The Impact of Gastrointestinal Modifications, Blood-Brain Barrier Transport, and Intracellular Metabolism on Polyphenol Bioavailability: An Overview

Polyphenols in Human Health and Disease

Volumn 1, Issue , 2013, Pages 591-604

  Corona, Giulia ^a   Vauzour, David ^b   Amini, Anna ^a   Spencer, Jeremy P E ^a  

^a UNIVERSITY OF READING   (United Kingdom)

^b UNIVERSITY OF EAST ANGLIA   (United Kingdom)

Author keywords

Absorption; Bioavailability; Blood brain barrier; Flavonoids; Gastrointestinal tract; Metabolism; Polyphenols

Indexed keywords

EID: 84902568354     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1016/B978-0-12-398456-2.00044-X     Document Type: Chapter

References (175)

1. Vauzour D., Rodriguez-Mateos A., Corona G., Oruna-Concha M.J., Spencer J.P. Polyphenols and human health: prevention of disease and mechanisms of action. Nutrients 2010, 2(11):1106-1131.
2. Kuriyama S., Shimazu T., Ohmori K., Kikuchi N., Nakaya N., Nishino Y., et al. Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study. JAMA 2006, 296(10):1255-1265.
3. Checkoway H., Powers K., Smith-Weller T., Franklin G.M., Longstreth W.T., Swanson P.D. Parkinson's disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake. Am J Epidemiol 2002, 155(8):732-738.
4. Lamport D.J., Dye L., Wightman J.D., Lawton C.L. The effects of flavonoid and other polyphenol consumption on cognitive performance: a systematic research review of human experimental and epidemiological studies. Nutrition and Aging 2012, 1(1):5-25.
5. Saunders C., Spencer J.P.E. Metabolic and immune risk factors for dementia and their modification by flavonoids: new targets for the prevention of cognitive impairment?. Nutrition and Aging 2012, 1(1):69-88.
6. Williams R.J., Spencer J.P., Rice-Evans C. Flavonoids: antioxidants or signalling molecules?. Free Radic Biol Med 2004, 36(7):838-849.
7. Corona G., Deiana M., Incani A., Vauzour D., Dessi M.A., Spencer J.P. Inhibition of p38/CREB phosphorylation and COX-2 expression by olive oil polyphenols underlies their anti-proliferative effects. Biochem Biophys Res Commun 2007, 362(3):606-611.
8. Corona G., Deiana M., Incani A., Vauzour D., Dessi M.A., Spencer J.P. Hydroxytyrosol inhibits the proliferation of human colon adenocarcinoma cells through inhibition of ERK1/2 and cyclin D1. Mol Nutr Food Res 2009, 53(7):897-903.
9. Spencer J.P. Beyond antioxidants: the cellular and molecular interactions of flavonoids and how these underpin their actions on the brain. Proc Nutr Soc 2010, 69(2):244-260.
10. Corona G., Spencer J.P., Dessi M.A. Extra virgin olive oil phenolics: absorption, metabolism, and biological activities in the GI tract. Toxicol Ind Health 2009, 25(4-5):285-293.
11. Miro-Casas E., Covas M.I., Farre M., Fito M., Ortuño J., Weinbrenner T., et al. Hydroxytyrosol disposition in humans. Clin Chem 2003, 49(6 Pt 1):945-952.
12. Miro-Casas E., Covas M.I., Fito M., Farre-Albadalejo M., Marrugat J., de la Torre R. Tyrosol and hydroxytyrosol are absorbed from moderate and sustained doses of virgin olive oil in humans. Eur J Clin Nutr 2003, 57(1):186-190.
13. Miró-Casas E., Farré Albaladejo M., Covas M.I., Rodriguez J.O., Menoyo Colomer E., Lamuela Raventós R.M., et al. Capillary gas chromatography-mass spectrometry quantitative determination of hydroxytyrosol and tyrosol in human urine after olive oil intake. Anal Biochem 2001, 294(1):63-72.
14. Visioli F., Galli C., Bornet F., Mattei A., Patelli R., Galli G., et al. Olive oil phenolics are dose-dependently absorbed in humans. FEBS Lett 2000, 468(2-3):159-160.
15. Miro Casas E., Farre Albadalejo M., Covas Planells M.I., Fito Colomer M., Lamuela Raventos R.M., de la Torre Fornell R. Tyrosol bioavailability in humans after ingestion of virgin olive oil. Clin Chem 2001, 47(2):341-343.
16. Visioli F., Caruso D., Plasmati E., Patelli R., Mulinacci N., Romani A., et al. Hydroxytyrosol, as a component of olive mill waste water, is dose-dependently absorbed and increases the antioxidant capacity of rat plasma. Free Radic Res 2001, 34(3):301-305.
17. Caruso D., Visioli F., Patelli R., Galli C., Galli G. Urinary excretion of olive oil phenols and their metabolites in humans. Metabolism 2001, 50(12):1426-1428.
18. D'Angelo S., Manna C., Migliardi V., Mazzoni O., Morrica P., Capasso G., et al. Pharmacokinetics and metabolism of hydroxytyrosol, a natural antioxidant from olive oil. Drug Metab Dispos 2001, 29(11):1492-1498.
19. Visioli F., Galli C., Grande S., Colonnelli K., Patelli C., Galli G., et al. Hydroxytyrosol excretion differs between rats and humans and depends on the vehicle of administration. J Nutr 2003, 133(8):2612-2615.
20. Tuck K.L., Freeman M.P., Hayball P.J., Stretch G.L., Stupans I. The in vivo fate of hydroxytyrosol and tyrosol, antioxidant phenolic constituents of olive oil, after intravenous and oral dosing of labeled compounds to rats. J Nutr 2001, 131(7):1993-1996.
21. Tuck K.L., Hayball P.J., Stupans I. Structural characterization of the metabolites of hydroxytyrosol, the principal phenolic component in olive oil, in rats. J Agric Food Chem 2002, 50(8):2404-2409.
22. Vissers M.N., Zock P.L., Roodenburg A.J., Leenen R., Katan M.B. Olive oil phenols are absorbed in humans. J Nutr 2002, 132(3):409-417.
23. Suárez M., Romero M.P., Macià A., Valls R.M., Fernández S., Solà R., et al. Improved method for identifying and quantifying olive oil phenolic compounds and their metabolites in human plasma by microelution solid-phase extraction plate and liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2009, 877(32):4097-4106.
24. Suárez M., Valls R.M., Romero M.P., Macià A., Fernández S., Giralt M., et al. Bioavailability of phenols from a phenol-enriched olive oil. Br J Nutr 2011, 106(11):1691-1701.
25. Rein D., Lotito S., Holt R.R., Keen C.L., Schmitz H.H., Fraga C.G. Epicatechin in human plasma: in vivo determination and effect of chocolate consumption on plasma oxidation status. J Nutr 2000, 130(8S Suppl.):2109S-2114S.
26. Richelle M., Tavazzi I., Enslen M., Offord E.A. Plasma kinetics in man of epicatechin from black chocolate. Eur J Clin Nutr 1999, 53(1):22-26.
27. Ho Y., Lee Y.L., Hsu K.Y. Determination of (+)-catechin in plasma by high-performance liquid chromatography using fluorescence detection. J Chromatogr B Biomed Appl 1995, 665(2):383-389.
28. Wang J.F., Schramm D.D., Holt R.R., Ensunsa J.L., Fraga C.G., Schmitz H.H., et al. A dose-response effect from chocolate consumption on plasma epicatechin and oxidative damage. J Nutr 2000, 130(8S Suppl.):2115S-2119S.
29. Baba S., Osakabe N., Yasuda A., Natsume M., Takizawa T., Nakamura T., et al. Bioavailability of (-)-epicatechin upon intake of chocolate and cocoa in human volunteers. Free Radic Res 2000, 33(5):635-641.
30. Mullen W., Borges G., Donovan J.L., Edwards C.A., Serafini M., Lean M.E., et al. Milk decreases urinary excretion but not plasma pharmacokinetics of cocoa flavan-3-ol metabolites in humans. Am J Clin Nutr 2009, 89(6):1784-1791.
31. Neilson A.P., George J.C., Janle E.M., Mattes R.D., Rudolph R., Matusheski N.V., et al. Influence of chocolate matrix composition on cocoa flavan-3-ol bioaccessibility in vitro and bioavailability in humans. J Agric Food Chem 2009, 57(20):9418-9426.
32. Neilson A.P., Sapper T.N., Janle E.M., Rudolph R., Matusheski N.V., Ferruzzi M.G. Chocolate matrix factors modulate the pharmacokinetic behavior of cocoa flavan-3-ol phase II metabolites following oral consumption by Sprague-Dawley rats. J Agric Food Chem 2010, 58(11):6685-6691.
33. Rodriguez-Mateos A., Jose Oruna-Concha M., Kwik-Uribe C., Vidal A., Spencer J.P. Influence of sugar type on the bioavailability of cocoa flavanols. Br J Nutr 2012, 108(12):2243-2250.
34. Ottaviani J.I., Momma T.Y., Heiss C., Kwik-Uribe C., Schroeter H., Keen C.L. The stereochemical configuration of flavanols influences the level and metabolism of flavanols in humans and their biological activity in vivo. Free Radic Biol Med 2011, 50(2):237-244.
35. Andres-Lacueva C., Monagas M., Khan N., Izquierdo-Pulido M., Urpi-Sarda M., Permanyer J., et al. Flavanol and flavonol contents of cocoa powder products: influence of the manufacturing process. J Agric Food Chem 2008, 56(9):3111-3117.
36. Ottaviani J.I., Momma T.Y., Kuhnle G.K., Keen C.L., Schroeter H. Structurally related (-)-epicatechin metabolites in humans: assessment using de novo chemically synthesized authentic standards. Free Radic Biol Med 2012, 52(8):1403-1412.
37. Donovan J.L., Crespy V., Oliveira M., Cooper K.A., Gibson B.B., Williamson G. (+)-Catechin is more bioavailable than (-)-catechin: relevance to the bioavailability of catechin from cocoa. Free Radic Res 2006, 40(10):1029-1034.
38. Kodama S., Yamamoto A., Matsunaga A., Yanai H. Direct enantioseparation of catechin and epicatechin in tea drinks by 6-Oα-d-glucosylβ-cyclodextrin-modified micellar electrokinetic chromatography. Electrophoresis 2004, 25(16):2892-2898.
39. Manach C., Williamson G., Morand C., Scalbert A., Remesy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 2005, 81(1 Suppl.):230S-242S.
40. 14C]procyanidin B2 in male rats. Drug Metab Dispos 2010, 38(2):287-291.
41. Donovan J.L., Manach C., Rios L., Morand C., Scalbert A., Remesy C. Procyanidins are not bioavailable in rats fed a single meal containing a grapeseed extract or the procyanidin dimer B3. Br J Nutr 2002, 87(4):299-306.
42. Baba S., Osakabe N., Natsume M., Terao J. Absorption and urinary excretion of procyanidin B2 [epicatechin-(4β-8)-epicatechin] in rats. Free Radic Biol Med 2002, 33(1):142-148.
43. Holt R.R., Lazarus S.A., Sullards M.C., Zhu Q.Y., Schramm D.D., Hammerstone J.F., et al. Procyanidin dimer B2 [epicatechin-(4β-8)-epicatechin] in human plasma after the consumption of a flavanol-rich cocoa. Am J Clin Nutr 2002, 76(4):798-804.
44. Kahle K., Huemmer W., Kempf M., Scheppach W., Erk T., Richling E. Polyphenols are intensively metabolized in the human gastrointestinal tract after apple juice consumption. J Agric Food Chem 2007, 55(26):10605-10614.
45. Espin J.C., Garcia-Conesa M.T., Tomas-Barberan F.A. Nutraceuticals: facts and fiction. Phytochemistry 2007, 68(22-24):2986-3008.
46. Gonthier M.P., Donovan J.L., Texier O., Felgines C., Remesy C., Scalbert A. Metabolism of dietary procyanidins in rats. Free Radic Biol Med 2003, 35(8):837-844.
47. Ward N.C., Croft K.D., Puddey I.B., Hodgson J.M. 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 2004, 52(17):5545-5549.
48. Ottaviani J.I., Kwik-Uribe C., Keen C.L., Schroeter H. Intake of dietary procyanidins does not contribute to the pool of circulating flavanols in humans. Am J Clin Nutr 2012, 95(4):851-858.
49. Prior R.L., Wu X. Anthocyanins: Structural characteristics that result in unique metabolic patterns and biological activities. Free Radic Res 2006, 40(10):1014-1028.
50. Matsumoto H., Ito K., Yonekura K., Tsuda T., Ichiyanagi T., Hirayama M., et al. Enhanced absorption of anthocyanins after oral administration of phytic acid in rats and humans. J Agric Food Chem 2007, 55(6):2489-2496.
51. Wiczkowski W., Romaszko E., Piskula M.K. Bioavailability of cyanidin glycosides from natural chokeberry (Aronia melanocarpa) juice with dietary-relevant dose of anthocyanins in humans. J Agric Food Chem 2010, 58(23):12130-12136.
52. Vitaglione P., Donnarumma G., Napolitano A., Galvano F., Gallo A., Scalfi L., et al. Protocatechuic acid is the major human metabolite of cyanidin-glucosides. J Nutr 2007, 137(9):2043-2048.
53. Kurilich A.C., Clevidence B.A., Britz S.J., Simon P.W., Novotny J.A. Plasma and urine responses are lower for acylated vs nonacylated anthocyanins from raw and cooked purple carrots. J Agric Food Chem 2005, 53(16):6537-6542.
54. Charron C.S., Kurilich A.C., Clevidence B.A., Simon P.W., Harrison D.J., Britz S.J., et al. Bioavailability of anthocyanins from purple carrot juice: effects of acylation and plant matrix. J Agric Food Chem 2009, 57(4):1226-1230.
55. Crozier A., Del Rio D., Clifford M.N. Bioavailability of dietary flavonoids and phenolic compounds. Mol Aspects Med 2010, 31(6):446-467.
56. Del Rio D., Borges G., Crozier A. Berry flavonoids and phenolics: bioavailability and evidence of protective effects. British J Nutr 2010, 104:S67-S90.
57. Felgines C., Talavéra S., Gonthier M.P., Texier O., Scalbert A., Lamaison J.L., et al. Strawberry Anthocyanins are recovered in urine as glucuro- and sulfoconjugates in humans. J Nutr 2003, 133(5):1296-1301.
58. Hollands W., Brett G.M., Dainty J.R., Teucher B., Kroon P.A. Urinary excretion of strawberry anthocyanins is dose dependent for physiological oral doses of fresh fruit. Mol Nutr Food Res 2008, 52(10):1097-1105.
59. Carkeet C., Clevidence B.A., Novotny J.A. Anthocyanin excretion by humans increases linearly with increasing strawberry dose. J Nutr 2008, 138(5):897-902.
60. Nielsen I.L.F., Dragsted L.O., Ravn-Haren G., Freese R., Rasmussen S.E. Absorption and excretion of black currant anthocyanins in humans and Watanabe heritable hyperlipidemic rabbits. J Agric Food Chem 2003, 51(9):2813-2820.
61. Milbury P.E., Vita J.A., Blumbergs J.B. Anthocyanins are bioavailable in humans following an acute dose of cranberry juice. J Nutr 2010, 140(6):1099-1104.
62. Tian Q.G., Giusti M.M., Stoner G.D., Schwartz S.J. Urinary excretion of black raspberry (Rubus occidentalis) anthocyanins and their metabolites. J Agric Food Chem 2006, 54(4):1467-1472.
63. Neveu VP-JJ, Vos F, Crespy V, du Chaffaut L, Mennen L, Knox C, et al. Phenol-Explorer. 2010.
64. Corona G., Tang F., Vauzour D., Rodriguez-Mateos A., Spencer J.P.E. Assessment of the anthocyanidin content of common fruits and development of a test diet rich in a range of anthocyanins. J Berry Res 2011, 1(4):209-216.
65. Mullen W., Edwards C.A., Serafini M., Crozier A. Bioavailability of pelargonidin-3-O-glucoside and its metabolites in humans following the ingestion of strawberries with and without cream. J Agric Food Chem 2008, 56(3):713-719.
66. Felgines C., Talavera S., Texier O., Gil-Izquierdo A., Lamaison J.L., Remesy C. Blackberry anthocyanins are mainly recovered from urine as methylated and glucuronidated conjugates in humans. J Agric Food Chem 2005, 53(20):7721-7727.
67. Kay C.D., Mazza G., Holub B.J. Anthocyanins exist in the circulation primarily as metabolites in adult men. J Nutr 2005, 135(11):2582-2588.
68. Azzini E., Vitaglione P., Intorre F., Napolitano A., Durazzo A., Foddai M.S., et al. Bioavailability of strawberry antioxidants in human subjects. Br J Nutr 2010, 104(8):1165-1173.
69. Felgines C., Krisa S., Mauray A., Besson C., Lamaison J.L., Scalbert A., et al. Radiolabelled cyanidin 3-O-glucoside is poorly absorbed in the mouse. Br J Nutr 2010, 103(12):1738-1745.
70. Borges G., Roowi S., Rouanet J.-M., Duthie G.G., Lean M.E.J., Crozier A. The bioavailability of raspberry anthocyanins and ellagitannins in rats. Mol Nutr Food Res 2007, 51(6):714-725.
71. Yang C.S., Lee M.J., Chen L. Human salivary tea catechin levels and catechin esterase activities: implication in human cancer prevention studies. Cancer Epidemiol Biomarkers Prev 1999, 8(1):83-89.
72. Tsuchiya H., Sato M., Kato H., Okubo T., Juneja L.R., Kim M. Simultaneous determination of catechins in human saliva by high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl 1997, 703(1-2):253-258.
73. Walle T., Browning A.M., Steed L.L., Reed S.G., Walle U.K. Flavonoid glucosides are hydrolyzed and thus activated in the oral cavity in humans. J Nutr 2005, 135(1):48-52.
74. Laires A., Pacheco P., Rueff J. Mutagenicity of rutin and the glycosidic activity of cultured cell-free microbial preparations of human faeces and saliva. Food Chem Toxicol 1989, 27(7):437-443.
75. Parisis D.M., Pritchard E.T. Activation of rutin by human oral bacterial isolates to the carcinogen-mutagen quercetin. Arch Oral Biol 1983, 28(7):583-590.
76. Macdonald I.A., Mader J.A., Bussard R.G. The role of rutin and quercitrin in stimulating flavonol glycosidase activity by cultured cell-free microbial preparations of human feces and saliva. Mutat Res 1983, 122(2):95-102.
77. Fenwick G.R., Heaney R.K., Mullin W.J. Glucosinolates and their breakdown products in food and food plants. Crit Rev Food Sci Nutr 1983, 18(2):123-201.
78. de Freitas V., Mateus N. Structural features of procyanidin interactions with salivary proteins. J Agric Food Chem 2001, 49(2):940-945.
79. Nishioka H., Nishi K., Kyokane K. Human saliva inactivates mutagenicity of carcinogens. Mutat Res 1981, 85(5):323-333.
80. Scalbert A., Morand C., Manach C., Remesy C. Absorption and metabolism of polyphenols in the gut and impact on health. Biomed Pharmacother 2002, 56(6):276-282.
81. Zhao Z., Egashira Y., Sanada H. Ferulic acid is quickly absorbed from rat stomach as the free form and then conjugated mainly in liver. J Nutr 2004, 134(11):3083-3088.
82. Lafay S., Gil-Izquierdo A., Manach C., Morand C., Besson C., Scalbert A. Chlorogenic acid is absorbed in its intact form in the stomach of rats. J Nutr 2006, 136(5):1192-1197.
83. Corona G., Tzounis X., Assunta Dessì M., Deiana M., Debnam E.S., Visioli F., et al. The fate of olive oil polyphenols in the gastrointestinal tract: implications of gastric and colonic microflora-dependent biotransformation. Free Radic Res 2006, 40(6):647-658.
84. Spencer J.P., Schroeter H., Rechner A.R., Rice-Evans C. Bioavailability of flavan-3-ols and procyanidins: gastrointestinal tract influences and their relevance to bioactive forms in vivo. Antioxid Redox Signal 2001, 3(6):1023-1039.
85. Gee J.M., DuPont M.S., Rhodes M.J., Johnson I.T. Quercetin glucosides interact with the intestinal glucose transport pathway. Free Radic Biol Med 1998, 25(1):19-25.
86. Felgines C., Texier O., Besson C., Lyan B., Lamaison J.-L., Scalbert A. Strawberry pelargonidin glycosides are excreted in urine as intact glycosides and glucuronidated pelargonidin derivatives in rats. Br J Nutr 2007, 98(6):1126-1131.
87. Passamonti S., Vrhovsek U., Vanzo A., Mattivi F. The stomach as a site for anthocyanins absorption from food. FEBS Lett 2003, 544(1-3):210-213.
88. Talavera S., Felgines C., Texier O., Besson C., Lamaison J.L., Remesy C. Anthocyanins are efficiently absorbed from the stomach in anesthetized rats. J Nutr 2003, 133(12):4178-4182.
89. Passamonti S., Vrhovsek U., Mattivi F. The interaction of anthocyanins with bilitranslocase. Biochem Biophys Res Commun 2002, 296(3):631-636.
90. Lin J.H., Chiba M., Baillie T.A. Is the role of the small intestine in first-pass metabolism overemphasized?. Pharmacol Rev 1999, 51(2):135-158.
91. Spencer J.P., Chowrimootoo G., Choudhury R., Debnam E.S., Srai S.K., Rice-Evans C. The small intestine can both absorb and glucuronidate luminal flavonoids. FEBS Lett 1999, 458(2):224-230.
92. Day A.J., Williamson G. Biomarkers for exposure to dietary flavonoids: a review of the current evidence for identification of quercetin glycosides in plasma. Br J Nutr 2001, 86(Suppl. 1):S105-110.
93. 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 2000, 130(11):2765-2771.
94. Hollman P.C., Bijsman M.N., van Gameren Y., Cnossen E.P., de Vries J.H., Katan M.B. The sugar moiety is a major determinant of the absorption of dietary flavonoid glycosides in man. Free Radic Res 1999, 31(6):569-573.
95. Manna C., Galletti P., Maisto G., Cucciolla V., D'Angelo S., Zappia V. Transport mechanism and metabolism of olive oil hydroxytyrosol in Caco-2 cells. FEBS Lett 2000, 470(3):341-344.
96. Spencer J.P., Schroeter H., Shenoy B., Srai S.K., Debnam E.S., Rice-Evans C. Epicatechin is the primary bioavailable form of the procyanidin dimers B2 and B5 after transfer across the small intestine. Biochem Biophys Res Commun 2001, 285(3):588-593.
97. Pérez-Vicente A., Gil-Izquierdo A., García-Viguera C. In vitro gastrointestinal digestion study of pomegranate juice phenolic compounds, anthocyanins, and vitamin C. J Agric Food Chem 2002, 50(8):2308-2312.
98. Fazzari M., Fukumoto L., Mazza G., Livrea M.A., Tesoriere L., Marco L.D. In vitro bioavailability of phenolic compounds from five cultivars of frozen sweet cherries (Prunus avium L.). J Agric Food Chem 2008, 56(10):3561-3568.
99. McDougall G.J., Dobson P., Smith P., Blake A., Stewart D. Assessing potential bioavailability of raspberry anthocyanins using an in vitro digestion system. J Agric Food Chem 2005, 53(15):5896-5904.
100. McDougall G.J., Fyffe S., Dobson P., Stewart D. Anthocyanins from red cabbage - stability to simulated gastrointestinal digestion. Phytochemistry 2007, 68(9):1285-1294.
101. Kay C.D., Kroon P.A., Cassidy A. The bioactivity of dietary anthocyanins is likely to be mediated by their degradation products. Mol Nutr Food Res 2009, 53(Suppl. 1):S92-101.
102. Kay C.D. Aspects of anthocyanin absorption, metabolism and pharmacokinetics in humans. Nutr Res Rev 2006, 19(1):137-146.
103. Kuhnle G., Spencer J.P., Chowrimootoo G., et al. Resveratrol is absorbed in the small intestine as resveratrol glucuronide. Biochem Biophys Res Commun 2000, 272(1):212-217.
104. Kuhnle G., Spencer J.P., Schroeter H., Shenoy B., Debnam E.S., Srai S.K., et al. Epicatechin and catechin are O-methylated and glucuronidated in the small intestine. Biochem Biophys Res Commun 2000, 277(2):507-512.
105. Crespy V., Morand C., Manach C., Besson C., Demigne C., Remesy C. Part of quercetin absorbed in the small intestine is conjugated and further secreted in the intestinal lumen. Am J Physiol 1999, 277(1 Pt 1):120-126.
106. Donovan J.L., Bell J.R., Kasim-Karakas S., German J.B., Walzem R.L., Hansen R.J., et al. Catechin is present as metabolites in human plasma after consumption of red wine. J Nutr 1999, 129(9):1662-1668.
107. Felgines C., Talavéra S., Gonthier M.P., Texier O., Scalbert A., Lamaison J.L., et al. Strawberry anthocyanins are recovered in urine as glucuro- and sulfoconjugates in humans. J Nutr 2003, 133(5):1296-1301.
108. Qin J., Li R., Raes J., Arumugam M., Burgdorf K.S., Manichanh C., et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010, 464(7285):59-65.
109. Aura A.-M. Microbial metabolism of dietary phenolic compounds in the colon. Phytochem Rev 2008, 7(3):407-429.
110. Del Rio D., Costa L.G., Lean M.E., Crozier A. Polyphenols and health: what compounds are involved?. Nutr Metab Cardiovasc Dis 2010, 20(1):1-6.
111. Selma M.V., Espin J.C., Tomas-Barberan F.A. Interaction between phenolics and gut microbiota: role in human health. J Agric Food Chem 2009, 57(15):6485-6501.
112. Scheline R.R. The metabolism of drugs and other organic compounds by the intestinal microflora. Acta Pharmacol Toxicol (Copenh) 1968, 26(4):332-342.
113. Borriello S.P., Setchell K.D., Axelson M., Lawson A.M. Production and metabolism of lignans by the human faecal flora. J Appl Bacteriol 1985, 58(1):37-43.
114. Glitso L.V., Mazur W.M., Adlercreutz H., et al. Intestinal metabolism of rye lignans in pigs. Br J Nutr 2000, 84(4):429-437.
115. Glitsø L.V., Mazur W.M., Adlercreutz H., Wähälä K., Mäkelä T., Sandström B., et al. In vitro metabolism of plant lignans: new precursors of mammalian lignans enterolactone and enterodiol. J Agric Food Chem 2001, 49(7):3178-3186.
116. Scheline R.R. Metabolism of phenolic acids by the rat intestinal microflora. Acta Pharmacol Toxicol (Copenh) 1968, 26(2):189-205.
117. Phipps A.N., Stewart J., Wright B., Wilson I.D. Effect of diet on the urinary excretion of hippuric acid and other dietary-derived aromatics in rat. A complex interaction between diet, gut microflora and substrate specificity. Xenobiotica 1998, 28(5):527-537.
118. Vauzour D., Houseman E.J., George T.W., Corona G., Garnotel R., Jackson K.G., et al. Moderate Champagne consumption promotes an acute improvement in acute endothelial-independent vascular function in healthy human volunteers. Br J Nutr 2010, 103(8):1168-1178.
119. Mulder T.P., Rietveld A.G., van Amelsvoort J.M. Consumption of both black tea and green tea results in an increase in the excretion of hippuric acid into urine. Am J Clin Nutr 2005, 81(1 Suppl.):256S-260S.
120. Aura A.M., O'Leary K.A., Williamson G., Ojala M., Bailey M., Puupponen-Pimiä R., et al. Quercetin derivatives are deconjugated and converted to hydroxyphenylacetic acids but not methylated by human fecal flora in vitro. J Agric Food Chem 2002, 50(6):1725-1730.
121. Rechner A.R., Smith M.A., Kuhnle G., Gibson G.R., Debnam E.S., Srai S.K., et al. Colonic metabolism of dietary polyphenols: influence of structure on microbial fermentation products. Free Radic Biol Med 2004, 36(2):212-225.
122. Hein E.M., Rose K., van't Slot G., Friedrich A.W., Humpf H.U. Deconjugation and degradation of flavonol glycosides by pig cecal microbiota characterized by fluorescence in situ hybridization (FISH). J Agric Food Chem 2008, 56(6):2281-2290.
123. Keppler K., Humpf H.U. Metabolism of anthocyanins and their phenolic degradation products by the intestinal microflora. Bioorg Med Chem 2005, 13(17):5195-5205.
124. Scheline R.R. The metabolism of (+)-catechin to hydroxyphenylvaleric acids by the intestinal microflora. Biochim Biophys Acta 1970, 222(1):228-230.
125. Lee M.J., Maliakal P., Chen L., Meng X., Bondoc F.Y., Prabhu S., et al. Pharmacokinetics of tea catechins after ingestion of green tea and (-)-epigallocatechin-3-gallate by humans: formation of different metabolites and individual variability. Cancer Epidemiol Biomarkers Prev 2002, 11(10 Pt 1):1025-1032.
126. Das N.P. Studies on flavonoid metabolism. Absorption and metabolism of (+)-catechin in man. Biochem Pharmacol 1971, 20(12):3435-3445.
127. Bokkenheuser V.D., Shackleton C.H., Winter J. Hydrolysis of dietary flavonoid glycosides by strains of intestinal Bacteroides from humans. Biochem J 1987, 248(3):953-956.
128. Schneider H., Schwiertz A., Collins M.D., Blaut M. Anaerobic transformation of quercetin-3-glucoside by bacteria from the human intestinal tract. Arch Microbiol 1999, 171(2):81-91.
129. Schneider H., Blaut M. Anaerobic degradation of flavonoids by Eubacterium ramulus. Arch Microbiol 2000, 173(1):71-75.
130. Kim D.H., Jung E.A., Sohng I.S., Han J.A., Kim T.H., Han M.J. Intestinal bacterial metabolism of flavonoids and its relation to some biological activities. Arch Pharm Res 1998, 21(1):17-23.
131. Aura A.M., Martin-Lopez P., O'Leary K.A., Williamson G., Oksman-Caldentey K.M., Poutanen K., et al. In vitro metabolism of anthocyanins by human gut microflora. Eur J Nutr 2005, 44(3):133-142.
132. Keppler K., Humpf H.-U. Metabolism of anthocyanins and their phenolic degradation products by the intestinal microflora. Bioorg Med Chem 2005, 13(17):5195-5205.
133. Fleschhut J., Kratzer F., Rechkemmer G., Kulling S. Stability and biotransformation of various dietary anthocyanins in vitro. Eur J Nutr 2006, 45(1):7-18.
134. Seeram N.P., Momin R.A., Nair M.G., Bourquin L.D. Cyclooxygenase inhibitory and antioxidant cyanidin glycosides in cherries and berries. Phytomedicine 2001, 8(5):362-369.
135. Han S.J., Ryu S.N., Trinh H.T., Joh E.H., Jang S.Y., Han M.J., et al. Metabolism of cyanidin-3-Oβ-D-glucoside isolated from black colored rice and its antiscratching behavioral effect in mice. J Food Sci 2009, 74(8):H253-H258.
136. Hassimotto N.M.A., Genovese M.I., Lajolo F.M. Absorption and metabolism of cyanidin-3-glucoside and cyanidin-3-rutinoside extracted from wild mulberry (Morus nigra L.) in rats. Nutr Res 2008, 28(3):198-207.
137. Gonzalez-Barrio R., Edwards C.A., Crozier A. Colonic catabolism of ellagitannins, ellagic acid, and raspberry anthocyanins: in vivo and in vitro studies. Drug Metab Dispos 2011, 39(9):1680-1688.
138. Manach C., Williamson G., Morand C., Scalbert A., Remesy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 2005, 81(1):230S-242S.
139. Spencer J.P., Schroeter H., Crossthwaithe A.J., Kuhnle G., Williams R.J., Rice-Evans C. Contrasting influences of glucuronidation and O-methylation of epicatechin on hydrogen peroxide-induced cell death in neurons and fibroblasts. Free Radic Biol Med 2001, 31(9):1139-1146.
140. Spencer J.P., Schroeter H., Kuhnle G., Srai S.K., Tyrrell R.M., Hahn U., et al. 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 2001, 354(Pt 3):493-500.
141. Spencer J.P., Kuhnle G.G., Williams R.J., Rice-Evans C. Intracellular metabolism and bioactivity of quercetin and its in vivo metabolites. Biochem J 2003, 372(Pt 1):173-181.
142. Proteggente A.R., Basu-Modak S., Kuhnle G., Gordon M.J., Youdim K., Tyrrell R., et al. Hesperetin glucuronide, a photoprotective agent arising from flavonoid metabolism in human skin fibroblasts. Photochem Photobiol 2003, 78(3):256-261.
143. Awad H.M., Boersma M.G., Boeren S., van Bladeren P.J., Vervoort J., Rietjens I.M. The regioselectivity of glutathione adduct formation with flavonoid quinone/quinone methides is pH-dependent. Chem Res Toxicol 2002, 15(3):343-351.
144. Awad H.M., Boersma M.G., Boeren S., van der Woude H., van Zanden J., van Bladeren P.J., et al. Identification of o-quinone/quinone methide metabolites of quercetin in a cellular in vitro system. FEBS Lett 2002, 520(1-3):30-34.
145. Wong C.C., Meinl W., Glatt H.R., Barron D., Stalmach A., Steiling H., et al. In vitro and in vivo conjugation of dietary hydroxycinnamic acids by UDP-glucuronosyltransferases and sulfotransferases in humans. J Nutr Biochem 2010, 21(11):1060-1068.
146. Moridani M.Y., Scobie H., O'Brien P.J. Metabolism of caffeic acid by isolated rat hepatocytes and subcellular fractions. Toxicol Lett 2002, 133(2-3):141-151.
147. Nguyen D.T., Hernandez-Montes E., Vauzour D., Schönthal A.H., Rice-Evans C., Cadenas E., et al. The intracellular genistein metabolite 5,7,3',4'-tetrahydroxyisoflavone mediates G2-M cell cycle arrest in cancer cells via modulation of the p38 signaling pathway. Free Radic Biol Med 2006, 41(8):1225-1239.
148. Peterson T.G., Coward L., Kirk M., Falany C.N., Barnes S. The role of metabolism in mammary epithelial cell growth inhibition by the isoflavones genistein and biochanin A. Carcinogenesis 1996, 17(9):1861-1869.
149. Monks T.J., Lau S.S. Biological reactivity of polyphenolic-glutathione conjugates. Chem Res Toxicol 1997, 10(12):1296-1313.
150. Crozier A., Jaganath I.B., Clifford M.N. Dietary phenolics: chemistry, bioavailability and effects on health. Nat Prod Rep 2009, 26(8):1001-1043.
151. Manach C., Scalbert A., Morand C., Remesy C., Jimenez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr 2004, 79(5):727-747.
152. Manach C., Williamson G., Morand C., Scalbert A., Remesy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 2005, 81(1 Suppl.):230S-242S.
153. Williamson G., Manach C. Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. Am J Clin Nutr 2005, 81(1 Suppl.):243S-255S.
154. Faria A., Mateus N., Calhau C. Flavonoid transport across blood-brain barrier: Implication for their direct neuroprotective actions. Nutrition and Aging 2012, 1(2):89-97.
155. Youdim K.A., Qaiser M.Z., Begley D.J., Rice-Evans C.A., Abbott N.J. Flavonoid permeability across an in situ model of the blood-brain barrier. Free Radic Biol Med 2004, 36(5):592-604.
156. Abd El Mohsen M.M., Kuhnle G., Rechner A.R., Schroeter H., Rose S., Jenner P., et al. Uptake and metabolism of epicatechin and its access to the brain after oral ingestion. Free Radic Biol Med 2002, 33(12):1693-1702.
157. van Praag H., Lucero M.J., Yeo G.W., Stecker K., Heivand N., Zhao C., et al. Plant-derived flavanol (-)epicatechin enhances angiogenesis and retention of spatial memory in mice. J Neurosci 2007, 27(22):5869-5878.
158. Ferruzzi M.G., Lobo J.K., Janle E.M., Cooper B., Simon J.E., Wu Q.L., et al. Bioavailability of gallic acid and catechins from grape seed polyphenol extract is improved by repeated dosing in rats: implications for treatment in Alzheimer's disease. J Alzheimers Dis 2009, 18(1):113-124.
159. Lin L.C., Wang M.N., Tseng T.Y., Sung J.S., Tsai T.H. Pharmacokinetics of (-)-epigallocatechin-3-gallate in conscious and freely moving rats and its brain regional distribution. J Agric Food Chem 2007, 55(4):1517-1524.
160. Suganuma M., Okabe S., Oniyama M., Tada Y., Ito H., Fujiki H. Wide distribution of [3H](-)-epigallocatechin gallate, a cancer preventive tea polyphenol, in mouse tissue. Carcinogenesis 1998, 19(10):1771-1776.
161. Peng H.W., Cheng F.C., Huang Y.T., Chen C.F., Tsai T.H. Determination of naringenin and its glucuronide conjugate in rat plasma and brain tissue by high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl 1998, 714(2):369-374.
162. Rangel-Ordonez L., Noldner M., Schubert-Zsilavecz M., Wurglics M. Plasma levels and distribution of flavonoids in rat brain after single and repeated doses of standardized Ginkgo biloba extract EGb 761(R). Planta Med 2010, 76(15):1683-1690.
163. Talavéra S., Felgines C., Texier O., Besson C., Gil-Izquierdo A., Lamaison J.L., et al. Anthocyanin metabolism in rats and their distribution to digestive area, kidney, and brain. J Agric Food Chem 2005, 53(10):3902-3908.
164. 3H]trans-resveratrol in rat tissues following oral administration. Br J Nutr 2006, 96(1):62-70.
165. Youdim K.A., Dobbie M.S., Kuhnle G., Proteggente A.R., Abbott N.J., Rice-Evans C. Interaction between flavonoids and the blood-brain barrier: in vitro studies. J Neurochem 2003, 85(1):180-192.
166. Serra A., Rubio L., Borras X., Macia A., Romero M.P., Motilva M.J. Distribution of olive oil phenolic compounds in rat tissues after administration of a phenolic extract from olive cake. Mol Nutr Food Res 2012, 56(3):486-496.
167. Meiergerd S.M., Schenk J.O. Striatal transporter for dopamine: catechol structure-activity studies and susceptibility to chemical modification. J Neurochem 1994, 62(3):998-1008.
168. Andres-Lacueva C., Shukitt-Hale B., Galli R.L., Jauregui O., Lamuela-Raventos R.M., Joseph J.A. Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutr Neurosci 2005, 8(2):111-120.
169. Passamonti S., Vrhovsek U., Vanzo A., Mattivi F. Fast access of some grape pigments to the brain. J Agric Food Chem 2005, 53(18):7029-7034.
170. Milbury P.E., Kalt W. Xenobiotic metabolism and berry flavonoid transport across the blood-brain barrier. J Agric Food Chem 2010, 58(7):3950-3956.
171. Kalt W., Blumberg J.B., McDonald J.E., Vinqvist-Tymchuk M.R., Fillmore S.A., Graf B.A., et al. Identification of anthocyanins in the liver, eye, and brain of blueberry-fed pigs. J Agric Food Chem 2008, 56(3):705-712.
172. Datla K.P., Christidou M., Widmer W.W., Rooprai H.K., Dexter D.T. Tissue distribution and neuroprotective effects of citrus flavonoid tangeretin in a rat model of Parkinson's disease. Neuroreport 2001, 12(17):3871-3875.
173. Williams R.J., Spencer J.P. Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease. Free Radic Biol Med 2012, 52(1):35-45.
174. Zini A., Del Rio D., Stewart A.J., Mandrioli J., Merelli E., Sola P., et al. Do flavan-3-ols from green tea reach the human brain?. Nutr Neurosci 2006, 9(1-2):57-61.
175. Spencer J.P., Vafeiadou K., Williams R.J., Vauzour D. Neuroinflammation: modulation by flavonoids and mechanisms of action. Mol Aspects Med 2012, 33(1):83-97.