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The absorption, metabolism and excretion of flavan-3-ols and procyanidins following the ingestion of a grape seed extract by rats

Published online by Cambridge University Press:  08 March 2007

Catherine Tsang ,
Cyril Auger ,
William Mullen ,
Aurélie Bornet ,
Jean-Max Rouanet ,
Alan Crozier  and
Pierre-Louis Teissedre
Catherine Tsang
Affiliation:
Plant Products & Human Nutrition Group, Graham Kerr Building, Division of Biochemistry & Molecular Biology, Institute of Biomedical & Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
Cyril Auger
Affiliation:
Unité Nutrition, GBSA, Place Eugéne Bataillon, Université Montpellier II, 34 095 Montpellier, France UMR 1083 Sciences Pour l'Œnologie, Centre d'Œnologie, Faculté de Pharmacie, 15, Av. Charles Flahault, BP 14491 Université Montpellier I, 34093 Montpellier cedex 5, France
William Mullen
Affiliation:
Plant Products & Human Nutrition Group, Graham Kerr Building, Division of Biochemistry & Molecular Biology, Institute of Biomedical & Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
Aurélie Bornet
Affiliation:
UMR 1083 Sciences Pour l'Œnologie, Centre d'Œnologie, Faculté de Pharmacie, 15, Av. Charles Flahault, BP 14491 Université Montpellier I, 34093 Montpellier cedex 5, France
Jean-Max Rouanet
Affiliation:
Unité Nutrition, GBSA, Place Eugéne Bataillon, Université Montpellier II, 34 095 Montpellier, France
Alan Crozier
Affiliation:
Plant Products & Human Nutrition Group, Graham Kerr Building, Division of Biochemistry & Molecular Biology, Institute of Biomedical & Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
Pierre-Louis Teissedre*
Affiliation:
UMR 1083 Sciences Pour l'Œnologie, Centre d'Œnologie, Faculté de Pharmacie, 15, Av. Charles Flahault, BP 14491 Université Montpellier I, 34093 Montpellier cedex 5, France
*
*Corresponding author: Dr P.-L. Teissedre, fax +33 (0)4 67 54 86 86, email [email protected]
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Abstract

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Rats were fed a grape seed extract (GSE) containing (+)-catechin, (−)-epicatechin and dimers, trimers, tetramers and polymeric procyanidins. Liver, kidney, brain and gastrointestinal (GI) tract together with plasma, urine and faeces were collected over a 24 h period and their flavan-3-ol content was analysed by HPLC with tandem mass spectrometry and diode array detection. Small amounts of the GSE flavan-3-ols moved out of the stomach and into the duodenum/jejunum, and to a greater extent the ileum 1 h after ingestion, and into the caecum after 2 h with relatively small amounts being detected in the colon after 3 h. The GI tract contained the parent GSE flavan-3-ols and procyanidins with only trace amounts of metabolites and there were no indications that proanthocyanidins were depolymerised in the GI tract releasing monomeric flavan-3-ols. Plasma contained exclusively catechin glucuronides and methylated glucuronide metabolites which were also detected in the liver and kidneys. These metabolites were also present in urine together with sulphated metabolites and low amounts of the procyanidin dimers B1, B2, B3 and B4 as well as the trimer C2 and an unknown GSE trimer. The amounts of (+)-catechin and (−)-epicatechin metabolites excreted in urine relative to the quantity of the monomers ingested were 27 and 36 %, respectively, after 24 h. This is similar to the levels of urinary excretion reported to occur by other investigators after feeding (−)-epicatechin to rats and provides further, albeit indirect, evidence that the procyanidin oligomers in the GSE were not depolymerised to monomers to any extent after ingestion. No convincing analytical data were obtained for the presence of flavan-3-ol metabolites in the brain.

Keywords

Flavan-3-olsProcyanidinsAbsorptionMetabolismExcretionRatsHPLC–MS–MS
Type
Research Article
Information
British Journal of Nutrition , Volume 94 , Issue 2 , August 2005 , pp. 170 - 181
Copyright
Copyright © The Nutrition Society 2005

References

Arts, MJ, Haenen, GR, Voss, HP & Bast, A (2001) Masking of antioxidant capacity by the interaction of flavonoids with protein. Food Chem Toxicol 39, 787–791.CrossRefGoogle ScholarPubMed
Auger, C, Al-Awwadi, N, Bornet, A, Rouanet, J-M, Gasc, F, Cros, G & Teissedre, P-L (2004) Catechins and procyanidins in Mediterranean diets. Food Res Int 37, 233–245.CrossRefGoogle Scholar
Baba, S, Osakabe, N, Natsume, M, Muto, Y, Takizawa, T & Terao, J (2001) Absorption and urinary excretion of (-)-epicatechin after administration of different levels of cocoa powder or (-)-epicatechin in rats. J Agric Food Chem 49, 6050–6056.CrossRefGoogle ScholarPubMed
Baba, S, Osakabe, N, Natsume, M & Terao, J (2002) Absorption and urinary excretion of procyanidin B 2 [epicatechin-(4β-8)-epicatechin] in rats. Free Rad Biol Med 33, 142–148.CrossRefGoogle Scholar
Bell, JR, Donovan, JL, Wong, R, Waterhouse, AL, German, JB, Walzem, RL & Kasim-Karakas, SE (2000) (+)-Catechin in human plasma after ingestion of a single serving of reconstituted red wine. Am J Clin Nutr 71, 103–108.CrossRefGoogle ScholarPubMed
Crozier, A (2003) Classification and biosynthesis of secondary plant products: an overview. In Plants: Diet and Health, pp. 27–48[Goldberg, G, editors]. British Nutrition Foundation London: Chapman & Hall.CrossRefGoogle Scholar
de Pascual-Teresa, S, Santos-Buelga, C & Rivas-Gonzalo, JC (2000) Quantitative analysis of flavan-3-ols in Spanish foodstuffs and beverages. J Agric Food Chem 48, 5331–5337.CrossRefGoogle ScholarPubMed
de Rijke, E, Zappey, H, Ariese, F, Gooijer, C & Brinkman, UATh (2003) Liquid chromatography with atmospheric pressure chemical ionisation and electrospray ionisation mass spectrometry of flavonoids with triple-quadrupole and ion trap instruments. J Chromatogr A 984, 45–58.CrossRefGoogle ScholarPubMed
Del Rio, D, Stewart, AJ, Mullen, W, Burns, J, Lean, MEJ, Brighenti, F & Crozier, A (2004) HPLC-MS n analysis of phenolic compounds and purine alkaloids in green and black tea. J Agric Food Chem 52, 2807–2815.CrossRefGoogle ScholarPubMed
Déprez, S, Brezillon, C, Rabot, S, Philippe, C, Mila, I, Lapierre, C & Scalbert, A (2000) Polymeric proanthocyanidins are catabolized by human colonic microflora into low-molecular-weight phenolic acids. J Nutr 130, 2733–2738.CrossRefGoogle ScholarPubMed
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. J Nutr 129, 1662–1668.CrossRefGoogle ScholarPubMed
Donovan, JL, Crespy, V, Manach, C, Morand, C, Besson, C, Scalbert, A & Rémésy, C (2001) Catechin is metabolized by both the small intestine and liver of rats. J Nutr 131, 1753–1757.CrossRefGoogle ScholarPubMed
Donovan, JL, Manach, C, Rios, L, Morand, C, Scalbert, A & Rémésy, C (2002) Procyanidins are not bioavailable in rats fed a single meal containing a grape seed extract or the procyanidin dimer B 3. Br J Nutr 87, 299–306.CrossRefGoogle Scholar
El Mohsen, MMA, Kuhnler, G, Rechner, AR, Schroeter, H, Rose, S, Jenner, P, Rice-Evans, CA (2002) Uptake and metabolism of epicatechin and its access to the brain after oral ingestion. Free Rad Biol Med 33, 1693–1702.CrossRefGoogle Scholar
Escribana-Bailón, T, Gutiérrez-Fernández, Y, Rivas-Gonzalo, JC & Santos-Buelga, C (1992) Characterization of procyanidins of Vitis vinifera variety Tinta del Páis grape seed. J Agric Food Chem 40, 1794–1799.CrossRefGoogle Scholar
Foo, LY, Lu, Y, Howell, AB & Vorsa, N (2000) The structure of cranberry proanthocyanidins which inhibit adherence of uropathogenic P-fimbriated Escherichia coli in vitro. Phytochemistry 54, 173–181.CrossRefGoogle ScholarPubMed
Friedrich, W, Ebenhardt, A & Galensa, R (2000) Investigation of proanthocyanidins by HPLC with electrospray ionisation mass spectrometry. Eur Food Res Technol 211, 56–64.CrossRefGoogle Scholar
Gonthier, M-P, Donovan, JL, Texier, O, Felgines, C, Rémésy, C & Scalbert, A (2003) Metabolism of dietary procyanidins in rats. Free Rad Biol Med 35, 837–844.CrossRefGoogle ScholarPubMed
Holt, RR, Lazarus, SA, Sullards, MC, Zhu, QY, Schramm, DD, Hammerstone, JF, Fraga, CG, Schmitz, HH & Keen, CL (2002) Procyanidin dimer B 2 [epicatechin-(4β-8)-epicatechin] in human plasma after the consumption of a flavanol-rich cocoa. Am J Clin Nutr 76, 798–804.CrossRefGoogle Scholar
Hvattum, E & Ekeberg, D (2002) Study of the collision-induced radical cleavage of flavonoid glycosides using negative electrospray ionisation tandem quadrupole mass spectrometry. J Mass Spectrom 38, 43–49.CrossRefGoogle Scholar
Koga, T, Moro, K, Nakamori, K, Yamakoshi, J, Hosoyama, H, Kataoka, S & Ariga, T (1999) Increase in oxidative potential of rat plasma by oral administration of proanthocyanidin-rich extract from grape seeds. J Agric Food Chem 47, 1892–1897.CrossRefGoogle ScholarPubMed
Kondo, K, Hirano, R, Matsumoto, A, Igarashi, O & Itakura, H (1996) Inhibition of LDL oxidation by cocoa. Lancet 9040, 1514.CrossRefGoogle Scholar
Kuhnle, G, Spencer, JPE, Schroeter, H, Shenoy, B, Debnam, ES, Srai, SKS, Rice-Evans, C & Hahn, U (2000) Epicatechin and catechin are O -methylated and glucuronidated in the small intestine. Biochem Biophys Res Commun 277, 507–512.CrossRefGoogle ScholarPubMed
Mullen, W, Boitier, A, Stewart, AJ & Crozier, A (2004) Flavonoid 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 1058, 163–168.CrossRefGoogle ScholarPubMed
Mullen, W, Graf, BA, Caldwell, ST, Hartley, RC, Duthie, GG, Edwards, CA, Lean, MEJ & Crozier, A (2002) Determination of flavonol metabolites in plasma and tissues of rats by HPLC-radiocounting and tandem mass spectrometry following oral ingestion of [2- 14 C]quercetin-4'-glucoside. J Agric Food Chem 50, 6902–6909.CrossRefGoogle ScholarPubMed
Nakamura, Y & Tonogai, Y (2003) Metabolism of grape seed polyphenols in the rat. J Agric Food Chem 51, 7215–7225.CrossRefGoogle ScholarPubMed
Natsume, M, Osakabe, N, Oyama, M, Sasaki, M, Baba, S, Nakamura, Y, Osawa, T & Terao, J (2003) Structures of (-)-epicatechin glucuronide identified from plasma and urine after oral ingestion of (-)-epicatechin: differences between human and rat. Free Rad Biol Med 34, 840–849.CrossRefGoogle ScholarPubMed
Piskula, MK & Terao, J (1998) Accumulation of (-)-epicatechin metabolites in rat plasma after oral administration and distribution of conjugation enzymes in rat tissues. J Nutr 128, 1172–1178.CrossRefGoogle ScholarPubMed
Prior, R (2003) Fruits and vegetables in the prevention of cellular oxidative damage. Am J Clin Nutr 78, 570S–578S.CrossRefGoogle ScholarPubMed
Rein, D, Lotito, S, Holt, RR, Keen, CL, Schmitz, HH & Fraga, CG (2000) Epicatechin in human plasma: in vivo determination and effect of chocolate consumption on plasma oxidation status. J Nutr 130, 2109S–2114S.CrossRefGoogle ScholarPubMed
Ricardo, da, Silva, JM, Rigaud, J, Cheynier, V, Cheminat, A & Moutounet, M (1991) Procyanidin dimers and trimers from grape seeds. Phytochemistry 30, 1259–1264.CrossRefGoogle Scholar
Rios, LY, Bennett, RN, Lazarus, SA, Rémésy, C, Scalbert, A & Williamson, G (2002) Cocoa procyanidins are stable during gastric transit in humans. Am J Clin Nutr 76, 1106–1110.CrossRefGoogle ScholarPubMed
Romeyer, FM, Macheix, J-J & Sapis, J-C (1986) Changes and importance of oligomeric procyanidins during maturation of grape seeds. Phytochemistry 25, 219–221.CrossRefGoogle Scholar
Ruf, JC, Berger, JL & Renaud, S (1995) Platelet rebound effect of alcohol withdrawal and wine drinking in rats. Arterioscler Thromb Vasc Biol 15, 140–144.CrossRefGoogle ScholarPubMed
Ryan, D, Robards, K, Prenzler, P, Jardine, D, Herlt, T & Antolovich, M (1999) Liquid chromatography with electrospray ionisation mass spectrometric detection of phenolic compounds from Olea europaea. J Chromatogr A 855, 529–537.CrossRefGoogle ScholarPubMed
Sanoner, P, Guyot, S, Marnet, N, Molle, D & Drilleau, JP (1999) Polyphenol profiles of French cider apple varieties ( Malus domestica sp.). J Agric Food Chem 47, 4847–4853.CrossRefGoogle ScholarPubMed
Santos-Buelga, C, Francia-Aricha, EM & Escibano-Bailón, MT (1995) Comparative flava-3-ol composition of seeds from different grape varieties. Food Chem 53, 197–201.CrossRefGoogle Scholar
Scalbert, A & Williamson, G (2000) Dietary intake and bioavailability of polyphenols. J Nutr 130, 2073S–2085S.CrossRefGoogle ScholarPubMed
Shui, G & Leong, LP (2004) Analysis of polyphenolic antioxidants in star fruit using liquid chromatography and mass spectrometry. J Chromatogr A 1022, 67–75.CrossRefGoogle ScholarPubMed
Steinberg, D, Carew, TE, Fielding, C, Fogelman, AM, Mahley, RW, Sniderman, AD & Zilversmit, DB (1989) Lipoproteins and the pathogenesis of atherosclerosis. Circulation 80, 719–723.CrossRefGoogle ScholarPubMed
Steinberg, FM, Bearden, MM & Keen, CL (2003) Cocoa and chocolate flavonoids: implications for cardiovascular health. J Am Diet Assoc 103, 215–223.CrossRefGoogle ScholarPubMed
Sun, B, Belchior, GP, Ricardo da Silva, JM & Spranger, MI (1999) Isolation and purification of dimeric and trimeric procyanidins from grape seeds. J Chromatogr A 841, 115–121.CrossRefGoogle Scholar
Teissedre, P-L, Frankel, EN, Waterhouse, AL, Peleg, H & German, JB (1996) Inhibition of in vitro human LDL oxidation by phenolic antioxidants from grapes and wines. J Sci Food Agric 70, 55–61.3.0.CO;2-X>CrossRefGoogle Scholar
Wang, JF, Schramm, DD, Holt, RR, Ensunsa, JL, Fraga, CG, Schmitz, HH & Keen, CL (2000) A dose–response effect from chocolate consumption on plasma epicatechin and oxidative damage. J Nutr 130, 2115S–2119S.CrossRefGoogle ScholarPubMed
Ward, NC, Croft, KD, Puddey, IB & Hodgson, JM (2004) Supplementation with grape seed polyphenols results in increased urinary excretion of 3-hydroxyphenylpropionic acid, an important metabolite of proanthocyanidins in humans. J Agric Food Chem 52, 5545–5549.CrossRefGoogle ScholarPubMed
Warden, BA, Smith, LS, Beecher, GR, Balentine, DA & Clevidence, BA (2001) Catechins are bioavailable in men and women drinking black tea throughout the day. J Nutr 131, 1731–1737.CrossRefGoogle ScholarPubMed
Waridel, P, Wolfender, J-L, Ndjoko, K, Hobby, KR, Major, HJ & Hostettmann, K (2001) Evaluation of quadrupole time-of-flight tandem mass spectrometry and ion-trap multiple-stage mass spectrometry for differentiation of C-glycosidic flavonoid isomers. J Chromatogr A 926, 29–41.CrossRefGoogle ScholarPubMed
Yamakoshi, J, Saito, M, Kataoka, S & Tokutake, S (2002) Procyanidin-rich extract from grape seeds prevents cataract formation in hereditary cataractous (ICR/f) rats. J Agric Food Chem 50, 4983–4988.CrossRefGoogle ScholarPubMed
Yang, CS, Chen, L, Lee, MJ, Balentine, D, Kuo, MC & Schantz, SP (1998) Blood and urine levels of tea catechins after ingestion of different amounts of green tea by human volunteers. Cancer Epidemiol Biomarkers Prev 7, 351–354.Google ScholarPubMed