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We investigated the anti\u2010fibrotic effect of DHI and its underlying mechanisms <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Rats subjected to bile duct ligation (BDL) were treated with DHI (25\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>, i.p.) for 14\u00a0days. Serum biochemical and liver tissue morphological analyses were performed. The human hepatic stellate cell line LX\u20102 served as a liver fibrosis model <jats:italic>in vitro<\/jats:italic>. Liver fibrogenic genes, yes\u2010associated protein (YAP) downstream genes and autophagy markers were examined using western blot and real\u2010time PCR analyses. Similar analyses were done in rat primary hepatic stellate cells (pHSCs). Autophagy flux was assessed by immunofluorescence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In BDL rats, DHI administration attenuated liver necrosis, bile duct proliferation and collagen accumulation and reduced the expression of genes associated with fibrogenesis, including <jats:italic>Tgfb1<\/jats:italic>, <jats:italic>Mmp\u20102<\/jats:italic>, <jats:italic>Acta2<\/jats:italic> and <jats:italic>Col1a1<\/jats:italic>. DHI (1, 5, 10\u00a0\u03bcmol\u00b7L<jats:sup>\u22121<\/jats:sup>) time\u2010 and dose\u2010dependently suppressed the protein level of COL1A1, TGF\u03b21 and \u03b1\u2010SMA in LX\u20102 cells and rat pHSCs. Furthermore, DHI blocked the nuclear translocation of YAP, which inhibited the YAP\/TEAD2 interaction and its downstream fibrogenic genes, connective tissue growth factor, SOX4 and survivin. This stimulated autophagic flux and accelerated the degradation of liver collagen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>DHI exerts anti\u2010fibrotic effects in BDL rats, LX\u20102 cells and rat pHSCs by inhibiting the YAP and TEAD2 complex and stimulating autophagy. These findings indicate that DHI may be a potential therapeutic for the treatment of liver fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13766","type":"journal-article","created":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T16:42:43Z","timestamp":1488559363000},"page":"1147-1160","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["The anti\u2010hepatic fibrosis effects of dihydrotanshinone I are mediated by disrupting the yes\u2010associated protein and transcriptional enhancer factor D2 complex and stimulating autophagy"],"prefix":"10.1111","volume":"174","author":[{"given":"Maoxu","family":"Ge","sequence":"first","affiliation":[{"name":"Key Laboratory of Biotechnology of Antibiotics Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing 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