Epigallocatechin gallate enhances biliary cholesterol secretion in healthy rats and lowers plasma and liver cholesterol in ethinylestradiol-treated rats

The beneficial effect of the major green tea catechin, epigallocatechin gallate (EGCG), on cholesterol homeostasis has been studied mainly in relation to the intestinal absorption of cholesterol; however, how EGCG affects cholesterol metabolism in the liver is not entirely known. The present study investigated the effect of EGCG on liver cholesterol metabolism in healthy and ethinylestradiol-treated rats. EGCG treatment reduced plasma total cholesterol in ethinylestradiol-treated animals and very low density lipoprotein cholesterol in both groups receiving EGCG. In healthy rats, despite the decrease in bile flow, EGCG markedly enhanced biliary secretion of cholesterol and phospholipids. These changes were correlated with increased expression of ATP-binding cassette transporter G5 and G8 and scavenger receptor class B type 1, and decreased expression of acyl-CoA:cholesterol acyltransferase. Ethinylestradiol treatment caused marked hepatic cholesterol accumulation with a concomitant liver weight increase and plasma cholesterol reduction. In ethinylestradiol-treated rats, EGCG co-administration attenuated the increase in liver cholesterol and liver weight. Furthermore, EGCG blunted induction of acyl-CoA:cholesterol acyltransferase and raised reduced levels of ATP-binding cassette transporter G5 and G8 and 3-hydroxy-3-methyl-glutaryl-CoA reductase in ethinylestradiol-treated rats. In conclusion, this study has demonstrated for the first time the ability of EGCG to enhance biliary cholesterol secretion and to attenuate ethinylestradiol-induced liver cholesterol accumulation. Changes in the expression of relevant enzymes and transporters suggest evidence of another mechanism that may contribute to the overall effect of EGCG on cholesterol metabolism and imply new physiological consequences of this widely used compound.