Toxicological aspects of the use of phenolic compounds in disease prevention

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Toxicological aspects of the use of phenolic compounds in disease prevention

The consumption of a diet low in fat and enhanced by fruits and vegetables, especially rich in phenolic compounds, may reduce risks of many civilization diseases. The use of traditional medicines, mainly derived from plant sources, has become an attractive segment in the management of many lifestyle diseases. Concerning the application of dietary supplements (based on phenolic compounds) in common practice, the ongoing debate over possible adverse effects of certain nutrients and dosage levels is of great importance. Since dietary supplements are not classified as drugs, their potential toxicities and interactions have not been thoroughly evaluated. First, this review will introduce phenolic compounds as natural substances beneficial for human health. Second, the potential dual mode of action of flavonoids will be outlined. Third, potential deleterious impacts of phenolic compounds utilization will be discussed: pro-oxidant and estrogenic activities, cancerogenic potential, cytotoxic effects, apoptosis induction and flavonoid-drug interaction. Finally, future trends within the research field will be indicated.

Agte V and Tarwadi K. (2010). The importance of nutrition in the prevention of ocular disease with special reference to cataract. Ophthalmic Res 44(3): 166-172.

Ahmad A, Asad SF, Singh S and Hadi SM. (2000). DNA breakage by resveratrol and Cu(II): reaction mechanism and bacteriophage inactivation. Cancer Lett 154: 29-37.

Angelone T, Pasqua T, Di Majo D, Quintieri AM, Filice E, Amodio N, Tota B, Giammanco M and Cerra MC. (2010). Distinct signalling mechanisms are involved in the dissimilar myocardial and coronary effects elicited by quercetin and myricetin, two red wine flavonols. Nutr Metab Cardiovasc Dis 21(5): 362-371.

Baraldo M. (2008). The influence of circadian rhytms on the kinetics of drugs in humans. Expert Opin Drug Metab Toxicol 4(2): 175-192.

Barjesteh van Waalwijk van Doorn-Khosrovani S, Janssen J, Maas LM, Godschalk RW, Nijhuis JG and Schooten FJ. (2007). Dietary flavonoids induce MLL translocations in primary human CD34+ cells. Carcinogenesis 28: 1703-1709.

Bhat KPL and Pezzuto JM. (2002). Cancer chemopreventive activity of resveratrol. Ann N Y Acad Sci 957: 210-229.

Birt DF, Hendrich S and Wang WQ. (2001). Dietary agents in cancer prevention: flavonoids and isoflavonoids. Pharmacol Ther 90: 157-177.

Biswal SS, Datta K, Shaw SD, Feng X, Robertson JD and Kehrer JP. (2000). Glutathione oxidation and mitochondrial depolarization as mechanisms of nordihydroguaiaretic acid-induced apoptosis in lipoxygenase-deficient FL5.12 cells. Toxicol Sci 53: 77-83.

Brazier NC, Mitchell AH and Levine MD. (2003). Understanding drug-herb interaction. Pharmacoepidemiol Drug Saf 12: 427-430.

Brown JP. (1980). A review of the genetic effects of naturally occurring flavonoids, anthraquinones and related compounds. Mut Res 75: 243-277.

Byrd JC, Shinn C, Waselenko JK, Fuchs EJ, Lehman TA, Nguyen PL, Flinn IW, Diehl LF, Sausville E and Grever MR. (1998). Flavopiridol induces apoptosis in chronic lymphocytic leukemia cells via activation of caspase-3 without evidence of bcl-2 modulation or dependence on functional p53. Blood 92: 3804-3816.

Canivenc-Lavier MC, Bentejac M, Leclerc MH, Siess MH, Latruffe N and Suschetet M. (1996). Differential effects of nonhydroxylated flavonoids as inducers of cytochrome P450 1A and 2B isozymes in rat liver. Toxicol Appl Pharmacol 136: 348-353.

Chung LY, Cheung TC, Kong SK, Fung KP, Choy YM, Chan ZY and Kwok TT. (2001). Induction of apoptosis by green tea catechins in human prostate cancer DU145 cells. Life Sci 68: 1207-1214.

Colalto C. (2010). Herbal interactions on absorption of drugs: Mechanisms of action and clinical risk assessment. Pharmacol Res 62: 207-227.

Cos P, De Bruyne T, Apers S, Vanden Berghe D, Pieters L and Vlietinck AJ. (2003). Phytoestrogens: recent developments. Planta Med 69: 589-599.

Crozier A, Del Rio D and Clifford MN. (2010). Bioavailability of dietary flavonoids and phenolic compounds. Mol Aspects Med 31(6): 446-467.

Csokay B, Prajda N, Weber G and Olah E. (1997). Molecular mechanisms in the antiproliferative action of quercetin. Life Sci 60: 2157-2163.

Cvorovic J, Tramer F, Granzotto M, Candussio L, Decorti G and Passamonti S. (2010). Oxidative stress-based cytotoxicity of delphinidin and cyanidin in colon cancer cells. Arch Biochem Biophys 501: 151-157.

Decker EA. (1997). Phenolics: pro-oxidants or antioxidants? Nutr Rev 55: 396-407.

Degli Esposti M. (1998). Inhibitors of NADH-ubiquinone reductase: an over-view. Biochim Biophys Acta 1364: 222-235.

Doostdar H, Burke MD and Mayer RT. (2000). Bioflavonoids: selective substrates and inhibitors for cytochrome P450 CYP1A and CYP1B1. Toxicology 144: 31-38.

Duffy C, Perez K and Partridge A. (2007). Implications of phytoestrogen intake for breast cancer. CA Can J Clin 57: 260-277.

Dunnick JK and Hailey JR. (1992). Toxicity and carcinogenicity studies of quercetin, a natural component of foods. Fundam Appl Toxicol 19: 423-431.

Duthie GG, Gardner PT and Kyle JA. (2003). Plant polyphenols: are they the new magic bullet? Proc Nutr Soc 62: 599-603.

EMEA Commitee on Herbal Medicinal Products. (2006). Guideline on the assessment of clinical safety and efficacy in the preparation of community herbal monographs for well-estabilished and of community herbal monographs/entries to the community list for traditional herbal medicinal products/substances/preparations. Avaible from: http://www.emea.europa.eu/pdfs/human/hmpc/10461305en.pdf

Fang N and Casida JE. (1998). Anticancer action of cube insecticide: correlation for rotenoid constituents between inhibition of NADH: ubiquinone oxidoreductase and induced ornithine decarboxylase activities. Proc Natl Acad Sci USA 95: 3380-3384.

Feng R, Ni HM, Wang SY, Tourkova IL, Shurin MR, Harada H and Yin XM. (2007). Cyanidin-3-rutinoside, a natural polyphenol antioxidant, selectively kills leukemic cells by induction of oxidative stress. J Biol Chem 282: 13468-13476.

Ferguson LR and Philpott M. (2008). Nutrition and mutagenesis. Annu Rev Nutr 28: 313-329.

Fischer PM and Lane DP. (2000). Inhibitors of cyclin-dependent kinases as anti-cancer therapeutics. Curr Med Chem 7: 1213-1245.

Formica JV and Regelson W. (1995). Review of the biology of quercetin and related bioflavonoids. Food Chem Toxicol 33: 1061-1080.

Fraga CG, Galleano M, Verstraeten SV and Oteiza PI. (2010). Basic biochemical mechanisms behind the health benefits of polyphenols. Mol Aspects Med 31: 435-445.

Franconi F, Brunelleschi S, Steardo L and Cuomo V. (2007). Gender differences in drug responses. Pharmacol Res 55(2): 81-95.

Fuhr U. (1998). Drug interactions with grapefruit juice. Extent, probablemechanism and clinical relevance. Drug Saf 18(4): 251-272.

Furukawa A, Oikawa S, Murata M, Hiraku Y and Kawanishi S. (2003). (_)-Epigallocatechin gallate causes oxidative damage to isolated and cellular DNA. Biochem Pharmacol 66: 1769-1778.

Galati G and O'Brien PJ. (2004). Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties. Free Radic Biol Med 37(3): 287-303.

Galati G, Sabzevari O, Wilson JX and O'Brien PJ. (2002). Pro-oxidant activity and cellular effects of the phenoxyl radicals of dietary flavonoids and other polyphenolics. Toxicology 177: 91-104.

Gerwirtz DA. (1991). Does bulk damage to DNA explain the cytostatic and cytotoxic effects of topoisomerase II inhibitors? Biochem Pharmacol 42: 2253-2258.

Ghosh D and Konishi T. (2007). Anthocyanins and anthocyanin-rich extracts: role in diabetes and eye function. Asia Pac J Clin Nutr 16(2): 200-208.

Gill WB. (1988). Effects on human males of in utero exposure to exogenous sex hormones, in Toxicity of hormones in perinatal life (Mori T and Nagasawa H eds) pp. 161-177, CRC, Boca Raton, FL.

Goldstein JC, Waterhouse P, Juin P, Evan GI and Green DR. (2000). The coordinate release of cytochrome c is rapid, complete, and kinetically invariant. Nat Cell Biol 2: 156-162.

Guarrera S, Sacerdote C, Fiorini L, Marsala R, Polidoro S, Gamberini S, Saletta F, Malaveille C, Talaska G, Vineis P and Matullo G. (2007). Expression of DNA repair and metabolic genes in response to a flavonoid-rich diet. Br J Nutr 98: 525-533.

Guengerich FP, Shimada T, Yun CH, Yamazaki H, Raney KD, Their R, Coles B and Harris TM. (1994). Interactions of ingested food, beverage, and tobacco components involving human cytochrome P4501A2, 2A6, 2E1, and 3A4 enzymes. Environ Health Perspect 102: 49-53.

Hadi SM, Asad SF, Singh S and Ahmad A. (2000). Putative mechanism for anticancer and apoptosis-inducing properties of plantderived polyphenolic compounds. IUBMB Life 50: 167-171.

Halliwell B. (2007). Dietary polyphenols: good, bad, or indifferent for your health? Cardiovasc Res 73: 341-347.

Halliwell B. (2008). Are polyphenols antioxidants or pro-oxidants? What do we learn from cell culture and in vivo studies? Arch Biochem Biophys 476(2): 107-112.

Halliwell B. (2009). The wanderings of a free radical. Free Radic Biol Med 46: 531-542.

Hirose M, Fukushima S, Sakata T, Inui M and Ito N. (1983). Effect of quercetin on two-stage carcinogenesis of the rat urinary bladder. Cancer Lett 21: 23-27.

Hodek P, Hanustiak P, Krizkova J, Mikelova R, Krizkova S, Stiborova M, Trnkova L, Horna A, Beklova M and Kizek R. (2006). Toxicological aspects of flavonoid interaction with biomacromolecules. Neuro Endocrinol Lett 27(Suppl 2): 14-17.

Hodek P, Trefil P and Stiborova M. (2002). Flavonoids—potent and versatile biologically active compounds interacting with cytochromes P450. Chem Biol Interact 139: 1-21.

Hou DX, Ose T, Lin S, Harazoro K, Imamura I, Kubo M, Uto T, Terahara N, Yoshimoto M and Fujii M. (2003). Anthocyanidins induce apoptosis in human promyelocytic leukemia cells: structure-activity relationship and mechanisms involved. Int J Oncol 23: 705-712.

Huang YT, Hwang JJ, Lee PP, Ke FC, Huang JH, Huang CJ, Kandaswami C, Middleton EJr and Lee MT. (1999). Effects of luteolin and quercetin, inhibitors of tyrosine kinase, on cell growth and metastasis-associated properties in A431 cells overexpressing epidermal growth factor receptor. Br J Pharmacol 128: 999-1010.

Ibrahim AR and Abul-Hajj YJ. (1990). Aromatase inhibition by flavonoids. J Steroid Biochem Mol Biol 37: 257-260.

Ito N, Hagiwara A, Tamano S, Kagawa M, Shibata MA, Kurata Y and Fukushima S. (1989). Lack of carcinogenicity of quercetin in F334/DuCrj rats. Jpn J Cancer Res 80: 317-325.

Izzo AA and Ernst E. (2001). Interactions between herbal medicines and prescribed drugs: a systematic review. Drugs 61(15): 2163-2175.

Jaganatah IB and Crozier A. (2010). Dietary flavonoids and phenolic compounds, in Plant Phenolics and Human Health (Fraga CG ed), pp. 1-50, John Wiley & Sons Inc., Hoboken, NJ.

Jaganathan SK and Mandal M. (2009). Antiproliferative effects of honey and of its polyphenols: a review. J Biomed Biotechnol 2009: 830616.

Kalt W, Hanneken A, Milbury P and Tremblay F. (2010). Recent research on polyphenolics in vision and eye health. J Agric Food Chem 58: 4001-4007.

Katdare M, Jinno H, Osborne MP and Telang NT. (1999). Negative growth regulation of oncogene-transformed human breast epithelial cells by phytochemicals: role of apoptosis. Ann N Y Acad Sci 889: 247-252.

Kellis JT and Vickery LE. (1984). Inhibition of human estrogen synthetase (aromatase) by flavones. Science 225: 1032-1034.

Kim JS, He L and Lemasters JJ. (2003). Mitochondrial permeability transition: a common pathway to necrosis and apoptosis. Biochem Biophys Res Commun 304: 463-470.

Klejdus B, Mikelova R, Petrlova J, Potesil D, Adam V, Stiborova M, Hodek P, Vacek J, Kizek R and Kuban V. (2005). Evaluation of isoflavone aglycon and glycoside distribution in soy plants and soybeans by fast column high-performance liquid chromatography coupled with a diode-array detector. J Agric Food Chem 53: 5848-5852.

Knekt P, Kumpulainen J, Järvinen R, Rissanen H, Heliövaara M, Reunanen A, Hakulinen T and Aromaa A. (2002). Flavonoid intake and risk of chronic diseases. Am J Clin Nutr 76(3): 560-568.

Kohn MC, Walker NJ, Kim AH and Portier CJ. (2001). Physiological modeling of a proposed mechanism of enzyme induction by TCD. Toxicology 162: 193-208.

Kong AN, Yu R, Chen C, Mandlekar S and Primiano T. (2000). Signal transduction events elicited by natural products: role of MAPK and caspase pathways in homeostatic response and induction of apoptosis. Arch Pharm Res 23(1): 1-16.

Kroemer G. (2003). Mitochondrial control of apoptosis: an introduction. Biochem Biophys Res Commun 304: 433-435.

Kuo SM. (1996). Antiproliferative potency of structurally distinct dietary flavonoids on human colon cancer cells. Cancer Lett 110: 41-48.

Lockwood B. (2008). The beneficial effects of soy isoflavones in osteoporosis of the elderly. Elderly Nutr AgroFood Ind Hi-tech 19(5): 38-41.

Makela S, Poutanen M, Kostian ML, Lehtimaki N Strauss L, Santti R and Vihko R. (1998). Inhibition of 17beta-hydroxysteroid oxidoreductase by flavonoids in breast and prostate cancer cells. Proc Soc Exp Biol Med 217(3): 310-316.

Messina M and Wood CE. (2008). Soy isoflavones, estrogen therapy, and breast cancer risk: analysis and commentary. Nutr J 7(1): 17-28.

Messina M, McCaskill-Stevens W and Lampe JW. (2006). Addressing the soy and breast cancer relatioship: review, commentary, and workshop proceedings. J Natl Can Inst 98(18): 1275-1284.

Metodiewa D, Jaiswal AK, Cenas N, Dickancaite E and Segura-Aguilar J. (1999). Quercetin may act as a cytotoxic pro-oxidant after its metabolic activation to semiquinone and quinoidal product. Free Radic Biol Med 26(1-2): 107-116.

Miadokova E. (2009). Isoflavonoids - an overview of their biological activities and potential health benefits. Interdiscip Toxicol 2(4): 211-218.

Middleton E and Kandaswami C. (1994). The impact of plant flavonoids on mammalian biology: implications for immunity, inflammation and cancer, in The flavonoids: advances in research since 1986 (Harborne JB ed) pp. 619-652, Chapman & Hall, London.

Miksicek RJ. (1995). Estrogenic flavonoids: structural requirements for biological activity. Proc Soc Exp Biol Med 208: 44-50.

Miniello VL, Moro GE, Tarantino M, Natile M, Granieri L and Armenio L. (2003). Soy-based formulas and phyto-oestrogens: a safety profile. Acta Paediatr Suppl 91: 93-100.

Morino K, Matsukura N, Kawachi T, Ohgaki H, Sugimura T and Hirono I. (1982). Carcinogenicity test of quercetin and rutin in golden hamsters by oral administration. Carcinogenesis 3: 93-97.

Newbold RR, Banks EP, Bullock B and Jefferson WN. (2001). Uterine adenocarcinoma in mice treated neonatally with genistein. Cancer Res 61(11): 4325-4328.

Ni H, Simile C, and Hardy AM. (2002). Utilization of complementary and alternative medicine by United States adults: results from the 1999 national health interview survey. Med Care 40: 353-358.

Omiecinski CJ, Remmel RP and Hosagrahara VP. (1999). Concise review of the cytochrome P450s and their roles in toxicology. Toxicol Sci 48: 151-156.

Oyama Y, Noguchi S, Nakata M, Okada Y, Yamazaki Y, Funai M, Chikahisa L and Kanemaru K. (1999). Exposure of rat thymocytes to hydrogen peroxide increases annexin V binding to membranes: inhibitory actions of deferoxamine and quercetin. Eur J Pharmacol 384: 47-52.

Pamukcu AM, Yalciner S, Hatcher JF and Bryan GT. (1980). Quercetin, a rat intestinal and bladder carcinogen present in bracken fern (Pteridium aquilinum). Cancer Res 40: 3468-3472.

Panes J, Gerritsen ME, Anderson DC, Miyasaka M and Granger DN. (1996). Apigenin inhibits tumor necrosis factor-induced intercellular adhesion molecule-1 upregulation in vivo. Microcirculation 3: 279-286.

Paschka AG, Butler R and Young CY. (1998). Induction of apoptosis in prostate cancer cell lines by the green tea component, (_)-epigallocatechin-3-gallate. Cancer Lett 130(1-2): 1-7.

Patil BS, Jayaprakasha GK, Chidambara Murthy KN and Vikram A. (2009). Bioactive compounds: historical perspectives, opportunities, and challenges. J Agric Food Chem 57(18): 8142-8160.

Rahman A, Shahabuddin A, Hadi SM and Parish JH. (1990). Complexes involving quercetin, DNA and Cu(II). Carcinogenesis 11(11): 2001-2003.

Rhone M and Basu A. (2008). Phytochemicals and age-related eye diseases. Nutr Rev 66(8): 465-472.

Rietjens IM, Boersma MG, van der Woude H, Jeurissen SM, Schutte ME and Alink GM. (2005). Flavonoids and alkenylbenzenes: mechanisms of mutagenic action and carcinogenic risk. Mutat Res 574(1-2): 124-138.

Rietjens IM, Huseiny WA, Boersma MG. (2011). Flavonoids and alkenylbenzenes: New concepts in bioactivation studies. Chem Biol Interact 190(1-2): 87-95.

Rietjens IM, Slob W, Galli C and Silano V. (2008). Risk assessment of botanical preparations intended for use in food and food supplements: emerging issues. Toxicol Lett 180(2): 131-136.

Rong Y, Yang EB, Zhang K and Mack P. (2000). Quercetin-induced apoptosis in the monoblastoid cell line U937 in vitro and the regulation of heat shock proteins expression. Anticancer Res 20: 4339-4345.

Ross JA. (1998). Maternal diet and infant leukemia: a role for DNA topoisomerase II inhibitors? Int J Cancer 11: 26-28.

Ross JA and Kasum CM. (2002). Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu Rev Nutr 22: 19-34.

Ross JA, Potter JD and Robison LL. (1994). Infant leukemia, topoisomerase II inhibitors, and the MLL gene. J Natl Cancer Inst 86: 1678-1680.

Russo M, Palumbo R, Tedesco I, Mazzarella G, Russo P, Iacomino G and Russo GL. (1999). Quercetin and anti-CD95(Fas/ Apo1) enhance apoptosis in HPBALL cell line. FEBS Lett 462: 322-328.

Rzymowska J, Gawron A, Pawlikowska-Pawlega B, Jakubowicz-Gil J and Wojcierowski J. (1999). The effect of quercetin on induction of apoptosis. Fol Histochem Cytobiol 37: 125-126.

Sakihama Y, Cohen MF, Grace SC and Yamasaki H. (2002). Plant phenolic antioxidant and pro-oxidant activities: phenolics-induced oxidative damage mediated by metals in plants. Toxicology 177: 67-80.

Scalbert A and Williamson G. (2000). Dietary intake and bioavailability of polyphenols. J Nutr 130: 2073S-2085S.

Schewe T, Steffen Y and Sies H. (2008). How do dietary flavanols improve vascular function? A position paper. Arch Biochem Biophys 476(2): 102-106.

Schilter B, Andersson C, Anton R, Constable A, Kleiner J, O'Brien J, Renwick AG, Korver O, Smit F and Walker R. (2003). Guidance for the safety assessment of botanicals and botanical preparations for use in food and food supplements. Food Chem Toxicol 41(12): 1625-1649.

Schroeter H, Spencer JP, Rice-Evans C and Williams RJ. (2001). Flavonoids protect neurons from oxidized low-density-lipoprotein-induced apoptosis involving c-Jun N-terminal kinase (JNK), c-Jun and caspase-3. Biochem J 358: 547-557.

So FV, Guthrie N, Chambers AF, Moussa M and Carroll KK. (1996). Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices. Nutr Cancer 26: 167-181.

Soriani M, Rice-Evans C and Tyrrell RM. (1998). Modulation of the UVA activation of haem oxygenase, collagenase and cyclooxygenase gene expression by (_)-epigallocatechin in human skin cells. FEBS Lett 439: 253-257.

Spencer JP, Rice-Evans C and Williams RJ. (2003a). Modulation of pro-survival Akt/protein kinase B and ERK1/2 signaling cascades by quercetin and its in vivo metabolites underlie their action on neuronal viability. J Biol Chem 278(37): 34783-34793.

Spencer JP, Kuhnle GG, Williams RJ and Rice-Evans C. (2003b). Intracellular metabolism and bioactivity of quercetin and its in vivo metabolites. Biochem J 372: 173-181.

Steiner C, Peters WH, Gallagher EP, Magee P, Rowland I and Pool-Zobel BL. (2007). Genistein protects human mammary epithelial cells from benzo(a) pyrene-7,8-dihydrodiol-9,10-epoxide and 4-hydroxy-2-nonenal genotoxicity by modulating the glutathione/glutathione S-transferase system. Carcinogenesis 28: 738-748.

Strick R, Strissel PL, Borgers S, Smith SL and Rowley JD. (2000). Dietary bioflavonoids induce cleavage in the MLL gene and may contribute to infant leukemia. Proc Natl Acad Sci USA 97: 4794-4795.

Surh YJ, Hurh YJ, Kang JY, Lee E, Kong G and Lee SJ. (1999). Resveratrol, an antioxidant present in red wine, induces apoptosis in human promyelocytic leukemia (HL-60) cells. Cancer Lett 140: 1-10.

Syed DN, Afaq F, Sarfaraz S, Khan N, Kedlaya R, Setaluri V and Mukhtar H. (2008). Delphinidin inhibits cell proliferation and invasion via modulation of Met receptor phosphorylation. Toxicol Appl Pharmacol 231(1): 52-60.

Takamura-Enya T, Ishihara J, Tahara S, Goto S, Totsuka T, Sugimura T and Wakabayashi K. (2003). Analysis of estrogenic activity of foodstuffs and cigarette smoke condensates using a yeast estrogen screening method. Food Chem Toxicol 41: 543-550.

Talavera S, Felgines C, Texier O, Besson C, Gil-Izquierdo A, Lamaison JL and Remesy C. (2005). Anthocyanin metabolism in rats and their distribution to digestive area, kidney, and brain. J Agric Food Chem 53: 3902-3908.

Tang DG and Porter AT. (1996). Apoptosis: a current molecular analysis. Pathol Oncol Res 2: 117-131.

Tang W and Stearns RA. (2001). Heterotropic cooperativity of cytochrome P450 3A4 and potential drug - drug interactions. Curr Drug Metab 2: 185-198.

Tassaneeyakul W, Birkett DJ, Veronese ME, McManus ME, Tukey RH, Quattrochi LC, Gelboin HV and Miners JO. (1993). Specificity of substrate and inhibitor probes for human cytochromes P450 1A1 and 1A2. J Pharmacol Exp Ther 265: 401-407.

Terada T and Inui K. (2007). Gene expression and regulation of drug transporter in the intestine and kidney. Biochem Pharmacol 73: 440-449.

Ueda S, Nakamura H, Masutani H, Sasada T, Takabayashi A, Yamaoka Y and Yodoi J. (2001). Baicalin induces apoptosis via mitochondrial pathway as pro-oxidant. Mol Pharmacol 38: 781-791.

van der Woude H, Gliszczynska-Swiglo A, Struijs K, Smeets A, Alink GM and Rietjens IM. (2003). Biphasic modulation of cell proliferation by quercetin at concentrations physiologically relevant in humans. Cancer Lett 200: 41-47.

Walle T, Vincent TS and Walle UK. (2003). Evidence of covalent binding of the dietary flavonoid quercetin to DNA and protein in human intestinal and hepatic cells. Biochem Pharmacol 65: 1603-1610.

Waller CL and McKinney JD. (1995). Three-dimensional quantitative structure-activity relationships of dioxins and dioxin-like compounds: model validation and Ah receptor characterization. Chem Res Toxicol 8: 847-858.

Wang IK, Lin-Shiau SY and Lin JK. (1999). Induction of apoptosis by apigenin and related flavonoids through cytochrome c release and activation of caspase-9 and caspase-3 in leukaemia HL-60 cells. Eur J Cancer 35: 1517-1525.

Wang LS and Stoner GD. (2008). Anthocyanins and their role in cancer prevention. Cancer Lett 269: 281-290.

Wang Y, Gho WM, Chan FL, Chen S and Leung LK. (2008). The red clover (Trifolium pratense) isoflavone biochanin A inhibits aromatase activity and expression. Brit J Nutr 99: 303-310.

Wei YQ, Zhao X, Kariya Y, Fukata H, Teshigawara K and Uchida A. (1994). Induction of apoptosis by quercetin: involvement of heat shock protein. Cancer Res 54: 4952-4957.

Wenzel U, Kuntz S, Brendel MD and Daniel H. (2000). Dietary flavone is a potent apoptosis inducer in human colon carcinoma cells. Cancer Res 60: 3823-3831.

Williams RJ, Spencer JP and Rice-Evans C. (2004). Flavonoids: antioxidants or signalling molecules? Free Radic Biol Med 36(7): 838-849.

Woodward G, Kroon P, Cassidy A and Kay C. (2009). Anthocyanin stability and recovery: implications for the analysis of clinical and experimental samples. J Agric Food Chem 57: 5271-5278.

Yamanaka A, Oda O and Nagao S. (1997). Green tea catechins such as (_)-epicatechin and (_)-epigallocatechin accelerate Cu2+-induced low density lipoprotein oxidation in propagation phase. FEBS Lett 401: 230-234.

Yang GY, Liao J, Kim K, Yurkow EJ and Yang CS. (1998). Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. Carcinogenesis 19: 611-616.

You L, Sar M, Bartolucci EJ, McIntyre BS and Sriperumbudur R. (2002). Modulation of mammary gland development in prepubertal male rats exposed to genistein and methoxychlor. Toxicol Sci 66: 216-225.

Ziberna L, Lunder M, Moze S, Vanzo A, Tramer F, Passamonti S and Drevensek G. (2010). Acute cardioprotective and cardiotoxic effects of bilberry anthocyanins in ischemia-reperfusion injury: beyond concentration-dependent antioxidant activity. Cardiovasc Toxicol 10(4): 283-94.

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