Cholesterol‐Lowering Effects and Mechanisms in View of Bile Acid Pathway of Resveratrol and Resveratrol Glucuronides

Resveratrol (Res) was previously reported to be capable of lowering plasma TC and LDL‐C. The mechanism behind Res is not clearly understood, although it is presumed to have an effect on bile acid metabolism in the liver: a significant way in eliminating cholesterol from the body. As one of the major metabolites of Res in the liver, resveratrol glucuronides (Gres) is suspected to also contribute to the overall cholestrol‐lowering activity of Res, which needs to be studied. In this research, when HepG2 steatosis hepatic cells were treated with Res and Gres at different concentration levels, Res and Gres showed similar activity in lowering cellular TC content. The presence of Res and Gres caused a significant increase in hepatic CYP7A1 and BSEP, indicating the increase in the synthesis and efflux of bile acids, respectively. The reduction of HMG‐CoAR tied to a decrease in de novo synthesis of cholesterol and the increase of ABCG5 suggested the increase of direct efflux of cholesterol. All above variations reduced the hepatic cholesterol level, which triggered the significant enhancement of LDLR, illustrating the improvement of clearance of LDL‐C from the plasma and prevention of atherosclerosis. Overall, this study demonstrated both Res and Gres might have capabilities in lowering hepatic cholesterol through increasing in the synthesis and efflux of bile acids, and decreasing in synthesis and increasing in the efflux of cholesterol. Gres would have preferred potential than Res because of its lower cytotoxicity, which indicated that the action of the metabolites should also be considered in the future studies.