Hostname: page-component-7c8c6479df-94d59 Total loading time: 0 Render date: 2024-03-27T19:56:32.133Z Has data issue: false hasContentIssue false

Plant polyphenols in cancer and heart disease: implications as nutritional antioxidants

Published online by Cambridge University Press:  14 December 2007

Garry G. Duthie*
Affiliation:
Division of Cellular Integrity, Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, UK
Susan J. Duthie
Affiliation:
Division of Cellular Integrity, Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, UK
Janet A. M. Kyle
Affiliation:
Division of Cellular Integrity, Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, UK
*
*Corresponding author: Dr Garry Duthie, fax +44 (0) 1224 716622, email ggd@rri.sari.ac.uk
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Certain dietary antioxidants such as vitamin E and vitamin C are important for maintaining optimum health. There is now much interest in polyphenolic products of the plant phenylpropanoid pathway as they have considerable antioxidant activity in vitro and are ubiquitous in our diet. Rich sources include tea, wine, fruits and vegetables although levels are affected by species, light, degree of ripeness, processing and storage. This confounds the formulation of databases for the estimation of dietary intakes. Most attention to date has focused on the flavonoids, a generic term which includes chalcones, flavones, flavanones, flavanols and anthocyanins. There is little convincing epidemiological evidence that intakes of polyphenols are inversely related to the incidence of cancer whereas a number of studies suggest that high intakes of flavonoids may be protective against CHD. In contrast, numerous cell culture and animal models indicate potent anticarcinogenic activity by certain polyphenols mediated through a range of mechanisms including antioxidant activity, enzyme modulation, gene expression, apoptosis, upregulation of gap junction communication and P-glycoprotein activation. Possible protective effects against heart disease may be due to the ability of some polyphenols to prevent the oxidation of LDL to an atherogenic form although anti-platelet aggregation activity and vasodilatory properties are also reported. However, some polyphenols are toxic in mammalian cells. Thus, until more is known about their bioavailability, metabolism and intracellular location, increasing intakes of polyphenols by supplements or food fortification may be unwise.

Type
Research Article
Copyright
Copyright © CABI Publishing 2000

References

Agullo, G, Gamet, L, Besson, C, Demigne, C & Remesy, C (1994) Quercetin exerts a preferential cytotoxic effect on active dividing colon carcinoma HT29 and Caco-2 cells. Cancer Letters 87, 5563.CrossRefGoogle ScholarPubMed
Ahmad, N, Feyes, DK, Nieminen, AL, Agarwal, R & Mukhtar, H (1997) Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells. Journal of The National Cancer Institute 89, 18811886.CrossRefGoogle ScholarPubMed
Ahmed, MS, Ainley, K, Parish, JH & Hadi, SM (1994 a) Free radical-induced fragmentation of proteins by quercetin. Carcinogenesis 15, 16271630.CrossRefGoogle ScholarPubMed
Ahmed, MS, Ramesh, V, Nagaraja, V, Parish, JH & Hadi, SM (1994 b) Mode of binding of quercetin to DNA. Mutagenesis 9, 193197.CrossRefGoogle ScholarPubMed
Alvi, NK, Rizvi, RY & Hadi, SM (1986) Interaction of quercetin with DNA. Bioscience Reports 6, 861868.CrossRefGoogle ScholarPubMed
Aviram, M & Fuhram, B (1998) Polyphenolic flavonoids inhibit macrophage-mediated oxidation of LDL and attenuate atherogenesis. Atherosclerosis 137, S45—S50.CrossRefGoogle ScholarPubMed
Barrow, A & Griffiths, LA (1971) The biliary excretion of hydroxyethylrutosides and other flavonoids in the rat. Biochemical Journal 125, 24P–25P.CrossRefGoogle ScholarPubMed
Beecher, GR, Warden, BA & Merken, H (1999) Analysis of tea polyphenols. Proceedings of the Society for Experimental Biology and Medicine 220, 267270.CrossRefGoogle ScholarPubMed
Benzie, IF, Szeto, YT, Strain, JJ & Tomlinson, B (1999) Consumption of green tea causes rapid increase in plasma antioxidant power in humans. Nutrition & Cancer 34, 8387.CrossRefGoogle ScholarPubMed
Blot, WJ, Chow, WH & McLaughlin, N (1996) Tea and cancer: a review of the epidemiological evidence. European Journal of Cancer Prevention 5, 425438.Google Scholar
Bourne, LC & RiceEvans, CA (1997) The effect of the phenolic antioxidant ferulic acid on the oxidation of low density lipoprotein depends on the pro-oxidant used. Free Radical Research 27, 337344.CrossRefGoogle ScholarPubMed
Bourne, LC & RiceEvans, CA (1999) Detecting and measuring bioavailability of phenolics and flavonoids in human: Pharmacokinetics of urinary excretion of dietary ferulic acid. Methods in Enzymology 299, 91106.CrossRefGoogle ScholarPubMed
Bravo, L (1998) Polyphenols: Chemistry, dietary sources, metabolism and nutritional significance. Nutrition Reviews 56, 317333.CrossRefGoogle ScholarPubMed
Brown, JE & RiceEvans, CA (1998) Luteolin-rich artichoke extract protects low density lipoprotein from oxidation in vitro. Free Radical Research 29, 247255.CrossRefGoogle ScholarPubMed
Brusick, D (1993) Genotoxicity of phenolic antioxidants. Toxicology and Industrial Health 9, 223230.CrossRefGoogle ScholarPubMed
Cao, GH & Prior, RL (1999) Anthocyanins are detected in human plasma after oral administration of an elderberry extract. Clinical Chemistry 45, 574576.CrossRefGoogle ScholarPubMed
Caltagirone, S, Ranelletti, FO, Rinelli, A, Maggiano, N, Colasante, A, Musiani, P, Aiello, FB & Piantelli, M (1997) Interaction with type II estrogen binding sites and antiproliferative activity of tamoxifen and quercetin in human non-small-cell lung cancer. American Journal of Respiratory Cell & Molecular Biology 17, 5159.CrossRefGoogle ScholarPubMed
Carbonneau, MA, Leger, CL, Descomps, B, Michel, F & Monnier, L (1998) Improvement in the antioxidant status of plasma and low density lipoprotein in subjects receiving a red wine phenolics mixture. Journal of the American Oil Chemists Society 75, 235240.CrossRefGoogle Scholar
Casalini, C, Lodovici, M, Briani, C, Paganelli, G, Remy, S, Cheynier, V & Dolara, P (1999) Effect of complex polyphenols and tannins from red wine (WCPT) on chemically induced oxidative DNA damage in the rat. European Journal of Nutrition 38, 190195.CrossRefGoogle ScholarPubMed
Chaumontet, C, Bex, V, GaillardSanchez, I, Seillanheberden, C, Suschetet, M & Martel, P (1994) Apigenin and tangeretin enhance gap junctional intercellular communication in rat-liver epithelial-cells. Carcinogenesis 15, 23252330.CrossRefGoogle ScholarPubMed
Chaumontet, C, Suschetet, M, HonikmanLeban, E, Krutovskikh, VA, Berges, R, LeBon, AM, Heberden, C, Shahin, MM, Yamasaki, H & Martel, P (1996) Lack of tumor-promoting effects of flavonoids: Studies on rat liver preneoplastic foci and on in vivo and in vitro gap junctional intercellular communication. Nutrition and Cancer 26, 251263.CrossRefGoogle ScholarPubMed
Chen, L, Lee, MJ, Li, H & Yang, CS (1997) Absorption, distribution, elimination of tea polyphenols in rats. Drug Metabolism & Disposition 25, 10451050.Google ScholarPubMed
Chen, ZP, Schell, JB, Ho, CT & Chen, KY (1998) Green tea epigallocatechin gallate shows a pronounced growth inhibitory effect on cancerous cells but not on their normal counterparts. Cancer Letters 129, 173179.CrossRefGoogle Scholar
Cherubini, A, Beal, MF & Frei, B (1999) Black tea increases the resistance of human plasma to lipid peroxidation in vitro but not ex vivo. Free Radical Biology & Medicine 27, 381387.CrossRefGoogle Scholar
Chesson, A, Russell, WR & Provan, GJ (1997) Metabolites of the phenylpropanoid pathway—common origin, common properties. In Polyphenols in Foods, pp. 1723. Luxembourg: Office for Official Publications of the European Communities.Google Scholar
Chi, CW, Chang, YF, Ou, YR, Hsieh, CC, Lui, YW, Peng, FK & Liu, TY (1997) Effect of quercetin on the in vitro and in vivo growth of mouse hepatoma cells. Oncology Reports 4, 10211024.Google ScholarPubMed
Chimi, H, Morel, I, Lescoat, G, Pasdeloup, N, Cillard, P & Cillard, J (1995) Inhibition of iron toxicity in rat hepatocyte culture by natural phenolic-compounds. Toxicology In Vitro 9, 695702.CrossRefGoogle ScholarPubMed
Choudhury, R, Srai, SK, Debnam, E & RiceEvans, CA (1999) Urinary excretion of hydroxycinnamates and flavonoids after oral intravenous administration. Free Radical Biology & Medicine 27, 278286.CrossRefGoogle Scholar
Combs, GF (1992) The Vitamins. Fundamental Aspects in Nutrition and Health. London: Academic Press Inc.Google Scholar
Critchfield, JW, Welsh, CJ, Phang, JM & Yeh, GC (1994) Modulation of adriamycin(r) accumulation and efflux by flavonoids in hct-15 colon cells—activation of p-glycoprotein as a putative mechanism. Biochemical Pharmacology 48, 14371445.CrossRefGoogle Scholar
Croft, KG (1998) The chemistry and biological effects of flavonoids and phenolic acids. Annals of the New York Academy of Sciences 20, 435442.CrossRefGoogle Scholar
Crozier, A, Lean, MEJ, McDonald, MS & Black, C (1997) Quantitative analysis of the flavonoid content of commercial tomatoes, onions, lettuce and celery. Journal of Agricultural and Food Chemistry 45, 490495.CrossRefGoogle Scholar
Csokay, B, Prajda, N, Weber, G & Olah, E (1997) Molecular mechanisms in the antiproliferative action of quercetin. Life Sciences 60, 21572163.CrossRefGoogle ScholarPubMed
Das, NP (1969) Studies on flavonoid metabolism. Degradation of (+)-catechin by rat intestinal contents. Biochimica et Biophysica Acta 177, 668670.CrossRefGoogle ScholarPubMed
Davila, JC, Lenherr, A &Acosta, D (1989) Protective effect of flavonoids on drug-induced hepatotoxicity in vitro. Toxicology 57, 267286.CrossRefGoogle ScholarPubMed
Dewick, PM (1997) Medicinal Natural Products: A Biosynthetic Approach. Chichester, England: John Wiley & Sons Ltd.Google Scholar
Diaz, MN, Frei, B, Vita, JA & Keaney, JF (1997) Antioxidants and atherosclerotic heart disease. New England Journal of Medicine 337, 408416.CrossRefGoogle ScholarPubMed
Di Carlo, G, Mascolo, N, Izzo, AA & Capasso, F (1999) Flavonoids: Old and new aspects of a class of natural therapeutic drugs. Life Sciences 65, 337353.CrossRefGoogle ScholarPubMed
Diplock, AT, Charleux, JL, Crozier-Willi, G, Kok, FJ, RiceEvans, CA, Roberfroid, M, Stahl, W & Vina-Ribes, J (1998) Functional food science and defence against reactive oxidative species. British Journal of Nutrition 80, S77–S112.CrossRefGoogle ScholarPubMed
Dong, X, Shou-Peng, Z & Zhen-Lun, G (1997) Quercetin induced apoptosis in human leukemia HL-60 cells. Acta Pharmacologica Sinica 18, 280283.Google Scholar
Donovan, JL, Bell, JR, Kasim-Karakas, S, German, JB, Walzem, RL, Hansen, RJ & Waterhouse, AL (1999) Catechin is present as metabolites in human plasma after consumption of red wine. Journal of Nutrition 129, 16621668.CrossRefGoogle ScholarPubMed
Duthie, GG (1999) Determination of activity of antioxidants in human subjects. Proceedings of the Nutrition Society 58, 110.CrossRefGoogle ScholarPubMed
Duthie, GG & Crozier, A (2000) Plant-derived phenolic antioxidants. Current Opinions in Lipidology 11, 4347.CrossRefGoogle ScholarPubMed
Duthie, GG, Pedersen, MW, Gardner, PT, Morrice, PC, Jenkinson A, McE, McPhail, DB & Steele, GM (1998) The effect of whisky and wine consumption on total phenol content and antioxidant capacity of plasma from healthy volunteers. European Journal of Clinical Nutrition 52, 733736.CrossRefGoogle ScholarPubMed
Duthie, SJ, Collins, AR, Duthie, GG & Dobson, VL (1997 a) Quercetin and myricetin protect against hydrogen peroxide-induced DNA damage (strand breaks and oxidized pyrimidines) in human lymphocytes. Mutation Research Genetic Toxicology EM 393, 223231.CrossRefGoogle ScholarPubMed
Duthie, SJ & Dobson, VL (1999) Dietary flavonoids protect human colonocyte DNA from oxidative attack in vitro. European Journal of Nutrition 38, 2834.CrossRefGoogle ScholarPubMed
Duthie, SJ, Johnson, W & Dobson, VL (1997 b) The effect of dietary flavonoids on DNA damage (strand breaks and oxidized pyrimidines) and growth in human cells. Mutation Research Genetic Toxicology EM 390, 141151.CrossRefGoogle ScholarPubMed
Elangovan, V, Sekar, N & Govindasamy, S (1994) Chemopreventive potential of dietary biflavonoids against 20-methylcholanthrene-induced tumorigenesis. Cancer Letters 87, 107113.CrossRefGoogle Scholar
Fenech, M, Stockly, C & Aitken, C (1997) Moderate wine consumption protects against hydrogen peroxide-induced damage. Mutagenesis 12, 289296.CrossRefGoogle Scholar
Ferrali, M, Signorini, C, Caciotti, B, Sugherini, L, Ciccoli, L, Giachetti, D & Comporti, M (1997) Protection against oxidative damage of erythrocyte membrane by the flavonoid quercetin and its relation to iron chelating activity. FEBS Letters 416, 123129.CrossRefGoogle ScholarPubMed
Fieschi, M, Codignola, A & Luppi Mosa, AM (1989) Mutagenic flavonol aglycones in infusions and in fresh and pickled vegetables. Food Science 54, 14921495.CrossRefGoogle Scholar
Formica, JV & Regelson, AW (1995) Review of the biology of quercetin and related bioflavanoids. Food and Chemical Toxicology 33, 10611080.CrossRefGoogle Scholar
Franke, AA, Cooney, RV, Custer, LJ, Mordan, LJ & Tanka, Y (1998) Inhibition of neoplastic transformation and bioavailability of dietary flavonoid agents. Advances in Experimental Medicine and Biology 439, 237248.CrossRefGoogle ScholarPubMed
Frankel, EN, Kanner, J, German, JB, Parks, E & Kinsella, JE (1993) Inhibition of oxidation of human low density lipoprotein by phenolic substances in red wine. Lancet 341, 454457.CrossRefGoogle ScholarPubMed
Freese, R, Basu, S, Hietanen, E, Nair, J, Nakachi, K, Bartsch, H & Mutanen, M (1999) Green tea extract decreases plasma malonaldehyde concentration but does not affect other indicators of oxidative stress, nitric oxide production, or hemostatic factors during a high-linoleic acid diet in healthy volunteers. European Journal of Nutrition 38, 149157.CrossRefGoogle Scholar
Fremont, L, Gozzelino, MT, Franchi, MP & Linard, A (1998) Dietary flavonoids reduce lipid peroxidation in rats fed polyunsaturated or monounsaturated fat diets. Journal of Nutrition 128, 14951502.CrossRefGoogle ScholarPubMed
Fuhrman, B, Lavy, A & Aviram, M (1995) Consumption of red wine with meals reduces the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation. American Journal of Clinical Nutrition 61, 549554.CrossRefGoogle ScholarPubMed
Funabiki, R, Takeshita, K, Miura, Y, Shibasto, M & Nagasawa, T (1999) Dietary supplement of G-rutin reduces oxidative damage in the rodent model. Journal of Agricultural and Food Chemistry 47, 10781082.CrossRefGoogle ScholarPubMed
Gandhi, RK & Khanduja, KL (1993) Impact of quercetin consumption on phase-i and phase-ii drug metabolizing enzymes in mice. Journal of Clinical Biochemistry and Nutrition 14, 107112.CrossRefGoogle Scholar
Gaspar, J, Rodrigues, A, Laires, A, Silva, F, Costa, S, Monteiro, MJ & Rueff, J (1994) On the mechanisms of genotoxicity and metabolism of quercetin. Mutagenesis 9, 445449.CrossRefGoogle ScholarPubMed
Geleijnse, JM, Launer, LJ, Hofman, A, Pols, HAP & Witteman, JCM (1999) Tea flavonoids may protect against atherosclerosis—The Rotterdam Study. Archives of Internal Medicine 159, 21702174.CrossRefGoogle ScholarPubMed
Gradelet, S, Astorg, P, Leclerc, J, Chevalier, J, Vernevaut, MF & Siess, MH (1996) Effects of canthaxanthin, astaxanthin, lycopene and lutein on liver xenobiotic-metabolizing enzymes in the rat. Xenobiotica 26, 4963.CrossRefGoogle ScholarPubMed
Graefe, EU, Derendorf, H & Veit, M (1999) Pharmacokinetics and bioavailability of the flavonol quercetin in humans. International Journal of Clinical Pharmacology & Therapeutics 37, 219233.Google ScholarPubMed
Grinberg, LN, Newmark, H, Kitrossky, N, Rahamim, E, Chevion, M & Rachmilewitz, EA (1997) Protective effects of tea polyphenols against oxidative damage to red blood cells. Biochemical Pharmacology 54, 973978.CrossRefGoogle ScholarPubMed
Grinberg, LN, Rachmilewitz, EA & Newmark, H (1994) Protective effects of rutin against hemoglobin oxidation. Biochemical Pharmacology 48, 643649.CrossRefGoogle ScholarPubMed
Halliwell, B (1987) Oxidants and human disease: some new concepts. FASEB Journal 1, 358364.CrossRefGoogle ScholarPubMed
Harborne, JB (1994) The Flavonoids: Advances in Research Since 1986. London: Chapman & Hall.CrossRefGoogle Scholar
Hayek, T, Fuhrman, B, Vaya, J, Rosenblat, M, Belinky, P, Coleman, R, Elis, A & Aviram, M (1997) 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. Arteriosclerosis Thrombosis & Vascular Biology 17, 27442752.CrossRefGoogle ScholarPubMed
Hermann, K (1988) On the occurrence of flavone glycosides in vegetables. Zeitschrift für Lebensmittel-Untersuchung und -Forschung 186, 15.CrossRefGoogle Scholar
Hertog, MGL, Hollman, PCH & Katan, MB (1992 a) Content of potentially anticarcinogenic flavonoids of 28 vegetables and 9 fruits commonly consumed in the Netherlands. Journal of Agricultural and Food Chemistry 40, 23792383.CrossRefGoogle Scholar
Hertog, MGL, Hollman, PCH & Venema, DP (1992 b) Optimization of a quantitative HPLC determination of potentially anticarcinogenic flavonoids in vegetables and fruits. Journal of Agricultural and Food Chemistry 40, 15911598.CrossRefGoogle Scholar
Hertog, MGL, Feskens, EJM, Hollman, PCH, Katan, MB & Kromhout, D (1993 a) Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen elderly study. Lancet 342, 10071011.CrossRefGoogle ScholarPubMed
Hertog, MGL, Hollman, PCH, Katan, MB & Kromhout, D (1993 b) Intake of potentially anticarcinogenic flavonoids and their determinants in adults in the Netherlands. Nutrition & Cancer 20, 2129.CrossRefGoogle ScholarPubMed
Hertog, MGL, Hollman, PCH & van de Putte, B (1993 c) Content of potentially anticarcinogenic flavonoids of tea infusions, wines, and fruit juices. Journal of Agricultural and Food Chemistry 41, 12421246.CrossRefGoogle Scholar
Hertog, MGL, Feskens, EJM, Hollman, PCH, Katan, MB & Kromhout, D (1994) Dietary flavonoids and cancer risk in the Zutphen elderly study. Nutrition & Cancer 22, 175184.CrossRefGoogle ScholarPubMed
Hertog, MGL, Kromhout, D, Aravanis, C, Blackburn, H, Buzina, R, Fidanza, F, Giampaoli, S, Jansen, A, Menotti, A & Nedeljkovic, S (1995) Flavonoid intake and long-term risk of coronary heart disease. Archives of Internal Medicine 27, 381386.CrossRefGoogle Scholar
Hertog, MGL, Sweetnam, PM, Fehily, AM, Elwood, PC & Kromhout, D (1997) Antioxidant flavonols and ischemic heart disease in a Welsh population of men: the Caerphilly Study. American Journal of Clinical Nutrition 65, 14891494.CrossRefGoogle Scholar
Hirano, T, Abe, K, Gotoh, M & Oka, K (1995) Citrus flavone tangeretin inhibits leukaemic HL-60 cell-growth partially through induction of apoptosis with less cytotoxicity on normal lymphocytes. British Journal of Cancer 72, 13801388.CrossRefGoogle ScholarPubMed
Hirano, T, Gotoh, M & Oka, K (1994) Natural flavonoids and lignans are potent cytostatic agents against human leukemic HL-60 cells. Life Sciences 55, 10611069.CrossRefGoogle ScholarPubMed
Hirono, I, Ueno, I, Hosaka, S, Takanashi, H, Matsushima, T, Sugimura, T & Natori, S (1981) Carcinogenicity examination of quercetin and rutin in aci rats. Cancer Letters 13, 1521.CrossRefGoogle ScholarPubMed
Hirose, M, Hoshiya, T, Akagi, K, Futakuchi, M & Ito, N (1994) Inhibition of mammary gland carcinogenesis by green tea catechins and other naturally occurring antioxidants in female Sprague–Dawley rats pretreated with 7,12-dimethylbenz[alpha]anthracene. Cancer Letters 83, 149156.CrossRefGoogle Scholar
Hodgson, JM, Proudfoot, JM, Croft, KD, Puddey, IB, Mori, TA & Beilin, LJ (1999) Comparison of the effects of black and green tea on in vitro lipoprotein oxidation in human serum. Journal of the Science of Food and Agriculture 79, 561566.3.0.CO;2-X>CrossRefGoogle Scholar
Hollman, PCH, de Vries, JHM, van Leeuwen, SD, Mengelers, MJB & Katan, MB (1995) Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers. American Journal of Clinical Nutrition 62, 12761282.CrossRefGoogle ScholarPubMed
Hollman, PCH & Katan, MB (1997) Absorption, metabolism and health effects of dietary flavonoids in man. Biomedicine and Pharmacotherapeutics 51, 305310.CrossRefGoogle ScholarPubMed
Hollman, PCH & Katan, MB (1998) Bioavailability and health effects of dietary flavonols in man. Archives of Toxicology Supplement 20, 237248.CrossRefGoogle ScholarPubMed
Hollman, PCH & Katan, MB (1999) Dietary flavonoids: Intake, health effects and bioavailability. Food and Chemical Toxicology 37, 937942.CrossRefGoogle ScholarPubMed
Hollman, PCH, van Trijp, JMP, Buysman, MNCP, Gaag, MSvd, Mengelers, MJB, de Vries, JHM & Katan, MB (1997 a) Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man. FEBS Letters 418, 152156.CrossRefGoogle ScholarPubMed
Hollman, PCH, van Trijp, JMP, Mengelers, MJB, de Vries, JHM & Katan, MB (1997 b) Bioavailability of the dietary antioxidant flavonol quercetin in man. Cancer Letters 114, 139140.CrossRefGoogle ScholarPubMed
Holvoet, P & Collen, D (1998) Oxidation of low density lipoproteins in the pathogenesis of atherosclerosis. Atherosclerosis 137, S33–S38.CrossRefGoogle ScholarPubMed
Holvoet, P, Perez, G & Zhao, Z (1995) Malonaldehyde-modified low density lipoproteins in patients with atherosclerotic disease. Journal of Clinical Investigation 95, 26112619.CrossRefGoogle Scholar
Ishikawa, T, Suzukawa, M, Ito, T, Yoshida, H, Ayaori, M, Nishiwaki, M, Yonemura, A, Hara, Y & Nakamura, H (1997) Effect of tea flavonoid supplementation on the susceptibility of low density lipoprotein to oxidative modification. American Journal of Clinical Nutrition 66, 261266.CrossRefGoogle ScholarPubMed
Ito, M, Kawaguchi, H, Sakota, Y, Otonari, J & Nitahara, H (1993) Effects of polyphenols, including flavonoids, on glutathione-S-transferase and glutathione-reductase. Bioscience, Biotechnology and Biochemistry 57, 16781680.Google Scholar
Jackson, MJ (1997) The assessment of bioavailability of micronutrients: Introduction. European Journal of Clinical Nutrition 51, 5152.Google ScholarPubMed
Kanazawa, K, Yamashita, T, Ashida, H & Danno, G (1998) Antimutagenicity of flavones and flavonols to heterocyclic amines by specific and strong inhibition of the cytochrome p450 1a family. Bioscience, Biotechnology and Biochemistry 62, 970977.CrossRefGoogle ScholarPubMed
Kandaswami, C, Perkins, E, Drzewiecki, G, Soloniuk, DS & Middleton, E Jr (1992) Differential inhibition of proliferation of human squamous cell carcinoma, gliosarcoma and embryonic fibroblast-like lung cells in culture by plant flavonoids. Anticancer Drugs 3, 525530.CrossRefGoogle ScholarPubMed
Kang, TB & Liang, NC (1997) Studies on the inhibitory effects of quercetin on the growth of HL-60 leukemia cells. Biochemical Pharmacology 54, 10131018.CrossRefGoogle ScholarPubMed
Kappus, H, Koster-Albrecht, D & Remmer, H (1979) 2-Hydroxyoestradiol and (+)-cyanidanol-3 prevent lipid peroxidation of isolated rat hepatocytes. Archives of Toxicology Supplement 2, 321326.CrossRefGoogle Scholar
Katdare, M, Osborne, MP & Telang, NT (1998) Inhibition of aberrant proliferation and induction of apoptosis in pre-neoplastic human mammary epithelial cells by natural phytochemicals. Oncology Reports 5, 311315.Google ScholarPubMed
Kerry, N & Abbey, M (1999) The isoflavone genistein inhibits copper and peroxyl radical mediated low density lipoprotein oxidation in vitro. Atherosclerosis 140, 341347.CrossRefGoogle Scholar
Kimira, M, Arai, Y, Shimoi, K & Watanabe, S (1998) Japanese intake of flavonoids and isoflavonoids from foods. Journal of Epidemiology 8, 168175.CrossRefGoogle ScholarPubMed
King, A & Young, G (1999) Characteristics and occurrence of phenolic phytochemicals. Journal of the American Dietetic Association 99, 213218.CrossRefGoogle ScholarPubMed
Kirk, EA, Sutherland, P, Wang, SA, Chait, A & LeBoeuf, RC (1998) Dietary isoflavones reduce plasma cholesterol and atherosclerosis in C57BL/6 mice but not LDL receptor-deficient mice. Journal of Nutrition 128, 954959.CrossRefGoogle Scholar
Klaunig, JE, Xu, Y, Han, C, Kamendulis, LM, Chen, JS, Heiser, C, Gordon, MS & Mohler, ER (1999) The effect of tea consumption on oxidative stress in smokers and non-smokers. Proceedings of the Society of Experimental Biology & Medicine 220, 249254.Google Scholar
Knekt, P, Jarvinen, R, Seppanen, R, Hellovaara, M, Teppo, L, Pukkala, E & Aromaa, A (1997) Dietary flavonoids and the risk of lung cancer and other malignant neoplasms. American Journal of Epidemiology 146, 223230.CrossRefGoogle ScholarPubMed
Knekt, P, Reunanen, A & Maatela, J (1996) Flavonoid intake and coronary mortality in Finland: a cohort study. British Medical Journal 312, 478481.CrossRefGoogle ScholarPubMed
Koga, T, Moro, K, Nakamori, K, Yamakoshi, J, Hosoyama, H, Kataoka, S & Ariga, T (1999) Increase in antioxidative potential of rat plasma by oral administration of proanthocyanidin-rich extract from grape seeds. Journal of Agricultural and Food Chemistry 47, 18921897.CrossRefGoogle ScholarPubMed
Krinsky, NI (1992) Mechanism of action of biological antioxidants. Proceedings of the Society of Experimental Biology and Medicine 200, 248254.CrossRefGoogle ScholarPubMed
Kritz, H & Sinzinger, H (1997) Tea consumption, lipid metabolism and atherosclerosis. Weiner Klinische Wochenschrift 109, 944988.Google ScholarPubMed
Kuhnau, J (1976) The flavonoids. A class of semi-essential food components: Their role in human nutrition. World Review of Nutrition & Dietetics 24, 11171191.Google ScholarPubMed
Kuo, SM (1996) Antiproliferative potency of structurally distinct dietary flavonoids on human colon cancer cells. Cancer Letters 110, 4148.CrossRefGoogle ScholarPubMed
Kuo, SM, Morehouse, HF & Lin, CP (1997) Effect of antiproliferative flavonoids on ascorbic acid accumulation in human colon adenocarcinoma cells. Cancer Letters 116, 131137.CrossRefGoogle ScholarPubMed
Lagarrigue, S, Chaumontet, C, Heberden, C, Martel, P & GaillardSanchez, I (1995) Suppression of oncogene-induced transformation by quercetin and retinoic acid in rat liver epithelial cells. Cellular & Molecular Biology Research 41, 551560.Google ScholarPubMed
Lairon, D & Amiot, MJ (1999) Flavonoids in food and natural antioxidants in wine. Current Opinions in Lipidology 10, 2328.CrossRefGoogle ScholarPubMed
Laranjinha, JAN, Almeida, LM & Madeira, VMC (1994) Reactivity of dietary phenolic acids and peroxyl radicals: antioxidant activity upon low density lipoprotein peroxidation. Biochemical Pharmacology 48, 487494.CrossRefGoogle ScholarPubMed
Leanderson, P, Faresjo, AO & Tagesson, C (1997) Green tea polyphenols inhibit oxidant-induced DNA strand breakage in cultured lung cells. Free Radical Biology and Medicine 23, 235242.CrossRefGoogle ScholarPubMed
Lin, JK, Chen, YC, Huang, YT & Lin-Shiau, SY (1997) Suppression of protein kinase C and nuclear oncogene expression as possible molecular mechanisms of cancer chemoprevention by apigenin and curcumin. Journal of Cellular Biochemistry Supplements 28/29, 3948.3.0.CO;2-X>CrossRefGoogle ScholarPubMed
Linseisen, J, Radtke, J & Wolfram, G (1997) Flavonoid intake of adults in a Bavarian subgroup of the national food consumption survey. Zeitschrift für Ernahrungswissenschaft 36, 403412.CrossRefGoogle Scholar
Lu, HQ, Niggemann, B & Zanker, KS (1996) Suppression of the proliferation and migration of oncogenic ras-dependent cell lines, cultured in a three-dimensional collagen matrix, by flavonoid-structured molecules. Journal of Cancer Research and Clinical Oncology 122, 335342.CrossRefGoogle Scholar
McAnlis, GT, McEneny, J, Pearce, J & Young, IS (1999) Absorption and antioxidant effects of quercetin from onions, in man. European Journal of Clinical Nutrition 53, 9296.CrossRefGoogle ScholarPubMed
McCarty, MF (1998) Polyphenol-mediated inhibition of ap-1 transactivating activity may slow cancer growth by impeding angiogenesis and tumor invasiveness. Medical Hypotheses 50, 511514.CrossRefGoogle ScholarPubMed
McDonald, MS, Hughes, M, Burns, J, Lean, MEJ, Matthews, D & Crozier, A (1998) Survey of the free and conjugated myricetin and quercetin content of red wines of different geographical origins. Journal of Agricultural and Food Chemistry 46, 368375.CrossRefGoogle ScholarPubMed
Majima, T, Tsutsumi, M, Nishino, H, Tsunoda, T & Konishi, Y (1998) Inhibitory effects of beta-carotene, palm carotene, and green tea polyphenols on pancreatic carcinogenesis initiated by N-nitrosobis(2-oxopropyl)amine in Syrian golden hamsters. Pancreas 16, 1318.CrossRefGoogle ScholarPubMed
Malaveille, C, Hautefeuille, A, Pignatelli, B, Talaska, G, Vineis, P & Bartsch, H (1998) Antimutagenic dietary phenolics as antigenotoxic substances in urothelium of smokers. Mutation Research—Fundamental and Molecular Mechanisms of Mutagenesis 402, 219224.CrossRefGoogle ScholarPubMed
Manach, C, Morand, C, Texier, O, Favier, ML, Agullo, G, Demigné, C, Régérat, F & Rémésy, C (1995) Quercetin metabolites in plasma of rats fed diets containing rutin or quercetin. Journal of Nutrition 125, 19111922.CrossRefGoogle ScholarPubMed
Manach, C, Texier, O, Régérat, F, Agullo, G, Demigné, C & Rémésy, C (1996) Dietary quercetin is recovered in rat plasma as conjugated derivatives of isorhamnetin and quercetin. Nutritional Biochemistry 7, 375380.CrossRefGoogle Scholar
Maridonneau, I, Braquet, P & Garay, RP (1986) Heterogeneous effect of flavonoids on K+ loss and lipid peroxidation induced by oxygen-free radicals in human red cells. Pharmacological Research Communications 18, 6172.CrossRefGoogle Scholar
Martin-Aragon, S, Benedi, JM & Villar, AM (1997) Modifications of antioxidant capacity and liquid peroxidation in mice under fraxetin treatment. Journal of Pharmacy and Pharmacology 49, 4952.CrossRefGoogle Scholar
Mehta, K, Pantazis, P, McQueen, T & Aggarwal, BB (1997) Antiproliferative effect of curcumin (diferuloylmethane) against human breast tumor cell lines. Anticancer Drugs 8, 470481.CrossRefGoogle ScholarPubMed
Melzig, MF, Loose, R & Schonherr, G (1997) Effect of flavonoids on daunomycin-induced toxicity in cultivated endothelial cells. Pharmazie 52, 793796.Google ScholarPubMed
Miura, YH, Tomita, I, Watanabe, T, Hirayama, T & Fukui, S (1998) Active oxygen generations by flavonoids. Biological & Pharmacological Bulletin 21, 9396.CrossRefGoogle ScholarPubMed
Miura, S, Watanabe, J, Sano, M, Tomita, T, Osawa, T, Hara, T & Tomita, I (1995) Effects of various natural antioxidants on the Cu (2+)-mediated oxidative modification of low density lipoprotein. Biological & Pharmacological Bulletin 18, 14.CrossRefGoogle Scholar
Miura, S, Watanabe, J, Tomita, T, Sano, M & Tomita, I (1994) The inhibitory effects of tea polyphenols (flavan-3-ol derivatives) on Cu2+ mediated oxidative modification of low density lipoprotein. Biological & Pharmacological Bulletin 17, 15671572.CrossRefGoogle ScholarPubMed
Miyake, Y, Yamamoto, K, Tsujhara, N & Osawa, T (1998) Protective effects of lemon flavonoids on oxidative stress in diabetic rats. Lipids 33, 689695.CrossRefGoogle ScholarPubMed
Miyazawa, T, Nakagawa, K, Kudo, M, Muraishi, K & Someya, K (1999) Direct intestinal absorption of red fruit anthocyanins, cyanidin-3-glucoside and cyanidin-3,5-diglucoside, into rats and humans. Journal of Agricultural & Food Chemistry 47, 10831092.CrossRefGoogle ScholarPubMed
Morel, I, Lescoat, G, Cogrel, P, Sergent, O, Pasdeloup, N, Brissot, P, Cillard, P & Cillard, J (1993) Antioxidant and iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures. Biochemical Pharmacology 45, 1319.CrossRefGoogle ScholarPubMed
Morino, K, Matsukura, N, Kawachi, T, Ohgaki, H, Sugimura, T & Hirono, I (1982) Carcinogenicity test of quercetin and rutin in golden-hamsters by oral-administration. Carcinogenesis 3, 9397.CrossRefGoogle ScholarPubMed
Morrice, PC, Wood, SG & Duthie, GG (2000) High performance liquid chromatographic determination of quercetin and isorhamnetin in rat tissues using beta-glucuronidase and acid hydrolysis. Journal of Chromatography B 738, 413417.CrossRefGoogle ScholarPubMed
Murray, CW, Booth, AN, de Eds, F & Jones, FT (1954) Absorption and metabolism of rutin and quercetin in the rabbit. Journal of the American Pharmacological Association 43, 361364.CrossRefGoogle ScholarPubMed
Musonda, CA, Helsby, N & Chipman, JK (1997) Effects of quercetin on drug metabolizing enzymes and oxidation of 2′,7-dichlorofluorescein in hepg2 cells. Human & Experimental Toxicology 16, 700708.CrossRefGoogle ScholarPubMed
Nakagawa, K, Ninomiya, M, Okubo, T, Aoi, N, Juneja, LR, Kim, M, Yamanaka, K & Miyazawa, T (1999) Tea catechin supplementation increases antioxidant capacity and prevents phospholipid hydroperoxidation in plasma of humans. Journal of Agricultural and Food Chemistry 47, 3996739973.CrossRefGoogle ScholarPubMed
Nakagawa, Y, Shetlar, ME & Wender, SH (1965) Urinary products from quercetin in neomycin-treated rats. Biochimica et Biophysica Acta 97, 233241.CrossRefGoogle ScholarPubMed
Nakayama, T, Yamada, M, Osawa, T & Kawakishi, S (1993) Suppression of active oxygen-induced cytotoxicity by flavonoids. Biochemical Pharmacology 45, 265267.Google ScholarPubMed
Negre Salvayre, A, Mabile, L, Delchambre, J & Salvayre, R (1995) α-Tocopherol, ascorbic acid, and rutin inhibit synergistically the copper-promoted LDL oxidation and the cytotoxicity of oxidized LDL to cultured endothelial cells. Biological Trace Element Research 47, 8191.CrossRefGoogle ScholarPubMed
Negre Salvayre, A & Salvayre, R (1992) Quercetin prevents the cytotoxicity of oxidized LDL on lymphoid cell lines. Free Radical Biology and Medicine 12, 101106.CrossRefGoogle ScholarPubMed
Ngomuo, AJ & Jones, RS (1996) Genotoxicity studies of quercetin and shikimate in vivo in the bone marrow of mice and gastric mucosal cells of rats. Veterinary and Human Toxicology 38, 176180.Google ScholarPubMed
Nielsen, SE, Young, JF, Daneshvar, B, Lauridsen, ST, Knuthsen, P, Sandstrom, B & Dragsted, LO (1999) Effect of parsley (Petroselinum crispum) intake on urinary apigenin excretion, blood antioxidant enzymes and biomarkers for oxidative stress in human subjects. British Journal of Nutrition 81, 447455.CrossRefGoogle ScholarPubMed
Nigdikar, SV, Williams, NR, Griffin, BA & Howard, AN (1998) Consumption of red wine polyphenols reduces the susceptibility of low density lipoproteins to oxidation in vivo. American Journal of Clinical Nutrition 68, 258265.CrossRefGoogle ScholarPubMed
Noroozi, M, Angerson, WJ & Lean, MEJ (1998) Effects of flavonoids and vitamin C on oxidative DNA damage to human lymphocytes. American Journal of Clinical Nutrition 67, 12101218.CrossRefGoogle ScholarPubMed
Noteborn, HPJM, Jansen, E, Benito, S & Mengelers, MJB (1997) Oral absorption and metabolism of quercetin and sugar-conjugated derivatives in specific transport systems. Cancer Letters 114, 175177.CrossRefGoogle ScholarPubMed
Obermeier, MT, White, RE & Yang, CS (1995) Effects of bioflavonoids on hepatic P450 activities. Xenobiotica 25, 575584.CrossRefGoogle ScholarPubMed
Okushio, K, Suzuki, M, Matsumoto, N, Nanjo, F & Hara, Y (1999) Identification of (–)-epicatechin metabolites and their metabolic fate in the rat. Drug Metabolism & Disposition 27, 309316.Google ScholarPubMed
Omenn, GS, Goodman, GE & Thornquist, MD (1996) Effects of a combination of beta-carotene and vitamin A on lung cancer and cardiovascular disease. New England Journal of Medicine 334, 11501155.CrossRefGoogle ScholarPubMed
Parshad, R, Sanford, KK, Price, FM, Steele, VE, Tarone, RE, Kelloff, GJ & Boone, CW (1998) Protective action of plant polyphenols on radiation-induced chromatid breaks in cultured human cells. Anticancer Research 18, 32633266.Google ScholarPubMed
Peterson, J & Dwyer, J (1998) Flavonoids: dietary occurrence and biochemical activity. Nutrition Research 18, 19952018.CrossRefGoogle Scholar
Plaumann, B, Fritsche, M, Rimpler, H, Brandner, G & Hess, RD (1996) Flavonoids activate wild-type p53. Oncogene 13, 16051614.Google ScholarPubMed
Pratico, D, Iuliano, L & Mauriello, A (1997) Localization of distinct F2-isoprostanes in human atherosclerotic lesions. Journal of Clinical Investigation 100, 20282034.CrossRefGoogle ScholarPubMed
Princen, HMG, van Duyvenvoorde, W, Buytenhek, R, Blonk, C, Tijburg, LBM, Langius, JAE, Meinders, E & Pijl, H (1998) No effect of consumption of green and black tea on plasma lipid and antioxidant levels and on LDL oxidation in smokers. Arteriosclerosis, Thrombosis & Vascular Biology 18, 833841.CrossRefGoogle ScholarPubMed
Puddey, IB & Croft, KD (1999) Alcohol, stroke and coronary heart disease. Are there anti-oxidants and pro-oxidants in alcoholic beverages that might influence the development of atherosclerotic cardiovascular disease. Neuroepidemiology 18, 292302.CrossRefGoogle ScholarPubMed
Raeissi, SD, Guo, ZY, Dobson, GL, Artursson, P & Hidalgo, IJ (1997) Comparison of cyp3a activities in a subclone of caco-2 cells (tc7) and human intestine. Pharmaceutical Research 14, 10191025.CrossRefGoogle Scholar
Rahman, A, Fazal, F, Greensill, J, Ainley, K, Parish, JH & Hadi, SM (1992) Strand scission in DNA induced by dietary flavonoids: role of Cu(I) and oxygen free radicals and biological consequences of scission. Molecular and Cellular Biochemistry 111, 39.CrossRefGoogle ScholarPubMed
Rapola, J, Virtamo, J & Ripatti, S (1997) Randomized trial of alpha-tocopherol and beta-carotene supplements on incidence of major coronary events in men with previous myocardial infarction. Lancet 349, 17151720.CrossRefGoogle ScholarPubMed
Renaud, S & de Longeril, M (1992) Wine alcohol, platelets and the French paradox for coronary heart disease. Lancet 339, 15231526.CrossRefGoogle ScholarPubMed
Ricchi, P, Pignata, S, DiPopolo, A, Memoli, A, Apicella, A, Zarrilli, R & Acquaviva, AM (1997) Effect of aspirin on cell proliferation and differentiation of colon adenocarcinoma caco2 cells. International Journal of Cancer 73, 880884.3.0.CO;2-7>CrossRefGoogle Scholar
RiceEvans, CA, Miller, NJ & Paganga, G (1997) Antioxidant properties of phenolic compounds. Trends in Plant Science 2, 152159.CrossRefGoogle Scholar
Rifici, VA, Stephen, EM, Schneider, SH & Khachadurian, AK (1999) Red wine inhibits the cell-mediated oxidation of LDL and HDL. Journal of the American College of Nutrition 18, 137143.CrossRefGoogle ScholarPubMed
Rimm, EB, Katan, MB, Ascherio, A, Stampfer, MJ & Willett, WC (1996) Relation between intake of flavonoids and risk for coronary heart disease in male health professionals. Annals of Internal Medicine 125, 384389.CrossRefGoogle ScholarPubMed
Robards, K & Antolovich, M (1997) Analytical chemistry of fruit bioflavonoids. Analyst 122, R11–R34.CrossRefGoogle Scholar
Roig, P, Cascon, E, Arola, L, Blade, C & Salvado, MJ (1999) Moderate red wine consumption protects the rat against oxidation in vivo. Life Sciences 6, 15171524.CrossRefGoogle Scholar
Sahu, SC & Gray, GC (1993) Interactions of flavonoids, trace metals and oxygen: nuclear DNA damage and lipid peroxidation induced by myricetin. Cancer Letters 70, 7379.CrossRefGoogle ScholarPubMed
Sahu, SC & Gray, GC (1994) Kaempferol-induced nuclear DNA damage and lipid peroxidation. Cancer Letters 85, 159164.CrossRefGoogle ScholarPubMed
Sahu, SC & Washington, MC (1991 a) Effects of antioxidants on quercetin-induced nuclear DNA damage and lipid peroxidation. Cancer Letters 60, 259264.CrossRefGoogle ScholarPubMed
Sahu, SC & Washington, MC (1991 b) Quercetin-induced lipid peroxidation and DNA damage in isolated rat-liver nuclei. Cancer Letters 58, 7579.CrossRefGoogle ScholarPubMed
Saito, D, Shirai, A, Matsushima, T, Sugimura, T & Hirono, I (1980) Test of carcinogenicity of quercetin, a widely distributed mutagen in food. Teratogenesis, Carcinogenesis and Mutagenesis 1, 213221.CrossRefGoogle ScholarPubMed
Scambia, G, Panici, PB, Ranelletti, FO, Ferrandina, G, Devincenzo, R, Piantelli, M, Masciullo, V, Bonanno, G, Isola, G & Mancuso, S (1994 a) Quercetin enhances transforming growth-factor beta(1) secretion by human ovarian-cancer cells. International Journal of Cancer 57, 211215.CrossRefGoogle ScholarPubMed
Scambia, G, Ranelletti, FO, Panici, PB, Devincenzo, R, Bonanno, G, Ferrandina, G, Piantelli, M, Bussa, S, Rumi, C, Cianfriglia, M & Mancuso, S (1994 b) Quercetin potentiates the effect of adriamycin in a multidrug-resistant mcf-7 human breast-cancer cell-line—p-glycoprotein as a possible target. Cancer Chemotherapy and Pharmacology 34, 459464.CrossRefGoogle Scholar
Schramm, DD, Collins, HE & German, JB (1999) Flavonoid transport by mammalian endothelial cells. Journal of Nutritional Biochemistry 10, 193197.CrossRefGoogle ScholarPubMed
Serafini, M, Ghiselli, A & Ferro-Luzzi, A (1996) In vivo antioxidant effect of green and black tea in man. European Journal of Clinical Nutrition 50, 2832.Google ScholarPubMed
Serafini, M, Maiani, G & Ferro-Luzzi, A (1998) Alcohol-free red wine enhances plasma antioxidant capacity in humans. Journal of Nutrition 128, 10031007.CrossRefGoogle ScholarPubMed
Sestili, P, Guidarelli, A, Dachá, M & Cantoni, O (1998) Quercetin prevents DNA single strand breakage and cytotoxicity caused by tert-butylhydroperoxide: free radical scvenging versus iron chelating mechanism. Free Radical Biology Medicine 25, 196200.CrossRefGoogle Scholar
Shimoi, K, Okada, H, Furugori, M, Goda, T, Suzuki, M, Hara, Y, Yamamoto, H & Kinae, N (1998) Intestinal absorption of luteolin and luteolin 7-O-beta-glucoside in rats and humans. FEBS Letters 438, 220224.CrossRefGoogle ScholarPubMed
Siess, MH, Mas, JP, Canivenc-Lavier, MC & Suschetet, M (1996) Time course of induction of rat hepatic drug-metabolizing enzyme activities following dietary administration of flavonoids. Journal of Toxicology and Environmental Health 49, 481496.Google ScholarPubMed
Skaper, SD, Fabris, M, Ferrari, V, Carbonare, MD & Leon, A (1997) Quercetin protects cutaneous tissue-associated cell types including sensory neurons from oxidative stress induced by glutathione depletion: Cooperative effects of ascorbic acid. Free Radical Biology and Medicine 22, 669678.CrossRefGoogle ScholarPubMed
Slater, TF (1984) Free-radical mechanisms in tissue injury. Biochemical Journal 222, 115.CrossRefGoogle ScholarPubMed
So, FV, Guthrie, N, Chambers, AF, Moussa, M & Carroll, KK (1996) Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices. Nutrition and Cancer 26, 167181.CrossRefGoogle ScholarPubMed
Spencer, JPE, Chowrimoto, G, Choudry, R, Debham, ES, Srai, SK & RiceEvans, CA (1999) The small intestine can both absorb and glucuronidate luminal flavonoids. FEBS Letters 458, 224230.CrossRefGoogle ScholarPubMed
Stagg, GV & Millin, DJ (1975) The nutritional and therapeutic value of tea—a review. Journal of the Science of Food and Agriculture 26, 14391459.CrossRefGoogle Scholar
Steinberg, D (1997) Low density lipoprotein and its pathological significance. Journal of Biological Chemistry 272, 2096320966.CrossRefGoogle Scholar
St Leger, AS, Cochrane, AL & Moore, F (1979) Factors associated with cardiac mortality in developed countries with particular reference to the consumption of wine. Lancet 12, 10171020.CrossRefGoogle Scholar
Suganuma, M, Okabe, S, Oniyama, M, Tada, Y, Ito, H & Fujika, H (1998) Wide distribution of [3H](–)-epigallocatechin gallate, a cancer preventative tea polyphenol in mouse tissue. Carcinogenesis 19, 17711776.CrossRefGoogle ScholarPubMed
Tamura, M, Kagawa, S, Tsuruo, Y, Ishimura, K & Morita, K (1994) Effects of flavonoid compounds on the activity of NADPH diaphorase prepared from the mouse-brain. Japanese Journal of Pharmacology 65, 372373.Google ScholarPubMed
Tijburg, LBM, Wiseman, SA, Meijer, GW & Weststrate, JA (1997) Effects of green tea, black tea and dietary lipophilic antioxidants on LDL oxidizability and atherosclerosis in hypercholesterolaemic rabbits. Atherosclerosis 135, 3747.CrossRefGoogle ScholarPubMed
Tsuda, T, Horio, F & Osawa, T (1999) Absorption and metabolism of cyan-O-beta-D-glucoside in rats. FEBS Letters 449, 179182.CrossRefGoogle ScholarPubMed
Uda, Y, Price, KR, Williamson, J & Rhodes, MJC (1997) Induction of the anticarcinogenic marker enzyme quinone reductase in murine hepatoma cells in vitro by flavonoids. Cancer Letters 120, 213216.CrossRefGoogle ScholarPubMed
Uddin, S & Choudhry, MA (1995) Quercetin, a bioflavonoid, inhibits the DNA synthesis of human leukemia cells. Biochemistry amd Molecular Biology International 36, 545550.Google ScholarPubMed
Ursini, F, Tubaro, F, Rong, J & Sevanian, A (1999) Optimization of nutrition: Polyphenols and vascular protection. Nutrition Reviews 57, 241249.CrossRefGoogle ScholarPubMed
van het Hof, KH, de Boer, HS, Wiseman, SA, Lien, N, Weststrate, JA & Tijburg, LB (1997) Consumption of green or black tea does not increase resistance of low-density lipoprotein to oxidation in humans. American Journal of Clinical Nutrition 66, 11251132.CrossRefGoogle Scholar
van het Hof, KH, Wiseman, SA, Yang, CS & Tijburg, LBM (1999) Plasma and lipoprotein levels of tea catechins following repeated tea consumption. Proceedings of the Society for Experimental Biology and Medicine 220, 203209.CrossRefGoogle ScholarPubMed
Venturi, M, Hambly, RJ, Glinghammar, B, Rafter, JJ & Rowland, IR (1997) Genotoxic activity in human faecal water and the role of bile acids: a study using the alkaline comet assay. Carcinogenesis 18, 23532359.CrossRefGoogle ScholarPubMed
Verma, AK, Johnson, JA, Gould, MN & Tanner, MA (1988) Inhibition of 7,12-dimethylbenz(a)anthracene-and N-nitrosomethylurea-induced rat mammary cancer by dietary flavonol quercetin. Cancer Research 48, 57545758.Google Scholar
Vertommen, J, Vandenenden, M, Simoens, L & Deleeuw, I (1994) Flavonoid treatment reduces glycation and lipid peroxidation in experimental diabetic rats. Phytotherapy Research 8, 430432.CrossRefGoogle Scholar
Viana, M, Barbas, C, Bonet, B, Bonet, MV, Castro, M, Fraile, MV & Herrera, E (1996) In vitro effects of a flavonoid-rich extract on LDL oxidation. Atherosclerosis 123, 8391.CrossRefGoogle ScholarPubMed
Wang, WQ & Goodman, MT (1999) Antioxidant property of dietary phenolic agents in a human LDL-oxidation ex vivo model. Nutrition Research 19, 191202.CrossRefGoogle Scholar
Waterhouse, AL, German, JB, Walzem, RL, Hansen, RJ & Kasim-Karakas, SE (1998) Is it time for a wine trial?. American Journal of Clinical Nutrition 68, 220221.CrossRefGoogle ScholarPubMed
Watson, DG & Oliveira, EJ (1999) Solid-phase extraction and gas chromatography mass spectrometry determination of kaempferol and quercetin in human urine after consumption of Ginkgo biloba tablets. Journal of Chromatography B 723, 203210.CrossRefGoogle ScholarPubMed
Westhuyzen, J (1997) The oxidation hypothesis of atherosclerosis: an update. Annals of Clinical & Laboratory Science 27, 110.Google ScholarPubMed
Whitehead, TP, Robinson, D, Allaway, S, Syms, J & Hale, A (1995) Effect of red wine ingestion on the antioxidant capacity of serum. Clinical Chemistry 41, 3235.CrossRefGoogle ScholarPubMed
Williamson, G, Plumb, GW, Uda, Y, Price, KR & Rhodes, MJC (1996) Dietary quercetin glycosides: antioxidant activity and induction of the anticarcinogenic phase II marker enzyme quinone reductase in Hepalclc7 cells. Carcinogenesis 17, 23852387.CrossRefGoogle ScholarPubMed
Woodford, FP & Whitehead, TP (1998) Is measuring serum antioxidant capacity clinically useful?. Annals of Clinical Biochemistry 35, 4856.CrossRefGoogle ScholarPubMed
Yang, CS, Yang, GY, Landau, JM, Kim, S & Liao, J (1998) Tea and tea polyphenols inhibit cell hyperproliferation, lung tumorigenesis, and tumor progression. Experimental Lung Research 24, 629639.CrossRefGoogle ScholarPubMed
Yochum, L, Kushi, LH, Meyer, K & Folsom, AR (1999) Dietary flavonoid intake and risk of cardiovascular disease in postmenopausal women. American Journal of Epidemiology 149, 943949.CrossRefGoogle ScholarPubMed
Yokozawa, T & Dong, E (1997) Influence of green tea and its three major components upon low-density lipoprotein oxidation. Experimental Toxicology and Pathology 49, 329335.CrossRefGoogle ScholarPubMed
Yoshina, K, Tomita, I, Sano, M, Oguni, I, Hara, Y & Nakano, M (1994) Effects of long term dietary supplementation of tea polyphenols on lipid peroxide levels in rats. Age 17, 7985.CrossRefGoogle Scholar
Young, JF, Nielsen, SE, Haraldsdottir, J, Daneshvar, B, Lauridsen, ST, Knuthsen, P, Crozier, A, Sandstrøm, B & Dragsted, LO (1999) Effect of fruit juice intake on urinary excretion and biomarkers of antioxidative status. American Journal of Clinical Nutrition 69, 8794.CrossRefGoogle ScholarPubMed
Zhai, S, Dai, RK, Friedman, FK & Vestal, RE (1998) Comparative inhibition of human cytochromes P450 1a1 and 1a2 by flavonoids. Drug Metabolism and Disposition 26, 989992.Google ScholarPubMed
Zhang, K, Yang, EB, Tang, WY, Wong, KP & Mack, P (1997) Inhibition of glutathione reductase by plant polyphenols. Biochemical Pharmacology 54, 10471053.CrossRefGoogle ScholarPubMed
Zhu, QY, Huang, Y, Tsang, D & Chen, ZY (1999) Regeneration of alpha-tocopherol in human low-density lipoprotein by green tea catechin. Journal of Agricultural and Food Chemistry 47, 20202025.CrossRefGoogle ScholarPubMed