evaluation-sesquiterpene-lactones-rat-model-paraquat-induced-acute

Evaluation of Sesquiterpene Lactones in a Rat Model of Paraquat-Induced Acute Lung Injury Using Untargeted Metabolomics

This study investigated the protective effects and potential mechanisms of sesquiterpene lactones from Eupatorium lindleyanum DC. (SLEL) against paraquat ...

Chongqing Medical University

Chongqing University of Chinese Medicine

To investigate the effect of total anthraquinone in Cassiae Semen on lipid peroxidation and peroxisome proliferator activated receptors gamma (PPAR-gamma) expression in liver tissues of rats with alcoholic fatty liver.

[Experiment study of total anthraquinone in cassiae semen on lipid peroxidation and PPAR-gamma expression in liver tissues of rats with alcoholic fatty liver].

 Immune checkpoint inhibitors (ICIs) have provided noteworthy benefits in multiple cancer patients. However, the efficacy of monotherapy of ICIs was very limited. In this study, we endeavored to explore whether losartan can modulate the solid tumor microenvironment (TME) and improve the therapeutic efficacy of anti-PD-L1 mAb in 4T1 mouse breast tumor model and the underlying mechanism.  The tumor-bearing mice were treated with control agents, losartan, anti-PD-L1 mAb or the dual agents. The blood and tumor tissues were respectively used for ELISA and immunohistochemical analysis. CD8-depletion and lung metastatic experiments were performed.  Compared to control group, losartan inhibited the expression of alpha-smooth muscle actin (α-SMA), deposition of collagen I in the tumor tissues. The concentration of transforming growth factor-β1 (TGF-β1) in the serum was low in the losartan treated group. Although losartan alone was ineffective, the combination of losartan and anti-PD-L1 mAb elicited dramatic antitumor effect. Immunohistochemical analysis revealed that there were more intra-tumoral infiltration of CD8 T cells and increased granzyme B production in the combination therapy group. In addition, the size of spleen was smaller in the combination therapy group, compared to monotherapy. The CD8-depleting Abs abrogated the antitumor efficacy of losartan and anti-PD-L1 mAb . The combination of losartan and anti-PD-L1 mAb significantly inhibited 4T1 tumor cells lung metastatic .  Our results indicated that losartan can modulate the tumor microenvironment, and improve the efficacy of anti-PD-L1 mAb.

Modulating the tumor microenvironment improves antitumor effect of anti-PD-L1 mAb in breast cancer.

To investigate the impact of Yemazhui (, HEL) against lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explore its underlying mechanism .

Yemazhui () ameliorates lipopolysaccharide-induced acute lung injury modulation of the toll-like receptor 4/nuclear factor kappa-B/nod-like receptor family pyrin domain-containing 3 protein signaling pathway and intestinal flora in rats.

 Acute lung injury (ALI) is a life-threatening respiratory condition and one of the leading causes of mortality worldwide, accounting for approximately 20% of global annual deaths. Despite its high prevalence and severity, effective therapeutic options remain limited.  DC., a traditional medicinal herb, has demonstrated therapeutic potential against pulmonary diseases, particularly ALI, in both clinical and experimental settings. However, the protective effects and underlying mechanisms of its characteristic sesquiterpene lactone components against ALI remain unclear.  This study aimed to evaluate the protective effects of sesquiterpene lactones from  DC. (SLEL) against lipopolysaccharide (LPS)-induced ALI both in vivo and in vitro. Furthermore, it sought to elucidate the underlying mechanisms by integrating network pharmacology, multi-omics approaches (transcriptomics, metabolomics, and 16S rRNA sequencing), and various molecular biology techniques.  SLEL significantly attenuated inflammatory injury in alveolar epithelial cells and alleviated pulmonary edema, hemorrhage, and inflammatory infiltration in rats, accompanied by reduced TNF-α, IL-6, and IL-1β levels and improved lung injury indices. Mechanistically, SLEL exerted dual suppression of the PI3K-Akt and MAPK-NF-κB pathways. Network pharmacology, molecular docking, and UPLC-MS analyses identified Eupalinolide A and Eupalinolide K as potential bioactive constituents, which were further validated to inhibit phosphorylation of key signaling proteins, thereby partially accounting for SLEL's pharmacological effects. Multi-omics integration further revealed that SLEL restored bile acid metabolism, reshaped gut microbial diversity, and reconstructed the microbiota-metabolite-inflammatory cytokine network, thereby maintaining gut-lung axis homeostasis and enhancing anti-inflammatory effects.  SLEL alleviates ALI through multi-component synergistic actions that suppress pro-inflammatory signaling and modulate the gut-lung axis. These findings highlight the potential of SLEL as a promising therapeutic candidate for the treatment of ALI.

Multi-Omics and Experimental Insights into the Protective Effects of Sesquiterpenoid Lactones from  DC. in Acute Lung Injury: Regulation of PI3K-Akt and MAPK-NF-κB Pathways.

Article	Year
[Experiment study of total anthraquinone in cassiae semen on lipid peroxidation and PPAR-gamma expression in liver tissues of rats with alcoholic fatty liver]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica\| PubMed ID: 22007555	2011
Modulating the tumor microenvironment improves antitumor effect of anti-PD-L1 mAb in breast cancer. BioImpacts : BI\| PubMed ID: 37193073	2023
Yemazhui () ameliorates lipopolysaccharide-induced acute lung injury modulation of the toll-like receptor 4/nuclear factor kappa-B/nod-like receptor family pyrin domain-containing 3 protein ... Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan\| PubMed ID: 38504536	2024
Multi-Omics and Experimental Insights into the Protective Effects of Sesquiterpenoid Lactones from DC. in Acute Lung Injury: Regulation of PI3K-Akt and MAPK-NF-κB Pathways. Pharmaceuticals (Basel, Switzerland)\| PubMed ID: 41155638	2025

Xianqin Luo

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