Suppression of diet-induced hypercholesterolaemia by saponins from Panax notoginseng in rats

• Investigate the hypocholesterolaemic and vascular protective effects of PNS.
• 28-Day treatment of PNS improved lipid profile in hypercholesterolaemic rats.
• PNS improved endothelium-mediated aortic relaxation.
• PNS gave its effect by changing the hepatic CYP7A1 and PPARα expressions.
• This study provides mechanistic explanation of PNS’s beneficial effects.

Panax notoginseng saponins (PNS) are major active constituents of P. notoginseng. This study investigated the mechanisms of the hypocholesterolaemic and atheroscleroprotective effects of PNS. It was found that treatment of PNS (30 or 100 mg/kg/day, p.o.) could significantly reduce elevated serum total cholesterol, triacylglycerol, low-density lipoprotein cholesterol and atherogenic index induced by feeding rats with high cholesterol diet for 28 days. High-density lipoprotein cholesterol could also be increased by PNS treatment. Additionally, PNS significantly enhanced the hypercholesterolaemia-induced reduction of superoxide dismutase activity in the liver. In hypercholesterolaemic rats, PNS significantly improved the endothelium-dependent vasodilatation, acetylcholine-induced nitric oxide production and endothelial nitric oxide synthase mRNA expression in a dose-dependent manner. It also significantly reversed the hypercholesterolaemia-induced changes in mRNA expressions of cholesterol 7α-hydroxylase and peroxisome proliferator-activated receptor α but not HMG-CoA reductase. The findings provided evidence for using PNS to prevent the development of hypercholesterolaemia and atherosclerosis. The hypocholesterolaemic activity of PNS is likely to be resulted from inducing the biosynthesis of bile acids from cholesterol and promoting the β-oxidation of fatty acids in the liver. The vasoprotective function of PNS may be brought about by increasing the gene expression of eNOS in endothelial cells, its antioxidative activity, or both.