Title: Modulation of Cholesterol and Triacylglycerol Biosynthesis by Citrus Polymethoxylated Favones Authors
|Kurowska, Elzbieta - KGK SYNERGIZE INC., ONTAR|
Submitted to: American Chemical Society Symposium Series
Publication Type: Book / Chapter
Publication Acceptance Date: January 31, 2006
Publication Date: July 13, 2006
Citation: Manthey, J.A., Kurowska, E.M. 2006. Modulation of cholesterol and triacylglycerol biosynthesis by citrus polymethoxylated flavones. In: Patil, B.S., Turner, N.D., Miller, E.G., Brodbelt, J.S., editors. Potential Health Benefits of Citrus. American Chemical Society Symposium Series 936. Washington, DC: American Chemical Society. p. 186-198. Interpretive Summary: Special compounds in orange peel, called polymethoxylated flavones, have been shown in a series of studies to lower blood serum cholesterol and triglycerides. An experiment with hamsters showed that these compounds were effective in lowering the bad low-density lipoprotein (LDL)-cholesterol, and triglycerides. Other experiments showed that these actions were due to at least three mechanisms. These mechanisms involved the inhibition and transport of key parts of the LDL molecule. Another mechanism involved the activation of an important cell signaling molecule in liver cells which control lipid formation. Additional mechanisms by which the polymethoxylated flavones act to prevent cardiovascular disease are discussed.
Technical Abstract: Citrus polymethoxylated flavones modulate the biosynthesis of cholesterol and triacylglycerols via multiple mechanisms. Tangeretin was shown to inhibit the activities of diacylglycerol acyltransferase and of microsomal triglyceride transfer protein as well as activate the membrane peroxisome proliferator-activated receptor in the human hepatoma HepG2 cell-line. These modulatory effects subsequently inhibit the assembly and secretion of apolipoprotein B-containing lipoproteins such as very low-density lipoprotein (VLDL) and the low-density lipoprotein (LDL). Nobiletin, but not tangeretin, inhibited macrophage acetylated LDL metabolism linked to the action of the specific class A scavenger receptor. This inhibitory effect blocked the formation of macrophage foam-cells which are essential to atherosclerotic plaque formation. In hamster feeding trials the polymethoxylated flavones dramatically lowered the serum total cholesterol, LDL+VLDL cholesterol as well as the levels of serum triacylglycerols. Total liver concentrations of tangeretin derivatives corresponded to hypolipidemic concentrations of intact tangeretin in earlier in vitro studies. If similar actions occur in humans, these compounds may be viable alternatives to the statin drugs to combat elevated cholesterol and triacylglycerols.