Abstract: Objective: This study aimed to clarify the regulatory effect and the mechanism of action of epigallocatechin gallate (EGCG) on cholesterol metabolism in rats. Methods: In vitro cell culture models (Caco-2 cells and BRL hepatocytes) and hyperglycemic rat model were established. In order to determine the possible mechanism for the regulation of cholesterol metabolism in rats by EGCG, the inhibition of bile acids across Caco-2 cell monolayers, the influx and efflux of cholesterol, serum cholesterol level and the expression of lipid metabolism-related genes were evaluated. Results: The transport of sodium glycocholate and sodium taurocholate across Caco-2 cell monolayers was significantly inhibited by EGCG (P < 0.05). EGCG also inhibited the influx of cholesterol in Caco-2 and increased the efflux of cholesterol from rat hepatocytes. The results of animal tests revealed that serum total cholesterol, triglyceride and low-density lipoprotein cholesterol levels were significantly lower in the EGCG-treated group than in the high-fat diet model group (P < 0.05), while high-density lipoprotein cholesterol levels were significantly higher (P < 0.05). Hematoxylin and eosin staining of the rat liver showed that liver steatosis was significantly attenuated by EGCG (P < 0.05). At the molecular level, the mRNA and protein expression of hydroxy methylglutaryl-CoA reductase were significantly decreased in the EGCG-treated group when compared with the model group, while the mRNA and protein expression levels of sterol regulatory element-binding protein-2, liver X receptor α and cholesterol 7α hydroxylase were significantly increased (P < 0.05). Conclusion: EGCG had multiple regulatory effects on cholesterol metabolism, and the underlying mechanism was attributed to the inhibition of bile acid re-absorption, the blocking of cholesterol influx, and the enhancement of cholesterol efflux as well as the regulation of the expression of cholesterol metabolism-related genes.

Key words: epigallocatechin gallate, reabsorption of bile acid, cholesterol uptake, cholesterol efflux, regulation mechanism