2,3,4′,5-tetrahydroxystilbene-2-O-β-d-glycoside attenuates atherosclerosis in apolipoprotein E-deficient mice: role of reverse cholesterol transport

Abstract

The aim of this study was to evaluate the potential effects of 2,3,4′,5-tetrahydroxystilbene-2-O-β-d-glucoside (TSG) on the development of atherosclerotic plaque in ApoE−/− mice, and explore the mechanisms involved. Our data showed that after 8 weeks of treatment, TSG ameliorated serum levels of total cholesterol, triglyceride, and low density lipoprotein cholesterol, and increased serum levels of high density lipoprotein cholesterol in ApoE−/− mice. TSG suppressed hepatic steatosis, the formation of atherosclerotic lesions, and the formation of macrophage foam cells in ApoE−/− mice. Moreover, TSG improved the expressions of hepatic SR-BI, ABCG5, and CYP7A1, and up-regulated the protein expressions of aortic ABCA1 and ABCG1. An in-vitro study showed that TSG promoted macrophage cholesterol efflux and increased the protein expressions of ABCA1 and ABCG1. Our findings provide evidence for a positive role of TSG in preventing atherosclerosis by promoting reverse cholesterol transport. These effects may be achieved by stimulating cholesterol efflux through ABCA1 and ABCG1, promoting SR-BI-mediated cholesterol uptake in the liver, increasing secretion of cholesterol into bile by ABCG5, and improving cholesterol metabolism by the CYP7A1 pathway. In addition, antioxidative and anti-inflammatory effects of TSG may also contribute to its inhibitory effects on atherosclerosis. Further study is needed to investigate whether other potential mechanisms are involved in TSG-mediated atheroprotection.