Comparison of Hesperetin and Its Metabolites for Cholesterol-Lowering and Antioxidative Efficacy in Hypercholesterolemic Hamsters

This study was performed to compare the hypolipidemic and antioxidant efficacy of hesperetin and its metabolites in hypercholesterolemic hamsters. The hamsters were fed a high-fat (10% coconut oil and 0.2% cholesterol, wt/wt) diet or a high-fat diet supplemented with hesperetin (0.02%) or hesperetin metabolites, 3,4-dihydroxyphenylpropionic acid (DHPP) (0.012%) and 3-methoxy-4-hydroxycinnamic acid (ferulic acid) (0.013%), for 12 weeks. Dietary DHPP and ferulic acid were found to have significantly decreased the levels of the plasma total cholesterol, non-high-density lipoprotein-cholesterol (HDL-C), apolipoprotein B, hepatic lipids, and cholesterol-regulating enzymes compared to the control group. In particular, ferulic acid was more potent with respect to raising HDL-C/total cholesterol ratio and paraoxonase levels while decreasing atherogenic index values. Hesperetin and its metabolites seemed to enhance antioxidant capacity by lowering the hydrogen peroxide and lipid peroxide (thiobarbituric acid-reactive substrates) levels. Among the hesperetin metabolites tested, the relative potency of ferulic acid for reducing the risks of atherosclerosis in hamsters was found to be greater.