Chinese Herbal Medicines最新文献

{"title":"Advanced applications of synthetic biology technology in biosynthesis of bioactive compounds from medicinal plants","authors":"Yingjun Liu ,&nbsp;Anying Ji ,&nbsp;Haiyang Jia ,&nbsp;Huan Sun","doi":"10.1016/j.chmed.2025.11.006","DOIUrl":"10.1016/j.chmed.2025.11.006","url":null,"abstract":"<div><div>Medicinal plants serve as valuable sources of bioactive compounds with critical applications across pharmaceutical, agricultural, and industrial sectors. Compared to chemical synthesis and plant extraction, synthetic biology offers a green, efficient, and sustainable alternative for producing bioactive compounds, which represents a state of art technology. However, this technology still faces several challenges, including overly long metabolic pathways, inadequate catalytic efficiency of key enzymes in the pathway, and incompatibility between gene elements and host cells, leading to low yields of target bioactive compounds. The development and application of regulatory tools in synthetic biology hold great promise for overcoming these obstacles. This review first summarizes the classification and biosynthesis of bioactive compounds based on structural types. Subsequently, recent advancements are outlined in regulation tools and their application in the heterologous production of bioactive compounds. This review aims to establish a foundation for the efficient production of bioactive compounds based on microbial cell factories. This not only has significant practical implications for reducing the resource consumption and environmental impact of traditional production methods, but also highlights the central role of synthetic biology in promoting the sustainable production of bioactive compounds derived from medicinal plants.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"18 1","pages":"Pages 11-28"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphological, physiological and biochemical changes and effects of polyamines on regulation of Anoectochilus roxburghii during flowering period","authors":"Weiwei Jiang ,&nbsp;Xiaoyun Yan ,&nbsp;Chenfei Lu ,&nbsp;Xiaowei Xu ,&nbsp;Enting Xu ,&nbsp;Dandan Chen ,&nbsp;Yuqiu Huang ,&nbsp;Qingsong Shao ,&nbsp;Aimin Lv","doi":"10.1016/j.chmed.2025.05.007","DOIUrl":"10.1016/j.chmed.2025.05.007","url":null,"abstract":"<div><h3>Objective</h3><div><em>Anoectochilus roxburghii</em> is a valuable medicinal and ornamental plant. The aim of this study is to investigate the morphological and biochemical responses during the flower development stages of <em>A. roxburghii</em>, and to assess the effects of exogenous polyamines (PAs) on bud differentiation and metabolism, thereby providing a theoretical basis for understanding the flowering form and physiology of <em>A. roxburghii</em>.</div></div><div><h3>Methods</h3><div>In this study, morphological and biochemical responses in flower development stages of <em>A. roxburghii</em> were investigated using paraffin sections and stereomicroscope. <em>A. roxburghii</em> was divided into five periods, including vegetative growth period, flower bud period, flowering period, late flowering period and fruiting period. During the flowering phase, specific biochemical parameters were measured, including soluble sugar content, superoxide dismutase (SOD) activity, soluble protein content, peroxidase (POD) activity, and catalase (CAT) activity. These measurements were conducted to understand the biochemical changes occurring within <em>A. roxburghii</em> during its flowering process. Furthermore, the effects of PAs on bud differentiation were examined. Additionally, the activities of <em>S</em>-adenosylmethionine decarboxylase (SAMDC) and polyamine oxidase (PAO), as well as the content of polyphenols, polysaccharides, and flavonoids in <em>A. roxburghii</em>, were measured after PA treatment to evaluate the metabolic changes induced by exogenous PAs.</div></div><div><h3>Results</h3><div>During the flowering phase of <em>A. roxburghii</em>, soluble sugar content and SOD activity were steadily declining. Soluble protein content was initially increasing and then reducing, and POD and CAT activities showed opposite pattern. In addition, the effects of exogenous PAs on bud differentiation were investigated. Results showed that 3 mmol/L putrescine or 0.3 mmol/L spermidine significantly promoted the bud differentiation of <em>A. roxburghii</em> and advanced the flowering. The activities of SAMDC, PAO, and the content of polyphenols, polysaccharides and flavonoids in <em>A. roxburghii</em> significantly increased after PA treatment, demonstrating that exogenous PA can accelerate metabolism and improved the active ingredients content.</div></div><div><h3>Conclusion</h3><div>The flower development of <em>A. roxburghii</em> was divided into five stages, with significant changes in soluble sugar, protein, POD, SOD, CAT, MDA, and PRO levels. Exogenous putrescine and spermidine enhanced bud differentiation and accelerated flowering, increasing SAMDC and PAO activities, suggesting accelerated PA metabolism. PAs also improved active component content. These findings provide a theoretical basis for studying flower morphology and PA-induced flowering regulation of <em>A. roxburghii</em>.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"18 1","pages":"Pages 212-224"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of proteomics and metabolomics data to understanding of health benefits of tea","authors":"Danicke Willemse,&nbsp;Mariam Rado,&nbsp;Mariska Lilly","doi":"10.1016/j.chmed.2025.11.009","DOIUrl":"10.1016/j.chmed.2025.11.009","url":null,"abstract":"<div><div>Tea is the second most widely consumed non-alcoholic beverage globally. While most teas originate from <em>Camellia sinensis</em> (L.) Kuntze plants, rooibos and honeybush teas are produced from <em>Aspalathus linearis</em> (Burm.f.) R.Dahlgren and <em>Cyclopia</em> species tea plants. Interest in tea and tea-derived components, has increased due to their well-known health benefits. The mechanisms of these health benefits are however poorly understood. Proteomics and metabolomics provide valuable tools to assess the mechanisms of the therapeutic effects of tea in disease treatment. This review summarizes the role played by proteomic and metabolomic studies in investigating the health benefits of <em>C. sinensis</em>, <em>A. linearis,</em> and <em>Cyclopia</em> spp<em>.</em> teas. Surprisingly, no proteomic and metabolomic studies investigating the health benefits of <em>A. linearis</em> and <em>Cyclopia</em> spp<em>.</em> teas and/or their components were identified in a literature search. However, 25 studies using proteomics and 16 studies using metabolomics to investigate the health benefits of <em>C. sinensis</em> teas and/or their components were identified in a literature search. Proteomics and metabolomics have been valuable tools for investigating the health benefits of <em>C. sinensis</em> teas and tea components, and will likely also prove valuable for investigating the effects of <em>A. linearis</em> and <em>Cyclopia</em> spp. teas on human health.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"18 1","pages":"Pages 124-141"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precise subcellular organelle-targeted analyses of hepatotoxicity of Polygonum multiflorum","authors":"Yijie Li ,&nbsp;Shuni Duan ,&nbsp;Yinhao Zhang ,&nbsp;Runping Liu ,&nbsp;Rong Sun ,&nbsp;Jianzhi Wu ,&nbsp;Zhi Ma ,&nbsp;Xiaojiaoyang Li","doi":"10.1016/j.chmed.2025.03.001","DOIUrl":"10.1016/j.chmed.2025.03.001","url":null,"abstract":"<div><h3>Objective</h3><div>Drug-induced liver injury (DILI) is an undesirable reaction caused by drugs, herbal medicines or supplements and may lead to acute liver failure. <em>Polygoni Multiflori Radix</em> (PMR, Heshouwu in Chinese) originated from the roots of <em>Polygonum multiflorum</em> is a popular traditional Chinese medicine (TCM) while potential hepatotoxicity limits its clinical application. The present study aims to elucidate the in-depth mechanism of PMR-induced organelle heterogeneity of hepatotoxicity.</div></div><div><h3>Methods</h3><div>Network pharmacology and available TCM transcriptomics databases including Integrated Traditional Chinese Medicine (ITCM) and HERB databases were conducted to identify the active ingredients of PMR with the potent ability to injure organelles including microsome, mitochondria, endoplasmic reticulum (ER), Golgi apparatus (GA), and lysosome. Organelles were isolated and cultured with adenosine triphosphate (ATP)-supplemented system. Western blotting and particle size characterization techniques were further performed to clarify the organelle heterogeneity of PMR-induced hepatotoxicity.</div></div><div><h3>Results</h3><div>Five representative organelles were isolated from mouse livers or hepatocytes and administrated with PMR-derived active components and monomers. The results of network pharmacology and virtual screening initially identified the components of PMR that may damage different organelles. By combining experimental verification, we found that five organelles studied in this research were the target organelles for flavonoid (FVN)’s affiliated compound quercetin (QC). Mitochondria were damaged mainly by kaempferol, anthraquinone (AQ) and its monomeric components. Meanwhile, QC and emodin showed effective toxicity on endoplasmic reticulum. For microsome, QC remained the most toxic monomer. For Golgi apparatus, <em>trans</em>-stilbene glycosides (<em>trans-</em>SG), AQ and emodin were the major toxic components in PMR. For lysosomes, total-SG, emodin and QC were the major toxic components in PMR.</div></div><div><h3>Conclusion</h3><div>Collectively, our findings revealed the organelle heterogeneity of PMR-induced hepatotoxicity and identified quercetin as a potential toxic component in PMR. This study provides a novel conjunct strategy to screen and discover potential toxic components and shapes the understanding of toxicity warning and clinically safe use of herbal medicines such as PMR.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"18 1","pages":"Pages 153-166"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chelidonine overcomes P-gp-mediated adriamycin resistance in MCF-7/ADR cells by inhibiting PDGFRβ/PI3K/Akt pathway","authors":"Xiang Zou ,&nbsp;Yuhang Zhang ,&nbsp;Kaili Liu ,&nbsp;Liyue Zhang ,&nbsp;Jianli Li ,&nbsp;Yue Zhang ,&nbsp;Xuerui Zhang ,&nbsp;Lei Yu ,&nbsp;Zhongyuan Qu","doi":"10.1016/j.chmed.2025.01.005","DOIUrl":"10.1016/j.chmed.2025.01.005","url":null,"abstract":"<div><h3>Objective</h3><div>Chemoresistance represents a major obstacle in breast cancer (BC) treatment. Chelidonine could prevent various tumor cell types. However, the effect and mechanism of chelidonine against BC chemotherapy resistance have not been elucidated. This paper aimed to explore the effect and mechanism of chelidonine on BC chemoresistance.</div></div><div><h3>Methods</h3><div>A CCK-8 assay, flow cytometry and fluorescence microscopy were applied to evaluate the resistance reversal effect of chelidonine on MCF-7/ADR cells. The signaling pathways by which chelidonine suppresses BC were predicted by network pharmacology and validated by Western blotting. The chemoresistant reversal mechanism of chelidonine was clarified using platelet-derived growth factor receptor-<em>β</em> (PDGFR<em>β</em>) silencing with small interfering RNA (siRNA), platelet-derived growth factor-BB (PDGF-BB) stimulation, Western blotting and real-time quantitative polymerase chain reaction (RT-qPCR).</div></div><div><h3>Results</h3><div>Chelidonine remarkably reversed adriamycin (ADR) resistance by decreasing P-glycoprotein (P-gp) expression and the efflux of ADR in MCF-7/ADR cells. Additionally, PDGFR<em>β</em> expression in MCF-7/ADR cells was markedly higher than that in MCF-7 cells (<em>P</em> &lt; 0.01), and PDGFR<em>β</em> knockdown prevented P-gp expression and intracellular ADR accumulation. Network pharmacology identified phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) as a primary pathway of chelidonine-inhibiting BC, which was verified by the marked underexpression of phosphorylated kappa B inhibitor protein kinase (p-IKK), phosphorylated inhibitor of nuclear factor-<em>κ</em>B (p-IKB), and nuclear factor-<em>κ</em>B (NF-<em>κ</em>B) and phosphatase and tensin homolog (PTEN) hyperexpression by chelidonine treatment (<em>P</em> &lt; 0.01). Notably, PDGFR<em>β</em> silencing enhanced the inhibitory effect of chelidonine on the activation of the PI3K/Akt pathway. Moreover, chelidonine suppressed PDGF-BB stimulation of the PDGFR<em>β</em>/PI3K/Akt axis.</div></div><div><h3>Conclusion</h3><div>These findings underscore the potential role of PDGFR<em>β</em> in regulating chemotherapy resistance in BC. Chelidonine could effectively overcome the resistance of MCF-7/ADR cells to ADR by targeting the PDGFR<em>β</em>/PI3K/Akt axis. Meanwhile, these findings highlight the potential of chelidonine as a promising natural chemoresistant agent for BC treatment.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"18 1","pages":"Pages 167-177"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of Siraitia grosvenorii: Applications, breeding, and biosynthesis of mogrosides","authors":"Zuliang Luo ,&nbsp;Yimei Zang ,&nbsp;Jiaxian Su ,&nbsp;Qi Tang ,&nbsp;Limei Pan ,&nbsp;Xiaojun Ma ,&nbsp;Chongnan Wang ,&nbsp;Changming Mo","doi":"10.1016/j.chmed.2025.11.005","DOIUrl":"10.1016/j.chmed.2025.11.005","url":null,"abstract":"<div><div><em>Siraitia grosvenorii</em> is a premier food-medicine homologous species recognised by China’s National Health Commission and produces mogrosides as its primary active component. These compounds exhibit biological activities, including the regulation of blood sugar, fat metabolism, and immune function regulation. They are classified as high-intensity, non-nutritive sweeteners with significant medicinal potential and nutritional value. This review systematically explores the applications of <em>S. grosvenorii</em> in traditional medicine and foods, with a focus on advances in the conservation of germplasm resources and the traditional breeding of elite varieties, mogroside biosynthetic pathways and the characterization of key genes, and synthetic biology platforms for mogroside production. We have identified the low content of mogroside V in <em>S. grosvenorii</em> as the main reason for its limited application. To address this issue, we propose two strategic approaches: enhancing mogroside content <em>in vivo</em> through molecular design breeding and developing three synthetic biology platforms for mogrosides synthesis to increase yields. These solutions offer viable ways to reduce production costs and expand the commercial use of <em>S. grosvenorii</em> medicines and sweeteners.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"18 1","pages":"Pages 59-76"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthetic biology empowers development of traditional Chinese medicine","authors":"Chun Li","doi":"10.1016/j.chmed.2025.11.010","DOIUrl":"10.1016/j.chmed.2025.11.010","url":null,"abstract":"","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"18 1","pages":"Pages 1-2"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From natural laboratory to drug discovery: Chemical structures, bioactivities, and biosynthesis of meroterpenoids from Ganoderma species","authors":"Shuang Peng ,&nbsp;Jianzhao Qi ,&nbsp;Chao Lin ,&nbsp;Zhichao Xu ,&nbsp;Zhenhao Li ,&nbsp;Chengwei Liu","doi":"10.1016/j.chmed.2025.03.003","DOIUrl":"10.1016/j.chmed.2025.03.003","url":null,"abstract":"<div><div>Meroterpenoids are secondary metabolites partially derived from the terpenoid biosynthetic pathway, and are widely distributed in plants, animals, and fungi. These natural products possess complex backbone structures and diverse bioactivities. <em>Ganoderma</em> meroterpenoids (GMs) form a distinct group of meroterpenoids were characterized by the presence of 1,2,4-trisubstituted phenyl and polyunsaturated terpene moieties. Various <em>Ganoderma</em> species have been extensively studied, leading to the discovery of several structurally unique meroterpenoids with significant pharmacological activities. After the first isolation and identification of GMs in 2 000, over 300 compounds from 14 species have been characterized for their structures and biological activities. The structures and activities of some GMs from different <em>Ganoderma</em> species vary greatly, probably due to significant differences in the genome and transcriptome of different <em>Ganoderma</em> species. We predicted the related enzymes based on the reported <em>Ganoderma</em> genome and proposed the biosynthetic pathway related to GMs. The results presented in this review provide a scientific foundation for the comprehensive exploration and utilization of diverse <em>Ganoderma</em> resources.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"18 1","pages":"Pages 29-44"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salvia miltiorrhiza water extract ameliorated cGAS-STING-mediated acute liver injury by blocking interaction between STING and TBK1","authors":"Chengwei Li ,&nbsp;Ran Xu ,&nbsp;Manlin Zhang ,&nbsp;Simin Chen ,&nbsp;Qing Yao ,&nbsp;Congyang Zheng ,&nbsp;Xianlin Wang ,&nbsp;Xinru Wen ,&nbsp;Xiaohe Xiao ,&nbsp;Yinghao Wang ,&nbsp;Zhaofang Bai","doi":"10.1016/j.chmed.2025.01.002","DOIUrl":"10.1016/j.chmed.2025.01.002","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the potential of <em>Salvia miltiorrhiza</em> water extract (SMWE) as a modulator of the cGAS-STING signaling pathway, which is implicated in the pathogenesis of immune and inflammatory disorders, and to elucidate its underlying mechanism of action through <em>in vitro</em> and <em>in vivo</em> experiments.</div></div><div><h3>Methods</h3><div>The cGAS-STING signaling pathway was activated in bone marrow-derived macrophages (BMDMs), Tohoku hospital pediatrics-1 (THP-1) cells, and peripheral blood mononuclear cells (PBMCs). The effect of SMWE on the expression of phosphorylated interferon regulatory factor 3 (IRF3) and phosphorylated STING after aberrant activation of the cGAS-STING pathway was detected by immunoblotting. Subsequently, real-time quantitative PCR was performed to detect changes in the mRNA levels of interferon type I (<em>IFN</em>), interferon-stimulated genes and inflammatory factors. The effect of SMWE on STING oligomerisation and the interaction between STING, Tank Binding Kinase 1 (TBK1) and IRF3 was investigated by immunoblotting. A model of acute liver injury (ALI) caused by lipopolysaccharide/<em>D</em>-galactosamine (LPS/<em>D</em>-GaIN) was used to test the effects of SMWE on inflammation mediated by the cGAS-STING signaling cascade.</div></div><div><h3>Results</h3><div>SMWE significantly inhibited the phosphorylation of STING and IRF3, thereby suppressing the activation of the cGAS-STING signaling pathway. It also stopped the cGAS-STING pathway from working by stopping the production of type I interferons and interferon-stimulated genes, like interferon-stimulated gene 15 (<em>ISG15</em>) and C-X-C motif chemokine ligand 10 (<em>CXCL10</em>). SMWE also reduced the production of pro-inflammatory cytokines, such as interleukin-6 (<em>IL-6</em>) and tumour necrosis factor-<em>α</em> (<em>TNF-α</em>). SMWE also significantly improved ALI resulting from LPS/<em>D</em>-GaIN by diminishing the hyperactivation of the cGAS-STING signalling pathway. Mechanistic analysis revealed that SMWE disrupted the interaction between STING and TBK1.</div></div><div><h3>Conclusion</h3><div>SMWE is a potent modulator of aberrant activation of the cGAS-STING pathway and is able to prevent and treat LPS/<em>D</em>-GaIN-induced ALI by inhibiting activation of the cGAS-STING pathway.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"17 4","pages":"Pages 768-778"},"PeriodicalIF":8.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145340581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rhein alleviates renal interstitial fibrosis by inhibiting Smad3 phosphorylation in TGF-β/Smad signalling pathway","authors":"Xiaoli Zheng ,&nbsp;Li Wang ,&nbsp;Yu Cheng ,&nbsp;Hao Lin ,&nbsp;Shundi Liu ,&nbsp;Xinjiang Chen ,&nbsp;Zheng Xiang","doi":"10.1016/j.chmed.2025.07.003","DOIUrl":"10.1016/j.chmed.2025.07.003","url":null,"abstract":"<div><h3>Objective</h3><div>The anthraquinone compound rhein (1,8-dihydroxy-3-carboxyanthraquinone), derived from <em>Rhei Radix</em> et <em>Rhizoma</em> (rhubarb, Dahuang in Chinese), exhibits notable anti-fibrotic effects. However, the mechanisms underlying these effects have not been fully elucidated. Suppressor of mothers against decapentaplegic 3 (Smad3) phosphorylation plays a crucial role in the canonical transforming growth factor-<em>β</em> (TGF-<em>β</em>)/Smad signalling pathway. In this study, we investigated the effect of rhein on the TGF-<em>β</em>/Smad signalling pathway in renal interstitial fibrosis (RIF).</div></div><div><h3>Methods</h3><div>A unilateral ischaemia–reperfusion injury (UIRI) rat model was employed to simulate renal injury and assess the therapeutic effect of rhein <em>in vivo</em>. <em>In vitro</em>, TGF-<em>β</em>1-stimulated NRK-52E rat renal epithelial cells and HK-2 human proximal tubular epithelial cells were used to mimic fibrotic conditions. Rhein’s interaction with Smad3 was further explored using molecular docking and bio-layer interferometry assays. Additionally, <em>Smad3</em> knockdown and overexpression studies were performed in HK-2 cells to elucidate the functional role of Smad3 in rhein-mediated anti-fibrotic activity.</div></div><div><h3>Results</h3><div>Rhein treatment significantly improved renal function and reduced fibrosis in UIRI rats, primarily by inhibiting Smad3 phosphorylation. Rhein treatment mitigated aberrant remodelling and extracellular matrix accumulation in both NRK-52E and HK-2 cells and in the UIRI rat model. The anti-fibrotic effects of rhein were attenuated by Smad3 deficiency but enhanced by Smad3 overexpression in HK-2 cells.</div></div><div><h3>Conclusion</h3><div>Rhein exerts its anti-fibrotic effects in renal interstitial fibrosis by targeting the TGF-<em>β</em>/Smad3 signaling pathway. Acting as a natural antagonist of Smad3, rhein offers promising potential for therapeutic development in renal fibrosis. These findings provide a new mechanistic insight for further clinical research and drug development.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"17 4","pages":"Pages 744-755"},"PeriodicalIF":8.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145340580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}