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Title: EFFECTS OF CITRUS POLYMETHOXYLATED FLAVONES ON BLOOD LIPID PROFILES IN HYPERCHOLESTEROLEMIC HAMSTERS

Author
item Manthey, John
item KUROWSKA, ELZBIETA - KGK, INC., CANADA

Submitted to: American Chemical Society National Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 7/20/2004
Publication Date: 8/17/2004
Citation: Manthey, J.A., Kurowska, E.M. 2004. Effects of citrus polymethoxylated flavones on blood lipid profiles in hypercholesterolemic hamsters. American Chemical Society National Meeting. Paper No. AGFD 140.

Interpretive Summary:

Technical Abstract: Orange peel contains methoxylated flavone aglycones, termed the polymethoxylated flavones (PMFs) which exhibit anticancer, anti-inflammatory, and cholesterol-lowering properties. Studies have shown the inhibition by these compounds of the net secretion of the LDL structural protein, apolipoprotein B, in HepG2 liver cells via multiple mechanisms. Feeding trials with hypercholesterolemic hamster have demonstrated the effects of these compounds in vivo. Diets containing 1% PMFs significantly reduced serum total and VLVL+LDL cholesterol, by 19-27%, and 32-40%, respectively. Reductions in the serum triacylglycerols were also observed. Comparable reductions in the total and VLDL+LDL cholesterol levels were achieved by feeding a 3% mixture of hesperidin and naringin (1:1), implying lower hypolipidemic potency of the flavanone glycosides vs. PMFs. Extensive quantitative and qualitative HPLC-MS analyses have been made of the metabolites of tangeretin (TAN) in hamster liver, serum and urine extracts. TAN is predominately converted to a diverse set of glucuronides of monohydroxy-tetramethoxyflavone and dihydroxy-trimethoxyflavone metabolites of TAN. Significant uptake of TAN is evident by the high blood serum concentrations of these metabolites. Concentrations of the metabolites in the hamster livers were comparable to the hypolipidemic concentrations of intact tangeretin measured in earlier in vitro experiments. Negligible immunotoxic and genetic toxic effects are observed in animal feeding studies for the PMFs. These results suggest that the PMFs may be valuable as cholesterol-lowering agents in the diet.