Intracellular metabolism and bioactivity of quercetin and its in vivo metabolites

Biochemical Journal

Volumn 372, Issue 1, 2003, Pages 173-181

  Spencer, Jeremy P E ^a   Kuhnle, Gunter G C ^a   Williams, Robert J ^a   Rice Evans, Catherine ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

Fibroblast; Flavonoid; Glucuronide; MS; O methylated; Oxidative stress

Indexed keywords

ACTIVATION ANALYSIS; METABOLISM; METABOLITES; OXIDATION;

CELLULAR EFFECTS;

BIOCHEMISTRY;

FLAVONOID; GLUCURONIDE; QUERCETIN;

APOPTOSIS; ARTICLE; BIOAVAILABILITY; CELL LYSATE; CELL METABOLISM; CELL PROTECTION; DETOXIFICATION; DIETARY INTAKE; DRUG ACTIVITY; GLUCURONIDATION; HUMAN; HUMAN CELL; HUMAN TISSUE; METABOLITE; METHYLATION; OXIDATIVE STRESS; PRIORITY JOURNAL; SKIN FIBROBLAST;

CHROMATOGRAPHY, LIQUID; FIBROBLASTS; HUMANS; MASS SPECTROMETRY; METHYLATION; OXIDATIVE STRESS; QUERCETIN;

EID: 0038291933     PISSN: 02646021     EISSN: None     Source Type: Journal    
DOI: 10.1042/BJ20021972     Document Type: Article

References (50)

1. Spencer, J. P. E., Schroeter, H, Crossthwaithe, A. J., Kuhnle, G., Williams, R. J. and Rice-Evans, C. (2001) Contrasting influences of glucuronidation and O-methylation of epicatechin on hydrogen peroxide-induced cell death in neurons and fibroblasts. Free Radical Biol. Med. 31, 1139-1146
2. Spencer, J. P. E., Schroeter, H., Kuhnle; G., Srai, S. K., Tyrrell, R. M., Hahn, U. and Rice-Evans, C. (2001) Epicatechin and its in vivo metabolite, 3′-O-methyl epicatechin, protect human fibroblasts from oxidative-stress-induced cell death involving caspase-3 activation. Biochem. J. 354, 493-500.
3. Schroeter, H., Spencer, J. P. E., Rice-Evans, C. and Williams, R. J. (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
4. Koga, T. and Meydani, M. (2001) Effect of plasma metabolites of (+)-catechin and quercetin on monocyte adhesion to human aortic endothelial cells. Am. J. Clin. Nutr. 73, 941-948
5. Richter, M., Ebermann, R. and Marian, B. (1999) Quercetin-induced apoptosis in colorectal tumor cells: possible role of EGF receptor signaling. Nutr. Cancer 34, 88-99
6. Wei, Y. Q., 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
7. Wang, I. K., Lin-Shiau, S. Y. and Lin, J. K. (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
8. Russo, M., Palumbo, R., Tedesco, I., Mazzarella, G., Russo, P., Iacomino, G. and Russo, G. L. (1999) Quercetin and anti-CD95(Fas/Apo1) enhance apoptosis in HPB-ALL cell line. FEBS Lett. 462, 322-328
9. Choi, J. A., Kim, J. Y., Lee, J. Y., Kang, C. M., Kwon, H. J., Yoo, Y. D., Kim, T. W., Lee, Y. S. and Lee, S. J. (2001) Induction of cell cycle arrest and apoptosis in human breast cancer cells by quercetin. Int. J. Oncol. 19, 837-844
10. Iwashita, K., Kobori, M., Yamaki, K. and Tsushida, T. (2000) Flavonoids inhibit cell growth and induce apoptosis in B16 melanoma 4A5 cells. Biosci. Biotechnol. Biochem. 64, 1813-1820
11. Ishikawa, Y. and Kitamura, M. (2000) Bioflavonoid quercetin inhibits mitosis and apoptosis of glomerular cells in vitro and in vivo. Biochem. Biophys. Res. Commun. 279, 629-634
12. Kobuchi, H., Roy, S., Sen, C. K., Nguyen, H. G. and Packer, L. (1999) Quercetin inhibits inducible ICAM-1 expression in human endothelial cells through the JNK pathway. Am. J. Physiol. 277, C403-C411
13. Ishige, K., Schubert, D. and Sagara, Y. (2001) Flavonoids protect neuronal cells from oxidative stress by three distinct mechanisms. Free Radical Biol. Med. 30, 433-446
14. Bestwick, C. S. and Milne, L. (2001) Quercetin modifies reactive oxygen levels but exerts only partial protection against oxidative stress within HL-60 cells. Biochim. Biophys. Acta 1528, 49-59
15. Spencer, J. P. E., Chowrimootoo, G., Choudhury, R., Debnam, E. S., Srai, S. K. and Rice-Evans, C. (1999) The small intestine can both absorb and glucuronidate luminal flavonoids. FEBS Lett. 458, 224-230
16. Shimoi, K., Okada, H., Furugori, M., Goda, T., Takase, S., Suzuki, M., Hara, Y., Yamamoto, H. and Kinae, N. (1998) Intestinal absorption of luteolin and luteolin 7-O-beta-glucoside in rats and humans. FEBS Lett. 438, 220-224
17. Scheline, R. R. (1999) In CRC Handbook of Mammalian Metabolism of Plant Compounds, pp. 243-295, CRC Press, Boca Ranton
18. Scalbert, A. and Williamson, G. (2000) Dietary intake and bioavailability of polyphenols. J. Nutr. 130, 2073S-2085S
19. Morand, C., Manach, C., Crespy, V. and Remesy, C. (2000) Respective bioavailability of quercetin aglycone and its glycosides in a rat model. Biofactors 12, 169-174
20. Galijatovic, A., Otake, Y., Walle, U. K. and Walle, T. (2001) Induction of UDP-glucuronosyltransferase UGT1A1 by the flavonoid chrysin in Caco-2 cells - potential role in carcinogen bioinactivation. Pharm. Res. 18, 374-379
21. Moridani, M. Y., Scobie, H., Salehi, P. and O'Brien, P. J. (2001) Catechin metabolism: glutathione conjugate formation catalyzed by tyrosinase, peroxidase, and cytochrome p450. Chem. Res. Toxicol. 14, 841-848
22. Boulton, D. W., Walle, U. K. and Walle, T. (1999) Fate of the flavonoid quercetin in human cell lines: chemical instability and metabolism. J. Pharm. Pharmacol. 51, 353-359
23. Spencer, J. P. E., Jenner, P., Daniel, S. E., Lees, A. J., Marsden, D. C. and Halliwell, B. (1998) Conjugates of catecholamines with cysteine and GSH in Parkinson's disease: Possible mechanisms of formation involving reactive oxygen species. J. Neurochem. 71, 2112-2122
24. Awad, H. M., Boersma, M. G., Boeren, S., van der Woude, H., van Zanden, J., van Bladeren, P. J., Vervoort, J. and Rietjens, I. M. (2002) Identification of o-quinone/quinone methide metabolites of quercetin in a cellular in vitro system. FEBS Lett. 520, 30-34
25. Awad, H. M., Boersma, M. G., Boeren, S., van Bladeren, P. J., Vervoort, J. and Rietjens, I. M. (2002) The regioselectivity of glutathione adduct formation with flavonoid quinone/quinone methides is pH-dependent. Chem. Res. Toxicol. 15, 343-351
26. Rietjens, I. M., Awad, H. M., Boersma, M. G., van Iersel, M. L., Vervoort, J. and van Bladeren, P. J. (2002) Structure activity relationships for the chemical behaviour and toxicity of electrophilic quinones/quinone methides. Adv. Exp. Med. Biol. 500, 11-21
27. Awad, H. M., Boersma, M. G., Vervoort, J. and Rietjens, I. M. (2000) Peroxidase-catalyzed formation of quercetin quJnone methide-glutathione adducts. Arch. Biochem. Biophys. 378, 224-233
28. Galati, G., Moridani, M. Y., Chan, T. S. and O'Brien, P. J. (2001) Peroxidative metabolism of apigenin and naringenin versus luteolin and quercetin: glutathione oxidation and conjugation. Free Radical Biol. Med. 30, 370-382
29. Awad, H. M., Boersma, M. G., Boeren, S., van Bladeren, P. J., Vervoort, J. and Rietjens, I. M. (2001) Structure-activity study on the quinone/quinone methide chemistry of flavonoids. Chem. Res. Toxicol. 14, 398-408
30. Iverson, S. L., Shen, L., Anlar, N. and Bolton, J. L. (1996) Bioactivation of estrone and its catechol metabolites to quinoid-glutathione conjugates in rat liver microsomes. Chem. Res. Toxicol. 9, 492-499
31. Metodiewa, D., Jaiswal, A. K., Cenas, N., Dickancaite, E. and Segura-Aguilar, J. (1999) Quercetin may act as a cytotoxic prooxidant after its metabolic activation to semiquinone and quinoidal product. Free Radical Biol. Med. 26, 107-116
32. Jorgensen, L. V., Cornett, C., Justesen, U., Skibsted, L. H. and Dragsted, L. O. (1998) Two-electron electrochemical oxidation of quercetin and kaempferol changes only the flavonoid C-ring. Free Radical Res. 29, 339-350
33. MacGregor, J. T. and Jurd, L. (1978) Mutagenicity of plant flavonoids: structural requirements for mutagenic activity in Salmonella typhimurium. Mutat. Res. 54, 297-309
34. Monks, T. J. and Lau, S. S. (1998) The pharmacology and toxicology of polyphenolic-glutathione conjugates. Annu. Rev. Pharmacol. Toxicol. 38, 229-255
35. Monks, T. J. and Lao, S. S. (1997) Biological reactivity of polyphenolic-glutathione conjugates. Chem. Res. Toxicol. 10, 1296-1313
36. Bolton, J. L. (2002) Quinoids, quinoid radicals, and phenoxyl radicals formed from estrogens and antiestrogens. Toxicology 177, 55-65
37. Cadenas, E. and Ernster, L. (1990) Effect of superoxide dismutase on the autoxidation of hydroquinones formed during DT-diaphorase catalysis and glutathione nucleophilic addition. Adv Exp. Med. Biol. 264, 37-44
38. Ishikawa, T. (1992) The ATP-dependent glutathione S-conjugate export pump. Trends Biochem. Sci. 17, 463-468
39. Carvalho, M., Hawksworth, G., Milhazes, N., Borges, F., Monks, T. J., Fernandes, E., Carvalho, F. and Bastos, M. L. (2002) Role of metabolites in MDMA (ecstasy)-induced nephrotoxicity: an in vitro study using rat and human renal proximal tubular cells. Arch. Toxicol. 76, 581-588
40. Spencer, J. P. E., Jenner, P. and Halliwell, B. (1995) Superoxide-dependent depletion of reduced glutathione by L-DOPA and dopamine. Relevance to Parkinson's disease. Neuroreport 6, 1480-1484
41. Shen, X. M. and Dryhurst, G. (1996) Further insights into the influence of L-cysteine on the oxidation chemistry of dopamine: Reaction pathways of potential relevance to Parkinson's disease. Chem. Res. Toxicol. 9, 751-763
42. Li, H., Shen, X. M. and Dryhurst, G. (1998) Brain mitochondria catalyze the oxidation of 7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H-1,4-benzothiazine-3-carboxylic acid (DHBT-1) to intermediates that irreversibly inhibit complex I and scavenge glutathione: potential relevance to the pathogenesis of Parkinson's disease. J. Neurochem. 71, 2049-2062
43. Spencer, J. P. E., Whiteman, M., Jenner, P. and Halliwell, B. (2002) 5-s-Cysteinyl-conjugates of catecholamines induce cell damage, extensive DNA base modification and increases in caspase-3 activity in neurons. J. Neurochem. 81, 122-129
44. Pawlikowska-Pawlega, B. and Gawron, A. (1995) Effect of quercetin on the growth of mouse fibroblast cells in vitro. Pol. J. Pharmacol. 47, 531-535
45. Yamashita, N. and Kawanishi, S. (2000) Distinct mechanisms of DNA damage in apoptosis induced by quercetin and luteolin. Free Radical Res. 33, 623-633
46. Mouria, M., Gokovskaya, A. S., Jong, Y., Buechler, P., Hines, O. J., Reber, H. A. and Pandol, S. J. (2002) Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome C release and apoptosis. Int. J. Cancer 98, 761-769
47. Skaper, S. D., Fabris, M., Ferrari, V., Dalle, C. M. and 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 Biol. Med. 22, 669-678
48. Shirai, M., Yamanishi, R., Moon, J. H., Murota, K. and Terao, J. (2002) Effect of quercet in and its conjugated metabolite on the hydrogen peroxide-induced intracellular production of reactive oxygen species in mouse fibroblasts. Biosci. Biotechnol. Biochem. 66, 1015-1021
49. Breinholt, V. M., Offord, E. A., Brouwer, C., Nielsen, S. E., Brosen, K. and Friedberg, T. (2002) In vitro investigation of cytochrome P450-mediated metabolism of dietary flavonoids. Food Chem. Toxicol. 40, 609-616
50. Shimoi, K., Saka, N., Kaji, K., Nozawa, R. and Kinae, N. (2000) Metabolic fate of luteolin and its functional activity at focal site. Biofactors 12, 181-186