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Investigating the Mechanism of &#946;-Elemene-Mediated LINC00511 Modulation to Suppress Cisplatin Resistance in Lung Cancer

Cisplatin resistance significantly limits the efficacy of chemotherapy in non-small cell lung cancer, necessitating the development of new strategies to ...

Changchun University of Chinese Medicine

Affiliated Hospital of Changchun University of Chinese Medicine

Artemisiae Annuae Herba has used as a medicine for more than 2 000 years. To infer based on the modern study results, Artemisiae Annuae Herba used for the treatment of malaria recorded in Zhou Hou Bei Ji Fang before 1 700 years should come from Artemisia annua. Based on the data of Chinese materia medica, from the field of treatment hotness and preventing attack of malaria etc., the Dao-di producing district of Artemisiae Annuae Herba should at Jingzhou (now Hubei) and surrounding areas in history. From the view of anti-malaria components artemisinin content, the Dao-di growing producing district of Artemisiae Annuae Herba should locate at Chongqing, Guangxi and its surrounding provinces. The study results showed that A. annua was harvested in flower bloom at autumn, and in this time it also had higher artemisinin content. If A. annua was stored exceed six months, artemisinin could be degraded about thirty percent. So it should be stored in a cool and dry place generally. Wild A. annua had a rich genetic diversity. Artemisinin content of A. annua breeding in experimental field could reache to two percent.

[Review on study of Dao-di herbs Artemisiae Annuae Herba].

It is known that menopausal osteoporosis (MOP) is the most typical form of osteoporosis, which is characterized by low bone mass and microstructure damage of the bone tissue, leading to increased bone fragility and risk of fracture. This study aimed to evaluate the protective effects of Oviductus Ranae protein hydrolyzate (ORPH) on the MOP in vivo.

Oviductus Ranae protein hydrolyzate prevents menopausal osteoporosis by regulating TGFβ/BMP2 signaling.

The flavonoid compound scutellarin (Scu) is a traditional Chinese medicine used to treat a variety of diseases; however, the use of scutellarein (Scue), the hydrolysate of Scu, and its mechanisms of action in Alzheimer's disease (AD) have not been fully elucidated. In the present study, the effects of Scue on amyloid β (Aβ)-induced AD-like pathology were investigated. An  model of inflammation and an aged rat model were used to confirm the effects of Scue.  MTT assays and flow cytometry were used to assess the effects of Scue on cell viability and apoptosis, respectively. A Morris water maze was used to evaluate spatial learning and memory, and the levels of Aβ deposition, superoxide dismutase, malondialdehyde, apoptosis, neuro-inflammatory factors and nuclear factor-κB (NF-κB) activation in hippocampal tissues  were measured to determine the effect of Scue in AD. Scue may be protective, as it decreased the apoptosis of hippocampal cells , inhibited Aβ-induced cognitive impairment, suppressed hippocampal neuro-inflammation and suppressed activation of NF-κB . Therefore, Scue may be a useful agent for the treatment of Aβ-associated pathology in the central nervous system through inhibition of the protein kinase B/NF-κB signaling pathway and thus, future studies are required to investigate the efficacy of Scue in patients with AD.

Scutellarein suppresses Aβ-induced memory impairment via inhibition of the NF-κB pathway  and .

Non-alcoholic fatty liver is one of the most common comorbidities of diabetes. It can cause disturbance of glucose and lipid metabolism in the body, gradually develop into liver fibrosis, and even cause liver cirrhosis. Mangiferin has a variety of pharmacological activities, especially for the improvement of glycolipid metabolism and liver injury. However, its poor oral absorption and low bioavailability limit its further clinical development and application. The modification of mangiferin derivatives is the current research hotspot to solve this problem.

Pharmacokinetic and metabolomic analyses of Mangiferin calcium salt in rat models of type 2 diabetes and non-alcoholic fatty liver disease.

The tumor microenvironment (TME) is composed of tumor cells, blood/lymphatic vessels, the tumor stroma, and tumor-infiltrating myeloid precursors (TIMPs) as a sophisticated pathological system to provide the survival environment for tumor cells and facilitate tumor metastasis. In TME, TIMPs, mainly including tumor-associated macrophage (TAM), tumor-associated dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs), play important roles in repressing the antitumor activity of T cell or other immune cells. Therefore, targeting those cells would be one novel efficient method to retard cancer progression. Numerous studies have shown that traditional Chinese medicine (TCM) has made extensive research in tumor immunotherapy. In the review, we demonstrate that Chinese herbal medicine (CHM) and its components induce tumor cell apoptosis, directly inhibiting tumor growth and invasion. Further, we discuss that TCM regulates TME to promote effective antitumor immune response, downregulates the numbers and function of TAMs/MDSCs, and enhances the antigen presentation ability of mature DCs. We also review the therapeutic effects of TCM herbs and their ingredients on TIMPs in TME and systemically analyze the regulatory mechanisms of TCM on those cells to have a deeper understanding of TCM in tumor immunotherapy. Those investigations on TCM may provide novel ideas for cancer treatment.

Impact of TCM on Tumor-Infiltrating Myeloid Precursors in the Tumor Microenvironment.

Sangbaipi decoction (SD), a traditional Chinese "Ancient Classical Prescription" consisting of eight medicinal materials, is usually used to treat asthma due to excess lung Qi and phlegm fire.

Establishment and Development of a Quality Evaluation Method for Sangbaipi Decoction.

Adriamycin (ADR)-based combination chemotherapy is the standard treatment for some patients with tumors in clinical, however, long-term application can cause dose-dependent cardiotoxicity. Pilose Antler, as a traditional Chinese medicine, first appeared in the Han Dynasty and has been used to treat heart disease for nearly a thousand years. Previous data revealed pilose antler polypeptide (PAP, 3.2KD) was one of its main active components with multiple biological activities for cardiomyopathy. PAP-3.2KD exerts protective effects againt myocardial fibrosis. The present study demonstrated the protective mechanism of PAP-3.2KD against Adriamycin (ADR)-induced myocardial injury through using animal model with ADR-induced myocardial injury. PAP-3.2KD markedly improved the weight increase and decreased the HW/BW index, heart rate, and ST height in ADR-induced groups. Additionally, PAP-3.2KD reversed histopathological changes (such as disordered muscle bundles, myocardial fibrosis and diffuse myocardial cellular edema) and scores of the heart tissue, ameliorated the myocardial fibrosis and collagen volume fraction through pathological examination, significantly increased the protein level of Bcl-2, and decreased the expression levels of Bax and caspase-3 in myocardial tissue by ELISA, compared to those in ADR-induced group. Furthermore, ADR stimulation induced the increased protein levels of TGF-β1 and SMAD2/3/4, the increased phosphorylation levels of SMAD2/3 and the reduced protein levels of SMAD7. The expression levels of protein above in ADR-induced group were remarkably reversed in PAP-3.2KD-treated groups. PAP-3.2KD ameliorated ADR-induced myocardial injury by regulating the TGF-β/SMAD signaling pathway. Thus, these results provide a strong rationale for the protective effects of PAP against ADR-induced myocardial injury, when ADR is used to treat cancer.

Pilose Antler Peptide-3.2KD Ameliorates Adriamycin-Induced Myocardial Injury Through TGF-β/SMAD Signaling Pathway.

Diabetic cardiomyopathy (DCM) is one of the many complications of diabetes. DCM leads to cardiac insufficiency and myocardial remodeling and is the main cause of death in diabetic patients. Abnormal lipid metabolism plays an important role in the occurrence and development of DCM. Huangqi Shengmai Yin (HSY) has previously been shown to alleviate signs of heart disease. Here, we investigated whether HSY could improve cardiomyopathy caused by type 1 diabetes mellitus (T1DM) and improve abnormal lipid metabolism in the diabetic heart. Streptozotocin (STZ) was used to establish the T1DM mouse model, and T1DM mice were subsequently treated with HSY for eight weeks. The changes in the cardiac conduction system, histopathology, blood myocardial injury indices, and lipid content and expression of proteins related to lipid metabolism were evaluated. Our results showed that HSY could improve electrocardiogram; decrease the serum levels of CK-MB, LDH, and BNP; alleviate histopathological changes in cardiac tissue; and decrease myocardial lipid content in T1DM mice. These results indicate that HSY has a protective effect against T1DM-induced myocardial injury in mice and that this effect may be related to the improvement in myocardial lipid metabolism.

Protective Effects of Huangqi Shengmai Yin on Type 1 Diabetes-Induced Cardiomyopathy by Improving Myocardial Lipid Metabolism.

Myocardial fibrosis (MF) is an important pathological process in which a variety of cardiovascular diseases transform into heart failure. The main manifestation of MF is the excessive deposition of collagen in the myocardium. Here, we explored whether Huangqi Shengmai Yin (HSY) can inhibit isoprenaline (ISO)-induced myocardial collagen deposition in rats, thereby reducing the cardiac dysfunction caused by MF. The results of echocardiography showed that HSY upregulated fractional shortening and ejection fraction, and reduced the left ventricular systolic dysfunction in the rats with MF. Pathological results showed that HSY protected myocardium, inhibited apoptosis, and effectively reduced collagen deposition. HSY also inhibited the expression of collagen I and III and α-smooth muscle actin (α-SMA) in the heart tissue. HSY increased the expression of Sirtuin 3 (Sirt3) and inhibited the protein levels of the components in the transforming growth factor-β (TGF-β)/Smad pathway. At the same time, it also regulated the expression of related proteins in the matrix metalloproteinases family. In summary, HSY played a therapeutic role in rats with ISO-induced MF by protecting myocardium and inhibiting collagen deposition. Therefore, HSY is a potential therapeutic agent for ameliorating MF.

Huangqi Shengmai Yin Ameliorates Myocardial Fibrosis by Activating Sirtuin3 and Inhibiting TGF-β/Smad Pathway.

Ginsenoside CK is the main metabolite of protopanaxadiol saponins in intestinal bacteria. Previous studies have shown that ginsenoside CK can affect many aspects of tumor development through a variety of mechanisms. However, few studies have reported the antimetastatic effects of ginsenoside CK in non-small-cell lung cancer (NSCLC). In this study, we explored the effect of ginsenoside CK on epithelial-mesenchymal transition (EMT) induced by TGF- in A549 cells and the potential molecular mechanisms. Our data showed that ginsenoside CK effectively prevented TGF--induced EMT, as indicated by the upregulation of E-cadherin and downregulation of vimentin. Furthermore, ginsenoside CK inhibited the metastatic ability of A549 cells in the tail vein lung metastasis model of nude mice. Additionally, ginsenoside CK decreased the expression of silent information regulator 2 homolog 1 (SIRT1) in the inhibition of EMT induced by TGF-. Moreover, the antimetastatic effect of ginsenoside CK was reversed by SIRT1 overexpression. Generally, our results indicated the antimetastatic effect and underlying mechanism of ginsenoside CK on TGF--induced EMT in A549 cells, suggesting that ginsenoside CK can be used as an effective antineoplastic agent.

Ginsenoside CK Inhibits TGF--Induced Epithelial-Mesenchymal Transition in A549 Cell via SIRT1.

Ginsenosides, as the most important constituents of ginseng, have been extensively investigated in cancer chemoprevention and therapeutics. Among the ginsenosides, Compound K (CK), a rare protopanaxadiol type of ginsenoside, has been most broadly used for cancer treatment due to its high anticancer bioactivity. However, the functional mechanism of CK in cancer is not well known. This review describes the structure, transformation and pharmacological activity of CK and discusses the functional mechanisms of CK and its metabolites, which regulate signaling pathways related to tumor growth and metastasis. CK inhibits tumor growth by inducing tumor apoptosis and tumor cell differentiation, regulates the tumor microenvironment by suppressing tumor angiogenesis-related proteins, and downregulates the roles of immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs). There is currently much research on the potential development of CK as a new strategy when administered alone or in combination with other compounds.

Functional Mechanism of Ginsenoside Compound K on Tumor Growth and Metastasis.

The water-soluble Morchella esculenta polysaccharide 2 (MEP2) was purified and isolated from an aqueous extract of the Morchella esculenta fruiting bodies. MEP2, having a molecular weight of 959 kDa, has a →4)-α-D-Glcp-(1→ glucan backbone, and this branch was substituted at the H-6 position by an α-D-Glcp-(1 → 4)-α-D-Glcp-(1→ residue and an α-D-Glcp-(1→ residue. The hepatoprotective activity and potential mechanism of action of MEP2 were also investigated. MEP2 ameliorated severe liver damage and regulated the liver function indicators and the alcohol-related enzyme levels in chronic alcohol-induced mice. Combined with biochemical detection, the gut microbiota, metabolites, and proteomics results revealed that MEP2 regulates the levels of hepatic cytokines related to inflammatory response and oxidative stress, as well as those of intestinal Bacteroides, Oscillospira, Parabacteroides, Alistipes, and Prevotella, through the ubiquitin-specific peptidase 10 (Usp10)/nuclear factor κB (NF-κB)/nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathway in the liver of mice induced by long-term alcohol intake. These data provide experimental evidence for the application of MEP2 in chronic alcohol-induced liver injury.

Structure and hepatoprotective activity of Usp10/NF-κB/Nrf2 pathway-related Morchella esculenta polysaccharide.

Ovarian cancer is a prevalent malignancy in the female reproductive system, representing a significantly fatal and incurable tumor. Chelerythrine (CHE), a natural benzopyridine alkaloid, has demonstrated a broad spectrum of anticancer activities. Nevertheless, the ovarian cancer inhibitory impact of CHE remains unclear. In this study, we investigated the cytotoxic mechanism and potential targets of CHE on in vitro cultures of A2780 and SKOV3 cells derived from ovarian cancer. Additionally, in vivo experiments were conducted to confirm the suppressive impact of CHE on tumor growth in nude mice. The findings revealed that CHE impeded the growth of A2780 and SKOV3 cells in a concentration-time-dependent manner and significantly suppressed the development of tumors in nude mice. CHE elevated the level of oxidative stress in tumor cells, prompted cell cycle halt in the S phase, and increased their mitochondrial membrane potential. Western blotting results demonstrated that CHE could modulate the expression of proteins associated with apoptotic and ferroptosis processes in A2780 and SKOV3 cells. Nrf2 was verified to be an upstream key target mediating the inhibitory impact of CHE on ovarian cancer cells. In summary, CHE exerts its anti-cancer effects on ovarian cancer by modulating Nrf2, inhibiting cellular proliferation, and promoting apoptosis and ferroptosis.

Chelerythrine induces apoptosis and ferroptosis through Nrf2 in ovarian cancer cells.

In this work, we developed a general synthesis method for the water-soluble lanthanide ion-doped NaYF upconversion (UC) nanoparticles (NPs) using triethylene glycol (TEG) as a high temperature solvent and diacid as a surfactant. Since the boiling point of the TEG is as high as 289.4 °C, the synthesis temperature can be correspondingly increased to a higher temperature that is a bit lower than this one. Therefore, water-soluble UCNPs with a small size (<50 nm) can be easily prepared. The nanocrystal growth temperature could be elevated from 180 °C to 285 °C due to the superiority of the high-temperature polar solvent environment introduced in this work. The temperature-dependent nanocrystal growth mechanism and luminescent properties of UCNPs are deeply explored. Different chain length diacids, , three-carbon chain length propanedioic acid (PDA), six-carbon chain length hexanedioic acid (HDA) and nine-carbon chain length azelaic acid (AA), were used in this work to prepare the water-soluble UCNPs in polar solution, and we finally found that the fluorescent intensity and water-stability are inversely proportional to the carbon chain length of the ligand. PDA was proved to be an optimum surfactant to prepare the most stable water-soluble UCNPs. As a result, the water-soluble UCNPs we prepared can also be successfully applied in the upconversion luminescent cell imaging. This study opens up new avenues for the synthesis of water-soluble UCNPs with small sizes and provides more opportunities for their applications in fields such as biological imaging and biological detection.

Article	Year
[Review on study of Dao-di herbs Artemisiae Annuae Herba]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica\| PubMed ID: 28901094	2016
Oviductus Ranae protein hydrolyzate prevents menopausal osteoporosis by regulating TGFβ/BMP2 signaling. Archives of gynecology and obstetrics\| PubMed ID: 30649603	2019
Scutellarein suppresses Aβ-induced memory impairment via inhibition of the NF-κB pathway and . Oncology letters\| PubMed ID: 31186780	2019
Pharmacokinetic and metabolomic analyses of Mangiferin calcium salt in rat models of type 2 diabetes and non-alcoholic fatty liver disease. BMC pharmacology & toxicology\| PubMed ID: 32762728	2020
Impact of TCM on Tumor-Infiltrating Myeloid Precursors in the Tumor Microenvironment. Frontiers in cell and developmental biology\| PubMed ID: 33748122	2021
Establishment and Development of a Quality Evaluation Method for Sangbaipi Decoction. Journal of AOAC International\| PubMed ID: 33909887	2022
Pilose Antler Peptide-3.2KD Ameliorates Adriamycin-Induced Myocardial Injury Through TGF-β/SMAD Signaling Pathway. Frontiers in cardiovascular medicine\| PubMed ID: 34124197	2021
Protective Effects of Huangqi Shengmai Yin on Type 1 Diabetes-Induced Cardiomyopathy by Improving Myocardial Lipid Metabolism. Evidence-based complementary and alternative medicine : eCAM\| PubMed ID: 34249132	2021
Huangqi Shengmai Yin Ameliorates Myocardial Fibrosis by Activating Sirtuin3 and Inhibiting TGF-β/Smad Pathway. Frontiers in pharmacology\| PubMed ID: 34483934	2021
Ginsenoside CK Inhibits TGF--Induced Epithelial-Mesenchymal Transition in A549 Cell via SIRT1. BioMed research international\| PubMed ID: 34934771	2021
Functional Mechanism of Ginsenoside Compound K on Tumor Growth and Metastasis. Integrative cancer therapies\| PubMed ID: 35615883	2022
Structure and hepatoprotective activity of Usp10/NF-κB/Nrf2 pathway-related Morchella esculenta polysaccharide. Carbohydrate polymers\| PubMed ID: 36657860	2023
Chelerythrine induces apoptosis and ferroptosis through Nrf2 in ovarian cancer cells. Cellular and molecular biology (Noisy-le-Grand, France)\| PubMed ID: 38650145	2024
A general synthesis method for small-size and water-soluble NaYF:Yb, Ln upconversion nanoparticles at high temperature. RSC advances\| PubMed ID: 39654919	2024

Xiaowei Huang

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