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

Phytother Res. 2017 Jan;31(1):132-139. doi: 10.1002/ptr.5741. Epub 2016 Oct 20.


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.

Keywords: AMPK; CPT-1; Hovenia dulcis; PPARα; Triton WR-1339; fatty liver.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Carnitine O-Palmitoyltransferase / metabolism
  • Disease Models, Animal
  • Humans
  • Hyperlipidemias / genetics*
  • Hyperlipidemias / metabolism
  • Lipid Metabolism / drug effects*
  • Lipoproteins, LDL / metabolism
  • Liver / pathology*
  • Mice
  • Non-alcoholic Fatty Liver Disease / drug therapy
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Oleic Acid / chemistry*
  • PPAR alpha / metabolism*
  • Rhamnaceae / chemistry*
  • Seeds / chemistry*


  • Lipoproteins, LDL
  • PPAR alpha
  • Oleic Acid
  • Carnitine O-Palmitoyltransferase
  • AMP-Activated Protein Kinases