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Absorption, excretion and metabolite profiling of methyl-, glucuronyl-, glucosyl- and sulpho-conjugates of quercetin in human plasma and urine after ingestion of onions

Published online by Cambridge University Press:  08 March 2007

William Mullen ,
Christine A. Edwards  and
Alan Crozier
William Mullen*
Affiliation:
Plant Products and Human Nutrition Group, Graham Kerr Building, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of GlasgowGlasgow G12 8QQ, UK
Christine A. Edwards
Affiliation:
Human Nutrition Section, University of GlasgowDivision of Developmental Medicine, Yorkhill Hospital, Glasgow G3 8SJUK
Alan Crozier
Affiliation:
Plant Products and Human Nutrition Group, Graham Kerr Building, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of GlasgowGlasgow G12 8QQ, UK
*
*Corresponding author: Professor Alan Crozier, fax +44 (0)141 330 5364, email a.crozier@bio.gla.ac.uk
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Abstract

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It is essential to have a thorough knowledge of the bioavailability and metabolism of dietary flavonols to understand their role in disease prevention. Lightly fried onions containing 275μmol flavonols, principally quercetin-4′-glucoside and quercetin-3,4′-diglucoside, were fed to healthy human volunteers and plasma and urine were collected over a 24h period. Samples were analysed by HPLC with diode array and tandem mass spectrometric detection. Five flavonol metabolites, quercetin-3′-sulphate, quercetin-3-glucuronide, isorhamnetin-3-glucuronide, a quercetin diglucuronide and a quercetin glucuronide sulphate, were detected in plasma in quantifiable amounts with trace quantities of six additional quercetin metabolites. Sub-micromolar peak plasma concentrations (cmax) of quercetin-3′-sulphate, quercetin-3-glucuronide, isorhamnetin-3-glucuronide and quercetin diglucuronide were observed 0.6–0.8h after ingestion. In contrast, the cmax of quercetin glucuronide sulphate was 2.5h. The elimination half-lives (t1/2) of quercetin-3′-sulphate, quercetin-3-glucuronide and quercetin diglucuronide were 1.71, 2.33 and 1.76h respectively, while the t1/2 of isorhamnetin-3-glucuronide was 5.34h and that of quercetin glucuronide sulphate was 4.54h. The profile of metabolites excreted in urine was markedly different to that of plasma with many of the major urinary components, including quercetin-3′-glucuronide, two quercetin glucoside sulphates and a methylquercetin diglucuronide, absent or present in only trace amounts in the bloodstream indicative of substantial phase II metabolism. Total urinary excretion of quercetin metabolites was 12·9μmol, corresponding to 4·7% of intake. If these samples had been subjected to hydrolysis, as in many previous studies, only quercetin and isorhamnetin would have been detected and quantified. The bioactivity of these metabolites should be considered.

Keywords

FlavonolsQuercetin glucosidesAbsorptionMetabolismExcretionManHPLC–MS2
Type
Research Article
Information
British Journal of Nutrition , Volume 96 , Issue 1 , January 2006 , pp. 107 - 116
Copyright
Copyright © The Nutrition Society 2006

References

Aziz, AA, Edwards, CA, Cahill, AP, Khan, KM, Finlay, IG, Lean, MEJ & Crozier, AAbsorption and excretion of the conjugated flavonols, quercetin-3,4'-diO-β- d -glucoside, quercetin-4'- O -β- d -glucoside and isorhamnetin-4'- O -β- d -glucoside, in human ileostomy volunteers after the consumption of onions. Molecular and Therapeutic Aspects of Redox Biochemistry. [Bahorun, T and Gurib-Fakim, A] London: London OICA International 2003 pp.194205.Google Scholar
Aziz, AA, Edwards, CA, Lean, MEJ & Crozier, AAbsorption and excretion of conjugated flavonols, including quercetin-4'- O -β-glucoside and isorhamnetin-4'- O -β-glucoside by human volunteers after the consumption of onions. Free Rad Res (1998) 29 257–269.CrossRefGoogle ScholarPubMed
Boersma, MG, vad der Woude, H, Bogaards, J, Boerens, S, Vervoort, J, Cnubben, NHP, van Iersel, MLPS, van Bladeren, PJ & Tietjens, IMCMRegioselectivity of phase II metabolism of luteolin and quercetin by UDP-glucuronyl transferases. Chem Res Toxicol (2002) 15 662–670.CrossRefGoogle Scholar
Caldwell, ST, Crozier, A & Hartley, RCIsotopic labelling of quercetin-4'- O -β-glucoside. Tetrahedron (2000) 56 4101–4106.CrossRefGoogle Scholar
Chen, G, Zhang, D, Jing, N, Yin, S, Falany, CN & Radominska-Pandya, AHuman intestinal sulfotransferases: identification and distribution. Toxicol Appl Pharmacol (2003) 187 186–197.CrossRefGoogle ScholarPubMed
Crozier, A, Lean, MEJ, McDonald, MS & Black, CQuantitative analysis of the flavonoid content of commercial tomatoes, onions, lettuce and celery. J Agric Food Chem (1998) 45 590–595.CrossRefGoogle Scholar
Crozier, A, Yokota, T, Jaganath, IB, Marks, S, Saltmarsh, M & Clifford, MNSecondary metabolites in fruits, vegetables and other plant-derived dietary components Plant Secondary Metabolites: Occurrence, Structure and Role in the Human Diet [Crozier, AAshihara, HClifford, MN] Oxford BlackwellsIn the Press 2006Google Scholar
Day, AJ, Gee, JM, DuPont, MS, Johnson, IT & Williamson, GAbsorption of quercetin-3-glucoside and quercetin-4'-glucoside in the rat small intestine: the role of lactase phloridzin hydrolase and sodium-dependent glucose transporter. Biochem Pharmacol (2003) 65 1199–1206.CrossRefGoogle Scholar
Day, AJ, Mellon, F, Barron, D, Sarrazin, G, Morgan, MRA & Williamson, GHuman metabolism of dietary flavonoids: identification of plasma metabolites of quercetin. Free Rad Res (2001) 35 941–952.CrossRefGoogle ScholarPubMed
Day, AJ & Williamson, GBiomarkers of dietary flavonoids: a review of the current evidence for identification of quercetin glycosides in plasma. Br J Nutr (2001) 86 S105–S110.CrossRefGoogle ScholarPubMed
Day, AJ & Williamson, GAbsorption of quercetin glycosides. Flavonoids in Health and Disease. pp. [Rice-Evans, CAPacker, L]. New York: Marcel Dekker 2003 391412Google Scholar
Déprez, S, Brezillon, C, Rabot, S, Philippe, C, Mila, I, Lapierre, C & Scalbert, APolymeric proanthocyanidins are catabolized by human colonic microflora into low-molecular-weight phenolic acids. J Nutr (2000) 130 2733–2738.CrossRefGoogle ScholarPubMed
De Santi, C, Pietrabissa, A, Spisni, R, Mosca, F & Pacifici, GMSulphation of reseveratrol, a natural product present in grapes and wine, in human liver and duodenum. Xenobiotica (2000) 30 609–617.CrossRefGoogle Scholar
Gonthier, M-P, Donovan, JL, Texier, O, Felgines, C, Rémésy, C & Scalbert, AMetabolism of dietary procyanidins in rats. Free Rad Biol Med (2003) 35 837–844.CrossRefGoogle ScholarPubMed
Graefe, EU, Wittig, J, Mueller, S, Riethling, A-K, Uehleke, B, Drewelow, B, Pforte, H, Jacobasch, G, Derendorf, H & Veit, MPharmacokinetics and bioavailability of quercetin glycosides in humans. J Clin Pharmacol (2001) 41 492–499.CrossRefGoogle ScholarPubMed
Hollman, PCH, van der Gaag, MS, Mengelers, MJB, van Trijp, JMP, de Vries, JHM & Katan, MBAbsorption and disposition kinetics of the dietary antioxidant quercetin in man. Free Rad Biol Med (1996) 21 703–707.CrossRefGoogle ScholarPubMed
Hollman, PCH, van Trip, JMP, Buysman, MNCP, van der Gaag, MS, Mengelers, MJB, de Vries, JHM & Katan, MBRelative bioavailability of the antioxidant quercetin from various foods. FEBS Lett (1997) 418 152–156.CrossRefGoogle ScholarPubMed
Matern, H & Matern, SFormation of bile acid glucosides and dilichyl phosphoglucose by microsomal glucosyl transferases in liver, kidney and intestine of man. Biochim Biophys Acta (1987) 921 1–6.CrossRefGoogle ScholarPubMed
Mauri, PL, Iemoli, L, Gardana, C, Riso, P, Simonetti, P, Porrini, M & Pietta, PGLiquid chromatography electrospray ionization mass spectrometric characterization of flavonol glycosides in tomatoes extracts and human plasma. Rapid Commun Mass Spectrom (1999) 13 924–931.3.0.CO;2-G>CrossRefGoogle ScholarPubMed
Moon, J-H, Makata, R, Oshima, S, Inakuma, T & Terao, JAccumulation of quercetin conjugates in blood plasma after the short-term ingestion of onions by women. Am J Regulatory Integrative Comp Physiol 2000 279 R461–R467.CrossRefGoogle ScholarPubMed
Mullen, W, Boitier, A, Stewart, AJ & Crozier, AFlavonoid metabolites in human plasma and urine after the consumption of red onions: analysis by liquid chromatography with photodiode array and full scan tandem mass spectrometric detection. J Chromatogr A (2004) 1058 163–168.CrossRefGoogle ScholarPubMed
Mullen, W, Graf, BA, Caldwell, ST, Hartley, RC, Duthie, GG, Lean, MEJ & Crozier, ADetermination of flavonol metabolites in plasma and tissues of rats by HPLC-radiocounting and tandem mass spectrometry following oral ingestion of [2- 14 C]quercetin-41-glucoside. J Chromatogr A (2002) 50 6902–6909.Google Scholar
Mullen, W, Hartley, RC & Crozier, ADetection and identification of 14 C-labelled flavonol metabolites by HPLC-radio-counting and tandem mass spectrometry. J Chromatogr A (2003) 1007 21–29.CrossRefGoogle Scholar
Murota, K & Terao, JAntioxidative flavonoid quercetin: implication of its intestinal absorption and metabolism. Arch Biochem Biophys (2003) 417 12–17.CrossRefGoogle ScholarPubMed
O'Leary, KA, Day, AJ, Needs, PW, Mellon, FA, O'Brien, NM & Williamson, GMetabolism of quercetin-7 and quercetin-3-glucuronides by an in vitro hepatic model: the role of human β-glucuronidase, sulfotransferase, catechol- O -methyltransferase and multi-resistant protein 2 (MRP2) inflavonoid metabolism. Biochem Pharmacol (2003) 65 479–491.CrossRefGoogle Scholar
Olthof, MR, Hollman, PCH, Buijsman, MNCP, Amelsvoort, JMM & Katan, MBChlorogenic acid, quercetin-3-rutinoside and black tea polyphenols are extensively metabolized in humans. J Nutr (2003) 133 1806–1814.CrossRefGoogle Scholar
Paganga, G & Rice-Evans, CAThe identification of flavonoids as glycosides in human plasma. FEBS Lett (1997) 401 78–82.CrossRefGoogle ScholarPubMed
Radominska-Pandya, A, Little, JM, Pandya, JT, Tephly, TR, King, CD, Barone, GW & Raufman, J-PUDP-glucuronyltransferases in human intestinal mucosa. Bichim Biophys Acta (1998) 1394 199–208.CrossRefGoogle Scholar
Tsushida, T & Suzuki, MIsolation of flavonoid-glycosides in onion and identification by chemical synthesis of the glycoside (Flavonoids in fruits and vegetables. Part I). Nippon Shokuhin Kagaku Kaishi (1995) 42 100–108.CrossRefGoogle Scholar
Wittig, J, Herderich, M, Graefe, EU & Veit, MIdentification of quercetin glucuronides in human plasma by high-performance liquid chromatography-tandem mass spectrometry. J Chromatogr B (2001) 753 237–243.CrossRefGoogle ScholarPubMed