Decursin and decursinol angelate-rich Angelica gigas Nakai extract suppresses de novo lipogenesis and alleviates nonalcoholic fatty liver disease and dyslipidemia in mice fed a high fat diet

•Decursin and decursinol angelate are main constituents of Angelica gigas Nakai extract.•Angelica gigas Nakai extract supplementation prevents HFD-induced NAFLD development.•Angelica gigas Nakai extract activates Sirt1-AMPK pathway. Metabolically beneficial effects of decursin and decursinol angelate have been reported. However, it is unclear whether Angelica gigas Nakai extract (AGNE), which is rich in decursin and decursinol angelate, can alleviate high-fat diet (HFD)-mediated non-alcoholic fatty liver disease and dyslipidemia. In this study, c57BL6/J mice were fed a HFD, or HFD with various doses of AGNE for 16weeks. Supplementation with AGNE attenuated glucose and insulin intolerance, hepatic steatosis and inflammation, and hypertriglyceridemia induced by the HFD. AGNE significantly suppressed hepatic de novo lipogenesis through activation of adenosine monophosphate-activated protein kinase (AMPK). HepG2 cells treated with free fatty acid mixture (oleate:palmitate=2:1) displayed increases of de novo lipogenesis and consequent lipid droplet formation. Addition of decursin or decursinol angelate increased Sirt1 expression, which suppressed lipid accumulation in HepG2 cells. These results indicate that the metabolic effects of AGNE may be related to the induction of Sirt1 and consequent activation of AMPK.