{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:55:44Z","timestamp":1786978544806,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"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":["82100647"],"award-info":[{"award-number":["82100647"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015401","name":"Key Research and Development Projects of Shaanxi Province","doi-asserted-by":"publisher","award":["2021ZDLSF02\u201006"],"award-info":[{"award-number":["2021ZDLSF02\u201006"]}],"id":[{"id":"10.13039\/501100015401","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Liver fibrosis, a pivotal pathological feature in the progression of chronic liver injury, currently lacks effective therapies. Sinomenine (SIN), a bioactive alkaloid derived from traditional Chinese medicine, demonstrates diverse pharmacological properties. However, its therapeutic potential and mechanisms in liver fibrosis remain inadequately characterized. This study investigates the anti\u2010fibrotic effects of SIN and its underlying molecular mechanisms. The anti\u2010fibrotic efficacy of SIN was evaluated in two murine models of liver fibrosis induced by carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    ) or bile duct ligation (BDL), along with transforming growth factor\u2010beta 1 (TGF\u2010\u03b21)\u2010stimulated rat hepatic stellate cells (HSC\u2010T6). Serum biochemical markers, histopathological analyses (Hematoxylin\u2013Eosin, Sirius red, and Masson's trichrome staining), immunofluorescence, and immunohistochemistry were employed to assess hepatic injury and collagen deposition. Western blotting elucidated molecular mechanisms. SIN administration significantly attenuated hepatic injury in CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2010 or BDL\u2010induced mice, as evidenced by reduced transaminase levels and improved histopathological features. In both in\u00a0vivo and in\u00a0vitro models, SIN suppressed fibrogenesis by decreasing collagen deposition and downregulating expression of \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA), matrix metalloproteinase 2 (MMP2), and collagen I. Mechanistically, SIN inhibited the TGF\u2010\u03b2\/SMAD pathway through reduced phosphorylation of SMAD2\/3 and attenuated c\u2010JUN signaling via diminished phosphorylated c\u2010JUN levels. Pretreatment with TP0427736 (a SMAD2\/3 inhibitor) or SP600125 (a c\u2010JUN inhibitor) synergistically enhanced SIN\u2010mediated \u03b1\u2010SMA suppression in HSC\u2010T6 cells. SIN ameliorates liver fibrosis through inhibition of TGF\u2010\u03b2\/SMAD and c\u2010JUN signaling pathways. These findings position SIN as a promising therapeutic candidate for liver fibrotic disorders.\n                  <\/jats:p>","DOI":"10.1002\/ptr.8502","type":"journal-article","created":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T23:44:49Z","timestamp":1748821489000},"page":"3182-3196","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sinomenine Ameliorates Liver Fibrosis by Blocking\n                    <scp>TGF<\/scp>\n                    \u2010\u03b2\/\n                    <scp>SMAD<\/scp>\n                    and c\u2010\n                    <scp>JUN<\/scp>\n                    Signaling"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2222-4908","authenticated-orcid":false,"given":"Yichao","family":"Du","sequence":"first","affiliation":[{"name":"Department of Gastroenterology The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an People's Republic of 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