Tetrahydroxystilbene 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 tetrahydroxystilbene glucoside (TSG) on atherosclerotic plaque development in ApoE knockout mice, and explore the mechanisms involved. Our data showed that after eight weeks treatment, TSG ameliorated serum levels of total cholesterol, triglyceride and low density lipoprotein cholesterol and increased serum level of high density lipoprotein cholesterol in ApoE knockout mice. TSG suppressed hepatic steatosis, atherosclerotic lesion formation and macrophage foam cell formation in ApoE knockout 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 macrophages cholesterol efflux and increased the protein expressions of ABCA1 and ABCG1. Our findings provided 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 of SR BI mediated cholesterol uptake of liver, increasing secretion of cholesterol into bile by ABCG5 and improving cholesterol metabolism by CYP7A1 pathway. In addition, antioxidative and antiinflammatory effect of TSG may also contribute to its inhibitory effects on atherosclerosis. The further study is needed to investigate whether other potential mechanisms are involved in the TSG mediated atheroprotection.