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

다국어 초록 (Multilingual Abstract)

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.

참고문헌 (Reference)

1 Local Food-Nutraceuticals Consortium, "Understanding local Mediterranean diets: a multidisciplinary pharmacological and ethnobotanical approach" 52 : 353-366, 2005

2 Chisolm GM, "The oxidative modification hypothesis of atherogenesis: an overview" 28 : 1815-1826, 2000

3 Terpstra AHM, "The hypocholesterolemic effect of dietary soybean protein vs. casein in hamsters fed cholesterol-enriched or cholesterol-free semipurified diets" 121 : 944-947, 1991

4 Bourn LC, "The effect of the phenolic antioxidant ferulic acid on the oxidation of low-density lipoprotein on the pro-oxidant used" 27 : 337-344, 1997

5 Honohan T., "Synthesis and metabolic fate of hesperetin-3-14C" 24 : 906-911, 1976

6 McCord JM, "Superoxide dismutase: an enzymatic function for erythrocuperine (hemocuperin)" 224 : 6049-6055, 1969

7 Paglia DE, "Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase" 70 : 158-169, 1967

8 Hulcher FH, "Simplified spectrophotometric assay for microsomal 3-hydroxy-3-methylglutaryl CoA reductase by measurement of coenzyme A" 14 : 625-631, 1973

9 Kukita H., "Serum apolipoprotein A-I, A-II and B levels and their discriminative values in relative of patients of coronary artery disease" 51 : 261-267, 1984

10 Wilcox LJ, "Secretion of hepatocyte apoB is inhibited by the flavonoids, naringenin and hesperetin, via reduced activity and expression of ACAT2 and MTP" 42 : 725-734, 2001

11 American Institute of Nutrition, "Report of the American Institute of Nutrition Ad Hoc Committee on Standards for Nutritional Studies" 107 : 1340-1348, 1977

12 American Institute of Nutrition, "Report of Ad Hoc Committee on Standards for Nutritional Studies" 110 : 1717-1726, 1980

13 Erickson SK, "Rat liver acyl-coenzyme A:cholesterol acyltransferase: its regulation in vivo and some of properties in vitro" 21 : 930-941, 1980

14 Erlund I., "Plasma kinetics and urinary excretion of the flavanones naringenin and hesperetin in humans after ingestion of orange juice and grapefruit juice" 131 : 235-241, 2001

15 Mackness MI, "Paraoxonase prevents accumulation of lipoperoxides in low-density lipoprotein" 286 : 152-154, 1991

16 Yokoyama M., "Oxidative stress and atherosclerosis" 4 : 110-115, 2004

17 Ardiansyah, "Novel effects of a single administration of ferulic acid on the regulation of blood pressure and the hepatic lipid metabolic profile in stroke-prone spontaneously hypertensive rats" 56 : 2825-2830, 2008

18 Shapiro DJ, "Micro assay for 3-hydroxy-3-methylglutaryl-CoA reductase in rat liver and in L-cell fibroblasts" 370 : 369-377, 1974

19 Billheimer DW, "Mevinolin and cholestipol stimulate receptor-mediated clearance of low density lipoprotein from plasma in familial hypercholesterolemia heterozygotes" 80 : 4124-4128, 1983

20 Booth AN, "Metabolic and glucosuria studies on naringin and phloridzin" 233 : 280-282, 1958

21 Budavari S., "Merck Index, 11th ed" Merck & Co 738-, 1989

22 Kim HK, "Lipid-lowering efficacy of hesperetin metabolites in high-cholesterol fed rats" 327 : 129-137, 2003

23 Marklund S., "Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase" 47 : 469-474, 1974

24 Soudami KK, "Inhibition of lipid peroxidation and cholesterol levels in mice by curcumin" 36 : 239-243, 1992

25 de Silva PP, "Hyperlipidaemic effect of fish oil in Bio F1B hamsters" 91 : 341-349, 2004

26 Walldius G., "High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study" 358 : 2026-2033, 2001

27 Pinto RE, "Glutathione reductase and glutathione peroxidase activities in hepatomous livers of rats treated with diethylnitrosamine" 32 : 307-309, 1973

28 Hertog MG, "Flavonoid intake and long-term risk of coronary heart disease and cancer in the Seven Countries study" 155 : 381-386, 1995

29 Knekt P., "Flavonoid intake and coronarymortality in Finland: a cohort study" 312 : 478-481, 1996

30 Wolff SP, "Ferrous ion oxidation in presence of ferric ion indicator xylenol orange for measurement of hydroperoxides" 233 : 182-189, 1994

31 de Haan JB, "Elevation in the ratio Cu/Zn-superoxide dismutase to glutathione peroxidase activity induces features of cellular senescence and this effect is mediated by hydrogen peroxide" 5 : 283-292, 1996

32 Vijayakumar RS, "Efficacy of piperine, an alkaloidal constituent from Piper nigrum on erythrocyte antioxidant status in high fat diet and antithyroid drug induced hyperlipidemic rats" 24 : 491-498, 2006

33 Sakamoto K., "Effect of gamma-oryzanol and cycloartenol ferulic acid ester on cholesterol diet induced hyperlipidemia in rats" 45 : 559-565, 1987

34 Kay NMR, "Drosophila to bacteriophage to erythrocyte; the erythrocyte as a model for molecular and membrane aging of terminally differentiated cells" 37 : 5-32, 1991

35 Hertog MG, "Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study" 342 : 1007-1011, 1993

36 Abei H., "Catalase, In: Methods of Enzymatic Analysis, Vol. 2" Academic Press 673-684, 1974

37 Ohkawa H., "Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction" 95 : 351-358, 1979

38 Wilcox LJ, "Antiatherogenic properties of naringenin, a citrus flavonoid" 17 : 160-178, 1999

39 Folch J., "A simple method for isolation and purification of total lipids from animal tissues" 226 : 497-509, 1957

40 Bradford MM, "A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding" 72 : 248-254, 1976