Modulation of Cholesterol and TriacylglycerolBiosynthesis by Citrus Polymethoxylated Flavones Cholesterol-Lowering Properties of Citrus Flavonoids

摘要

Citrus polymethoxylated flavones modulate the biosynthesisof cholesterol and triacylglycerols via multiple mechanisms.Tangeretin inhibits the activities of diacylglycerolacyltransferase and of microsomal triglyceride transferprotein, as well as activates the membrane peroxisomeproliferator-activated receptor in human hepatoma HepG2cells. These modulatory effects subsequently inhibit theassembly and secretion of apolipoprotein B-containinglipoproteins, such as the very low-density lipoprotein (VLDL)and the low-density lipoprotein (LDL). Nobiletin, but nottangeretin, inhibited macrophage acetylated LDL metabolismlinked to the action of the specific class A scavenger receptor.This inhibitory effect blocked the formation of macrophagefoam-cells, which are essential to atherosclerotic plaqueformation. In hamster feeding trials the polymethoxylatedflavones dramatically lowered serum total cholesterol,LDL+VLDL cholesterol, as well as the levels of serumtriacylglycerols. Total liver concentrations of tangeretinderivatives corresponded to hypolipidemic concentrations ofintact tangeretin in earlier in vitro studies. If similar actionsoccur in humans, these compounds may be viable alternativesto the statin drugs to combat elevated cholesterol andtriacylglycerols.