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This study sought to evaluate the insulin-sensitizing effect of paeoniflorin (PF) on high-fat diet-induced NAFLD and possible molecular mechanisms. Male Sprague Dawley rats were fed a high-fat diet (HFD) for 10 weeks to establish the NAFLD model, and PF (20\u2009mg\/kg\/d) was gavaged to the NAFLD rats for another four weeks. Our results demonstrated that HFD resulted in hepatocellular ballooning, micro-\/macrovesicular steatosis, and oxidative stress in the liver, accompanied by increased serum total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels and homeostasis model of insulin resistance (HOMA-IR) index. PF treatment improved the biochemical and histopathological changes in NAFLD rats. Moreover, we also found that PF could inhibit lipid ectopic deposition via regulating lipid metabolism (inhibiting lipid synthesis of cholesterol and <jats:italic>de novo<\/jats:italic> pathway), and exert insulin sensitizing effect by regulating the insulin signaling pathway IRS\/Akt\/GSK3\u03b2 and anti-oxidation. The study findings suggest that PF has therapeutic potential against NAFLD and that it acts through multiple signaling pathways.<\/jats:p>","DOI":"10.1038\/srep44819","type":"journal-article","created":{"date-parts":[[2017,3,16]],"date-time":"2017-03-16T11:17:03Z","timestamp":1489663023000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Beneficial effects of paeoniflorin on non-alcoholic fatty liver disease induced by high-fat diet in rats"],"prefix":"10.1038","volume":"7","author":[{"given":"Zhihong","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongying","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieru","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzao","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,16]]},"reference":[{"key":"BFsrep44819_CR1","doi-asserted-by":"publisher","first-page":"5169","DOI":"10.2174\/13816128113199990336","volume":"19","author":"N Bhala","year":"2013","unstructured":"Bhala, N., Jouness, R. 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