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

Abstract

Abstract. 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 highfat 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.

Ginseng and Diabetes: The Evidences from In Vitro, Animal and Human Studies

“…One of the most efficient ways to modulate glucose metabolism in diabetic patients would be a perturbation on hepatic glucose production. Recently, ginsenoside Rb 2 , Re and Rg 1 were reported to suppress the hepatic gluconeogenesis in H4IIE and HepG2 cells, respectively, via activation of AMP-activated protein kinase (AMPK) [41,49,50].…”

Pharmacological Effects of Ginseng on Liver Functions and Diseases: A Minireview

“…In another related study, the same group revealed ginsenoisde Re to lower blood glucose and lipid level via activation of AMPK pathway in HepG2 cells and high-fat diet fed mice, suggesting therapeutic benefits on type 2 diabetic patients with insulin resistance and dyslipidemia [70]. …”

Ginsenoside Rb1 Attenuates Agonist-Induced Contractile Response via Inhibition of Store-Operated Calcium Entry in Pulmonary Arteries of Normal and Pulmonary Hypertensive Rats

“…It has been used widely as a tonic for various disorders in China, Korea and Japan for over two thousand years and is now a popular herbal remedy worldwide. Ginsenosides, the bioactive ingredients of ginseng, have been proven to provide therapeutic effects affecting the cardiovascular, endocrine, immune, and central nervous systems [6,7,8,9]. Ginsenosides are generally classified into two categories, namely the panaxadiols and the panaxatriols.…”