Ginsenoside Re lowers blood glucose and lipid levels via activation of AMP-activated protein kinase in HepG2 cells and high-fat diet fed mice

Int J Mol Med. 2012 Jan;29(1):73-80. doi: 10.3892/ijmm.2011.805. Epub 2011 Oct 3.


Ginsenoside Re is a protopanaxatriol-type saponin isolated from Panax ginseng berry. Although anti-diabetic and anti-hyperlipidemic effects of Re have been reported by several groups, its mechanism of action is largely unknown until now. Here, we examine anti-diabetic and anti-hyperlipidemic activities of Re and action mechanism(s) in human HepG2 hepatocytes and high-fat diet fed C57BL/6J mice. Re suppresses the hepatic glucose production via induction of orphan nuclear receptor small heterodimer partner (SHP), and inhibits lipogenesis via suppression of sterol regulatory element binding protein-1c (SREBP-1c) and its target gene [fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD1)] transcription. These effects were mediated through activation of AMP-activated protein kinase (AMPK), and abolished when HepG2 cells were treated with an AMPK inhibitor, Compound C. C57BL/6J mice were randomly divided into five groups: regular diet fed group (RD), high-fat diet fed group (HFD) and the HFD plus Re (5, 10, 20 mg/kg) groups. Re treatment groups were fed a high-fat diet for 6 weeks, and then orally administered Re once a day for 3 weeks. The in vitro results are likely to hold true in an in vivo experiment, as Re markedly lowered blood glucose and triglyceride levels and protected against hepatic steatosis in high-fat diet fed C57BL/6J mice. In conclusion, the current study suggest that ginsenoside Re improves hyperglycemia and hyperlipidemia through activation of AMPK, and confers beneficial effects on type 2 diabetic patients with insulin resistance and dyslipidemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • AMP-Activated Protein Kinases / metabolism*
  • Analysis of Variance
  • Animals
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism*
  • Diet, High-Fat*
  • Drugs, Chinese Herbal
  • Fatty Liver / metabolism
  • Gene Expression Regulation / drug effects
  • Ginsenosides / pharmacology*
  • Gluconeogenesis / drug effects
  • Hep G2 Cells
  • Humans
  • Lipids / blood*
  • Lipogenesis / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Protein Serine-Threonine Kinases / metabolism
  • Random Allocation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Triglycerides / blood
  • Triglycerides / metabolism


  • Blood Glucose
  • Drugs, Chinese Herbal
  • Ginsenosides
  • Lipids
  • Triglycerides
  • ginsenoside Re
  • Protein Serine-Threonine Kinases
  • STK11 protein, human
  • AMP-Activated Protein Kinase Kinases
  • AMP-Activated Protein Kinases