{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:33:52Z","timestamp":1791588832637,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973555"],"award-info":[{"award-number":["81973555"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007847","name":"Natural Science Foundation of Jilin Province","doi-asserted-by":"publisher","award":["YDZJ202501ZYTS270"],"award-info":[{"award-number":["YDZJ202501ZYTS270"]}],"id":[{"id":"10.13039\/100007847","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Vincamine has extensive biological and pharmaceutical activity. We examined the hepatoprotective effects and mechanisms by which vincamine suppresses hepatic fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Hepatic stellate cells (HSCs), TGF\u2010<jats:italic>\u03b2<\/jats:italic> stimulated, were cultured with either vincamine, farnesoid X receptor (NR1H4; FXR) agonist or antagonist. Further, C57BL\/6 mice were given thioacetamide (TAA) to induce hepatic fibrosis and subsequently treated with vincamine or curcumin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Vincamine regulated the deposition of extracellular matrix (ECM), inflammatory factors and S100A4, and up\u2010regulated FXR and TGR5 (GPBA receptor) in activated HSCs, by activating FXR. FXR deficiency blocked vincamine effect on FXR, TGR5, <jats:italic>\u03b1<\/jats:italic>\u2010smooth muscle actin (<jats:italic>\u03b1<\/jats:italic>\u2010SMA) and IL1R1 in activated LX\u20102 cells. Vincamine corrected ECM imbalance, inflammatory secretion and FXR\/TGR5 down\u2010regulation in activated LX\u20102 cells with stimulating medium from LPS\u2010primed THP\u20101 cells. S100A4 deficiency increased FXR and TGR5, and decreased IL\u20101\u03b2 expression in activated THP\u20101. Further, S100A4 deficiency in activated macrophages could elevate FXR and TGR5 expression in activated LX\u20102, strengthening the impact of vincamine on <jats:italic>\u03b1<\/jats:italic>\u2010SMA and IL\u20101\u03b2 expression. Further, vincamine reduced serum ALT\/AST levels, liver and intestinal histopathological changes, and caused ECM accumulation and protected the intestinal barrier in thioacetamide\u2010induced hepatic fibrosis mice. Vincamine decreased inflammatory factors e.g. caspase 1 and IL\u20101\u03b2, and inhibited the S100A4\u2010mediated FXR\u2010TGR5 pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Vincamine significantly reverses hepatic fibrosis via inhibiting S100A4 involved in the crosstalk between macrophages and HSCs, and by activating the FXR\u2010TGR5 pathway. Targeting the S100A4\u2010mediated FXR dependence on modulating the liver environment may be the key target of vincamine in inhibiting hepatic fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.17471","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T04:54:51Z","timestamp":1739422491000},"page":"2447-2465","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Vincamine ameliorates hepatic fibrosis via inhibiting S100A4\u2010mediated farnesoid X receptor activation: based on liver microenvironment and enterohepatic circulation dependence"],"prefix":"10.1111","volume":"182","author":[{"given":"Yu\u2010Chen","family":"Jiang","sequence":"first","affiliation":[{"name":"Key Laboratory for Traditional Chinese Korean Medicine Research (State Ethnic Affairs); College of Pharmacy Yanbian University  Yanji 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