Peroxisome proliferator-activated receptor α is involved in the regulation of lipid metabolism by ginseng

Abstract

1. Peroxisome proliferator-activated receptor α (PPARα) regulates the expression of the key genes involved in lipid metabolism following activation of this receptor by various ligands. Ginseng, a highly valuable medicine in oriental societies, is also reported to modulate lipid metabolism, although the mechanism of its action remains unknown. In order to test our hypothesis that ginseng exerts its effects by altering PPARα-mediated pathways, the effects of Korean red ginseng on PPARα function and serum lipid profiles were investigated using in vivo and in vitro approaches. 2. In vivo administration of ginseng extract (GE) and ginsenosides (GS) not only inhibited mRNA levels of acyl-CoA oxidase, a rate-limiting enzyme for PPARα-mediated peroxisomal fatty acid β-oxidation, induced by the potent PPARα ligand Wy14,643 in a dose- and time-dependent manner, but also inhibited the induction of PPARα target genes expected following treatment with Wy14,643. 3. Consistent with the in vivo data, both GE and GS caused dose-dependent decreases in the endogenous expression of a luciferase reporter gene containing the PPAR responsive element (PPRE), while GS significantly decreased the magnitude of reporter gene activation in the presence of Wy14,643. 4. Serological studies demonstrated that, compared with vehicle-treated mice, treatment with GS significantly increased serum concentrations of total cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol. Compared to groups treated with Wy14,643 alone, which significantly decreased serum triglyceride and HDL cholesterol levels versus controls, coadministration of either GE or GS with Wy14,643 modestly increased serum triglycerides and HDL cholesterol. 5. These results indicate that the effects of ginseng on serum lipid profiles may be mediated by changes in the expression of PPARα target genes, providing the first evidence that in vivo and in vitro treatments of ginseng modulate PPARα action. In addition, these data suggest that ginseng can act as an inhibitor of PPARα function, which may have therapeutic implications.