Department of Pharmacology, Faculty of Medicine in Hradec Kralove, Charles University in Prague, 500 38 Hradec Kralove, Czech Republic.
Eur J Pharmacol. 2012 Sep 15;691(1-3):38-45. doi: 10.1016/j.ejphar.2012.06.034. Epub 2012 Jul 5.
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.
绿茶中主要儿茶素表没食子儿茶素没食子酸酯（EGCG）对胆固醇稳态的有益影响主要与胆固醇的肠道吸收有关；然而，EGCG 如何影响肝脏中的胆固醇代谢尚不完全清楚。本研究调查了 EGCG 对健康和己烯雌酚处理的大鼠肝脏胆固醇代谢的影响。EGCG 处理降低了己烯雌酚处理动物的血浆总胆固醇和两组 EGCG 处理动物的极低密度脂蛋白胆固醇。在健康大鼠中，尽管胆汁流量减少，但 EGCG 明显增强了胆汁中胆固醇和磷脂的分泌。这些变化与 ATP 结合盒转运蛋白 G5 和 G8 以及清道夫受体 B 类 1 的表达增加以及酰基辅酶 A：胆固醇酰基转移酶的表达减少有关。己烯雌酚处理导致明显的肝内胆固醇蓄积，伴有肝重增加和血浆胆固醇降低。在己烯雌酚处理的大鼠中，EGCG 共同给药可减轻肝内胆固醇和肝重的增加。此外，EGCG 减弱了酰基辅酶 A：胆固醇酰基转移酶的诱导作用，并提高了己烯雌酚处理大鼠中 ATP 结合盒转运蛋白 G5 和 G8 以及 3-羟基-3-甲基戊二酰辅酶 A 还原酶的降低水平。总之，这项研究首次证明了 EGCG 增强胆汁胆固醇分泌和减轻己烯雌酚诱导的肝内胆固醇蓄积的能力。相关酶和转运蛋白表达的变化表明，这可能是 EGCG 对胆固醇代谢整体作用的另一种机制，并暗示了这种广泛使用的化合物的新的生理后果。
