRF5 POLYMORPHISMS; GENETIC-VARIANTS; EXTRACT; CELLS; DISEASE; BETA; ASSOCIATION AB Mangiferin is a natural polyphenol and the predominant effective component of Mangifera indica Linn. leaves. For hundreds of years, Mangifera indica Linn. leaf has been used as an ingredient in numerous traditional Chinese medicine preparations for the treatment of bronchitis. However, the pharmacological mechanism of mangiferin in the treatment of bronchitis remains to be elucidated. Macrophage classical activation is important role in the process of bronchial airway inflammation, and interferon regulatory factor 5 (IRF5) has been identified as a key regulatory factor for macrophage classical activation. The present study used the THP-1 human monocyte cell line to investigate whether mangiferin inhibits macrophage classical activation via suppressing IRF5 expression in vitro. THP-1 cells were differentiated to macrophages by phorbol 12-myristate 13-acetate. Macrophages were polarized to M1 macrophages following stimulation with lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma). Flow cytometric analysis was conducted to detect the M1 macrophages. Reverse transcription-quantitative polymerase chain reaction was used to investigate cellular IRF5 gene expression. Levels of proinflammatory cytokines and IRF5 were assessed following cell culture and cellular homogenization using enzyme-linked immunosorbent assay. IRF5 protein and nuclei co-localization was performed in macrophages with laser scanning confocal microscope immunofluorescence analysis. The results of the present study demonstrated that mangiferin significantly inhibits LPS/IFN-gamma stimulation-induced classical activation of macrophages in vitro and markedly decreases proinflammatory cytokine release. In addition, cellular IRF5 expression was markedly downregulated. These results suggest that the inhibitory effect of mangiferin on classical activation of macrophages may be exerted via downregulation of cellular IRF5 expression levels. C1 [Wei, Zhiquan] Guangxi Univ Chinese Med, Zhuang Med Coll, Guangxi Sci Expt Ctr Tradit Chinese Med, Nanning 530001, Guangxi, Peoples R China. [Yan, Li] Guangxi Univ Chinese Med, Zhuang Med Coll, Lab Basis & Applicat Res Zhuang Med Formulas, Nanning 530001, Guangxi, Peoples R China. [Chen, Yixin; Deng, Jiagang] Guangxi Key Lab Pharmacodynam Studies Tradit Chie, 179 Mingxiudong Rd, Nanning 530001, Guangxi, Peoples R China. [Bao, Chuanhong] Guangxi Univ Chinese Med, Ruikang Affiliated Hosp, Dept Pharm, Nanning 530012, Guangxi, Peoples R China. [Deng, Jing] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA. C3 Guangxi University of Chinese Medicine; Guangxi University of Chinese Medicine; Guangxi University of Chinese Medicine; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard Medical School RP Deng, JG (corresponding author), Guangxi Key Lab Pharmacodynam Studies Tradit Chie, 179 Mingxiudong Rd, Nanning 530001, Guangxi, Peoples R China. EM jg_deng@hotmail.com FU National Natural Science Foundation of China [81260666]; Guangxi Key Laboratory of Pharmacodynamics Studies of Traditional Chinese Medicine [14-A-01-03] FX The present study was supported by the National Natural Science Foundation of China (grant no. 81260666), the Guangxi Key Laboratory of Pharmacodynamics Studies of Traditional Chinese Medicine (grant no. 14-A-01-03). The authors would also like to thank all the staff of Guangxi College and University Laboratory of Basis and Application Research of Zhuang Medicine Formulas for their helpful technical assistance. 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Med. Rep. PD AUG PY 2016 VL 14 IS 2 BP 1091 EP 1098 DI 10.3892/mmr.2016.5352 PG 8 WC Oncology; Medicine, Research & Experimental WE Science Citation Index Expanded (SCI-EXPANDED) SC Oncology; Research & Experimental Medicine GA DQ9UK UT WOS:000379554600007 PM 27277156 OA Green Submitted, hybrid DA 2026-03-26 ER PT J AU Zhu, W Jin, ZS Yu, JB Liang, J Yang, QD Li, FJ Shi, XK Zhu, XD Zhang, XL AF Zhu, Wei Jin, Zaishun Yu, Jianbo Liang, Jun Yang, Qingdong Li, Fujuan Shi, Xuekui Zhu, Xiaodong Zhang, Xiaoli TI Baicalin ameliorates experimental inflammatory bowel disease through polarization of macrophages to an M2 phenotype SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Baicalin; Colitis; M2 macrophage; IRF4; IRF5 ID EXPERIMENTAL COLITIS; ULCERATIVE-COLITIS; STEM-CELLS; LIPOPOLYSACCHARIDE; PATHWAY; ACTIVATION; INDUCTION; RATS AB Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of the intestinal tract. Baicalin, originally isolated from the root of the Chinese herb Huangqin (Scutellaria baicalensis Georgi) and its main active ingredient, has a protective effect against inflammatory responses in several diseases. The present study investigated the effects of baicalin on macrophage polarization and its therapeutic role in IBD. Murine peritoneal macrophages and mice with colitis were treated with baicalin. Macrophage subset distribution, M1 and M2 macrophage-associated mRNA expression, and interferon regulatory factor 4 and 5 (IRF4 and IRF5) expression were analyzed. siRNA transfection into mouse peritoneal macrophages was utilized to suppress IRF4. Fluorescence-activated cell sorting, western blot, and real-time PCR analyses were performed. Baicalin (50 M) limited lipopolysaccharide (LPS)-induced M1 macrophage polarization; decreased LPS-induced tumor necrosis factor alpha, interleukin (IL)-23, and IRF5 expression; and increased IL-10, arginase-1 (Arg-1), and IRF4 expression. siRNA-mediated IRF4 silencing significantly impaired baicalin activity. Furthermore, pretreatment with baicalin (100 mg/kg) in mice with dextran sodium sulfate (DSS)-induced colitis ameliorated the severity of colitis and significantly decreased the disease activity index (baicalin group, 333 +/- 0.52 vs. DSS group, 5.67 +/- 1.03). Baicalin (100 mg/kg) also repressed IRF5 protein expression and promoted IRF4 protein expression in the lamina propria mononuclear cells, and induced macrophage polarization to the M2 phenotype. In summary, our results showed that baicalin upregulates IRF4 protein expression and reverses LPS-induced macrophage subset redistribution. Thus, baicalin alleviates DSS-induced colitis by modulating macrophage polarization to the M2 phenotype. (C) 2016 Elsevier B.V. All rights reserved. C1 [Zhu, Wei; Li, Fujuan; Shi, Xuekui; Zhu, Xiaodong; Zhang, Xiaoli] Mudanjiang Med Coll, Dept Immunol, 3 Tongxiang St, Mudanjiang, Peoples R China. [Jin, Zaishun; Yu, Jianbo] Mudanjiang Med Coll, Dept Pathol, Mudanjiang, Peoples R China. [Liang, Jun] Mudanjiang Med Coll, Dept Histoembryol, Mudanjiang, Peoples R China. [Yang, Qingdong] Mudanjiang Med Coll, Dept Lab Anim, Mudanjiang, Peoples R China. C3 Mudanjiang Medical University; Mudanjiang Medical University; Mudanjiang Medical University; Mudanjiang Medical University RP Zhu, XD; Zhang, XL (corresponding author), Mudanjiang Med Coll, Dept Immunol, 3 Tongxiang St, Mudanjiang, Peoples R China. EM xiaodongzhu@126.com; xiaoli2595@126.com RI Zhu, Xiao-Dong/I-4500-2018 FU National Natural Science Foundation [81271628]; Key Laboratory of Myocardial Ischemia (Harbin Medical University), Chinese Ministry of Education [KF201204]; Open Topic of the Key Laboratory of Neurobiology, General Colleges and Universities in Heilongjiang Province of China [2012HLJKLNT-04]; Science and Technology Foundation of Mudanjiang Medical College [Z5201312]; Mudanjiang Science and Technology Foundation [z2015s0043] FX This study was funded by the National Natural Science Foundation Projects (No. 81271628), the Key Laboratory of Myocardial Ischemia (Harbin Medical University), Chinese Ministry of Education (No. KF201204), the Open Topic of the Key Laboratory of Neurobiology, General Colleges and Universities in Heilongjiang Province of China (No. 2012HLJKLNT-04), the Science and Technology Foundation of Mudanjiang Medical College (No. Z5201312), and the Mudanjiang Science and Technology Foundation (No. z2015s0043). 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Immunopharmacol. PD JUN PY 2016 VL 35 BP 119 EP 126 DI 10.1016/j.intimp.2016.03.030 PG 8 WC Immunology; Pharmacology & Pharmacy WE Science Citation Index Expanded (SCI-EXPANDED) SC Immunology; Pharmacology & Pharmacy GA DM2XX UT WOS:000376212500014 PM 27039210 DA 2026-03-26 ER PT J AU Iwanowycz, S Wang, JF Altomare, D Hui, Y Fan, DP AF Iwanowycz, Stephen Wang, Junfeng Altomare, Diego Hui, Yvonne Fan, Daping TI Emodin Bidirectionally Modulates Macrophage Polarization and Epigenetically Regulates Macrophage Memory SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; INFLAMMATORY RESPONSE; MOLECULAR-MECHANISM; TRAINED IMMUNITY; RAT MODEL; ACTIVATION; GAMMA; MONOCYTE; EXPRESSION; PROTEIN AB Macrophages are pleiotropic cells capable of performing a broad spectrum of functions. Macrophage phenotypes are classified along a continuum between the extremes of proinflammatory M1 macrophages and anti-inflammatory M2 macrophages. The seemingly opposing functions of M1 and M2 macrophages must be tightly regulated for an effective and proper response to foreign molecules or damaged tissue. Excessive activation of either M1 or M2 macrophages contributes to the pathology of many diseases. Emodin is a Chinese herb-derived compound and has shown potential to inhibit inflammation in various settings. In this study, we tested the ability of emodin to modulate the macrophage response to both M1 and M2 stimuli. Primary mouse macrophages were stimulated with LPS/IFN gamma or IL4 with or without emodin, and the effects of emodin on gene transcription, cell signaling pathways, and histone modifications were examined by a variety of approaches, including microarray, quantitative real-time PCR, Western blotting, chromatin immunoprecipitation, and functional assays. We found that emodin bidirectionally tunes the induction of LPS/IFN gamma- and IL4-responsive genes through inhibiting NF kappa B/IRF5/STAT1 signaling and IRF4/STAT6 signaling, respectively. Thereby, emodin modulates macrophage phagocytosis, migration, and NO production. Furthermore, emodin inhibited the removal of H3K27 trimethylation (H3K27m3) marks and the addition of H3K27 acetylation (H3K27ac) marks on genes required for M1 or M2 polarization of macrophages. In conclusion, our data suggest that emodin is uniquely able to suppress the excessive response of macrophages to both M1 and M2 stimuli and therefore has the potential to restore macrophage homeostasis in various pathologies. C1 [Iwanowycz, Stephen; Wang, Junfeng; Hui, Yvonne; Fan, Daping] Univ S Carolina, Sch Med, Dept Cell Biol & Anat, 6439 Garners Ferry Rd,Bldg 1,C36, Columbia, SC 29209 USA. [Altomare, Diego] Univ S Carolina, South Carolina Coll Pharm, Dept Drug Discovery & Biomed Sci, Columbia, SC 29208 USA. C3 University of South Carolina System; University of South Carolina Columbia; University of South Carolina System; University of South Carolina Columbia; Medical University of South Carolina RP Fan, DP (corresponding author), Univ S Carolina, Sch Med, Dept Cell Biol & Anat, 6439 Garners Ferry Rd,Bldg 1,C36, Columbia, SC 29209 USA. EM daping.fan@uscmed.sc.edu RI ; Wang, Junfeng/AAJ-3248-2020 OI Fan, Daping/0000-0002-4729-761X; Wang, Junfeng/0000-0001-7410-2534 FU National Institutes of Health [HL116626, AT003961-8455]; Office of Integrative Activities; Office Of The Director [1317771] Funding Source: National Science Foundation FX This work was supported by National Institutes of Health Grants HL116626 and AT003961-8455. The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. 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Biol. Chem. PD MAY 27 PY 2016 VL 291 IS 22 BP 11491 EP 11503 DI 10.1074/jbc.M115.702092 PG 13 WC Biochemistry & Molecular Biology WE Science Citation Index Expanded (SCI-EXPANDED) SC Biochemistry & Molecular Biology GA DN7NZ UT WOS:000377264800003 PM 27008857 OA hybrid DA 2026-03-26 ER PT J AU Zhou, YY Zhang, TT Wang, XF Wei, XW Chen, YZ Guo, LY Zhang, JF Wang, CQ AF Zhou, Yaoyao Zhang, Tiantian Wang, Xiaofei Wei, Xiaowei Chen, Yizhu Guo, Lingyu Zhang, Junfeng Wang, Changqian TI Curcumin Modulates Macrophage Polarization Through the Inhibition of the Toll-Like Receptor 4 Expression and its Signaling Pathways SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article DE Curcumin; Macrophage polarization; TLR4; MAPK; NF-kappa B; Atherosclerosis ID NF-KAPPA-B; INFLAMMATORY RESPONSES; CELLS; ACTIVATION; MURINE; TARGET; MAPK AB Background: Curcumin, the active ingredient in curcuma rhizomes, has a wide range of therapeutic effects. However, its atheroprotective activity in human acute monocytic leukemia THP-1 cells remains unclear. We investigated the activity and molecular mechanism of action of curcumin in polarized macrophages. Methods: Phorbol myristate acetate (PMA)-treated THP-1 cells were differentiated to macrophages, which were further polarized to M1 cells by lipopolysaccharide ([PS; 1 mu g/m1) and interferon (IFN)-gamma (20 ng/ml) and treated with varying curcumin concentrations. [H-3]thymidine (H-3-TdR) incorporation assays were utilized to measure curcumin-induced growth inhibition. The expression of tumor necrosis factor-alpha (INF-alpha), interleukin (IL-6), and IL-12B (p40) were measured by quantitative real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Macrophage polarization and its mechanism were evaluated by flow cytometry and western blot. Additionally, toll-like receptor 4 (TLR4) small interfering RNA and mitogen-activated protein kinase (MAPK) inhibitors were used to further confirm the molecular mechanism of curcumin on macrophage polarization. Results: Curcumin dose-dependently inhibited M1 macrophage polarization and the production of TNF-alpha, IL-6, and IL-12B (p40). It also decreased TLR4 expression, which regulates M1 macrophage polarization. Furthermore, curcumin significantly inhibited the phosphorylation of ERK, JNK, p38, and nuclear factor (NF)-kappa B. In contrast, siTLR4 in combination with p-JNK, p-ERK, and p-p38 inhibition reduced the effect of curcumin on polarization. Conclusions: Curcumin can modulate macrophage polarization through TLR4-mediated signaling pathway inhibition, indicating that its effect on macrophage polarization is related to its anti-inflammatory and atheroprotective effects. Our data suggest that curcumin could be used as a therapeutic agent in atherosclerosis. Copyright (C) 2015 S. Karger AG, Basel C1 [Zhou, Yaoyao; Zhang, Tiantian; Wang, Xiaofei; Wei, Xiaowei; Chen, Yizhu; Guo, Lingyu; Zhang, Junfeng] Shanghai Jiao Tong Univ, Dept Cardiol, Peoples Hosp 3, Sch Med, Shanghai 201900, Peoples R China. [Wang, Changqian] Shanghai Jiao Tong Univ, Dept Cardiol, Peoples Hosp 9, Sch Med, Shanghai 201900, Peoples R China. C3 Shanghai Jiao Tong University; Shanghai Jiao Tong University RP Zhang, JF (corresponding author), Shanghai Jiao Tong Univ, Dept Cardiol, Peoples Hosp 3, Sch Med, 280 Mohe Rd, Shanghai 201900, Peoples R China. EM jfzhang_dr@163.com RI zhang, junfeng/JHT-7871-2023; Wei, Xiaowei/KHT-4099-2024 OI zhou, yaoyao/0000-0002-9224-8040 FU Shanghai Municipal Natural Science Foundation [12ZR1417400]; Shanghai Shen-kang Municipal Hospital Appropriate Technology Popularization and Application Program [SHDC12012210] FX This work was supported by grants from Shanghai Municipal Natural Science Foundation [12ZR1417400 to Junfeng Zhang] and Shanghai Shen-kang Municipal Hospital Appropriate Technology Popularization and Application Program [NO. SHDC12012210 to Junfeng Zhang]. 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Physiol. Biochem. PD MAY PY 2015 VL 36 IS 2 BP 631 EP 641 DI 10.1159/000430126 PG 11 WC Cell Biology; Physiology WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology; Physiology GA CK1CW UT WOS:000355944000019 PM 25998190 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Ding, JR Su, JH Zhang, L Ma, J AF Ding, Jurong Su, Jianhua Zhang, Li Ma, Jian TI Crocetin Activates Foxp3 Through TIPE2 in Asthma-Associated Treg Cells SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article DE OVA; Asthma; Crocetin; Regulatory T cells (Treg); Foxp3; Tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2) ID REGULATORY T-CELLS; ALLERGIC LUNG INFLAMMATION; MACROPHAGE POLARIZATION; IMMUNE HOMEOSTASIS; EXPRESSION; TOLERANCE; SAFFRON; PROMOTE; MICE; TGF-BETA-1 AB Background/Aims: Regulatory T cells (Treg) are critical regulators of asthma. Crocetin is isolated from Chinese herb saffron and is a natural carotenoid dicarboxylic acid with anti-inflammatory potential. However, the effects of Crocetin on asthma as well as the underlying mechanisms have not been studied. Methods: We used Crocetin to treat mice with established ovalbumin (OVA)-induced asthma. We purified CD4+ CD25+ Treg cells by flow cytometry and analyzed the levels of two immunoregulatory proteins Foxp3 and tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2) in Treg cells. We depleted either Foxp3 or TIPE2 in mouse lung through lentivirus-mediated delivery of shRNA, and analyzed their effects on severity of asthma and Treg cells after Crocetin treatment. Results: Crocetin treatment significantly reduced the severity of an ovalbumin (OVA)-induced asthma in mice. Moreover, Crocetin significantly increased the levels of TIPE2 and Foxp3 in Treg cells and the number of Treg cells. Depletion of Foxp3 abolished the increased in Treg cells, and the effects of Crocetin on the severity of asthma, without affecting TIPE2 levels in Treg cells. On the other hand, depletion of TIPE2 abolished both the increased in Treg cells and the effects of Crocetin on the severity of asthma, through suppressing Foxp3. Conclusion: Crocetin may activate Foxp3 through TIPE2 in asthma-associated Treg cells to mitigate the severity of asthma. (C) 2015 The Author(s) Published by S. Karger AG, Basel C1 [Ding, Jurong; Zhang, Li; Ma, Jian] Tongji Univ Med, Shanghai Pulm Hosp, Dept Emergency, Shanghai 200433, Peoples R China. [Su, Jianhua] Fudan Univ, Sch Med, Dept Respirat, Huashan Hosp,Baoshan Branch, Shanghai 200433, Peoples R China. C3 Tongji University; Fudan University RP Zhang, L (corresponding author), Tongji Univ Med, Shanghai Pulm Hosp, Dept Emergency, 507 Zhengmin Rd, Shanghai 200433, Peoples R China. 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PY 2015 VL 37 IS 6 BP 2425 EP 2433 DI 10.1159/000438595 PG 9 WC Cell Biology; Physiology WE Science Citation Index Expanded (SCI-EXPANDED) SC Cell Biology; Physiology GA DA8RC UT WOS:000368072800030 PM 26646898 OA Green Submitted, gold DA 2026-03-26 ER PT J AU Zhang, ZY Li, MC Wang, Y Wu, J Li, JP AF Zhang, Zhenyu Li, Mingchao Wang, Yan Wu, Jian Li, Jiaping TI Higenamine promotes M2 macrophage activation and reduces Hmgb1 production through HO-1 induction in a murine model of spinal cord injury SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Higenamine; M2 macrophages; Hmgb1; HO-1; SCI ID ISCHEMIA-REPERFUSION INJURY; PPAR-GAMMA ACTIVATION; HEME OXYGENASE-1; INFLAMMATORY RESPONSE; ISCHEMIA/REPERFUSION INJURY; MYOCARDIAL-ISCHEMIA; NEURONAL APOPTOSIS; INTESTINAL DAMAGE; HUMAN MONOCYTES; MICE AB Spinal cord injury (SCI) is considered to be primarily associated with loss of motor function and leads to the activation of diverse cellular mechanisms in the central nervous system to attempt to repair the damaged spinal cord tissue. Higenamine (HG) (1-[(4-hydroxyphenyl) methyl]-1,2,3,4-tetrahydroisoquinoline-6,7-diol), an active ingredient of Aconiti Lateralis Radix Praeparata, has been traditionally used as a heart stimulant and anti-inflammatory agent in oriental countries. However, the function and related mechanism of HG on SCI have never been investigated. In our current study, HG treatment displayed increased myelin sparring and enhanced spinal cord repair process. The numbers of CD4(+) T cells, CD8(+) T cells, Ly6G(+) neutrophils and CD11b(+) macrophages were all significantly lower in the HG-treated group than that in the control group after SCI. HG administration increased the expression of IL-4 and IL-10 and promoted M2 macrophage activation. Significantly reduced Hmgb1 expression was also observed in HG-treated mice with SCI. Furthermore, HG treatment promoted HO-1 production. The increased number of M2 macrophages, decreased expression of Hmgb1 and promoted locomotor recovery induced by HG were all reversed with additional HO-1 inhibitor treatment In conclusion, HG promotes M2 macrophage activation and reduces Hmgb1 expression dependent on HO-1 induction and then promotes locomotor function after SCI. (C) 2014 Elsevier B.V. All rights reserved. C1 [Zhang, Zhenyu; Li, Mingchao; Wu, Jian; Li, Jiaping] Harbin Med Univ, Affiliated Hosp 1, Dept Orthoped, Harbin, Peoples R China. [Wang, Yan] Hainan Prov Peoples Hosp, Haikou, Hainan Province, Peoples R China. C3 Harbin Medical University RP Zhang, ZY (corresponding author), Harbin Med Univ, Affiliated Hosp 1, Dept Orthoped, 23 Youzheng St, Harbin, Peoples R China. 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