Hypolipidemic Effects and Absorption of Citrus Polymethoxylated Flavones in Hamsters with Diet-Induced Hypercholesterolemia

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Abstract
Formulations containing citrus polymethoxylated flavones (PMFs), mainly tangeretin, or citrus flavanone glucosides, hesperidin and naringin, were evaluated for cholesterol-lowering potential in hamsters with diet-induced hypercholesterolemia. PMF metabolites were also investigated. Diets containing 1% PMFs significantly reduced serum total and very low-density lipoprotein (VLDL) + LDL cholesterol (by 19−27 and 32−40%, respectively) and either reduced or tended to reduce serum triacylglycerols. Comparable reductions were achieved by feeding a 3% mixture of hesperidin and naringin (1:1, w/w), implying lower hypolipidemic potency of the hesperidin/naringin vs PMFs. HPLC-MS analysis identified high serum, liver, and urine concentrations of tangeretin metabolites including dihydroxytrimethoxyflavone and monohydroxytetramethoxyflavone glucuronides and aglycones. Total liver concentrations of tangeretin derivatives corresponded to hypolipidemic concentrations of intact tangeretin in earlier experiments in vitro. This suggests that PMFs are novel flavonoids with cholesterol- and triacylglycerol-lowering potential and that elevated levels of PMF metabolites in the liver might be directly responsible for their hypolipidemic effects in vivo. Keywords: Polymethoxylated flavones; cholesterol; triacylglycerols; hamster; tangeretin metabolites; serum; liver; urine