Chinese MedicinePub Date : 2025-07-01DOI: 10.1186/s13020-025-01165-3
Yu-Xin Jin, Hang-Qi Hu, Jia-Cheng Zhang, Yu-Tian Zhu, Hao-Lin Zhang, Xi-Yan Xin, Rui-Wen Fan, Yang Ye, Yin Li, Dong Li
{"title":"Mechanistic insights into the Bushen Huatan Huoxue Formula and its components in ameliorating obesity-associated polycystic ovary syndrome.","authors":"Yu-Xin Jin, Hang-Qi Hu, Jia-Cheng Zhang, Yu-Tian Zhu, Hao-Lin Zhang, Xi-Yan Xin, Rui-Wen Fan, Yang Ye, Yin Li, Dong Li","doi":"10.1186/s13020-025-01165-3","DOIUrl":"10.1186/s13020-025-01165-3","url":null,"abstract":"<p><strong>Background: </strong>Bushen Huatan Huoxue Formula (BHHF), a traditional Chinese medicine decoction, demonstrates potential in treating polycystic ovary syndrome (PCOS), a prevalent endocrine disorder in women of reproductive age that is closely associated with obesity and metabolic dysregulation. However, the underlying molecular mechanisms of BHHF's action remain unclear. This study aimed to evaluate the therapeutic efficacy of BHHF in obesity-associated PCOS and investigate its regulatory mechanisms related to metabolic homeostasis.</p><p><strong>Methods: </strong>In vivo, three-week-old female Sprague Dawley rats were divided into seven groups: control, dehydroepiandrosterone (DHEA), high-fat diet (HFD), model (HFD + DHEA), low-dose BHHF, high-dose BHHF, and metformin. The PCOS model was induced by DHEA injection. BHHF was administered by gastric gavage for four weeks. Body weight, fat volume, glucose tolerance, and insulin sensitivity were measured. Ovarian histology, hormone analysis, RNA extraction, quantitative real-time PCR, protein extraction, western blotting, and proteomics studies were also conducted. In vitro, 3T3-L1 cells were used to assess lipid accumulation, mitochondrial function, and the effects of BHHF-containing serum.</p><p><strong>Results: </strong>BHHF restored reproductive cyclicity and polycystic ovarian morphology, reduced testosterone and anti-Müllerian hormone levels, and increased estradiol levels. It also alleviated weight gain, reduced fat volume, improved glucose tolerance, and enhanced insulin sensitivity. Proteomics analysis revealed that BHHF activated the AMPK signaling pathway and promoted white adipose tissue browning. In vitro, BHHF-containing serum suppressed lipid accumulation and enhanced mitochondrial oxygen consumption. The bioactive components of BHHF-Bushen (BS), Huatan (HT), and Huoxue (HX) -exhibited specific functions. BS improved estrous cyclicity and ovarian morphology; HT regulated glucose and lipid metabolism and promoted adipose browning; and HX modulated mitochondrial bioenergetics and redox homeostasis.</p><p><strong>Conclusion: </strong>BHHF exerts multi-targeted therapeutic effects on obesity-associated PCOS by regulating metabolic-reproductive crosstalk. Its components act synergistically, offering a novel therapeutic strategy for PCOS treatment. Future research should focus on identifying core active compounds and optimizing treatment according to individual PCOS phenotypes.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"20 1","pages":"99"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2025-07-01DOI: 10.1186/s13020-025-01150-w
Rushuang Cai, Chunying Li, Yong Zhao, Haisheng Yuan, Xiaomeng Zhang, Aihua Liang, Yan Yi
{"title":"Traditional Chinese medicine in diabetic kidney disease: multifaceted therapeutic mechanisms and research progress.","authors":"Rushuang Cai, Chunying Li, Yong Zhao, Haisheng Yuan, Xiaomeng Zhang, Aihua Liang, Yan Yi","doi":"10.1186/s13020-025-01150-w","DOIUrl":"10.1186/s13020-025-01150-w","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is a severe complication of diabetes and a leading cause of end-stage renal disease (ESRD). It is characterized by a complex pathogenesis that involves genetic, epigenetic, metabolic, and multifactorial elements. Current therapeutic approaches for DKD have significant limitations. In contrast, Traditional Chinese Medicine (TCM), with its personalized treatment based on syndrome differentiation, shows potential to modulate multiple pathological pathways implicated in DKD. This review provides a detailed examination of DKD pathogenesis and the progress in TCM research, offering valuable insights for DKD treatment research and clinical practice.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"20 1","pages":"95"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2025-07-01DOI: 10.1186/s13020-025-01147-5
Kangyu Zhou, Mengyao Shi, Ruyi Chen, Yang Zhang, Yunjie Sheng, Chaoying Tong, Gang Cao, Dan Shou
{"title":"Natural phytochemical-based strategies for antibiofilm applications.","authors":"Kangyu Zhou, Mengyao Shi, Ruyi Chen, Yang Zhang, Yunjie Sheng, Chaoying Tong, Gang Cao, Dan Shou","doi":"10.1186/s13020-025-01147-5","DOIUrl":"10.1186/s13020-025-01147-5","url":null,"abstract":"<p><strong>Background: </strong>Biofilms contribute to the persistence of infectious diseases, complicate the treatment of chronic infections and pose a significant global health threat. However, the effectiveness of antibacterial therapies is often limited by poor penetration of antibiotics, as well as the horizontal transfer of antibiotic resistance genes among bacteria. Phytochemicals remain a promising source for developing novel antibiofilm agents.</p><p><strong>Methods: </strong>A systematic search of literatures was conducted using PubMed, Web of Science, Google scholar, and CNKI, with keywords related to \"phytochemicals\", \"natural products\", \"natural compounds\", \"alkaloids\", \"polyphenols\", \"terpenoids\", \"quinones\", \"nanomaterials\", \"biofilms\", \"biofilm formation\", \"biofilm inhibition\", and \"structure-activity relationship\" focusing on studies published from 2014 to 2025.</p><p><strong>Results: </strong>A total of 38 most extensively studied natural phytochemicals, including alkaloids, flavonoids (i.e., flavonols, flavanols, and chalcones), quinones, non-flavonoid polyphenols, terpenes and others, were systematically screened based on relevant articles from the past decade. Phytochemicals mainly work by targeting quorum sensing systems, reducing virulence factor production, preventing the initial adhesion and targeting the extracellular polymeric substances of biofilms. Well-designed phytochemical-based nanomaterials can enhance permeability, drug loading efficiency, target drug delivery and sustained drug release of phytochemicals, thereby increasing their antibiofilm efficacy.</p><p><strong>Conclusion: </strong>Phytochemicals represent a promising therapeutic source for the elimination of bacterial biofilms and associated infections both in the form of molecules or nanomaterials. By synthesizing current progress and identifying future directions, phytochemical-based strategies may inspire innovative solutions and promote translational efforts in combating biofilm-associated challenges in clinical and environmental contexts.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"20 1","pages":"96"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2025-07-01DOI: 10.1186/s13020-025-01149-3
Chengliang Zhong, Qingyuan Liu, Shengxuan Guo, Deyang Sun, Boyang Wang, Siyuan Hu, Xinmin Li, Weibo Zhao, Ying Ding, Bin Yuan, Jing Liu, Long Xiang, Nan Li, Zheng Xue, Yan Li, Yiqun Teng, Rongsong Yi, Shao Li, Rong Ma
{"title":"A computational-based new treatment strategy with three-armed RCT on Mycoplasma pneumoniae pneumonia in children.","authors":"Chengliang Zhong, Qingyuan Liu, Shengxuan Guo, Deyang Sun, Boyang Wang, Siyuan Hu, Xinmin Li, Weibo Zhao, Ying Ding, Bin Yuan, Jing Liu, Long Xiang, Nan Li, Zheng Xue, Yan Li, Yiqun Teng, Rongsong Yi, Shao Li, Rong Ma","doi":"10.1186/s13020-025-01149-3","DOIUrl":"10.1186/s13020-025-01149-3","url":null,"abstract":"<p><p>Mycoplasma pneumoniae pneumonia (MPP) is a common type of pneumonia among school-aged children and adolescents. Jinzhen Oral Liquid (JZOL) and Azithromycin (AZ) are commonly used treatments in traditional Chinese medicine (TCM) and Western medicine, respectively. There are several clinical and basic research reports on their solo effect against MPP, enabling their combined treatment to become possible. However, the mechanisms and specific pharmacodynamics of their combined therapy remain unclear. In this study, we conducted a mechanistic analysis of the combination of JZOL and AZ based on network target, elucidating their modular network regulatory mechanisms. The modular mechanisms involve four modules, including hormone response, cell differentiation and migration, signal transduction, oxygen and hypoxia response, centered by TNF signaling pathway-mediated regulation. Under the instruction of computational analysis, we conducted a randomized, double-blind, three-armed, parallel-controlled, multicenter clinical study of different doses of JZOL combined with AZ for the treatment of MPP in children. The objective of clinical research is to evaluate the synergistic effect of different doses of JZOL combined with AZ in the treatment of children with MPP, shortening the course of disease and improving prognosis, while observing the safety of clinical application. At the study endpoint, the median time to clinical recovery showed statistically significant differences (The double-dose group lasts for 5 days, the regular-dose group lasts for 6 days, and the placebo group lasts for 8 days), which were also observed between groups for time to complete fever remission, time to relief of cough/phlegm, effective rate of chest X-ray improvement, and rate of healing of TCM symptoms. Different doses of JZOL combined with AZ have shown the effects of shortening the course of the disease, relieving the symptoms, and improving the prognosis. The research program composed of computational prediction and clinical trials can significantly accelerate the research and development process and identify more effective treatment with good safety, which is worthy of clinical promotion. Chinese Clinical Trial Registry ChiCTR1800019007.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"20 1","pages":"97"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Decoding the anti-thrombotic effects of leonurine: a multimodal approach combining TCM repositioning and mTOR signaling.","authors":"Xin Dong, Shuaibing Jia, Leifeng Zhang, Yong Liang, Jianhua Zhang, Yi Zhun Zhu","doi":"10.1186/s13020-025-01160-8","DOIUrl":"10.1186/s13020-025-01160-8","url":null,"abstract":"<p><strong>Background: </strong>As a natural small molecule compound, Leonurine have great potential for application in the treatment of cardiovascular diseases. However, there is still a gap in the treatment of thrombosis with Leonurine.</p><p><strong>Methods: </strong>A multimodal heterogeneous network is constructed using ETCM and STRING databases, integrating herbs, ingredients, targets and diseases. A reposition model constructed by random walk and random forests is used to predict the relationship between Leonurine and diseases. In addition, network pharmacology, molecular docking and molecular dynamics are used as computer-aided methods to confirm the target of Leonurine. Finally, CCK-8 assay, Flow cytometry, Western Blotting, and mouse experiments are used to validate the therapeutic potential of Leonurine from the perspective of biological wet experiments.</p><p><strong>Results: </strong>Firstly, based on the accurate prediction results evaluated by indicators, Leonurine is evaluated to have potential therapeutic effects on thrombotic diseases. Through computer-aided methods, mTOR is identified as a potential regulatory factor and may have a similar regulatory mechanism to the marketed drug Everolimus. Experimental results demonstrate that Leonurine reduces thrombotic cell apoptosis and promotes endothelial cell proliferation by inhibiting mTOR signaling. Additionally, in vivo studies show decrease mTOR expression in thrombotic tissues following Leonurine treatment.</p><p><strong>Conclusions: </strong>These findings underscore mTOR's critical role in mediating Leonurine's anti-thrombotic effects, supported by both computational and experimental evidence. The study provides a foundation for the application of TCM-derived compounds in modern medicine, particularly in thrombosis treatment.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"20 1","pages":"98"},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12220451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"From traditional medicine to modern medicine: the importance of TCM regulatory science (TCMRS) as an emerging discipline.","authors":"Hua Hua, Jian-Yuan Tang, Jun-Ning Zhao, Ting Wang, Jun-Hua Zhang, Jiang-Yong Yu, Chang-Ming Yang, Yan-Ling Ai, Qiao-Xian Luo","doi":"10.1186/s13020-025-01152-8","DOIUrl":"10.1186/s13020-025-01152-8","url":null,"abstract":"<p><p>Traditional Chinese medicine (TCM) has become a standardized medical system through systematic development across global healthcare practices. However, concerns persist regarding the safety, efficacy and quality of traditional medicinal products. Traditional Chinese medicine regulatory science (TCMRS) has emerged as an interdisciplinary field to address these challenges. This discipline integrates multidisciplinary knowledge to develop new tools, standards and approaches for systematic evaluation of benefit-risk profiles. This approach aims to ensure the quality, safety, and efficacy of TCM products, while also supporting the development of scientifically grounded regulatory frameworks that accommodate traditional medicine's distinctive characteristics. Through comprehensive quality management from raw material sourcing to production processes and clinical validation, developing and adopting TCMRS is entrusted to significantly strengthen its regulatory oversight. This review examines the critical scientific challenges in the modernization process of TCM, analyzes the conceptual foundations of TCMRS, evaluates its pivotal role in pharmaceutical transformation, and highlights its essential function in preserving traditional knowledge while fostering therapeutic innovation. Key challenges for TCMRS implementation include reconciling traditional epistemologies with modern pharmaceutical paradigms, standardizing complex herbal formulations, and developing rigorous evaluation protocols for decoctions and compound preparations. The integration of advanced methodologies, including systems biology, network pharmacology, artificial intelligence, and nanotechnology, into regulatory frameworks, combined with enhanced international cooperation, remains a crucial strategy for tackling global public health challenges. Future development trajectories for TCMRS will prioritize lifecycle management strategies, technology-driven innovation systems, and global knowledge-sharing initiatives, propelled by advancements in life sciences and information technology. This evolution requires careful balancing of three fundamental elements: theoretical development in traditional medicine, integration of emerging technologies, and maintenance of regulatory system stability. It is crucial to innovate the working mechanisms of the TCMRS researcher alliance and the global policy-coordination mechanism for TCM regulation, enhance the conversion of basic disciplines into regulatory applications, and support the establishment of an excellent TCM regulatory system with scientific decision-making. These efforts are essential for promoting the high-quality development of the TCM industry and boosting its international influence and presence.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"20 1","pages":"92"},"PeriodicalIF":5.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12199503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2025-06-18DOI: 10.1186/s13020-025-01141-x
Kun Liu, Li Zheng, Qian-Yu Huang, Hong-Ji Li, Cheng Li, Hui Zhao, Ze-Bing Ye, Hao Wang, Xu-Feng Qi, Meng Wang
{"title":"Natural product library screening identifies Darutigenol for the treatment of myocardial infarction and ischemia/reperfusion injury.","authors":"Kun Liu, Li Zheng, Qian-Yu Huang, Hong-Ji Li, Cheng Li, Hui Zhao, Ze-Bing Ye, Hao Wang, Xu-Feng Qi, Meng Wang","doi":"10.1186/s13020-025-01141-x","DOIUrl":"10.1186/s13020-025-01141-x","url":null,"abstract":"<p><strong>Introduction: </strong>Ischemic heart diseases are the leading cause of death worldwide due to the inability of regeneration of adult cardiomyocytes (CMs). Natural products from medical herbs are an important source of innovative drugs for many diseases including cardiovascular diseases.</p><p><strong>Objectives: </strong>In this study, we set out to screen novel small-molecule therapies from natural products to protect heart against ischemic injury.</p><p><strong>Methods: </strong>High-throughput screening was performed using a natural product library to identify the potential small molecules which can promote survival of CMs under ischemic and ischemic/reperfusion conditions. In addition, myocardial infarction (MI) and ischemia/reperfusion (I/R) mice models were used to evaluate the in vivo effects of the screened candidate. We also applied various analysis including cell viability, qPCR, Western blot, immunofluorescent staining, echocardiography, Masson's staining, TTC staining, and network pharmacology.</p><p><strong>Results: </strong>High-throughput screening showed that the small molecule compound Darutigenol (Dar), derived from the Chinese traditional herb Herba Siegesbeckiae, could significantly promote CM survival and proliferation under ischemic conditions. Moreover, I/R-induced CM apoptosis and ROS generation could be significantly reduced by Dar treatment. In addition, in vivo administration of Dar was able to attenuate MI- and I/R-induced cardiac injury in adult mice by decreasing fibrosis and apoptosis, thereby improving cardiac function. Network pharmacology analysis and molecule docking assay showed that Dar has the highest binding affinity with AKT1 protein. Western blotting assay further revealed that AKT1 activation was significantly enhanced by Dar administration in the infarcted hearts.</p><p><strong>Conclusions: </strong>Our data revealed that the small molecule compound Dar, screened from the natural product library in this study, is capable of protecting heart against MI and I/R injury by activating AKT1 pathway. These findings enrich the natural product candidates for cardiovascular disease treatment and provide new insights into potential therapeutic agents for MI and I/R injury.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"20 1","pages":"90"},"PeriodicalIF":5.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Wenshen Zhuanggu formula inhibits tumor-exosomes induced bone pre-metastasis niche formation in primary breast cancer mice.","authors":"Qionglian Huang, Hanjuan Ning, Jue Wang, Weiwei Liu, Sheng Liu, Jianyi Wang, Xianghui Han","doi":"10.1186/s13020-025-01136-8","DOIUrl":"10.1186/s13020-025-01136-8","url":null,"abstract":"<p><strong>Background: </strong>The therapy for breast cancer bone metastasis (BCBM) still needs profound investigation. Focusing on the formation of bone pre-metastasis niche (BPMN) is a crucial tache for BCBM treatment. Wenshen Zhuanggu Formula (WSZG) is a typical traditional Chinese medicine (TCM) prescription with ability of clinically palliating bone pain and ameliorating the quality of life of BCBM patients. This study aims to elucidate the inhibitory effect and underlying mechanism of WSZG on BPMN formation induced by tumor-derived exosomes.</p><p><strong>Methods: </strong>Bone precursor cells were exposed to exosomes derived from MDA-MB-231BO cells (BO-exo, 50 μg/mL) and treated by WSZG (10 or 20 μg/mL) in vitro. A primary breast cancer mouse model with propensity of BPMN was established by pre-educating BO-exo and then subcutaneously injecting MDA-MB-231BO cells into mammary fat pads. After the modeled mice were orally administrated WSZG (6.5 or 13 g crude herb kg<sup>-1</sup> d<sup>-1</sup>) for 28 days, bone architecture and bone parameters of tibia were analyzed using micro-CT. The absorbed exosomes by bone precursor cells were investigated using confocal microscopy. Osteoclastic and osteoblastic differentiation were examined by TRAP, ALP and qRT-PCR. The levels of protein related to bone metabolism and extracellular matrix (ECM) were detected by ELISA and IHC methods.</p><p><strong>Results: </strong>The results showed that BO-exo elicited the vicious bone microenvironment to form BPMN in bone-tropic primary BC mice. WSZG encouragingly targeted BO-exo to hinder osteoclastic differentiation (ACP5, c-Fos, Ctsk, MMP9, NFATc1), improve focal bone lesions (BMD, Tb.N, Tb.Th, Tb.Sp, Conn-Dens. and BV/TV), and downregulate the expression levels of bone metabolism markers (ICTP, BALP, TRACP-5b) and bone ECM proteins (bone sialoprotein, elastin, fibronectin, osteopontin, collagen I and vitronectin).</p><p><strong>Conclusions: </strong>This study denotes the enhanced effects of BO-exo and highly inhibitive possibility by WSZG treatment on BPMN formation, shaping bone metastatic landscape of BC and informing the treatment of early-stage BCBM in terms of TCM.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"20 1","pages":"88"},"PeriodicalIF":5.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2025-06-16DOI: 10.1186/s13020-025-01109-x
Yuping Qiu, Shupei Li, Mingzuo Jiang, Ang Huang, Ya Yang, Xi Chen, Hui Li, Zhizhou Yang, Juan Wei, Ji Xuan
{"title":"Quercetagetin alleviates liver fibrosis in non-alcoholic fatty liver disease by promoting ferroptosis of hepatic stellate cells through GPX4 ubiquitination.","authors":"Yuping Qiu, Shupei Li, Mingzuo Jiang, Ang Huang, Ya Yang, Xi Chen, Hui Li, Zhizhou Yang, Juan Wei, Ji Xuan","doi":"10.1186/s13020-025-01109-x","DOIUrl":"10.1186/s13020-025-01109-x","url":null,"abstract":"<p><strong>Background: </strong>Lang Qing A Ta (Huagan Tongluo Fang, HGTLF) is a Tibetan medicine with significant anti-liver fibrosis effects and good efficacy in the treatment of liver diseases, including non-alcoholic fatty liver disease (NAFLD). Quercetagetin (QG) has been identified as an active ingredient of HGTLF that is absorbed into the blood. This study aims to investigate the role of QG in the anti-liver fibrosis effect of HGTLF in NAFLD.</p><p><strong>Methods: </strong>CCl<sub>4</sub> injection-induced liver fibrosis and high-fat, high-cholesterol diet-induced non-alcoholic steatohepatitis (NASH) mouse models were established. Transforming growth factor-β1 (TGF-β1)-induced hepatic stellate cells (HSCs) were used as in vitro models. The effect of QG on the stability and degradation pathway of glu-tathione peroxidase 4 (GPX4) protein was investigated.</p><p><strong>Results: </strong>QG improved liver function and hyperlipidemia in CCl<sub>4</sub>-injected mice and NASH mice, and alleviated hepatic lipid deposition and hepatic fibrosis. TGF-β1 treatment promoted the expression of α-smooth muscle actin and fibrosis-related genes, while QG reversed this phenomenon and inhibited HSC activation. QG increased the intracellular labile iron pool and lipid reactive oxygen species in HSCs. Treatment with the ferroptosis inhibitor ferrostatin-1 reversed the inhibitory effect of QG on TGF-β1-induced HSC activation. QG reduced GPX4 protein stability and regulated GPX4 K167 ubiquitination via the membrane-associated ring-CH-type finger 8 (MARCHF8)-mediated ubiquitin-proteasome pathway. Interference with MARCHF8 attenuated the effect of QG and promoted HSC activation induced by TGF-β1.</p><p><strong>Conclusion: </strong>QG, the active ingredient of HGTLF, can induce ferroptosis of HSCs by targeting the degradation of GPX4 through ubiquitination and inhibit HSC activation, thereby alleviating liver fibrosis in NAFLD.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"20 1","pages":"89"},"PeriodicalIF":5.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}