{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:55:18Z","timestamp":1787237718345,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,8,5]],"date-time":"2014-08-05T00:00:00Z","timestamp":1407196800000},"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":"crossref","award":["81072687"],"award-info":[{"award-number":["81072687"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"New Drug Innovation of the Shanghai Science and Technology Development Foundation","award":["10431900200"],"award-info":[{"award-number":["10431900200"]}]},{"name":"Shanghai Sixth People's Hospital Science Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2015,4]]},"abstract":"Abstract<\/jats:title>\n \n Background & Aims<\/jats:title>\n \n Luteolin has been reported to exert antifibrogenic effects in\n CC<\/jats:styled-content>\n l\n 4<\/jats:sub>\n \u2010induced hepatic fibrosis in mice. However, limited information is available on the cellular and molecular events responsible for this effect. This study focused on the action of luteolin on hepatic stellate cells (\n HSC<\/jats:styled-content>\n s) and the relevant signalling molecules and pathways as well as the antifibrotic efficacy in multiple models of fibrosis.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The\n in vitro<\/jats:italic>\n effect of luteolin on rat\n HSC<\/jats:styled-content>\n s and\n HSC<\/jats:styled-content>\n \u2010T6 cells was assessed using proliferation assays, invasion chamber, quantitative real\u2010time\n PCR<\/jats:styled-content>\n analysis and Western blotting. The\n in vivo<\/jats:italic>\n effect of luteolin on progression of fibrosis was assessed in three experimental rat models induced by\n CC<\/jats:styled-content>\n l\n 4<\/jats:sub>\n , dimethylnitrosamine (\n DMN<\/jats:styled-content>\n ) and bile duct ligation (\n BDL<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Luteolin inhibited proliferation, migration, collagen synthesis as well as expression of fibrosis\u2010related genes in the activated\n HSC<\/jats:styled-content>\n s and\n HSC<\/jats:styled-content>\n \u2010T6 cells stimulated with or without transforming growth factor\u2010\u03b21(\n TGF<\/jats:styled-content>\n \u03b21) or platelet\u2010derived growth factor (\n PDGF<\/jats:styled-content>\n ). Luteolin induced\n HSC<\/jats:styled-content>\n apoptosis associated with the increased caspase 3 activity and p53 expression, and induced G1 arrest with the decreased expression of bcl\u20102, Cyclin E and p\u2010Cdk\u20102. Moreover, luteolin significantly inhibited\n PDGF<\/jats:styled-content>\n and\n TGF<\/jats:styled-content>\n \u03b21\u2010simulated phosphorylation of\n AKT<\/jats:styled-content>\n and Smad pathway.\n In vivo<\/jats:italic>\n study showed that luteolin administration markedly alleviated hepatic fibrosis along with reduced elevations of alanine aminotransferase and aspartate aminotransferase.\n HSC<\/jats:styled-content>\n s were found to undergo apoptosis and decreased expression of p\u2010Smad2 and p\u2010\n AKT<\/jats:styled-content>\n in luteolin\u2010treated animals.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This study demonstrates that luteolin prevents the progression of liver fibrosis through multiple mechanisms and indicates that luteolin has potential for effective treatment of liver fibrosis.<\/jats:p>\n 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