Xuefei Yang , Yuedan Wang , Shan Liu , Haijie Ji , Jiaqi Zhang , Lin lv , Mengxiong Lu , Ping Wang , Fengyun Wang , Xudong Tang
{"title":"The modified Zuojin formula (SQQT) associates ILC2-linked JAK-2/STAT5/c-Myc cascade and gastric metaplasia regression","authors":"Xuefei Yang , Yuedan Wang , Shan Liu , Haijie Ji , Jiaqi Zhang , Lin lv , Mengxiong Lu , Ping Wang , Fengyun Wang , Xudong Tang","doi":"10.1016/j.jep.2026.121345","DOIUrl":"10.1016/j.jep.2026.121345","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The modified Zuojin formula (SQQT) has been clinically prescribed for gastric metaplasia (GM) for several decades in China. The therapeutic efficacy of SQQT and potential mechanisms have been demonstrated in our previous studies. This research will further investigate its mechanism in the immune microenvironment.</div></div><div><h3>Aim of the study</h3><div>We aimed to determine the influence of SQQT on the ILC2-mediated JAK-2/STAT5/c-Myc pathway during GM.</div></div><div><h3>Methods</h3><div>The mechanism of GM in patients was measured through single-cell RNA sequencing. The constituents of SQQT have been examined before. The role of SQQT targets JAK-2/STAT5/c-Myc pathway was verified by network pharmacology and molecular docking. The model of GM was induced by tamoxifen (5 mg/20 g), CD90.2 protein (200 μg) or SQQT (1.69, 3.38, 6.76 g/kg) was given to treat GM mice. The SQQT mechanism was confirmed by both <em>in vitro</em> and <em>in vivo</em> studies. Histological analysis, serum cytokines, and protein levels were assessed.</div></div><div><h3>Results</h3><div>Single-cell RNA sequencing analysis indicated that ILC2 increased in the GM patients, the goblet cells in GM were probably transferred from endocrine cells. Compounds in SQQT are related to cell proliferation and can bind to the JAK-2/STAT5/c-Myc pathway proteins. The main components of SQQT, can spontaneously bind to the JAK-2 protein in 9 sites. Tamoxifen caused body weight decrease, spleen weight increase, stomach injury, ILC2 increase, and cytokines increase in the GM group. After examining the cytokines, IL-5 was the only one significantly increased in the GM group. CD90.2 and SQQT can alleviate histological changes of the stomach corpus, inflammation cytokines, and other GM-related indicators. Moreover, cell proliferation and JAK-2 pathway markers were depressed in GM mice. Besides, SQQT protects GES-1 cells from IL-5 injury related to upregulating JAK-2/STAT5/c-Myc proteins in 24h, 48h and 72h.</div></div><div><h3>Conclusion</h3><div>The mechanism of SQQT protected the stomach from metaplasia associated to ILC2 activation and the subsequent cell proliferation through IL-5/JAK-2/STAT5/c-Myc pathway.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121345"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiayi Lin , Yu Sun , Yukun Pan , Huimin Liu , Yue Gao , Shuyi Lv , Yangyang Li , Lili Song , Yubo Li
{"title":"Integrating metabolomics, network pharmacology and molecular dynamics simulations reveals that Xiehuang San targets CLCF1-STAT3 to restore insulin signaling in T2DM","authors":"Jiayi Lin , Yu Sun , Yukun Pan , Huimin Liu , Yue Gao , Shuyi Lv , Yangyang Li , Lili Song , Yubo Li","doi":"10.1016/j.jep.2026.121284","DOIUrl":"10.1016/j.jep.2026.121284","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Xiehuang San</em> (XHS) is a classical Chinese herbal formula with analgesic, anti-inflammatory, gastrointestinal-regulating and hypoglycemic effects, but its specific regulatory mechanisms remain incompletely understood.</div></div><div><h3>Aim of the study</h3><div>To evaluate the effects of XHS on T2DM, with a particular focus on its metabolic and molecular mechanisms.</div></div><div><h3>Materials and methods</h3><div>C57BL/6J mice were induced with T2DM using a high-fat diet combined with streptozotocin. T2DM mice were treated with XHS for 4 weeks to assess blood glucose control and metabolism. Serum metabolomics were analyzed by UPLC-Q-TOF/MS. Network pharmacology integrated drug-metabolite-disease associations. Molecular docking and dynamics simulations assessed the binding of active compounds to targets. RT-qPCR and Western blot were used to determine gene and protein expression levels. An in vitro model was established to validate the effects of XHS on T2DM.</div></div><div><h3>Results</h3><div>XHS significantly improved T2DM pathology. Compared to the diabetic Mod group, XHS reduced fasting blood glucose levels, enhances glucose tolerance and improves insulin resistance and sensitivity. 24 dysregulated metabolites were corrected after treatment. Network pharmacology predicted that the key target of XHS in T2DM treatment is the CLCF1-STAT3 pathway. Licochalcone B, Wogonin and Apigenin are predicted to exhibit strong binding affinity for this pathway. Both in vitro and in vivo models, XHS effectively inhibits the activation of the CLCF1-STAT3 signalling pathway and protects insulin signalling.</div></div><div><h3>Conclusion</h3><div>This study combines metabolomics and network pharmacology to reveal that XHS exerts anti-diabetic effects by remodeling glycerophospholipid metabolism and inhibiting CLCF1-STAT3 signaling. These findings support the application of XHS in the treatment of T2DM.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121284"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hairong Zhao , Xue Wang , Kunkun Li , Jie Zhao , Jiapeng Wang , Yihao Che , Jingyu Zhang , Huai Xiao , Dexiao Wang , Qian Wang , Lijuan Li , Yu Zhao , Chenggui Zhang
{"title":"TLR4-antagonizing bioactive components from Blaps rynchopetera polysaccharide-glycoprotein complex: Biolayer interferometry-mass spectrometry identification and NF-κB-mediated anti-inflammation","authors":"Hairong Zhao , Xue Wang , Kunkun Li , Jie Zhao , Jiapeng Wang , Yihao Che , Jingyu Zhang , Huai Xiao , Dexiao Wang , Qian Wang , Lijuan Li , Yu Zhao , Chenggui Zhang","doi":"10.1016/j.jep.2026.121328","DOIUrl":"10.1016/j.jep.2026.121328","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Blaps rynchopetera</em> Fairmaire (Coleoptera: Tenebrionidae), a traditional medicinal insect employed by the Yi and Dai ethnic communities in Yunnan, China, has long been utilized for treating inflammatory conditions such as fever, mumps, and gastritis. Its potential application in managing symptoms akin to neuroinflammatory disorders provides an ethnopharmacological basis for this investigation. However, the bioactive components underpinning its anti-inflammatory properties, particularly its polysaccharides, remain poorly investigated.</div></div><div><h3>Aim of the study</h3><div>This study aimed to isolate the polysaccharide fraction from <em>Blaps rynchopetera</em> Fairmaire (BRPs), characterize its structure, and evaluate its anti-neuroinflammatory activity in cellular and animal models, with a focus on the TLR4/NF-κB pathway.</div></div><div><h3>Materials and methods</h3><div>BRPs were extracted from whole insects using hot water and purified by ethanol precipitation. Structural characterization was performed via HPAEC-PAD, GPC-RI-MALS, SEM, and FT-IR. The anti-neuroinflammatory effects and TLR4/NF-κB or MAPK signaling pathway were investigated in LPS-stimulated primary microglia and a TLR4-overexpressing (TLR4-OE) HEK293 cell model for target validation. TLR4-binding components within BRPs were identified using the affinity-based technique of biolayer interferometry-mass spectrometry (BLI-MS). The in <em>vivo</em> efficacy of the TLR4-affinity enriched fraction (BRPs-AEF) was further assessed in a mouse model of transient middle cerebral artery occlusion/reperfusion (MCAO/R).</div></div><div><h3>Results</h3><div>BRPs was a polysaccharide-glycoprotein complex containing 77.88% carbohydrates (dominant glucose and galactose) and 8.51% protein, with a porous microstructure and α-glycosidic linkages. In primary microglia, BRPs dose-dependently suppressed LPS-induced production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and inhibited the activation of TLR4/NF-κB activation and MAPK signaling pathways. Using a BLI-MS strategy, 10 unique TLR4-binding proteins (e.g., WH2 domain proteins and calreticulin) and 21 interaction peptides were identified within BRPs. This TLR4-mediated mechanism was functionally validated in TLR4-OE cells. In MCAO/R mice, BRPs-AEF significantly reduced cerebral infarction, improved neurological deficits, attenuated neuroinflammation, and preserved neuronal integrity in a murine stroke model.</div></div><div><h3>Conclusions</h3><div>These results demonstrate that BRPs from <em>B. rynchopetera</em> alleviate neuroinflammation through multi-target mechanisms, with the TLR4/NF-κB pathway being a major and directly validated target. This work provides pharmacological insights supporting the traditional use of this insect and illustrates a targeted approach for identifying bioactive constituents from complex mixtures.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121328"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shaoliang Li , Pengning Wu , Yue Wang, Dehao Wang, Haihua Qian, Dan Zhang
{"title":"Tianwangbuxiandan decoction alleviates constipation and associated emotional disorders via regulating the brain-gut axis: Involving MAPK/ERK/JNK signaling pathways","authors":"Shaoliang Li , Pengning Wu , Yue Wang, Dehao Wang, Haihua Qian, Dan Zhang","doi":"10.1016/j.jep.2026.121308","DOIUrl":"10.1016/j.jep.2026.121308","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Tianwang Buxin Dan (TWBXD) is a classical Chinese formula traditionally prescribed to “nourish Yin, calm the mind and relieve bowel stagnation” in disorders characterized by heart-kidney disharmony, insomnia, anxiety, and constipation. However, the mechanistic basis associating its gut-regulating and emotion-modulating effects along the gut-brain axis remains unclear.</div></div><div><h3>Aim of the study</h3><div>To investigate whether TWBXD ameliorates functional constipation comorbid with emotional disturbances by modulating mitogen-activated protein kinase/Extracellular Signal-Regulated Kinase/c-Jun N-terminal Kinase (MAPK/ERK/JNK) signaling, hypothalamic-pituitary-adrenal (HPA)-axis activity, and autophagy-related mitochondrial integrity in the colon and hippocampus.</div></div><div><h3>Materials and methods</h3><div>A diphenoxylate-induced rat model of functional constipation with anxiety/depression-like behavior was treated with low, medium, or high doses of TWBXD. Intestinal transit, fecal parameters, and distal colonic transit were also assessed. Emotional behaviors were evaluated using open-field and elevated plus-maze tests. Colonic and hippocampal histopathology and ultrastructure were examined using hematoxylin and eosin staining, Nissl staining, and transmission electron microscopy. Serum corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) levels were measured using enzyme-linked immunosorbent assay. MAPK/ERK/JNK-related proteins and brain-derived neurotrophic factor (BDNF) were analyzed by Western blotting. The major chemical constituents of TWBXD were characterized using ultra-high-performance liquid chromatography-tandem mass spectrometry(UHPLC–MS/MS).</div></div><div><h3>Results</h3><div>TWBXD dose-dependently improved intestinal transit, fecal moisture, and body weight gain, and alleviated anxiety-/depression-like behaviors. TWBXD preserved colonic mucosal architecture and hippocampal neuronal integrity, mitigated mitochondrial swelling and excessive autophagic vacuole formation, downregulated colonic phosphorylated ERK (p-ERK), phosphorylated JNK, and phosphorylated p38, restored hippocampal BDNF expression while normalizing p-ERK levels, and reduced serum CRF, ACTH, and CORT levels.</div></div><div><h3>Conclusion</h3><div>TWBXD exerts multi-target therapeutic effects on functional constipation with emotional disturbances by suppressing MAPK/ERK/JNK overactivation, normalizing HPA-axis hyperactivity, and protecting mitochondrial structure and autophagy along the gut-brain axis, providing mechanistic support for its traditional use in gut-brain-related disorders.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121308"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing Fang , Mengya Wu , Jiao Yu , Junwei Zhao , Yuzhen Liu , Yu Cui , Yunna Chen , Shuang Han , Weidong Chen , Daiyin Peng , Liang Yao
{"title":"Mechanistic study of Dendrobium huoshanense polysaccharides improving ulcerative colitis by promoting Lachnoclostridium edouardi metabolism of short-chain fatty acids","authors":"Jing Fang , Mengya Wu , Jiao Yu , Junwei Zhao , Yuzhen Liu , Yu Cui , Yunna Chen , Shuang Han , Weidong Chen , Daiyin Peng , Liang Yao","doi":"10.1016/j.jep.2026.121321","DOIUrl":"10.1016/j.jep.2026.121321","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Dendrobium huoshanense</em> C. Z. Tang et S. J. Cheng (DH) is a traditional medicinal herb with a long history of medicinal use in the treatment of gastrointestinal disorders. It has therapeutic effects on chronic atrophic gastritis, superficial gastritis, and duodenal ulcer, while also promoting gastric juice secretion and gastrointestinal motility. <em>Dendrobium huoshanense</em> polysaccharides (DHP) is an active ingredient extracted from it and has a variety of pharmacological activities, but its mechanism of action on ulcerative colon is worthy of further study.</div></div><div><h3>Aims of this study</h3><div>This study aimed to investigate whether DHP could alleviate ulcerative colitis (UC) by activating PPARγ and to elucidate the mechanism behind it in relation to the short-chain fatty acid (SCFAs) content metabolized by gut microbiota.</div></div><div><h3>Methods</h3><div>This study initially validated the preventive effects of DHP on UC using an animal model. The key gut microbiota affected by DHP were identified by 16S rRNA. The potential mechanism of DHP treatment for UC was demonstrated by LC-MS/MS to detect the levels of SCFAs, and by immunofluorescence and Western blotting to detect the expression of PPARγ/NF-κB pathway proteins. This potential mechanism was further confirmed by a fecal microbiota transplantation (FMT) experiment. Finally, through the in-depth study of the different intestinal flora regulated by DHP, <em>Lachnoclostridium edouardi</em> was found to be related to the production of SCFAs, and the effect of metabolites produced by DHP fermented by this strain on the inflammation of colonic epithelial cells was investigated through <em>in vitro</em> fermentation experiments, to clarify the intestinal strains that are specifically regulated by DHP.</div></div><div><h3>Results</h3><div>The results showed that DHP significantly alleviated UC symptoms and reduced colonic tissue damage in mice, while restoring the balance of the intestinal microbiota. In addition, DHP substantially increased the concentration of SCFAs in the colon. These shifts triggered PPARγ activation and inhibited NF-κB phosphorylation in the colon tissue, effectively reducing inflammation and improving UC outcomes. The FMT assay further validated that the preventive benefits of DHP were mediated through the intestinal flora. Meanwhile, the DHP-specifically regulated strain <em>Lachnoclostridium edouardi</em> showed markedly higher short-chain fatty acid content in metabolites produced by fermentation with DHP <em>in vitro</em> and effectively suppressed inflammation in colonic epithelial cells.</div></div><div><h3>Conclusions</h3><div>This study suggests that DHP can play a role in the treatment of UC by modulating short-chain fatty acid metabolism in the gut microbiota and activating the PPARγ/NF-κB pathway. Moreover, DHP was able to promote the content of SCFAs produced by the metabolism of the <em>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121321"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Long He , Zhuotai Zhong , Fengbin Liu , Shuting Wen
{"title":"Berberine alleviates DSS-induced colitis by modulating macrophage phenotype via PPAR-γ/ mTOR/HIF-1α signaling pathway","authors":"Long He , Zhuotai Zhong , Fengbin Liu , Shuting Wen","doi":"10.1016/j.jep.2026.121350","DOIUrl":"10.1016/j.jep.2026.121350","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Berberine (BBR), an isoquinoline alkaloid derived from Chinese herbal drugs of <em>Coptis chinensis Franch.</em> and <em>Phellodendron chinense C.K. Schneid.</em>, 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.</div></div><div><h3>Aim of the study</h3><div>The present study aimed to explore the modulation effect of BBR on M2 macrophage polarization and elucidate the underlying mechanism.</div></div><div><h3>Materials and methods</h3><div>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.</div></div><div><h3>Results</h3><div>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-γ) 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-1α signaling pathway. Nevertheless, the modulation efficiency of BBR on M2 macrophage polarization and mTOR/HIF-1α pathway were abrogated upon the application of GW9662 both <em>in vivo</em> and <em>in vitro</em>.</div></div><div><h3>Conclusion</h3><div>BBR significantly contribute to drive M2 macrophage polarization via the PPAR-γ/mTOR/HIF-1α axis, and further confirmed the considerable approach of BBR for the clinical treatment of UC.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121350"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146180478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinxin Wang , Panpan Wang , Zhen Wang , Junbai Ma , Shiyi Song , Lingyang Kong , Xinyi Zhang , Wei Ma , Xiubo Liu
{"title":"Senecio scandens Buch. - Ham.: A comprehensive review of botany, phytochemistry, biological activity, toxicity, quality control, application, and practical domain","authors":"Xinxin Wang , Panpan Wang , Zhen Wang , Junbai Ma , Shiyi Song , Lingyang Kong , Xinyi Zhang , Wei Ma , Xiubo Liu","doi":"10.1016/j.jep.2026.121303","DOIUrl":"10.1016/j.jep.2026.121303","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Senecio scandens</em> Buch.-Ham., a medicinal herb from the Asteraceae family, contains flavonoids, terpenoids, and alkaloids as its primary bioactive compounds. It is commonly used in the treatment of ocular diseases and dermatological conditions. However, with its expanding applications across various fields, growing attention has been directed toward the potential safety concerns associated with its use.</div></div><div><h3>Aim of the review</h3><div>This article systematically reviews existing literature on <em>S. scandens</em>, examining its botany, phytochemistry, biological activity, toxicity, applications, and development utilization, to provide a theoretical basis for in-depth exploration of its pharmacological mechanisms and resource development.</div></div><div><h3>Materials and methods</h3><div>This study conducted a systematic review of literature on <em>S. scandens</em> published from 1972 to 2025, based on databases including PubMed and Web of Science. Plants names are provided in accordance with \"The Plant List\" (<span><span>https://wfoplantlist.org/</span><svg><path></path></svg></span>).</div></div><div><h3>Result</h3><div>Over 200 chemical constituents, primarily flavonoids, terpenoids, and alkaloids, have been isolated and identified from <em>S. scandens</em>, endowing it with diverse biological activities such as anti-inflammatory, antibacterial, antioxidant, and anti-tumor effects. To address potential hepatorenal toxicity from its pyrrolizidine alkaloids, relevant safety guidelines have been gradually established alongside various clinical dosage forms. It is also widely used in fields including medicine, animal husbandry, agriculture, and cosmetics.</div></div><div><h3>Conclusion</h3><div>By systematically reviewing the botany, phytochemistry, biological activity, toxicity, application, and development and utilization of <em>S. scandens</em>, this paper identifies key utilization obstacles, proposes future research directions, and provides a theoretical framework for its further development.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121303"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qingyu Liu , Ran Nie , Bo Fan , Wenhui Wu , Jianbin Ge , Lizhong Zhu , Juan Ye , Xiaoyan Sun , Peng Cao , Chunping Hu
{"title":"Soufeng Sanjie formula and its active ingredient formononetin alleviate osteoarthritis via PPARG-AKT-ERK1/2 promoted cartilage extracellular matrix anabolism","authors":"Qingyu Liu , Ran Nie , Bo Fan , Wenhui Wu , Jianbin Ge , Lizhong Zhu , Juan Ye , Xiaoyan Sun , Peng Cao , Chunping Hu","doi":"10.1016/j.jep.2026.121320","DOIUrl":"10.1016/j.jep.2026.121320","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>In Traditional Chinese Medicine (TCM), osteoarthritis (OA) is referred to as \"Gu Bi\" (bone bi syndrome), which is characterized by chronic joint disease, cartilage damage, and deterioration of the extracellular matrix (ECM). The Soufeng Sanjie formula (SF), comprising Scolopendra, Scorpions, Astragali radix, and Black soybean seed coats, is traditionally employed in the treatment of \"bone bi\" disease and has been utilized in managing OA. Nonetheless, the effects of SF on ECM deterioration and cartilage destruction in OA, as well as its principal bioactive components, remain inadequately understood.</div></div><div><h3>Aim of the study</h3><div>This study aims to investigate SF's therapeutic potential against ECM deterioration and cartilage destruction in OA, explore its underlying mechanisms, and identify its primary bioactive components.</div></div><div><h3>Materials and methods</h3><div>A mouse model of knee OA was established via anterior cruciate ligament transection (ACLT). The analgesic effect of SF on arthritis pain was assessed by measuring cold pain thresholds. Cartilage damage was evaluated using Safranin O-fast green staining and the Osteoarthritis Research Society International (OARSI) scores. Immunohistochemical staining was employed to evaluate the influence of SF on cartilage metabolism, whereas cellular experiments were conducted to examine SF's capacity to enhance chondrocyte anabolism. The expression levels of SRY-box transcription factor 9 (SOX9), collagen type II alpha 1 (COL2A1), and aggrecan (ACAN) were analyzed using Western blotting and quantitative reverse transcription polymerase chain reaction (qPCR). Alcian blue staining was utilized to identify the bioactive components of SF that affect chondrocyte anabolism. This was further supported by preliminary analyses using network pharmacology and molecular docking techniques.</div></div><div><h3>Results</h3><div>SF has been shown to effectively reduce cartilage degradation and enhance the expression of SOX9, ACAN, and COL2A1 in the cartilage of OA mice. Furthermore, SF promotes ECM anabolism in chondrocyte cells, as evidenced by the increased production of chondrocyte acidic polysaccharides and elevated mRNA levels of SOX9, ACAN, and COL2A1. Additionally, Formononetin (FMN) was screened as a key compound of SF with the ability to enhance cartilage ECM anabolism. FMN significantly upregulated the expression of SOX9, ACAN, and COL2A1, alleviated pain symptoms, and reduced cartilage damage in OA mice. Network pharmacology and molecular docking analyses indicated that FMN targets the peroxisome proliferator-activated receptor gamma (PPARG), thereby activating the AKT and ERK1/2 signaling pathways in chondrocyte cells. And the chondroprotective effect of FMN is attenuated by PPARG inhibitors. Additionally, both CETSA and SPR analyses demonstrated direct binding between FMN and PPARG.</div></div><div><h3>Conclusion</h3><div>Our stud","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121320"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kaiyang Liu , Yue Ren , Yanxia Liu , Yanling Zhang
{"title":"Scutellaria baicalensis Georgi and its active component scutellarin alleviate asthma in rats by modulating the gut microbiota-bile acid axis","authors":"Kaiyang Liu , Yue Ren , Yanxia Liu , Yanling Zhang","doi":"10.1016/j.jep.2026.121304","DOIUrl":"10.1016/j.jep.2026.121304","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The Complete Works of Jingyue recorded that <em>Scutellaria baicalensis Georgi</em> (SBG, Huangqin) cleared heat and relieved asthma from Ming Dynasty. SBG possesses a long history of medicinal use and has demonstrated efficacy in treating respiratory diseases. Building on these traditional applications, recent studies have reported its anti-asthmatic.</div><div>Yet, it's unclear whether SBG improves asthma via gut microbiota modulation or which component is key.</div></div><div><h3>Aim of the study</h3><div>This study established an asthma model and employed 16S rRNA sequencing and metabolomics approaches to investigate the active components and underlying mechanisms of SBG in the treatment of bronchial asthma through gut-lung axis.</div></div><div><h3>Materials and methods</h3><div>An innovative combined approach was employed, utilizing Ultra-high-performance liquid chromatography/Q/Q/Q Exactive HFX mass spectrometry (UHPLC-QE-MS), 16S rRNA sequencing, metabolomics, and molecular biology to analyze the effective components of SBG, the changes in gut microbiota, and the endogenous metabolic mechanisms involved in the improvement of bronchial asthma.</div></div><div><h3>Results</h3><div>SBG and scutellarin reduced airway (Rrs) and elastic resistance (Ers) (<em>P</em> < 0.05) in asthmatic rats, alleviated lung inflammation, and decreased serum IL-2 levels (<em>P</em> < 0.05). They also mitigated mucosal damage and inflammatory infiltration, restoring colonic homeostasis and increasing beneficial gut bacteria. Multi-omics analysis suggested SBG acts through the bile acid pathway, modulating bile salt transformation, biosynthesis, and transport. Fecal microbiota transplantation (FMT) from treated rats to germ-free rats partially replicated the anti-asthma effects, indicating SBG and scutellarin inhibit asthma by up-regulating <em>Bifidobacterium animalis</em>. This bacterium produced cholic acid, especially when treated with SBG or scutellarin, showing anti-inflammatory and anti-allergic properties.</div></div><div><h3>Conclusion</h3><div>SBG and its core blood-absorbed component scutellarin augment <em>Bifidobacterium animalis</em>, stimulate cholic acid production, modulate the bile acid pathway, and alleviate pulmonary inflammation and allergic reactions, exerting anti-asthma effects.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121304"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tingting Chen , Xinglishang He , Xuannan Chen , Wenyue Zhang , Bo Li , Chu Chu , Guiyuan Lv , Suhong Chen
{"title":"Advances in the pharmacology and mechanism of anti-skin aging in Tonifying Traditional Chinese Medicines","authors":"Tingting Chen , Xinglishang He , Xuannan Chen , Wenyue Zhang , Bo Li , Chu Chu , Guiyuan Lv , Suhong Chen","doi":"10.1016/j.jep.2026.121233","DOIUrl":"10.1016/j.jep.2026.121233","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>According to the Traditional Chinese Medicine (TCM) tenet that “internal imbalances manifest externally,” skin aging reflects deficiencies in qi, blood, and organ systems—particularly the liver and kidneys. Tonifying Traditional Chinese Medicines (TTCM) address these root causes, nourishing the skin and delaying aging through internal regulation, as documented in classical texts including the <em>Shennong Ben Cao Jing</em> and the <em>Compendium of Materia Medica</em>.</div></div><div><h3>Aim of the study</h3><div>This article systematically reviews the anti-skin-aging mechanisms of TTCM by integrating traditional applications with modern pharmacological evidence. It explores their multi-component, multi-target, and multi-pathway actions, evaluates current experimental models, and investigates the emerging role of artificial intelligence (AI) in advancing TTCM research.</div></div><div><h3>Materials and methods</h3><div>We systematically searched PubMed, China National Knowledge Infrastructure (CNKI), Web of Science and Scopus for articles published from January 2015 to August 2025 with keywords such as “skin aging”, “anti-aging” and the Latin names of TTCM (e.g. <em>Panax ginseng</em>, <em>Astragalus membranaceus</em>). Cellular, animal and clinical studies were analyzed for active constituents, molecular targets, ageing biomarkers and related signalling pathways.</div></div><div><h3>Results</h3><div>TTCM demonstrates anti-skin-aging effects through systemic regulation of organ function and qi–blood–yin–yang balance. At the molecular level, TTCM attenuates senescence through antioxidative, anti-inflammatory, extracellular matrix (ECM) stabilizing mechanisms, mediated by modulation of multiple pathways, such as Mitogen-Activated Protein Kinase (MAPK), Tumor Protein p53 (p53) and Nuclear factor erythroid 2–related factor 2 (Nrf2), exemplifying a “holistic regulation–targeted intervention” therapeutic paradigm.</div></div><div><h3>Conclusions</h3><div>TTCM exerts anti-skin-aging effects through multi-component, multi-target and multi-pathway synergism. We strongly recommend the further integration of TTCM with modern medicine and in-depth mechanistic studies to promote translational applications.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121233"},"PeriodicalIF":5.4,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146064159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}