Genes & Nutrition

, Volume 5, Issue 1, pp 75–87

Improving the oral bioavailability of beneficial polyphenols through designed synergies

Review

Abstract

A substantial and growing consumer demand exists for plant-based functional foods that improve general health and wellbeing. Amongst consumed phytochemicals, the polyphenolic compounds tend to be the most bioactive. Many commonly consumed polyphenols have been shown to have specific and potent health-promoting activities when assessed by high-throughput in vitro assays and when administered to experimental animals by injection. However, very few have been shown to have any beneficial effects in animals or man when orally consumed, because of the poor bioavailability exhibited by most polyphenols following the ingestion. Consumed polyphenols, like most pharmaceuticals, are regarded as xenobiotics by the body and must overcome many barriers, including extensive enzymatic and chemical modification during digestion and absorption, to reach their site(s) of action. This is especially true for polyphenols targeting the brain, which is protected by the tightly regulated blood–brain barrier. Interestingly, many polyphenols are also known to specifically modify some of the metabolic and transport processes that govern bioavailability. Therefore, the opportunity exists to increase the bioactivity of beneficial polyphenols by designing specific synergistic interactions with polyphenols that improve their oral bioavailability. This hypothesis and review paper will discuss some of the endogenous systems that limit the bioavailability of ingested polyphenols to the body and the brain, and the means by which bioavailability may be improved by specifically designing synergies between orally consumed polyphenols.

Keywords

Bioavailability Phases 1 and 2 metabolism ABC transporters Polyphenol Synergy Functional food 

References

  1. 1.
    Andreasen MF, Kroon PA, Williamson G, Garcia-Conesa MT (2001) Esterase activity able to hydrolyze dietary antioxidant hydroxycinnamates is distributed along the intestine of mammals. J Agric Food Chem 49:5679–5684CrossRefPubMedGoogle Scholar
  2. 2.
    Bailey DG, Spence JD, Munoz C, Arnold JM (1991) Interaction of citrus juices with felodipine and nifedipine. Lancet 337:268–269CrossRefPubMedGoogle Scholar
  3. 3.
    Barone GW, Gurley BJ, Ketel BL, Lightfoot ML, Abul-Ezz SR (2000) Drug interaction between St. John’s wort and cyclosporine. Ann Pharmacother 34:1013–1016CrossRefPubMedGoogle Scholar
  4. 4.
    Bormann J, Demisch L, Gurtelmeyer R, Koch R, Schatton W (1991) Cerebral-activating extract. US Patent 755814Google Scholar
  5. 5.
    Bouayed J, Rammal H, Dicko A, Younos C, Soulimani R (2007) Chlorogenic acid, a polyphenol from Prunus domestica (Mirabelle), with coupled anxiolytic and antioxidant effects. J Neurol Sci 262:77–84CrossRefPubMedGoogle Scholar
  6. 6.
    Brand W, Schutte ME, Williamson G, van Zanden JJ, Cnubben NH, Groten JP, van Bladeren PJ, Rietjens IM (2006) Flavonoid-mediated inhibition of intestinal ABC transporters may affect the oral bioavailability of drugs, food-borne toxic compounds and bioactive ingredients. Biomed Pharmacother 60:508–519CrossRefPubMedGoogle Scholar
  7. 7.
    Butterweck V, Derendorf H (2008) Potential of pharmacokinetic profiling for detecting herbal interactions with drugs. Clin Pharmacokinet 47:383–397CrossRefPubMedGoogle Scholar
  8. 8.
    Chimenti F, Cottiglia F, Bonsignore L, Casu L, Casu M, Floris C, Secci D, Bolasco A, Chimenti P, Granese A, Befani O, Turini P, Alcaro S, Ortuso F, Trombetta G, Loizzo A, Guarino I (2006) Quercetin as the active principle of Hypericum hircinum exerts a selective inhibitory activity against MAO-A: extraction, biological analysis, and computational study. J Nat Prod 69:945–949CrossRefPubMedGoogle Scholar
  9. 9.
    Choi JS, Choi BC, Choi KE (2004) Effect of quercetin on the pharmacokinetics of oral cyclosporine. Am J Health Syst Pharm 61:2406–2409PubMedGoogle Scholar
  10. 10.
    Crespy V, Morand C, Besson C, Manach C, Demigne C, Remesy C (2002) Quercetin, but not its glycosides, is absorbed from the rat stomach. J Agric Food Chem 50:618–621CrossRefPubMedGoogle Scholar
  11. 11.
    Dahan A, Altman H (2004) Food–drug interaction: grapefruit juice augments drug bioavailability—mechanism, extent and relevance. Eur J Clin Nutr 58:1–9CrossRefPubMedGoogle Scholar
  12. 12.
    Day AJ, Bao YP, Morgan MRA, Williamson G (2000) Conjugation position of quercetin glucuronides and effect on biological activity. Free Radic Biol Med 29:1234–1243CrossRefPubMedGoogle Scholar
  13. 13.
    Day AJ, Mellon F, Barron D, Sarrazin G, Morgan MR, Williamson G (2001) Human metabolism of dietary flavonoids: identification of plasma metabolites of quercetin. Free Radic Res 35:941–952CrossRefPubMedGoogle Scholar
  14. 14.
    Durr D, Stieger B, Kullak-Ublick GA, Rentsch KM, Steinert HC, Meier PJ, Fattinger K (2000) St John’s Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin Pharmacol Ther 68:598–604CrossRefPubMedGoogle Scholar
  15. 15.
    Eaton EA, Walle UK, Lewis AJ, Hudson T, Wilson AA, Walle T (1996) Flavonoids, potent inhibitors of the human P-form phenolsulfotransferase: potential role in drug metabolism and chemoprevention. Drug Metab Dispos 24:232–237PubMedGoogle Scholar
  16. 16.
    Fernstrom JD (1990) Aromatic amino acids and monoamine synthesis in the central nervous system: influence of the diet. J Nutr Biochem 1:508–517CrossRefPubMedGoogle Scholar
  17. 17.
    Fisher MB, Paine MF, Strelevitz TJ, Wrighton SA (2001) The role of hepatic and extrahepatic UDP-glucuronosyltransferases in human drug metabolism. Drug Metab Rev 33:273–297CrossRefPubMedGoogle Scholar
  18. 18.
    Fuhr U, Klittich K, Staib AH (1993) Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man. Br J Clin Pharmacol 35:431–436PubMedGoogle Scholar
  19. 19.
    Gandhi L, Harding MW, Neubauer M, Langer CJ, Moore M, Ross HJ, Johnson BE, Lynch TJ (2007) A phase II study of the safety and efficacy of the multidrug resistance inhibitor VX-710 combined with doxorubicin and vincristine in patients with recurrent small cell lung cancer. Cancer 109:924–932CrossRefPubMedGoogle Scholar
  20. 20.
    Gardner DM, Shulman KI, Walker SE, Tailor SA (1996) The making of a user friendly MAOI diet. J Clin Psychiatry 57:99–104PubMedGoogle Scholar
  21. 21.
    Graefe EU, Wittig J, Mueller S, Riethling AK, Uehleke B, Drewelow B, Pforte H, Jacobasch G, Derendorf H, Veit M (2001) Pharmacokinetics and bioavailability of quercetin glycosides in humans. J Clin Pharmacol 41:492–499CrossRefPubMedGoogle Scholar
  22. 22.
    Greenblatt DJ, von Moltke LL, Harmatz JS, Chen G, Weemhoff JL, Jen C, Kelley CJ, LeDuc BW, Zinny MA (2003) Time course of recovery of cytochrome p450 3A function after single doses of grapefruit juice. Clin Pharmacol Ther 74:121–129CrossRefPubMedGoogle Scholar
  23. 23.
    Halberstadt AL, Buell MR, Masten VL, Risbrough VB, Geyer MA (2008) Modification of the effects of 5-methoxy-N, N-dimethyltryptamine on exploratory behavior in rats by monoamine oxidase inhibitors. Psychopharmacology (Berl) 201:55–66CrossRefGoogle Scholar
  24. 24.
    Han XH, Hong SS, Hwang JS, Lee MK, Hwang BY, Ro JS (2007) Monoamine oxidase inhibitory components from Cayratia japonica. Arch Pharm Res 30:13–17CrossRefPubMedGoogle Scholar
  25. 25.
    Hardebo JE, Owman C (1980) Barrier mechanisms for neurotransmitter monoamines and their precursors at the blood–brain interface. Ann Neurol 8:1–31CrossRefPubMedGoogle Scholar
  26. 26.
    Harris RM, Wood DM, Bottomley L, Blagg S, Owen K, Hughes PJ, Waring RH, Kirk CJ (2004) Phytoestrogens are potent inhibitors of estrogen sulfation: implications for breast cancer risk and treatment. J Clin Endocrinol Metab 89:1779–1787CrossRefPubMedGoogle Scholar
  27. 27.
    Hennessy M, Kelleher D, Spiers JP, Barry M, Kavanagh P, Back D, Mulcahy F, Feely J (2002) St Johns wort increases expression of P-glycoprotein: implications for drug interactions. Br J Clin Pharmacol 53:75–82CrossRefPubMedGoogle Scholar
  28. 28.
    Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockmoller J, Johne A, Cascorbi I, Gerloff T, Roots I, Eichelbaum M, Brinkmann U (2000) Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci USA 97:3473–3478CrossRefPubMedGoogle Scholar
  29. 29.
    Hong J, Lambert JD, Lee SH, Sinko PJ, Yang CS (2003) Involvement of multidrug resistance-associated proteins in regulating cellular levels of (−)-epigallocatechin-3-gallate and its methyl metabolites. Biochem Biophys Res Commun 310:222–227CrossRefPubMedGoogle Scholar
  30. 30.
    Hu M, Chen J, Lin H (2003) Metabolism of flavonoids via enteric recycling: mechanistic studies of disposition of apigenin in the Caco-2 cell culture model. J Pharmacol Exp Ther 307:314–321CrossRefPubMedGoogle Scholar
  31. 31.
    Ingelman-Sundberg M, Sim SC, Gomez A, Rodriguez-Antona C (2007) Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Ther 116:496–526CrossRefPubMedGoogle Scholar
  32. 32.
    Janisch KM, Williamson G, Needs P, Plumb GW (2004) Properties of quercetin conjugates: modulation of LDL oxidation and binding to human serum albumin. Free Radic Res 38:877–884CrossRefPubMedGoogle Scholar
  33. 33.
    Jovanovich SV, Steenken S, Simic MG, Hara Y (1998) Flavonoids in health and disease. In: Rice-Evans C, Packer L (eds) Flavonoids in health and disease. Marcel Dekker, NY, pp 137–161Google Scholar
  34. 34.
    Kennedy DO, Pace S, Haskell C, Okello EJ, Milne A, Scholey AB (2006) Effects of cholinesterase inhibiting sage (Salvia officinalis) on mood, anxiety and performance on a psychological stressor battery. Neuropsychopharmacology 31:845–852CrossRefPubMedGoogle Scholar
  35. 35.
    Khor SP, Hsu A (2007) The pharmacokinetics and pharmacodynamics of levodopa in the treatment of Parkinson’s disease. Curr Clin Pharmacol 2:234–243CrossRefPubMedGoogle Scholar
  36. 36.
    Kim RB, Leake BF, Choo EF, Dresser GK, Kubba SV, Schwarz UI, Taylor A, Xie HG, McKinsey J, Zhou S, Lan LB, Schuetz JD, Schuetz EG, Wilkinson GR (2001) Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin Pharmacol Ther 70:189–199CrossRefPubMedGoogle Scholar
  37. 37.
    Lambert JD, Sang SM, Yang CS (2007) Biotransformation of green tea polyphenols and the biological activities of those metabolites. Mol Pharmaceutics 4:819–825CrossRefGoogle Scholar
  38. 38.
    Lewis DF, Ito Y (2008) Human cytochromes P450 in the metabolism of drugs: new molecular models of enzyme–substrate interactions. Expert Opin Drug Metab Toxicol 4:1181–1186CrossRefPubMedGoogle Scholar
  39. 39.
    Lown KS, Kolars JC, Thummel KE, Barnett JL, Kunze KL, Wrighton SA, Watkins PB (1994) Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel: lack of prediction by the erythromycin breath test. Drug Metab Dispos 22:947–955PubMedGoogle Scholar
  40. 40.
    Maish WA, Hampton EM, Whitsett TL, Shepard JD, Lovallo WR (1996) Influence of grapefruit juice on caffeine pharmacokinetics and pharmacodynamics. Pharmacotherapy 16:1046–1052PubMedGoogle Scholar
  41. 41.
    Maitland ML, DiRienzo A, Ratain MJ (2006) Interpreting disparate responses to cancer therapy: the role of human population genetics. J Clin Oncol 24:2151–2157CrossRefPubMedGoogle Scholar
  42. 42.
    Manach C, Scalbert A, Morand C, Remesy C, Jimenez L (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79:727–747PubMedGoogle Scholar
  43. 43.
    Manach C, Williamson G, Morand C, Scalbert A, Remesy C (2005) Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 81:230S–242SPubMedGoogle Scholar
  44. 44.
    Markowitz JS, Donovan JL, DeVane CL, Taylor RM, Ruan Y, Wang JS, Chavin KD (2003) Effect of St John’s wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA 290:1500–1504CrossRefPubMedGoogle Scholar
  45. 45.
    Markus CR (2008) Dietary amino acids and brain serotonin function: implications for stress-related affective changes. Neuromolecular Med 10(4):247–258Google Scholar
  46. 46.
    Markus CR, Olivier B, Panhuysen GE, Van Der Gugten J, Alles MS, Tuiten A, Westenberg HG, Fekkes D, Koppeschaar HF, de Haan EE (2000) The bovine protein alpha-lactalbumin increases the plasma ratio of tryptophan to the other large neutral amino acids, and in vulnerable subjects raises brain serotonin activity, reduces cortisol concentration, and improves mood under stress. Am J Clin Nutr 71:1536–1544PubMedGoogle Scholar
  47. 47.
    Markus R, Panhuysen G, Tuiten A, Koppeschaar H (2000) Effects of food on cortisol and mood in vulnerable subjects under controllable and uncontrollable stress. Physiol Behav 70:333–342CrossRefPubMedGoogle Scholar
  48. 48.
    McKenna DJ, Towers GH, Abbott F (1984) Monoamine oxidase inhibitors in South American hallucinogenic plants: tryptamine and beta-carboline constituents of ayahuasca. J Ethnopharmacol 10:195–223CrossRefPubMedGoogle Scholar
  49. 49.
    Molnar J, Gyemant N, Tanaka M, Hohmann J, Bergmann-Leitner E, Molnar P, Deli J, Didiziapetris R, Ferreira MJ (2006) Inhibition of multidrug resistance of cancer cells by natural diterpenes, triterpenes and carotenoids. Curr Pharm Des 12:287–311CrossRefPubMedGoogle Scholar
  50. 50.
    Monteiro M, Farah A, Perrone D, Trugo LC, Donangelo C (2007) Chlorogenic acid compounds from coffee are differentially absorbed and metabolized in humans. J Nutr 137:2196–2201PubMedGoogle Scholar
  51. 51.
    Moon YJ, Morris ME (2007) Pharmacokinetics and bioavailability of the bioflavonoid biochanin A: effects of quercetin and EGCG on biochanin A disposition in rats. Mol Pharm 4:865–872CrossRefPubMedGoogle Scholar
  52. 52.
    Moon YJ, Wang X, Morris ME (2006) Dietary flavonoids: effects on xenobiotic and carcinogen metabolism. Toxicol In Vitro 20:187–210CrossRefPubMedGoogle Scholar
  53. 53.
    Moore LB, Goodwin B, Jones SA, Wisely GB, Serabjit-Singh CJ, Willson TM, Collins JL, Kliewer SA (2000) St. John’s wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci USA 97:7500–7502CrossRefPubMedGoogle Scholar
  54. 54.
    Morris ME, Zhang S (2006) Flavonoid-drug interactions: effects of flavonoids on ABC transporters. Life Sci 78:2116–2130CrossRefPubMedGoogle Scholar
  55. 55.
    Mukherjee PK, Kumar V, Mal M, Houghton PJ (2007) Acetylcholinesterase inhibitors from plants. Phytomedicine 14:289–300CrossRefPubMedGoogle Scholar
  56. 56.
    Murakami T, Takano M (2008) Intestinal efflux transporters and drug absorption. Expert Opin Drug Metab Toxicol 4:923–939CrossRefPubMedGoogle Scholar
  57. 57.
    Obach RS (2000) Inhibition of human cytochrome P450 enzymes by constituents of St. John’s Wort, an herbal preparation used in the treatment of depression. J Pharmacol Exp Ther 294:88–95PubMedGoogle Scholar
  58. 58.
    Pal D, Mitra AK (2006) MDR- and CYP3A4-mediated drug-drug interactions. J Neuroimmune Pharmacol 1:323–339CrossRefPubMedGoogle Scholar
  59. 59.
    Patel J, Buddha B, Dey S, Pal D, Mitra AK (2004) In vitro interaction of the HIV protease inhibitor ritonavir with herbal constituents: changes in P-gp and CYP3A4 activity. Am J Ther 11:262–277CrossRefPubMedGoogle Scholar
  60. 60.
    Peng WX, Li HD, Zhou HH (2003) Effect of daidzein on CYP1A2 activity and pharmacokinetics of theophylline in healthy volunteers. Eur J Clin Pharmacol 59:237–241CrossRefPubMedGoogle Scholar
  61. 61.
    Perloff MD, von Moltke LL, Stormer E, Shader RI, Greenblatt DJ (2001) Saint John’s wort: an in vitro analysis of P-glycoprotein induction due to extended exposure. Br J Pharmacol 134:1601–1608CrossRefPubMedGoogle Scholar
  62. 62.
    Piscitelli SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J (2000) Indinavir concentrations and St John’s wort. Lancet 355:547–548CrossRefPubMedGoogle Scholar
  63. 63.
    Piscitelli SC, Burstein AH, Welden N, Gallicano KD, Falloon J (2002) The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis 34:234–238CrossRefPubMedGoogle Scholar
  64. 64.
    Pittler MH, Ernst E (2003) Kava extract for treating anxiety. Cochrane Database Syst Rev 1:CD003383Google Scholar
  65. 65.
    Quintieri L, Palatini P, Nassi A, Ruzza P, Floreani M (2008) Flavonoids diosmetin and luteolin inhibit midazolam metabolism by human liver microsomes and recombinant CYP 3A4 and CYP3A5 enzymes. Biochem Pharmacol 75:1426–1437CrossRefPubMedGoogle Scholar
  66. 66.
    Radtke J, Linseisen J, Wolfram G (1998) Phenolic acid intake of adults in a Bavarian subgroup of the national food consumption survey. Z Ernahrungswiss 37:190–197CrossRefPubMedGoogle Scholar
  67. 67.
    Rodeiro I, Donato MT, Lahoz A, Garrido G, Delgado R, Gomez-Lechon MJ (2008) Interactions of polyphenols with the P450 system: possible implications on human therapeutics. Mini Rev Med Chem 8:97–106CrossRefPubMedGoogle Scholar
  68. 68.
    Rojas P, Rojas C, Ebadi M, Montes S, Monroy-Noyola A, Serrano-Garcia N (2004) EGb761 pretreatment reduces monoamine oxidase activity in mouse corpus striatum during 1-methyl-4-phenylpyridinium neurotoxicity. Neurochem Res 29:1417–1423CrossRefPubMedGoogle Scholar
  69. 69.
    Ruschitzka F, Meier PJ, Turina M, Luscher TF, Noll G (2000) Acute heart transplant rejection due to Saint John’s wort. Lancet 355:548–549CrossRefPubMedGoogle Scholar
  70. 70.
    Salgueiro JB, Ardenghi P, Dias M, Ferreira MB, Izquierdo I, Medina JH (1997) Anxiolytic natural and synthetic flavonoid ligands of the central benzodiazepine receptor have no effect on memory tasks in rats. Pharmacol Biochem Behav 58:887–891CrossRefPubMedGoogle Scholar
  71. 71.
    Sousa T, Paterson R, Moore V, Carlsson A, Abrahamsson B, Basit AW (2008) The gastrointestinal microbiota as a site for the biotransformation of drugs. Int J Pharm 363:1–25CrossRefPubMedGoogle Scholar
  72. 72.
    Sridar C, Goosen TC, Kent UM, Williams JA, Hollenberg PF (2004) Silybin inactivates cytochromes P450 3A4 and 2C9 and inhibits major hepatic glucuronosyltransferases. Drug Metab Dispos 32:587–594CrossRefPubMedGoogle Scholar
  73. 73.
    Stein GE, Gurwith MJ (1984) Amoxicillin potassium clavulanate, a beta-lactamase-resistant antibiotic combination. Clin Pharm 3:591–599PubMedGoogle Scholar
  74. 74.
    Stevenson DE, Cooney JM, Jensen DJ, Wibisono R, Adaim A, Skinner MA, Zhang J (2008) Comparison of enzymically glucuronidated flavonoids with flavonoid aglycones in an in vitro cellular model of oxidative stress protection. In Vitro Cell Dev Biol Anim 44:73–80CrossRefPubMedGoogle Scholar
  75. 75.
    Stevenson DE, Hurst RD (2007) Polyphenolic phytochemicals—just antioxidants or much more? Cell Mol Life Sci 64:2900–2916CrossRefPubMedGoogle Scholar
  76. 76.
    Suri S, Taylor MA, Verity A, Tribolo S, Needs PW, Kroon PA, Hughes DA, Wilson VG (2008) A comparative study of the effects of quercetin and its glucuronide and sulfate metabolites on human neutrophil function in vitro. Biochem Pharmacol 76:645–653CrossRefPubMedGoogle Scholar
  77. 77.
    Tildesley NT, Kennedy DO, Perry EK, Ballard CG, Savelev S, Wesnes KA, Scholey AB (2003) Salvia lavandulaefolia (Spanish sage) enhances memory in healthy young volunteers. Pharmacol Biochem Behav 75:669–674CrossRefPubMedGoogle Scholar
  78. 78.
    Urquhart BL, Tirona RG, Kim RB (2007) Nuclear receptors and the regulation of drug-metabolizing enzymes and drug transporters: implications for interindividual variability in response to drugs. J Clin Pharmacol 47:566–578CrossRefPubMedGoogle Scholar
  79. 79.
    Vaidyanathan JB, Walle T (2003) Cellular uptake and efflux of the tea flavonoid (−)epicatechin-3-gallate in the human intestinal cell line Caco-2. J Pharmacol Exp Ther 307:745–752CrossRefPubMedGoogle Scholar
  80. 80.
    van de Wetering K, Burkon A, Feddema W, Bot A, de Jonge H, Somoza V, Borst P (2008) Intestinal BCRP/Bcrp1 and MRP3/Mrp3 are involved in the pharmacokinetics of resveratrol. Mol Pharmacol 75(4):876–885CrossRefPubMedGoogle Scholar
  81. 81.
    Wacher VJ, Silverman JA, Zhang Y, Benet LZ (1998) Role of P-glycoprotein and cytochrome P450 3A in limiting oral absorption of peptides and peptidomimetics. J Pharm Sci 87:1322–1330CrossRefPubMedGoogle Scholar
  82. 82.
    Walle T, Browning AM, Steed LL, Reed SG, Walle UK (2005) Flavonoid glucosides are hydrolyzed and thus activated in the oral cavity in humans. J Nutr 135:48–52PubMedGoogle Scholar
  83. 83.
    Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE (2004) Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos 32:1201–1208CrossRefPubMedGoogle Scholar
  84. 84.
    Williams JA, Ring BJ, Cantrell VE, Campanale K, Jones DR, Hall SD, Wrighton SA (2002) Differential modulation of UDP-glucuronosyltransferase 1A1 (UGT1A1)-catalyzed estradiol-3-glucuronidation by the addition of UGT1A1 substrates and other compounds to human liver microsomes. Drug Metab Dispos 30:1266–1273CrossRefPubMedGoogle Scholar
  85. 85.
    Woodahl EL, Ho RJ (2004) The role of MDR1 genetic polymorphisms in interindividual variability in P-glycoprotein expression and function. Curr Drug Metab 5:11–19CrossRefPubMedGoogle Scholar
  86. 86.
    Wu CC, Sheen LY, Chen HW, Kuo WW, Tsai SJ, Lii CK (2002) Differential effects of garlic oil and its three major organosulfur components on the hepatic detoxification system in rats. J Agric Food Chem 50:378–383CrossRefPubMedGoogle Scholar
  87. 87.
    Xing J, Chen X, Zhong D (2005) Absorption and enterohepatic circulation of baicalin in rats. Life Sci 78:140–146CrossRefPubMedGoogle Scholar
  88. 88.
    Yang CS, Lambert JD, Ju J, Lu G, Sang S (2007) Tea and cancer prevention: molecular mechanisms and human relevance. Toxicol Appl Pharmacol 224:265–273CrossRefPubMedGoogle Scholar
  89. 89.
    Youdim KA, Dobbie MS, Kuhnle G, Proteggente AR, Abbott NJ, Rice-Evans C (2003) Interaction between flavonoids and the blood–brain barrier: in vitro studies. J Neurochem 85:180–192PubMedCrossRefGoogle Scholar
  90. 90.
    Youdim KA, Qaiser MZ, Begley DJ, Rice-Evans CA, Abbott NJ (2004) Flavonoid permeability across an in situ model of the blood–brain barrier. Free Radic Biol Med 36:592–604CrossRefPubMedGoogle Scholar
  91. 91.
    Youdim MB, Edmondson D, Tipton KF (2006) The therapeutic potential of monoamine oxidase inhibitors. Nat Rev Neurosci 7:295–309CrossRefPubMedGoogle Scholar
  92. 92.
    Zevin S, Benowitz NL (1999) Drug interactions with tobacco smoking: an update. Clin Pharmacokinet 36:425–438CrossRefPubMedGoogle Scholar
  93. 93.
    Zhang L, Zuo Z, Lin G (2007) Intestinal and hepatic glucuronidation of flavonoids. Mol Pharm 4:833–845CrossRefPubMedGoogle Scholar
  94. 94.
    Zhang YC, Benet LZ (2001) The gut as a barrier to drug absorption—combined role of cytochrome P450 3A and P-glycoprotein. Clin Pharmacokinet 40:159–168CrossRefPubMedGoogle Scholar
  95. 95.
    Zhou S, Gao Y, Jiang W, Huang M, Xu A, Paxton JW (2003) Interactions of herbs with cytochrome P450. Drug Metab Rev 35:35–98CrossRefPubMedGoogle Scholar
  96. 96.
    Zhou S, Lim LY, Chowbay B (2004) Herbal modulation of P-glycoprotein. Drug Metab Rev 36:57–104CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Functional Foods and HealthThe New Zealand Institute for Plant and Food Research LimitedAucklandNew Zealand
  2. 2.Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand
  3. 3.Plant and Food ResearchAucklandNew Zealand

Personalised recommendations