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European Journal of Nutrition

, Volume 45, Issue 2, pp 88–96 | Cite as

The bioavailability of polyphenols is highly governed by the capacity of the intestine and of the liver to secrete conjugated metabolites

  • M. Silberberg
  • C. MorandEmail author
  • T. Mathevon
  • C. Besson
  • C. Manach
  • A. Scalbert
  • C. Remesy
ORIGINAL CONTRIBUTION

Summary

Background

After ingestion of a complex meal containing foods and beverages of plant origin, different polyphenols are likely to be simultaneously present in the intestine. However, almost nothing is known about their interactions and possible consequences on their bioavailability.

Aim of the study

The present study deals with the intestinal absorption and splanchnic metabolism of three polyphenols, genistein, hesperetin and ferulic acid (FA),when perfused in the small intestine alone or in combination, at different doses (15 and 120 µM).

Methods

The fate of polyphenols in the small intestine was studied using a rat in situ intestinal perfusion model. Polyphenols were analysed in perfusate, bile and plasma by HPLC.

Results

Whatever the perfused dose, the efficiency of the net transfer towards the enterocyte was similar for the three polyphenols and not significantly modified by any association between these molecules. However, FA largely differed from the two flavonoids by its low intestinal secretion of conjugates. When perfused at 15 µM, the secretion of conjugates back to the lumen represented 6.2% of the net transfer into the enterocytes for FA compared to 25.5 and 20 % for genistein and hesperetin respectively. Intestinal conjugation and secretion of conjugates back to the gut lumen varied with the dose of flavonoids: saturation of conjugation was observed for the highest dose or when a high dose of a second flavonoid was perfused simultaneously. Intensity of the biliary secretion substantially differed among tested polyphenols: 7.7% of the net transfer for FA vs 50% for genistein or hesperetin. The extent of the enterohepatic cycling of these polyphenols was proportional to the perfused dose and unaffected by the simultaneous presence of different compounds in the intestine.

Conclusion

Genistein and hesperetin appeared less available than FA for peripheral tissues because of a high intestinal and biliary secretion of their conjugates. Moreover, data suggest that a high polyphenol intake may improve their bioavailability due to saturation of the intestinal secretion of conjugates.

Key words

rats polyphenols in situ perfusion intestinal metabolism biliary secretion 

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References

  1. 1.
    Bravo L (1998) Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr Rev 56:317–333Google Scholar
  2. 2.
    Scalbert A, Manach C, Morand C, Rémésy C, Jiménez L (2005) Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr 45(4):287–306CrossRefGoogle Scholar
  3. 3.
    Manach C, Scalbert A, Morand C, Remesy C, Jimenez L (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79:727–747Google Scholar
  4. 4.
    Hollman PCH, van Trijp JMP, Buysman MNCP, Gaag MSvd, Mengelers MJB, de Vries JHM, Katan MB (1997) Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man. FEBS Lett 418:152–156CrossRefGoogle Scholar
  5. 5.
    Manach C, Morand C, Texier O, Favier ML, Agullo G, Demigne C, Regerat F, Remesy C (1995) Quercetin metabolites in plasma of rats fed diets containing rutin or quercetin. J Nutr 125:1911–1922Google Scholar
  6. 6.
    Crespy V, Morand C, Besson C, Cotelle N, Vezin H, Demigne C, Remesy C (2003) The splanchnic metabolism of flavonoids highly differed according to the nature of the compound. Am J Physiol Gastrointest Liver Physiol 284:G980–G988Google Scholar
  7. 7.
    Clifford MN (1999) Chlorogenic acids and other cinnamates – nature, occurrence and dietary burden. J Sci Food Agric 79:362–372CrossRefGoogle Scholar
  8. 8.
    Rousseff RL, Martin SF, Youtsey CO (1987) Quantitative survey of narirutin, naringin, heperidin, and neohesperidin in citrus. J Agric Food Chem 35:1027–1030 Google Scholar
  9. 9.
    Reinli K, Block G (1996) Phytoestrogen content of foods – a compendium of literature values. Nutr Cancer Int J 26:123–148Google Scholar
  10. 10.
    Setchell KD (1998) Phytoestrogens: the biochemistry, physiology, and implications for human health of soy isoflavones. Am J Clin Nutr 68:1333S–1346SGoogle Scholar
  11. 11.
    Setchell KD, Lydeking–Olsen E (2003) Dietary phytoestrogens and their effect on bone: evidence from in vitro and in vivo, human observational, and dietary intervention studies. Am J Clin Nutr 78:593S–609SGoogle Scholar
  12. 12.
    Jung UJ, Kim HJ, Lee JS, Lee MK, Kim HO,Park EJ,Kim HK,Jeong TS,Choi MS (2003) Naringin supplementation lowers plasma lipids and enhances erythrocyte antioxidant enzyme activities in hypercholesterolemic subjects. Clin Nutr 22:561–568Google Scholar
  13. 13.
    Kim HJ, Oh GT, Park YB, Lee MK, Seo HJ, Choi MS (2004) Naringin alters the cholesterol biosynthesis and antioxidant enzyme activities in Ldl receptorknockout mice under cholesterol fed condition. Life Sci 74:1621–1634Google Scholar
  14. 14.
    Kim HK, Jeong TS, Lee MK, Park YB, Choi MS (2003) Lipid–lowering efficacy of hesperetin metabolites in high–cholesterol fed rats. Clin Chim Acta 327:129–137CrossRefGoogle Scholar
  15. 15.
    Yang MZ,Tanaka T,Hirose Y,Deguchi T, Mori H, Kawada Y (1997) Chemopreventive effects of diosmin and hesperidin on N–butyl–N–(4–hydroxybutyl) nitrosamine–induced urinarybladder carcinogenesis in male Icr mice. Int J Cancer 73:719–724 CrossRefGoogle Scholar
  16. 16.
    Berkarda B, Koyuncu H, Soybir G, Baykut F (1998) Inhibitory effect of hesperidin on tumour initiation and promotion in mouse skin. Res Exp Med (Berl) 198:93–99 CrossRefGoogle Scholar
  17. 17.
    Tanaka T, Kawabata K, Kakumoto M, Makita H, Matsunaga K,Mori H, Satoh K, Hara A, Murakami A, Koshimizu K, Ohigashi H (1997) Chemoprevention of azoxymethane–induced rat colon carcinogenesis by a xanthine oxidase inhibitor, 1’–acetoxychavicol acetate. Jpn J Cancer Res 88:821–830Google Scholar
  18. 18.
    Crespy V,Morand C,Manach C, Besson C, Demigne C, Remesy C (1999) Part of quercetin absorbed in the small intestine is conjugated and further secreted in the intestinal lumen. Am J Physiol Gastrointest Liver Physiol 277: G120–G126Google Scholar
  19. 19.
    Walgren RA,Walle UK,Walle T (1998) Transport of quercetin and its glucosides across human intestinal epithelial caco–2 cells. Biochem Pharmacol 55:1721–1727CrossRefGoogle Scholar
  20. 20.
    Wolffram S, Weber T, Grenacher B, Scharrer E (1995) A Na+–dependent mechanism is involved in mucosal uptake of cinnamic acid across the jejunal brush border in rats. J Nutr 125: 1300–1308Google Scholar
  21. 21.
    Ader P,Grenacher B,Langguth P, Scharrer E,Wolffram S (1996) Cinnamate uptake by rat small intestine: transport kinetics and transepithelial transfer. Experimental Physiology 81:943–955Google Scholar
  22. 22.
    Konishi Y, Shimizu M (2003) Transepithelial transport of ferulic acid by monocarboxylic acid transporter in caco–2 cell monolayers. Biosci Biotechnol Biochem 67:856–862Google Scholar
  23. 23.
    Andlauer W, Kolb J, Furst P (2000) Absorption and metabolism of genistin in the isolated rat small intestine. FEBS Lett 475:127–130CrossRefGoogle Scholar
  24. 24.
    Spencer JP, Chowrimootoo G, Choudhury R, Debnam ES, Srai SK, Rice– Evans C (1999) The small intestine can both absorb and glucuronidate luminal flavonoids. FEBS Lett 458:224–230CrossRefGoogle Scholar
  25. 25.
    Crespy V,Morand C, Besson C,Manach C, Demigne C, Remesy C (2001) Comparison of the intestinal absorption of quercetin, phloretin and their glucosides in rats. 131:2109–2114 Google Scholar
  26. 26.
    Walle T,Walle UK, Halushka PV (2001) Carbon dioxide is the major metabolite of quercetin in humans. J Nutr 131: 2648–2652Google Scholar
  27. 27.
    Ayrton A, Morgan P (2001) Role of transport proteins in drug absorption, distribution and excretion. Xenobiotica 31:469–497Google Scholar
  28. 28.
    Liu Y,Hu M (2002) Absorption and metabolism of flavonoids in the caco–2 cell culture model and a perused rat intestinal model. Drug Metab Dispos 30: 370–377CrossRefGoogle Scholar
  29. 29.
    Matsumoto H, Ikoma Y, Sugiura M, Yano M, Hasegawa Y (2004) Identification and quantification of the conjugated metabolites derived from orally administered hesperidin in rat plasma. J Agric Food Chem 52:6653–6659Google Scholar
  30. 30.
    Manach C,Texier O,Régérat F,Agullo G, Demigné C, Rémésy C (1996) Dietary quercetin is recovered in rat plasma as conjugated derivatives of isorhamnetin and quercetin. Nutr Biochem 7:375–380CrossRefGoogle Scholar
  31. 31.
    Sfakianos J,Coward L,Kirk M, Barnes S (1997) Intestinal uptake and biliary excretion of the isoflavone genistein in rats. J Nutr 127:1260–1268Google Scholar
  32. 32.
    Yasuda T, Kano Y, Saito K–I, Ohsawa K (1994) Urinary and biliary metabolites of daidzin and daidzein in rats. Biol Pharm Bull 17:1369–1374Google Scholar
  33. 33.
    Yasuda T, Mizunuma S,Kano Y, Saito K, Oshawa K (1996) Urinary and biliary metabolites of genistein in rats. Biol Pharm Bull 19:413–417Google Scholar
  34. 34.
    Rondini L, Peyrat–Maillard MN, Marsset– Baglieri A, Berset C (2002) Sulfated ferulic acid is the main in vivo metabolite found after short–term ingestion of free ferulic acid in rats. J Agric Food Chem 50:3037–3041 CrossRefGoogle Scholar
  35. 35.
    Felgines C,Texier O,Morand C,Manach C, Scalbert A, Regerat F, Remesy C (2000) Bioavailability of the flavanone naringenin and its glycosides in rats. Am J Physiol Gastrointest Liver Physiol 279:G1148–G1154Google Scholar
  36. 36.
    King RA, Bursill DB (1998) Plasma and urinary kinetics of the isoflavones daidzein and genistein after a single soy meal in humans. Am J Clin Nutr 67:867–872 Google Scholar

Copyright information

© Steinkopff-Verlag 2005

Authors and Affiliations

  • M. Silberberg
    • 1
  • C. Morand
    • 1
    Email author
  • T. Mathevon
    • 2
  • C. Besson
    • 1
  • C. Manach
    • 1
  • A. Scalbert
    • 1
  • C. Remesy
    • 1
  1. 1.Laboratoire des Maladies Métaboliques et des Micronutriments I. N. R. A. Centre de Recherche de Clermont–Ferrand/TheixSaint Genés–ChampanelleFrance
  2. 2.Centre Hospitalier Universitaire de Clermont–Ferrand Service Accueil UrgencesClermont–FerrandFrance

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