Ginsenoside Rg2 has been previously reported to reduce glucose
production and adipogenesis in adipose tissue. However, the effects
of ginsenosides Rg2 on hepatic lipid metabolism remain vacant. In
this study, we found that ginsenoside Rg2 treatment significantly
attenuated oleic acid and palmitic acid (OA&PA)-induced intracellular
lipid deposition and oxidative stress in mouse primary hepatocytes.
C57BL/6J mice that are fed with a high-fat diet (HFD) and treated
with ginsenosides Rg2 displayed decreased body weight, reversed hepatic
steatosis, and improved glucose tolerance and insulin sensitivity.
Ginsenoside Rg2 administration significantly ameliorated HFD-induced
hepatic oxidative stress and apoptosis. Moreover, Ginsenoside Rg2
had a good affinity with Sirtuin1 (SIRT1) and regulated its expression
in vivo and in vitro. Deficiency of SIRT1 eliminated the therapeutic
effect of ginsenoside Rg2 on lipid accumulation and overproduction
of reactive oxygen species (ROS) in OA&PA-induced mice primary
hepatocytes. Ginsenoside Rg2 treatment failed to alter the lipid and
glucose disorder in hepatic SIRT1 deficient mice feeding on HFD. SIRT1
deficiency dissolves the therapeutic effect of ginsenoside Rg2 on
oxidative stress and hepatocyte apoptosis induced by HFD. In summary,
ginsenoside Rg2 plays a therapeutic role in HFD-induced hepatosteatosis
of mice by decreasing the lipogenesis process and improving antioxidant
capacity in an SIRT1-dependent manner.