Absorption and metabolism of flavonoids

Free Radical Biology and Medicine

Volumn 36, Issue 7, 2004, Pages 829-837

  Walle, Thomas ^a  

^a MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

Absorption; Flavonoids; Free radicals; Metabolism; Quercetin

Indexed keywords

CARRIER PROTEIN; CATECHIN; CHRYSIN; CYANIDIN 3 GLUCOSIDE; CYTOCHROME P450; DIOSMETIN; EPICATECHIN; FLAVONOID; FLAVONOID GLYCOSIDE; GALANGIN; ISOFLAVONE; ISOQUERCITRIN; KAEMPFERIDE; KAEMPFEROL; LUTEOLIN; PHYTOESTROGEN; QUERCETIN; QUERCETIN 4' GLUCOSIDE; UNCLASSIFIED DRUG;

AEROBIC METABOLISM; BIOAVAILABILITY; DIET; DIETARY INTAKE; DRUG BLOOD LEVEL; DRUG HALF LIFE; DRUG METABOLISM; ENZYME ACTIVITY; HUMAN; HYDROLYSIS; MEMBRANE TRANSPORT; NONHUMAN; PRIORITY JOURNAL; REVIEW; XENOBIOTIC METABOLISM;

ABSORPTION; ANTHOCYANINS; ANTICARCINOGENIC AGENTS; BIOLOGICAL AVAILABILITY; FLAVONOIDS; GLUCOSIDES; HUMANS; MEMBRANE TRANSPORT PROTEINS; MOLECULAR STRUCTURE; OXIDATION-REDUCTION; TEA;

EID: 1642528478     PISSN: 08915849     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.freeradbiomed.2004.01.002     Document Type: Review

References (82)

1. Kühnau J. The flavonoids. A class of semi-essential food components: their role in human nutrition. World Rev. Nutr. Diet. 24:1976;117-191.
2. Middleton E.J., Kandaswami C., Theoharides T.C. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol. Rev. 52:2000;673-751.
3. Rice-Evans C. Flavonoid antioxidants. Curr. Med. Chem. 8:2001;797-807.
4. Havsteen B.H. The biochemistry and medical significance of the flavonoids. Pharmacol. Ther. 96:2002;67-202.
5. Williamson G., Plumb G.W., Uda Y., Price K.R., Rhodes M.J.C. Dietary quercetin glycosides: antioxidant activity and induction of the anticarcinogenic phase II marker enzyme quinone reductase in Hepa1c1c7 cells. Carcinogenesis. 17:1996;2385-2387.
6. Griffiths L.A., Barrow A. Metabolism of flavonoid compounds in germ-free rats. Biochem. J. 130:1972;1161-1162.
7. Bokkenheuser V.D., Shackleton C.H.L., Winter J. Hydrolysis of dietary flavonoid glycosides by strains of intestinal Bacteroides from humans. Biochem. J. 248:1987;953-956.
8. Hollman P.C.H., de Vries J.H.M., van Leeuwen S.D., Mengelers M.J.B., Katan M.B. Absorption of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers. Am. J. Clin. Nutr. 62:1995;1276-1282.
9. Walgren R.A., Lin J.-T., Kinne R.K.-H., Walle T. Cellular uptake of dietary flavonoid quercetin 4′-β-glucoside by sodium-dependent glucose transporter SGLT1. J. Pharmacol. Exp. Ther. 294:2000;837-843.
10. Wolffram S., Blöck M., Ader P. Quercetin-3-glucoside is transported by the glucose carrier SGLT1 across the brush border membrane of rat small intestine. J. Nutr. 132:2002;630-635.
11. Walgren R.A., Karnaky K.J. Jr., Lindenmayer G.E., Walle T. Efflux of dietary flavonoid quercetin 4′-β-glucoside across human intestinal Caco-2 cell monolayers by apical multidrug resistance-associated protein-2. J. Pharmacol. Exp. Ther. 294:2000;830-836.
12. Walle T., Otake Y., Walle U.K., Wilson F.A. Quercetin glucosides are completely hydrolyzed in ileostomy patients before absorption. J. Nutr. 130:2000;2658-2661.
13. Day A.J., DuPont M.S., Ridley S., Rhodes M., Rhodes M.J.C., Morgan M.R.A., Williamson G. Deglycosylation of flavonoid and isoflavonoid glycosides by human small intestine and liver β-glucosidase activity. FEBS Lett. 436:1998;71-75.
14. Ioku K., Pongpiriyadacha Y., Konishi Y., Takei Y., Nakatani N., Terao J. β-Glucosidase activity in the rat small intestine toward quercetin monoglucosides. Biosci. Biotechnol. Biochem. 62:1998;1428-1431.
15. Day A.J., Cañada F.J., Diaz J.C., Kroon P.A., Mclauchlan R., Faulds C.B., Plumb G.W., Morgan M.R.A., Williamson G. Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Lett. 468:2000;166-170.
16. Erlund I., Kosonen T., Alfthan G., Mäenpää J., Perttunen K., Kenraali J., Parantainen J., Aro A. Pharmacokinetics of quercetin from quercetin aglycone and rutin in healthy volunteers. Eur. J. Clin. Pharmacol. 56:2000;545-553.
17. Moon J.-H., Nakata R., Oshima S., Inakuma T., Terao J. Accumulation of quercetin conjugates in blood plasma after the short-term ingestion of onion by women. Am. J. Physiol. Regulatory Integrative Comp. Physiol. 279:2000;R461-R467.
18. Graefe E.U., Wittig J., Mueller S., Riethling A.-K., Uehleke B., Drewelow B., Pforte H., Jacobasch G., Derendorf H., Veit M. Pharmacokinetics and bioavailability of quercetin glycosides in humans. J. Clin. Pharmacol. 41:2001;492-499.
19. Sesink A.L.A., O'Leary K.A., Hollman P.C.H. Quercetin glucuronides but not glucosides are present in human plasma after consumption of quercetin-3-glucoside or quercetin-4′-glucoside. J. Nutr. 131:2001;1938-1941.
20. Cova D., De Angelis L., Giavarini F., Palladini G., Perego R. Pharmacokinetics and metabolism of oral diosmin in healthy volunteers. Int. J. Clin. Pharmacol. Ther. Toxicol. 30:1992;29-33.
21. Shimoi K., Okada H., Furugori M., Goda T., Takase S., Suzuki M., Hara Y., Yamamoto H., Kinae N. Intestinal absorption of luteolin and luteolin 7-O-β-glucoside in rats and humans. FEBS Lett. 438:1998;220-224.
22. Manach C., Morand C., Demigné C., Texier O., Régé rat F., Rémésy C. Bioavailability of rutin and quercetin in rats. FEBS Lett. 409:1997;12-16.
23. Gee J.M., DuPont M.S., Day A.J., Plumb G.W., Williamson G., Johnson I.T. Intestinal transport of quercetin glycosides in rats involves both deglycosylation and interaction with the hexose transport pathway. J. Nutr. 130:2000;2765-2771.
24. 14C]quercetin-4′-glucoside. J. Agric. Food Chem. 50:2002;6902-6909.
25. Walle T., Alston T., Browning A., Reed S., Walle U.K. Effect of dietary flavonoids on oral cancer cell proliferation: bioactivation by saliva and antiproliferative mechanisms. Second Annual AACR International Conference Frontiers in Cancer Prevention Research, Phoenix, AZ:2003.
26. Tsuda T., Horio F., Osawa T. Absorption and metabolism of cyanidin 3-O-β-D-glucoside in rats. FEBS Lett. 449:1999;179-182.
27. Miyazawa T., Nakagawa K., Kudo M., Muraishi K., Someya K. Direct intestinal absorption of red fruit anthocyanins, cyanidin-3-glucoside and cyanidin-3,5-diglucoside, into rats and humans. J. Agric. Food Chem. 47:1999;1083-1091.
28. Bub A., Watzl B., Heeb D., Rechkemmer G., Briviba K. Malvidin-3- glucoside bioavailability in humans after ingestion of red wine, dealcoholized red wine and red grape juice. Eur. J. Nutr. 40:2001;113-120.
29. Wu X., Cao G., Prior R.L. Absorption and metabolism of anthocyanins in elderly women after consumption of elderberry or blueberry. J. Nutr. 132:2002;1865-1871.
30. Gugler R., Leschik M., Dengler H.J. Disposition of quercetin in man after single oral and intravenous doses. Eur. J. Clin. Pharmacol. 9:1975;229-234.
31. Ferry D.R., Smith A., Malkhandi J., Fyfe D.W., deTakats P.G., Anderson D., Baker J., Kerr D.J. Phase I clinical trial of the flavonoid quercetin: pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin. Cancer Res. 2:1996;659-668.
32. Walle T., Walle U.K., Halushka P.V. Carbon dioxide is the major metabolite of quercetin in humans. J. Nutr. 131:2001;2648-2652.
33. 14C] quercetin in the ACI rat. Jap. J. Exp. Med. 53:1983;41-50.
34. Boulton D.W., Walle U.K., Walle T. Extensive binding of the bioflavonoid quercetin to human plasma proteins. J. Pharm. Pharmacol. 50:1998;243-249.
35. Walle T., Otake Y., Brubaker J.A., Walle U.K., Halushka P.V. Disposition and metabolism of the flavonoid chrysin in normal volunteers. Br. J. Clin. Pharmacol. 51:2001;143-146.
36. Walle U.K., Galijatovic A., Walle T. Transport of the flavonoid chrysin and its conjugated metabolites by the human intestinal cell line Caco-2. Biochem. Pharmacol. 58:1999;431-438.
37. Manach C., Texier O., Morand C., Crespy V., Régérat F., Demigné C., Rémésy C. Comparison of the bioavailability of quercetin and catechin in rats. Free Radic. Biol. Med. 27:1999;1259-1266.
38. Hou Y.C., Chao P.D.L., Ho H.J., Wen C.C., Hsiu S.L. Profound difference in pharmacokinetics between morin and its isomer quercetin in rats. J. Pharm. Pharmacol. 55:2003;199-203.
39. 14C]cyanidanol-3 in man following oral administration. Xenobiotica. 13:1983;279-286.
40. Yang C.S., Chen L., Lee M.J., Balentine D.A., Kuo M.C., Schantz S.P. Blood and urine level of tea catechins after ingestion of different amounts of green tea by human volunteers. Cancer Epidemiol. Biomarkers Prev. 7:1998;351-354.
41. Baba S., Osakabe N., Yasuda A., Nasume M., Takizawa T., Nakamura T., Terao J. Bioavailability of (-)-epicatechin upon intake of chocolate and cocoa in human volunteers. Free Radic. Res. 33:2000;635-641.
42. Chow H.H.S., Cai Y., Alberts D.S., Hakim I., Dorr R., Shahi F., Crowell J.A., Yang C.S., Hara Y. Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenol E. Cancer Epidemiol. Biomarkers Prev. 10:2001;53-58.
43. Warden B.A., Smith L.S., Beecher G.R., Balentine D.A., Clevidence B.A. Catechins are bioavailable in men and women drinking black tea throughout the day. J. Nutr. 131:2001;1731-1737.
44. Chen L., Lee M.-J., Li H., Yang C.S. Absorption, distribution and elimination of tea polyphenols in rats. Drug Metab. Dispos. 25:1997;1045-1050.
45. Takizawa Y., Morota T., Takeda S., Aburada M. Pharmacokinetics of (-)-epicatechin-3-O-gallate, an active component of Onpi-to, in rats. Biol. Pharm. Bull. 26:2003;608-612.
46. Hong J., Lu H., Meng X., Ryu J.-H., Hara Y., Yang C.S. Stability, cellular uptake, biotransformation, and efflux of tea polyphenol (-)-epigallocatechin-3-gallate in HT-29 human colon adenocarcinoma cells. Cancer Res. 62:2002;7241-7246.
47. Vaidyanathan J.B., Walle T. Cellular uptake and efflux of the tea flavonoid (-)-epicatechin-3-gallate in the human intestinal cell line Caco-2. J. Pharmacol. Exp. Ther. 307:2003;745-752.
48. Vaidyanathan J.B., Walle T. Glucuronidation and sulfation of the tea flavonoid (-)-epicatechin by the human and rat enzymes. Drug Metab. Dispos. 30:2002;897-903.
49. Walle T., Walle U.K. The β-D-glucoside and sodium-dependent glucose transporter 1 (SGLT1)-inhibitor phloridzin is transported by both SGLT1 and multidrug resistance-associated proteins 1/2. Drug Metab. Dispos. 31:2003;1288-1291.
50. Tsyrlov I.B., Mikhailenko V.M., Gelboin H.V. Isozyme- and species-specific susceptibility of cDNA-expressed CYP1A P-450s to different flavonoids. Biochim. Biophys. Acta. 1205:1994;325-335.
51. Lee H., Yeom H., Kim Y.G., Yoon C.N., Jin C., Choi J.S., Kim B.R., Kim D.H. Structure-related inhibition of human hepatic caffeine N3-demethylation by naturally occurring flavonoids. Biochem. Pharmacol. 55:1998;1369-1375.
52. Zhai S., Renke D., Friedman F.K., Vestal R.E. Comparative inhibition of human cytochromes P450 1A1 and 1A2 by flavonoids. Drug Metab. Dispos. 26:1998;989-992.
53. Moon T., Chi M.H., Kim D.-H., Yoon C.N., Choi Y.-S. Quantitative structure-activity relationships (QSAR) study of flavonoid derivatives for inhibition of cytochrome P450 1A2. Quant. Struct.-Act. Relat. 19:2000;257-263.
54. Duarte Silva I., Rodrigues A.S., Gaspar J., Laires A., Rueff J. Metabolism of galangin by rat cytochromes P450: relevance to the genotoxicity of galangin. Mutat. Res. 393:1997;247-257.
55. Duarte Silva I., S. R.A., Gaspar J., Maia R., Laires A., Rueff J. Involvement of rat cytochrome 1A1 in the biotransformation of kaempferol to quercetin: relevance to the genotoxicity of kaempferol. Mutagenesis. 12:1997;383-390.
56. Nielsen S.E., Breinholt V., Justesen U., Cornett C., Dragsted L.O. In vitro biotransformation of flavonoids by rat liver microsomes. Xenobiotica. 28:1998;389-401.
57. Doostdar H., Burke M.D., Mayer R.T. Bioflavonoids: selective substrates and inhibitors for cytochrome P450 CYP1A and CYP1B1. Toxicology. 144:2000;31-38.
58. Otake Y., Walle T. Oxidation of the flavonoids galangin and kaempferide by human liver microsomes and CYP1A1, CYP1A2 and CYP2C9. Drug Metab. Dispos. 30:2001;103-105.
59. Hu M., Krausz K., Chen J., Ge X., Li J., Gelboin H.L., Gonzalez F.J. Identification of CYP1A2 as the main isoform for the phase I hydroxylated metabolism of genistein and a prodrug converting enzyme of methylated isoflavones. Drug Metab. Dispos. 31:2003;924-931.
60. Yilmazer M., Stevens J.F., Deinzer M.L., Buhler D.R. In vitro biotransformation of xanthohumol, a flavonoid from hops (Humulus lupulus), by rat liver microsomes. Drug Metab. Dispos. 29:2001;223-231.
61. Otake Y., Hsieh F., Walle T. Glucuronidation versus oxidation of the flavonoid galangin by human liver microsomes and hepatocytes. Drug Metab. Dispos. 30:2002;576-581.
62. Wittig J., Herderich M., Graefe E.U., Veit M. Identification of quercetin glucuronides in human plasma by high-performance liquid chromatography-tandem mass spectrometry. J. Chromatogr. 753:2001;237-243.
63. Boutin J.A., Meunier F., Lambert P.H., Hennig P., Bertin D., Serkiz B., Volland J.P. In vivo and in vitro glucuronidation of the flavonoid diosmetin in rats. Drug Metab. Dispos. 21:1993;1157-1166.
64. Galijatovic A., Otake Y., Walle U.K., Walle T. Extensive metabolism of the flavonoid chrysin by human Caco-2 and Hep G2 cells. Xenobiotica. 29:1999;1241-1256.
65. Boersma M.G., van der Woude H., Bogaards J., Boeren S., Vervoort J., Cnubben N.H.P., van Iersel I.M.C.M., van Bladeren P.J., Rietjens I.M.C.M. Regioselectivity of phase II metabolism of luteolin and quercetin by UDP-glucuronosyl transferases. Chem. Res. Toxicol. 15:2002;662-670.
66. Lu H., Meng X., Li C., Sang S., Patten C., Sheng S., Hong J., Bai N., Winnik B., Ho C.-T., Yang C.S. Glucuronides of tea catechins: enzymology of biosynthesis and biological activities. Drug Metab. Dispos. 31:2003;452-461.
67. O'Leary K.A., Day A.J., Needs P.W., Sly W.S., O'Brien N.M., Williamson G. Flavonoid glucuronides are substrates for human liver β-glucuronidase. FEBS Lett. 503:2001;103-106.
68. Shimoi K., Saka N., Nozawa R., Sato M., Amano I., Nakayama T., Kinae N. Deglucuronidation of a flavonoid, luteolin monoglucuronide, during inflammation. Drug Metab. Dispos. 29:2001;1521-1524.
69. Zhu B.T., Ezell E.L., Liehr J.G. Catechol-O-methyltransferase-catalyzed rapid O-methylation of mutagenic flavonoids: metabolic inactivation as a possible reason for their lack of carcinogenicity in vivo. J. Biol. Chem. 269:1994;292-299.
70. Rechner A.R., Kuhnle G., Bremner P., Hubbard G.P., Moore K.P., Rice-Evans C.A. The metabolic fate of dietary polyphenols in humans. Free Radic. Biol. Med. 33:2002;220-235.
71. Aura A.-M., O'Leary K.A., Williamson G., Ojala M., Bailey M., Puupponen-Pimiä R., Nuutila A.M., Oksman-Caldentey K.-M., Poutanen K. Quercetin derivatives are deconjugated and converted to hydroxyphenylacetic acids but not methylated by human fecal flora in vitro. J. Agric. Food Chem. 50:2002;1725-1730.
72. Galati G., Moridani M.Y., Chan T.S., O'Brien P.J. Peroxidative metabolism of apigenin and naringenin versus luteolin and quercetin: glutathione oxidation and conjugation. Free Radic. Biol. Med. 30:2001;370-382.
73. Boulton D.W., Walle U.K., Walle T. Fate of the flavonoid quercetin in human cell lines: chemical instability and metabolism. J. Pharm. Pharmacol. 51:1999;353-359.
74. Walle T., Vincent T.S., Walle U.K. Evidence of covalent binding of the dietary flavonoid quercetin to DNA and protein in human intestinal and hepatic cells. Biochem. Pharmacol. 65:2003;1603-1610.
75. Morand C., Crespy V., Manach C., Besson C., Demigné C., Rémésy C. Plasma metabolites of quercetin and their antioxidant properties. Am. J. Physiol. 275:1998;R212-R219.
76. Manach C., Morand C., Crespy V., Demigné C., Texier O., Régérat F., Rémésy C. Quercetin is recovered in human plasma as conjugated derivatives which retain antioxidant properties. FEBS Lett. 426:1998;331-336.
77. Yamamoto N., Moon J.-H., Tsushida T., Nagao A., Terao J. Inhibitory effect of quercetin metabolites and their related derivatives on copper ion-induced lipid peroxidation in human low-density lipoprotein. Arch. Biochem. Biophys. 372:1999;347-354.
78. Miyake Y., Shimoi K., Kumazawa S., Yamamoto K., Kinae N., Osawa T. Identification and antioxidant activity of flavonoid metabolites in plasma and urine of eriocitrin-treated rats. J. Agric. Food Chem. 48:2000;3217-3224.
79. Moon J.-H., Tsushida T., Nakahara K., Terao J. Identification of quercetin 3-O-β-D-glucuronide as an antioxidative metabolite in rat plasma after oral administration of quercetin. Free Radic. Biol. Med. 30:2001;1274-1285.
80. Whitley A.C., Stoner G.D., Darby M.V., Walle T. Intestinal epithelial cell accumulation of the cancer preventive polyphenol ellagic acid: extensive binding to protein and DNA. Biochem. Pharmacol. 66:2003;907-915.
81. Lambert J.D., Yang C.S. Cancer chemopreventive activity and bioavailability of tea and tea polyphenols. Mutat. Res. 523-424:2003;201-208.
82. Stoner G.D., Gupta A. Etiology and chemoprevention of esophageal squamous cell carcinoma. Carcinogenesis. 22:2001;1737-1746.