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Liver fibrosis is a consequence of wound-healing responses to chronic liver insult and may progress to liver cirrhosis if not controlled. This study investigated the protection against liver fibrosis by isorhamnetin. <jats:italic>Methods<\/jats:italic>. Mouse models of hepatic fibrosis were established by intraperitoneal injection of carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) or bile duct ligation (BDL). Isorhamnetin 10 or 30\u2009mg\/kg was administered by gavage 5 days per week for 8 weeks in the CCl<jats:sub>4<\/jats:sub> model and for 2 weeks in the BDL model. Protein and mRNA expressions were assayed by western blotting, immunohistochemistry, and quantitative real-time polymerase chain reaction. <jats:italic>Results<\/jats:italic>. Isorhamnetin significantly inhibited liver fibrosis in both models, inhibiting hepatic stellate cell (HSC) activation, extracellular matrix (ECM) deposition, and autophagy. The effects were associated with downregulation of transforming growth factor <jats:italic>\u03b2<\/jats:italic>1 (TGF-<jats:italic>\u03b2<\/jats:italic>1) mediation of Smad3 and p38 mitogen-activated protein kinase (MAPK) signaling pathways. <jats:italic>Conclusion<\/jats:italic>. Isorhamnetin protected against liver fibrosis by reducing ECM formation and autophagy via inhibition of TGF-<jats:italic>\u03b2<\/jats:italic>1-mediated Smad3 and p38 MAPK signaling pathways.<\/jats:p>","DOI":"10.1155\/2019\/6175091","type":"journal-article","created":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T19:30:56Z","timestamp":1564601456000},"page":"1-14","source":"Crossref","is-referenced-by-count":109,"title":["Isorhamnetin Inhibits Liver Fibrosis by Reducing Autophagy and Inhibiting Extracellular Matrix Formation via the TGF-<i>\u03b2<\/i>1\/Smad3 and TGF-<i>\u03b2<\/i>1\/p38 MAPK Pathways"],"prefix":"10.1155","volume":"2019","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2408-2181","authenticated-orcid":true,"given":"Ning","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Shanghai Tenth People\u2019s Hospital, Tongji University, School of Medicine, Shanghai 200072, China"},{"name":"Shanghai Tenth Hospital, School of 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