Hovenia Dulcis Extract Reduces Lipid Accumulation in Oleic Acid‐Induced Steatosis of Hep G2 Cells via Activation of AMPK and PPARα/CPT‐1 Pathway and in Acute Hyperlipidemia Mouse Model

Hovenia dulcis Thunb. (HDT) was known to have anti‐fatigue, anti‐diabetes, neuroprotective, and hepatoprotective effects. In the present study, the anti‐fatty liver mechanism of HDT was elucidated in oleic acid (OA)‐treated Hep G2 cells and acute hyperlipidemia mouse model using Triton WR‐1339. Here, HDT activated p‐AMP‐activated protein kinase (p‐AMPK), proliferator activated receptor‐α, carnitine palmitoyltransferase and also inhibited the expression of lipogenesis and cholesterol synthesis proteins, such as 3‐hydroxy‐3‐methylglutaryl‐CoA reductase, sterol regulatory element binding protein‐1c, SREBP‐2, and fatty acid synthase in OA‐treated Hep G2 cells. Conversely, AMPK inhibitor compound C blocked the anti‐fatty liver effect of HDT to induce AMPK phosphorylation and decrease 3‐hydroxy‐3‐methylglutaryl‐CoA reductase and lipid accumulation by oil red O staining in OA‐treated Hep G2 cells. Additionally, HDT pretreatment protected against the increase of serum total cholesterol, triglyceride, low‐density lipoprotein cholesterol and phospholipid in an acute hyperlipidemia mouse model with enhancement of glutathione reductase, glutathione peroxidase, superoxide dismutase, and catalase activities. Taken together, HDT inhibits OA‐induced hepatic lipid accumulation via activation of AMPK and proliferator activated receptor‐α/carnitine palmitoyltransferase signaling and enhancement of antioxidant activity as a potent candidate for nonalcoholic fatty liver disease and hyperlipidemia. Copyright © 2016 John Wiley & Sons, Ltd.