Attenuation of lipid peroxidation and hyperlipidemia by quercetin glucoside in the aorta of high cholesterol-fed rabbit

Antioxidative activity of dietary flavonoids is suggested to be, at least partly, responsible for a wide variety of their biological effects relating to anti-atherosclerosis. However, it is not known whether dietary flavonoids reach to the target site and act as antioxidants. In this study, we tried to evaluate the antioxidative effect of quercetin 3-O-β-d-glucoside (Q3G), a typical flavonoid present in vegetables, in rabbit aorta. New Zealand White rabbits were fed a control diet (control group), 2.0% cholesterol diet (HC group) and 2.0% cholesterol plus 0.1% Q3G (HC + Q3G group) for one month. The amounts of total cholesterol, triacylglycerol and total fatty acids in both the plasma and aorta were significantly lower in the HC + Q3G group as compared with the HC group. Quercetin was detected in the aorta of the HC + Q3G group after enzymatic deconjugation, indicating that quercetin accumulated as conjugated metabolites in the aorta. The contents of TBA-reacting substances (TBARS) and cholesteryl ester hydroperoxides (CEOOH) in the aorta of the HC + Q3G group were significantly lower than those in the HC group. The aorta of HC + Q3G group was more resistant than that of HC group in copper ion-induced lipid peroxidation ex vivo. HC + Q3G group accumulated a higher amount of vitamin E per total cholesterol than HC group in the aorta. These results strongly suggest that quercetin glucosides accumulate in the aorta as their metabolites and attenuate lipid peroxidation occurring in the aorta, along with the attenuation of hyperlipidemia.

[1]  T. Walle Absorption and metabolism of flavonoids. , 2004, Free radical biology & medicine.

[2]  C. Rice-Evans,et al.  Cellular uptake and metabolism of flavonoids and their metabolites: implications for their bioactivity. , 2004, Archives of biochemistry and biophysics.

[3]  R. Ferrari,et al.  Oxidative stress in cardiovascular disease: myth or fact? , 2003, Archives of biochemistry and biophysics.

[4]  G. FitzGerald,et al.  Oxidative stress and cardiovascular injury: Part II: animal and human studies. , 2003, Circulation.

[5]  J. Terao,et al.  Antioxidative flavonoid quercetin: implication of its intestinal absorption and metabolism. , 2003, Archives of biochemistry and biophysics.

[6]  J. Keaney,et al.  Beyond LDL oxidation: ROS in vascular signal transduction. , 2003, Free radical biology & medicine.

[7]  H. Morawietz,et al.  NADPH oxidase in endothelial cells: impact on atherosclerosis. , 2003, Antioxidants & redox signaling.

[8]  L. Oberley,et al.  Activation of NAD(P)H oxidase by lipid hydroperoxides: mechanism of oxidant-mediated smooth muscle cytotoxicity. , 2003, Free radical biology & medicine.

[9]  T. Murase,et al.  Beneficial effects of tea catechins on diet-induced obesity: stimulation of lipid catabolism in the liver , 2002, International Journal of Obesity.

[10]  M. Lean,et al.  Determination of flavonol metabolites in plasma and tissues of rats by HPLC-radiocounting and tandem mass spectrometry following oral ingestion of [2-(14)C]quercetin-4'-glucoside. , 2002, Journal of agricultural and food chemistry.

[11]  A. Reunanen,et al.  Flavonoid intake and risk of chronic diseases. , 2002, The American journal of clinical nutrition.

[12]  M. Yoshizumi,et al.  Quercetin glucuronide prevents VSMC hypertrophy by angiotensin II via the inhibition of JNK and AP-1 signaling pathway. , 2002, Biochemical and biophysical research communications.

[13]  Mi-Kyung Lee,et al.  Quercetin dihydrate and gallate supplements lower plasma and hepatic lipids and change activities of hepatic antioxidant enzymes in high cholesterol-fed rats. , 2002, International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition.

[14]  J. Terao,et al.  Identification of quercetin 3-O-beta-D-glucuronide as an antioxidative metabolite in rat plasma after oral administration of quercetin. , 2001, Free radical biology & medicine.

[15]  D. Steinberg,et al.  The oxidative modification hypothesis of atherosclerosis: does it hold for humans? , 2001, Trends in cardiovascular medicine.

[16]  M. Aviram,et al.  Flavonoids protect LDL from oxidation and attenuate atherosclerosis , 2001, Current opinion in lipidology.

[17]  D. Barron,et al.  Human metabolism of dietary flavonoids: Identification of plasma metabolites of quercetin , 2001, Free radical research.

[18]  T. Inakuma,et al.  Protection by quercetin and quercetin 3-O-β-D-glucuronide of peroxynitrite-induced antioxidant consumption in human plasma low-density lipoprotein , 2001, Free radical research.

[19]  G. Williamson,et al.  Conjugation position of quercetin glucuronides and effect on biological activity. , 2000, Free radical biology & medicine.

[20]  T. Inakuma,et al.  Accumulation of quercetin conjugates in blood plasma after the short-term ingestion of onion by women. , 2000, American journal of physiology. Regulatory, integrative and comparative physiology.

[21]  J. Terao,et al.  Flavonoids and membrane lipid peroxidation inhibition. , 1999, Nutrition.

[22]  D. Harrison,et al.  Increased NADH-oxidase-mediated superoxide production in the early stages of atherosclerosis: evidence for involvement of the renin-angiotensin system. , 1999, Circulation.

[23]  J. Terao,et al.  Quercetin metabolites inhibit copper ion‐induced lipid peroxidation in rat plasma 1 , 1998, FEBS letters.

[24]  O. Texier,et al.  Quercetin is recovered in human plasma as conjugated derivatives which retain antioxidant properties , 1998, FEBS letters.

[25]  B. Holub,et al.  Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects. , 1998, The Journal of nutrition.

[26]  J. Terao,et al.  Inhibition of mammalian 15-lipoxygenase-dependent lipid peroxidation in low-density lipoprotein by quercetin and quercetin monoglucosides. , 1998, Archives of biochemistry and biophysics.

[27]  R. Coleman,et al.  Reduced progression of atherosclerosis in apolipoprotein E-deficient mice following consumption of red wine, or its polyphenols quercetin or catechin, is associated with reduced susceptibility of LDL to oxidation and aggregation. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[28]  E. Feskens,et al.  Dietary Flavonoids, Antioxidant Vitamins, and Incidence of Stroke: The Zutphen Study , 1996 .

[29]  Paul Knekt,et al.  Flavonoid intake and coronary mortality in Finland: a cohort study , 1996, BMJ.

[30]  T. Tsushida,et al.  Flavonoid in Fruits and Vegetables Part I. Isolation of Flavonoid-Glycosides in Onion and Identification by Chemical Synthesis of the Glycosides , 1995 .

[31]  D. Harrison,et al.  Hypercholesterolemia increases endothelial superoxide anion production. , 1993, The Journal of clinical investigation.

[32]  M. Sugano,et al.  Tea catechins decrease micellar solubility and intestinal absorption of cholesterol in rats. , 1992, Biochimica et biophysica acta.

[33]  J L Witztum,et al.  Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. , 1989, The New England journal of medicine.

[34]  J. Steinberg Book ReviewAmbulatory Pediatric Care , 1989 .

[35]  K. Herrmann Flavonols and flavones in food plants: a review† , 1976 .

[36]  M. M. Bradford A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[37]  W. J. Dyer,et al.  A rapid method of total lipid extraction and purification. , 1959, Canadian journal of biochemistry and physiology.

[38]  J. Terao,et al.  Effect of quercetin conjugates on vascular permeability and expression of adhesion molecules , 2004, BioFactors.

[39]  C. Rice-Evans,et al.  Structure-antioxidant activity relationships of flavonoids and phenolic acids. , 1996, Free radical biology & medicine.

[40]  J. Terao,et al.  Coulometric detection in high-performance liquid chromatographic analysis of cholesteryl ester hydroperoxides. , 1996, Free radical biology & medicine.

[41]  D Kromhout,et al.  Intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands. , 1993, Nutrition and cancer.

[42]  D. Steinberg,et al.  Role of oxidised low density lipoprotein in atherogenesis. , 1993, British heart journal.

[43]  W. Bors,et al.  Flavonoids as antioxidants: determination of radical-scavenging efficiencies. , 1990, Methods in enzymology.

[44]  H. Esterbauer,et al.  Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. , 1990, Methods in enzymology.

[45]  S. Aust,et al.  Microsomal lipid peroxidation. , 1978, Methods in enzymology.

[46]  J. Kuhana THE FLAVONOIDS; A CLASS OF SEMI-ESSENTIAL FOOD COMPONENTS: THEIR ROLE IN HUMAN NUTRITION , 1976 .

[47]  J. Kühnau The flavonoids. A class of semi-essential food components: their role in human nutrition. , 1976, World review of nutrition and dietetics.