Association of GLP-1 secretion with anti-hyperlipidemic effect of ginsenosides in high-fat diet fed rats.

Ginsenosides, major bioactive constituents in Panax ginseng, have been shown to exert anti-hyperlipidemia effects. However, the underlying mechanism was not well-elucidated due to the low bioavailability of ginsenosides. Glucagon-like peptide-1 (GLP-1) was considered to be a critical regulator of energy homeostasis. Our previous studies have showed that ginseng total saponins (GTS) exhibited antidiabetic effects partly via modulating GLP-1 release. The aim of this study was to investigate the potential role of GLP-1 in anti-hyperlipidemia effect of GTS in rats fed with high-fat diet. Male Sprague-Dawley rats were fed with normal diet (CON) or high-fat diet (HFD) for 4 weeks. Then, the HFD rats orally received vehicle (HFD), 150 mg/kg/day (HFD-GL) and 300 mg/kg/day of GTS (HFD-GH) for another 4 weeks, respectively. Four-week GTS treatment significantly ameliorated hyperlipidemia, decreased body fat, liver weight and improved insulin resistance. It was found that high-dose GTS treatment increased portal GLP-1 level induced by glucose loading, accompanied by increased intestinal GLP-1 content, L-cell number and prohormone convertase 3 mRNA expression. Data from NCI-H716 cells showed that both GTS and ginsenoside Rb1 significantly increased GLP-1 secretion as well as proglucagon mRNA level in NCI-H716 cells supplemented with 10% HFD-rat serum. Hyperlipidemia and insulin resistance were attenuated effectively in response to GTS treatment. These improvements may be associated with the increased secretion of GLP-1.