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Planta Med 2012; 78(13): 1428-1457
DOI: 10.1055/s-0031-1298536
Mechanism of Herb-Drug Interactions
Reviews
Georg Thieme Verlag KG Stuttgart · New York

Phenotyping Studies to Assess the Effects of Phytopharmaceuticals on In Vivo Activity of Main Human Cytochrome P450 Enzymes

Gregor Zadoyan
1   ITECRA GmbH & Co. KG, Cologne, Germany
,
Uwe Fuhr
1   ITECRA GmbH & Co. KG, Cologne, Germany
2   Department of Pharmacology, Clinical Pharmacology Unit, University of Cologne, Cologne, Germany
› Author Affiliations
Further Information

Publication History

received 25 January 2012
revised 11 April 2012

accepted 15 April 2012

Publication Date:
15 May 2012 (online)

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Abstract

The extensive use of herbal drugs and their multiple components and modes of action suggests that they may also cause drug interactions by changing the activity of human cytochrome P450 enzymes. The purpose of the present review is to present the available data for the top 14 herbal drug sales in the U. S. Studies describing the effects of herbal drugs on phenotyping substrates for individual CYPs were identified by a comprehensive MEDLINE search. Drugs included Allium sativum (Liliaceae), Echinacea purpurea (Asteraceae), Serenoa repens (Arecaceae), Ginkgo biloba (Ginkgoaceae), Vaccinium macrocarpon (Ericaceae), Glycine max (Fabaceae), Panax ginseng (Araliaceae), Actea racemosa (Ranunculaceae), Hypericum perforatum (Hypericaceae), Silybum marianum (Asteraceae), Camellia sinensis (Theaceae), Valeriana officinalis (Valerianaceae), Piper methysticum (Piperaceae), and Hydrastis canadensis (Ranunculaceae) preparations. We identified 70 clinical studies in 69 publications. The majority of the herbal drugs appeared to have no clear effects on most of the CYPs examined. If there was an effect, there was mild inhibition in almost all cases, as seen with garlic or kava effects on CYP2E1 and with soybean components on CYP1A2. The most pronounced effects were induction of CYP3A and other CYPs by St. Johnʼs wort and the inhibitory effect of goldenseal on CYP3A and CYP2D6, both being borderline between mild and moderate in magnitude. With the exceptions of St. Johnʼs wort and goldenseal, the information currently available suggests that concomitant intake of the herbal drugs addressed here is not a major risk for drugs that are metabolized by CYPs.

Key words

cytochrome P450 - cocktail interaction studies - herb-drug interaction - phytopharmaceuticals - botanicals - herbal products
 

  • References

  • 1 Moore LB, Goodwin B, Jones SA, Wisely GB, Serabjit-Singh CJ, Willson TM, Collins JL, Kliewer SA. St. Johnʼs wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci USA 2000; 97: 7500-7502
    CrossrefPubMedGoogle Scholar
  • 2 Bailey DG, Spence JD, Munoz C, Arnold JM. Interaction of citrus juices with felodipine and nifedipine. Lancet 1991; 337: 268-269
    CrossrefPubMedGoogle Scholar
  • 3 Fuhr U, Jetter A, Kirchheiner J. Appropriate phenotyping procedures for drug metabolizing enzymes and transporters in humans and their simultaneous use in the “cocktail” approach. Clin Pharmacol Ther 2007; 81: 270-283
    CrossrefPubMedGoogle Scholar
  • 4 Huang SM, Zhang L. Guidance for industry: drug interaction studies – study design, data analysis, implications for dosing, and labeling recommendations. Available at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM072101.htm Accessed December 02, 2011
    PubMedGoogle Scholar
  • 5 European Medicines Agency. Guideline on the investigation of drug interactions. Available at http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/05/WC500090112.pdf Accessed December 02, 2011
    PubMedGoogle Scholar
  • 6 US Food and Drug Administration. Drug development and drug interactions: table of substrates, inhibitors and inducers. Available at http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm Accessed December 02, 2011
    PubMedGoogle Scholar
  • 7 Tanaka E, Kurata N, Yasuhara H. How useful is the “cocktail approach” for evaluating human hepatic drug metabolizing capacity using cytochrome P450 phenotyping probes in vivo?. J Clin Pharm Ther 2003; 28: 157-165
    CrossrefPubMedGoogle Scholar
  • 8 Zhou H, Tong Z, McLeod JF. “Cocktail” approaches and strategies in drug development: valuable tool or flawed science?. J Clin Pharmacol 2004; 44: 120-134
    CrossrefPubMedGoogle Scholar
  • 9 Turpault S, Brian W, Van Horn R, Santoni A, Poitiers F, Donazzolo Y, Boulenc X. Pharmacokinetic assessment of a five-probe cocktail for CYPs 1A2, 2C9, 2C19, 2D6 and 3A. Br J Clin Pharmacol 2009; 68: 928-935
    CrossrefPubMedGoogle Scholar
  • 10 Zhang L. A regulatory perspective on the utilization of cocktail approach in assessing drug interactions. Available at http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/UCM237160.htm Accessed December 02, 2011
    PubMedGoogle Scholar
  • 11 Zhang L, Reynolds KS, Zhao P, Huang SM. Drug interactions evaluation: an integrated part of risk assessment of therapeutics. Toxicol Appl Pharmacol 2010; 243: 134-145
    CrossrefPubMedGoogle Scholar
  • 12 US Food and Drug Administration. Guidances (Drugs). Available at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm Accessed December 02, 2011
    PubMedGoogle Scholar
  • 13 Ma JD, Nguyen ET, Tsunoda SM, Greenberg HE, Gorski JC, Penzak SR, Lee LS. Assessment of oral midazolam limited sampling strategies to predict area under the concentration time curve (AUC) during cytochrome P450 (CYP) 3A baseline, inhibition and induction or activation. Int J Clin Pharmacol Ther 2010; 48: 847-853
    PubMedGoogle Scholar
  • 14 Fuhr U, Beckmann-Knopp S, Jetter A, Luck H, Mengs U. The effect of silymarin on oral nifedipine pharmacokinetics. Planta Med 2007; 73: 1429-1435
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Zadoyan G, Rokitta D, Klement S, Dienel A, Hoerr R, Gramatte T, Fuhr U. Effect of Ginkgo biloba special extract EGb 761(R) on human cytochrome P450 activity: a cocktail interaction study in healthy volunteers. Eur J Clin Pharmacol 2012; 68: 553-560
    CrossrefPubMedGoogle Scholar
  • 16 Blumenthal M, Ferrier GKL, Cavaliere C. Total sales of herbal supplements in United States show steady growth. Herbal Gram 2006; 71: 64-66
    PubMedGoogle Scholar
  • 17 Borrelli F, Capasso R, Izzo AA. Garlic (Allium sativum L.): adverse effects and drug interactions in humans. Mol Nutr Food Res 2007; 51: 1386-1397
    CrossrefPubMedGoogle Scholar
  • 18 Lanzotti V. The analysis of onion and garlic. J Chromatogr A 2006; 1112: 3-22
    CrossrefPubMedGoogle Scholar
  • 19 Shord SS, Shah K, Lukose A. Drug-botanical interactions: a review of the laboratory, animal, and human data for 8 common botanicals. Integr Cancer Ther 2009; 8: 208-227
    PubMedGoogle Scholar
  • 20 Butterweck V, Derendorf H. Potential of pharmacokinetic profiling for detecting herbal interactions with drugs. Clin Pharmacokinet 2008; 47: 383-397
    CrossrefPubMedGoogle Scholar
  • 21 Gallicano K, Foster B, Choudhri S. Effect of short-term administration of garlic supplements on single-dose ritonavir pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 2003; 55: 199-202
    CrossrefPubMedGoogle Scholar
  • 22 Hsu A, Granneman GR, Cao G, Carothers L, el-Shourbagy T, Baroldi P, Erdman K, Brown F, Sun E, Leonard JM. Pharmacokinetic interactions between two human immunodeficiency virus protease inhibitors, ritonavir and saquinavir. Clin Pharmacol Ther 1998; 63: 453-464
    CrossrefPubMedGoogle Scholar
  • 23 Cox MC, Low J, Lee J, Walshe J, Denduluri N, Berman A, Permenter MG, Petros WP, Price DK, Figg WD, Sparreboom A, Swain SM. Influence of garlic (Allium sativum) on the pharmacokinetics of docetaxel. Clin Cancer Res 2006; 12: 4636-4640
    CrossrefPubMedGoogle Scholar
  • 24 Macan H, Uykimpang R, Alconcel M, Takasu J, Razon R, Amagase H, Niihara Y. Aged garlic extract may be safe for patients on warfarin therapy. J Nutr 2006; 136: 793S-795S
    PubMedGoogle Scholar
  • 25 Markowitz JS, Devane CL, Chavin KD, Taylor RM, Ruan Y, Donovan JL. Effects of garlic (Allium sativum L.) supplementation on cytochrome P450 2D6 and 3A4 activity in healthy volunteers. Clin Pharmacol Ther 2003; 74: 170-177
    CrossrefPubMedGoogle Scholar
  • 26 Piscitelli SC, Burstein AH, Welden N, Gallicano KD, Falloon J. The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis 2002; 34: 234-238
    CrossrefPubMedGoogle Scholar
  • 27 Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Cui Y, Ang CY. Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St Johnʼs wort, garlic oil, Panax ginseng and Ginkgo biloba . Drugs Aging 2005; 22: 525-539
    CrossrefPubMedGoogle Scholar
  • 28 Taylor JA, Weber W, Standish L, Quinn H, Goesling J, McGann M, Calabrese C. Efficacy and safety of echinacea in treating upper respiratory tract infections in children: a randomized controlled trial. JAMA 2003; 290: 2824-2830
    CrossrefPubMedGoogle Scholar
  • 29 Freeman C, Spelman K. A critical evaluation of drug interactions with Echinacea spp. Mol Nutr Food Res 2008; 52: 789-798
    CrossrefPubMedGoogle Scholar
  • 30 Gertsch J, Schoop R, Kuenzle U, Suter A. Echinacea alkylamides modulate TNF-alpha gene expression via cannabinoid receptor CB2 and multiple signal transduction pathways. FEBS Lett 2004; 577: 563-569
    CrossrefPubMedGoogle Scholar
  • 31 Gorski JC, Huang SM, Pinto A, Hamman MA, Hilligoss JK, Zaheer NA, Desai M, Miller M, Hall SD. The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo . Clin Pharmacol Ther 2004; 75: 89-100
    CrossrefPubMedGoogle Scholar
  • 32 Penzak SR, Robertson SM, Hunt JD, Chairez C, Malati CY, Alfaro RM, Stevenson JM, Kovacs JA. Echinacea purpurea significantly induces cytochrome P450 3A activity but does not alter lopinavir-ritonavir exposure in healthy subjects. Pharmacotherapy 2010; 30: 797-805
    CrossrefPubMedGoogle Scholar
  • 33 Wittkowsky AK. Warfarin and other coumarin derivatives: pharmacokinetics, pharmacodynamics, and drug interactions. Semin Vasc Med 2003; 3: 221-230
    Article in Thieme ConnectPubMedGoogle Scholar
  • 34 Abdul MI, Jiang X, Williams KM, Day RO, Roufogalis BD, Liauw WS, Xu H, Matthias A, Lehmann RP, McLachlan AJ. Pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects. Br J Clin Pharmacol 2010; 69: 508-515
    CrossrefPubMedGoogle Scholar
  • 35 Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Carrier J, Khan IA, Edwards DJ, Shah A. In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto. Clin Pharmacol Ther 2004; 76: 428-440
    CrossrefPubMedGoogle Scholar
  • 36 Gurley BJ, Swain A, Hubbard MA, Williams DK, Barone G, Hartsfield F, Tong Y, Carrier DJ, Cheboyina S, Battu SK. Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: effects of milk thistle, black cohosh, goldenseal, kava kava, St. Johnʼs wort, and Echinacea . Mol Nutr Food Res 2008; 52: 755-763
    CrossrefPubMedGoogle Scholar
  • 37 Gerber GS. Saw palmetto for the treatment of men with lower urinary tract symptoms. J Urol 2000; 163: 1408-1412
    CrossrefPubMedGoogle Scholar
  • 38 Markowitz JS, Donovan JL, Devane CL, Taylor RM, Ruan Y, Wang JS, Chavin KD. Multiple doses of saw palmetto (Serenoa repens) did not alter cytochrome P450 2D6 and 3A4 activity in normal volunteers. Clin Pharmacol Ther 2003; 74: 536-542
    CrossrefPubMedGoogle Scholar
  • 39 Diamond BJ, Shiflett SC, Feiwel N, Matheis RJ, Noskin O, Richards JA, Schoenberger NE. Ginkgo biloba extract: mechanisms and clinical indications. Arch Phys Med Rehabil 2000; 81: 668-678
    PubMedGoogle Scholar
  • 40 Abdel-Kader R, Hauptmann S, Keil U, Scherping I, Leuner K, Eckert A, Muller WE. Stabilization of mitochondrial function by Ginkgo biloba extract (EGb 761). Pharmacol Res 2007; 56: 493-502
    CrossrefPubMedGoogle Scholar
  • 41 Tchantchou F, Xu Y, Wu Y, Christen Y, Luo Y. EGb 761 enhances adult hippocampal neurogenesis and phosphorylation of CREB in transgenic mouse model of Alzheimerʼs disease. FASEB J 2007; 21: 2400-2408
    CrossrefPubMedGoogle Scholar
  • 42 Tchantchou F, Lacor PN, Cao Z, Lao L, Hou Y, Cui C, Klein WL, Luo Y. Stimulation of neurogenesis and synaptogenesis by bilobalide and quercetin via common final pathway in hippocampal neurons. Int J Alzheimers Dis 2009; 18: 787-798
    PubMedGoogle Scholar
  • 43 Elovic EP, Zafonte RD. Ginkgo biloba: applications in traumatic brain injury. J Head Trauma Rehabil 2001; 16: 603-607
    CrossrefPubMedGoogle Scholar
  • 44 Cohen-Salmon C, Venault P, Martin B, Raffalli-Sebille MJ, Barkats M, Clostre F, Pardon MC, Christen Y, Chapouthier G. Effects of Ginkgo biloba extract (EGb 761) on learning and possible actions on aging. J Physiol 1997; 91: 291-300
    PubMedGoogle Scholar
  • 45 Thiagarajan G, Chandani S, Harinarayana Rao S, Samuni AM, Chandrasekaran K, Balasubramanian D. Molecular and cellular assessment of Ginkgo biloba extract as a possible ophthalmic drug. Exp Eye Res 2002; 75: 421-430
    PubMedGoogle Scholar
  • 46 Rioufol G, Pietri S, Culcasi M, Loufoua J, Staat P, Pop C, Drieu K, Ovize M. Ginkgo biloba extract EGb 761 attenuates myocardial stunning in the pig heart. Basic Res Cardiol 2003; 98: 59-68
    CrossrefPubMedGoogle Scholar
  • 47 DeFeudis FV. A brief history of EGb 761 and its therapeutic uses. Pharmacopsychiatry 2003; 36: S2-S7
    Article in Thieme ConnectPubMedGoogle Scholar
  • 48 Greenblatt DJ, von Moltke LL, Luo Y, Perloff ES, Horan KA, Bruce A, Reynolds RC, Harmatz JS, Avula B, Khan IA, Goldman P. Ginkgo biloba does not alter clearance of flurbiprofen, a cytochrome P450-2C9 substrate. J Clin Pharmacol 2006; 46: 214-221
    CrossrefPubMedGoogle Scholar
  • 49 Jiang X, Williams KM, Liauw WS, Ammit AJ, Roufogalis BD, Duke CC, Day RO, McLachlan AJ. Effect of ginkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2005; 59: 425-432
    CrossrefPubMedGoogle Scholar
  • 50 Yin OQ, Tomlinson B, Waye MM, Chow AH, Chow MS. Pharmacogenetics and herb-drug interactions: experience with Ginkgo biloba and omeprazole. Pharmacogenetics 2004; 14: 841-850
    CrossrefPubMedGoogle Scholar
  • 51 Lei HP, Wang G, Wang LS, Ou-yang DS, Chen H, Li Q, Zhang W, Tan ZR, Fan L, He YJ, Zhou HH. Lack of effect of Ginkgo biloba on voriconazole pharmacokinetics in Chinese volunteers identified as CYP2C19 poor and extensive metabolizers. Ann Pharmacother 2009; 43: 726-731
    CrossrefPubMedGoogle Scholar
  • 52 Robertson SM, Davey RT, Voell J, Formentini E, Alfaro RM, Penzak SR. Effect of Ginkgo biloba extract on lopinavir, midazolam and fexofenadine pharmacokinetics in healthy subjects. Curr Med Res Opin 2008; 24: 591-599
    CrossrefPubMedGoogle Scholar
  • 53 Lei HP, Ji W, Lin J, Chen H, Tan ZR, Hu DL, Liu LJ, Zhou HH. Effects of Ginkgo biloba extract on the pharmacokinetics of bupropion in healthy volunteers. Br J Clin Pharmacol 2009; 68: 201-206
    CrossrefPubMedGoogle Scholar
  • 54 Markowitz JS, Donovan JL, Lindsay DeVane C, Sipkes L, Chavin KD. Multiple-dose administration of Ginkgo biloba did not affect cytochrome P-450 2D6 or 3A4 activity in normal volunteers. J Clin Psychopharmacol 2003; 23: 576-581
    CrossrefPubMedGoogle Scholar
  • 55 Penzak SR, Busse KH, Robertson SM, Formentini E, Alfaro RM, Davey Jr. RT. Limitations of using a single postdose midazolam concentration to predict CYP3A-mediated drug interactions. J Clin Pharmacol 2008; 48: 671-680
    CrossrefPubMedGoogle Scholar
  • 56 Uchida S, Yamada H, Li XD, Maruyama S, Ohmori Y, Oki T, Watanabe H, Umegaki K, Ohashi K, Yamada S. Effects of Ginkgo biloba extract on pharmacokinetics and pharmacodynamics of tolbutamide and midazolam in healthy volunteers. J Clin Pharmacol 2006; 46: 1290-1298
    CrossrefPubMedGoogle Scholar
  • 57 Zuo XC, Zhang BK, Jia SJ, Liu SK, Zhou LY, Li J, Zhang J, Dai LL, Chen BM, Yang GP, Yuan H. Effects of Ginkgo biloba extracts on diazepam metabolism: a pharmacokinetic study in healthy Chinese male subjects. Eur J Clin Pharmacol 2010; 66: 503-509
    CrossrefPubMedGoogle Scholar
  • 58 Aston JL, Lodolce AE, Shapiro NL. Interaction between warfarin and cranberry juice. Pharmacotherapy 2006; 26: 1314-1319
    CrossrefPubMedGoogle Scholar
  • 59 Zuo Y, Wang C, Zhan J. Separation, characterization, and quantitation of benzoic and phenolic antioxidants in American cranberry fruit by GC-MS. J Agric Food Chem 2002; 50: 3789-3794
    CrossrefPubMedGoogle Scholar
  • 60 McKay DL, Blumberg JB. Cranberries (Vaccinium macrocarpon) and cardiovascular disease risk factors. Nutr Rev 2007; 65: 490-502
    CrossrefPubMedGoogle Scholar
  • 61 Pham DQ, Pham AQ. Interaction potential between cranberry juice and warfarin. Am J Health Syst Pharm 2007; 64: 490-494
    CrossrefPubMedGoogle Scholar
  • 62 Griffiths P. The role of cranberry juice in the treatment of urinary tract infections. Br J Community Nurs 2003; 8: 557-561
    PubMedGoogle Scholar
  • 63 Ngo N, Yan Z, Graf TN, Carrizosa DR, Kashuba AD, Dees EC, Oberlies NH, Paine MF. Identification of a cranberry juice product that inhibits enteric CYP3A-mediated first-pass metabolism in humans. Drug Metab Dispos 2009; 37: 514-522
    CrossrefPubMedGoogle Scholar
  • 64 Howell AB, Foxman B. Cranberry juice and adhesion of antibiotic-resistant uropathogens. JAMA 2002; 287: 3082-3083
    CrossrefPubMedGoogle Scholar
  • 65 Ushijima K, Tsuruoka S, Tsuda H, Hasegawa G, Obi Y, Kaneda T, Takahashi M, Maekawa T, Sasaki T, Koshimizu TA, Fujimura A. Cranberry juice suppressed the diclofenac metabolism by human liver microsomes, but not in healthy human subjects. Br J Clin Pharmacol 2009; 68: 194-200
    CrossrefPubMedGoogle Scholar
  • 66 Greenblatt DJ, von Moltke LL, Perloff ES, Luo Y, Harmatz JS, Zinny MA. Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: in vitro and clinical studies. Clin Pharmacol Ther 2006; 79: 125-133
    CrossrefPubMedGoogle Scholar
  • 67 Mohammed Abdul MI, Jiang X, Williams KM, Day RO, Roufogalis BD, Liauw WS, Xu H, McLachlan AJ. Pharmacodynamic interaction of warfarin with cranberry but not with garlic in healthy subjects. Br J Pharmacol 2008; 154: 1691-1700
    PubMedGoogle Scholar
  • 68 Lilja JJ, Backman JT, Neuvonen PJ. Effects of daily ingestion of cranberry juice on the pharmacokinetics of warfarin, tizanidine, and midazolam – probes of CYP2C9, CYP1A2, and CYP3A4. Clin Pharmacol Ther 2007; 81: 833-839
    CrossrefPubMedGoogle Scholar
  • 69 Grenier J, Fradette C, Morelli G, Merritt GJ, Vranderick M, Ducharme MP. Pomelo juice, but not cranberry juice, affects the pharmacokinetics of cyclosporine in humans. Clin Pharmacol Ther 2006; 79: 255-262
    CrossrefPubMedGoogle Scholar
  • 70 Wu Z, Rodgers RP, Marshall AG. Characterization of vegetable oils: detailed compositional fingerprints derived from electrospray ionization fourier transform ion cyclotron resonance mass spectrometry. J Agric Food Chem 2004; 52: 5322-5328
    CrossrefPubMedGoogle Scholar
  • 71 Messina M, Messina V. The role of soy in vegetarian diets. Nutrients 2010; 2: 855-888
    CrossrefPubMedGoogle Scholar
  • 72 Kishida T, Nagamoto M, Ohtsu Y, Watakabe M, Ohshima D, Nashiki K, Mizushige T, Izumi T, Obata A, Ebihara K. Lack of an inducible effect of dietary soy isoflavones on the mRNA abundance of hepatic cytochrome P-450 isozymes in rats. Biosci Biotechnol Biochem 2004; 68: 508-515
    CrossrefPubMedGoogle Scholar
  • 73 Peng WX, Li HD, Zhou HH. Effect of daidzein on CYP1A2 activity and pharmacokinetics of theophylline in healthy volunteers. Eur J Clin Pharmacol 2003; 59: 237-241
    CrossrefPubMedGoogle Scholar
  • 74 Chen Y, Xiao CQ, He YJ, Chen BL, Wang G, Zhou G, Zhang W, Tan ZR, Cao S, Wang LP, Zhou HH. Genistein alters caffeine exposure in healthy female volunteers. Eur J Clin Pharmacol 2011; 67: 347-353
    CrossrefPubMedGoogle Scholar
  • 75 Wang G, Xiao CQ, Li Z, Guo D, Chen Y, Fan L, Qian RH, Peng XJ, Hu DL, Zhou HH. Effect of soy extract administration on losartan pharmacokinetics in healthy female volunteers. Ann Pharmacother 2009; 43: 1045-1049
    CrossrefPubMedGoogle Scholar
  • 76 Anderson GD, Rosito G, Mohustsy MA, Elmer GW. Drug interaction potential of soy extract and Panax ginseng . J Clin Pharmacol 2003; 43: 643-648
    PubMedGoogle Scholar
  • 77 Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs 2009; 69: 1777-1798
    CrossrefPubMedGoogle Scholar
  • 78 Lee MH, Jeong JH, Seo JW, Shin CG, Kim YS, In JG, Yang DC, Yi JS, Choi YE. Enhanced triterpene and phytosterol biosynthesis in Panax ginseng overexpressing squalene synthase gene. Plant Cell Physiol 2004; 45: 976-984
    CrossrefPubMedGoogle Scholar
  • 79 Shibata S. Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J Korean Med Sci 2001; 16: S28-S37
    PubMedGoogle Scholar
  • 80 Lee SH, Ahn YM, Ahn SY, Doo HK, Lee BC. Interaction between warfarin and Panax ginseng in ischemic stroke patients. J Alternat Complement Med 2008; 14: 715-721
    CrossrefPubMedGoogle Scholar
  • 81 Briskin DP. Medicinal plants and phytomedicines. Linking plant biochemistry and physiology to human health. Plant Physiol 2000; 124: 507-514
    CrossrefPubMedGoogle Scholar
  • 82 Vogler BK, Pittler MH, Ernst E. The efficacy of ginseng. A systematic review of randomised clinical trials. Eur J Clin Pharmacol 1999; 55: 567-575
    CrossrefPubMedGoogle Scholar
  • 83 Jiang X, Williams KM, Liauw WS, Ammit AJ, Roufogalis BD, Duke CC, Day RO, McLachlan AJ. Effect of St Johnʼs wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2004; 57: 592-599
    CrossrefPubMedGoogle Scholar
  • 84 Rhyu MR, Lu J, Webster DE, Fabricant DS, Farnsworth NR, Wang ZJ. Black cohosh (Actaea racemosa, Cimicifuga racemosa) behaves as a mixed competitive ligand and partial agonist at the human mu opiate receptor. J Agric Food Chem 2006; 54: 9852-9857
    CrossrefPubMedGoogle Scholar
  • 85 Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Khan IA, Shah A. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005; 77: 415-426
    CrossrefPubMedGoogle Scholar
  • 86 Gurley B, Hubbard MA, Williams DK, Thaden J, Tong Y, Gentry WB, Breen P, Carrier DJ, Cheboyina S. Assessing the clinical significance of botanical supplementation on human cytochrome P450 3A activity: comparison of a milk thistle and black cohosh product to rifampin and clarithromycin. J Clin Pharmacol 2006; 46: 201-213
    CrossrefPubMedGoogle Scholar
  • 87 Borrelli F, Izzo AA. Herb-drug interactions with St Johnʼs wort (Hypericum perforatum): an update on clinical observations. AAPS J 2009; 11: 710-727
    CrossrefPubMedGoogle Scholar
  • 88 Markowitz JS, DeVane CL, Boulton DW, Carson SW, Nahas Z, Risch SC. Effect of St. Johnʼs wort (Hypericum perforatum) on cytochrome P-450 2D6 and 3A4 activity in healthy volunteers. Life Sci 2000; 66: PL133-PL139
    CrossrefPubMedGoogle Scholar
  • 89 Wang Z, Gorski JC, Hamman MA, Huang SM, Lesko LJ, Hall SD. The effects of St Johnʼs wort (Hypericum perforatum) on human cytochrome P450 activity. Clin Pharmacol Ther 2001; 70: 317-326
    PubMedGoogle Scholar
  • 90 Wenk M, Todesco L, Krahenbuhl S. Effect of St Johnʼs wort on the activities of CYP1A2, CYP3A4, CYP2D6, N-acetyltransferase 2, and xanthine oxidase in healthy males and females. Br J Clin Pharmacol 2004; 57: 495-499
    CrossrefPubMedGoogle Scholar
  • 91 Roby CA, Anderson GD, Kantor E, Dryer DA, Burstein AH. St Johnʼs Wort: effect on CYP3A4 activity. Clin Pharmacol Ther 2000; 67: 451-457
    CrossrefPubMedGoogle Scholar
  • 92 Markowitz JS, Donovan JL, DeVane CL, Taylor RM, Ruan Y, Wang JS, Chavin KD. Effect of St Johnʼs wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA 2003; 290: 1500-1504
    CrossrefPubMedGoogle Scholar
  • 93 Wang LS, Zhu B, Abd El-Aty AM, Zhou G, Li Z, Wu J, Chen GL, Liu J, Tang ZR, An W, Li Q, Wang D, Zhou HH. The influence of St Johnʼs Wort on CYP2C19 activity with respect to genotype. J Clin Pharmacol 2004; 44: 577-581
    CrossrefPubMedGoogle Scholar
  • 94 Wang LS, Zhou G, Zhu B, Wu J, Wang JG, Abd El-Aty AM, Li T, Liu J, Yang TL, Wang D, Zhong XY, Zhou HH. St Johnʼs wort induces both cytochrome P450 3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omeprazole. Clin Pharmacol Ther 2004; 75: 191-197
    CrossrefPubMedGoogle Scholar
  • 95 Mai I, Bauer S, Perloff ES, Johne A, Uehleke B, Frank B, Budde K, Roots I. Hyperforin content determines the magnitude of the St Johnʼs wort-cyclosporine drug interaction. Clin Pharmacol Ther 2004; 76: 330-340
    CrossrefPubMedGoogle Scholar
  • 96 Arold G, Donath F, Maurer A, Diefenbach K, Bauer S, Henneicke-von Zepelin HH, Friede M, Roots I. No relevant interaction with alprazolam, caffeine, tolbutamide, and digoxin by treatment with a low-hyperforin St Johnʼs wort extract. Planta Med 2005; 71: 331-337
    Article in Thieme ConnectPubMedGoogle Scholar
  • 97 Mueller SC, Majcher-Peszynska J, Uehleke B, Klammt S, Mundkowski RG, Miekisch W, Sievers H, Bauer S, Frank B, Kundt G, Drewelow B. The extent of induction of CYP3A by St. Johnʼs wort varies among products and is linked to hyperforin dose. Eur J Clin Pharmacol 2006; 62: 29-36
    PubMedGoogle Scholar
  • 98 Mueller SC, Majcher-Peszynska J, Mundkowski RG, Uehleke B, Klammt S, Sievers H, Lehnfeld R, Frank B, Thurow K, Kundt G, Drewelow B. No clinically relevant CYP3A induction after St. Johnʼs wort with low hyperforin content in healthy volunteers. Eur J Clin Pharmacol 2009; 65: 81-87
    CrossrefPubMedGoogle Scholar
  • 99 Hall SD, Wang Z, Huang SM, Hamman MA, Vasavada N, Adigun AQ, Hilligoss JK, Miller M, Gorski JC. The interaction between St Johnʼs wort and an oral contraceptive. Clin Pharmacol Ther 2003; 74: 525-535
    CrossrefPubMedGoogle Scholar
  • 100 Murphy PA, Kern SE, Stanczyk FZ, Westhoff CL. Interaction of St. Johnʼs Wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding. Contraception 2005; 71: 402-408
    CrossrefPubMedGoogle Scholar
  • 101 Pfrunder A, Schiesser M, Gerber S, Haschke M, Bitzer J, Drewe J. Interaction of St Johnʼs wort with low-dose oral contraceptive therapy: a randomized controlled trial. Br J Clin Pharmacol 2003; 56: 683-690
    CrossrefPubMedGoogle Scholar
  • 102 Smith PF, Bullock JM, Booker BM, Haas CE, Berenson CS, Jusko WJ. Induction of imatinib metabolism by Hypericum perforatum . Blood 2004; 104: 1229-1230
    CrossrefPubMedGoogle Scholar
  • 103 Frye RF, Fitzgerald SM, Lagattuta TF, Hruska MW, Egorin MJ. Effect of St Johnʼs wort on imatinib mesylate pharmacokinetics. Clin Pharmacol Ther 2004; 76: 323-329
    CrossrefPubMedGoogle Scholar
  • 104 Andren L, Andreasson A, Eggertsen R. Interaction between a commercially available St. Johnʼs wort product (Movina) and atorvastatin in patients with hypercholesterolemia. Eur J Clin Pharmacol 2007; 63: 913-916
    CrossrefPubMedGoogle Scholar
  • 105 Portoles A, Terleira A, Calvo A, Martinez I, Resplandy G. Effects of Hypericum perforatum on ivabradine pharmacokinetics in healthy volunteers: an open-label, pharmacokinetic interaction clinical trial. J Clin Pharmacol 2006; 46: 1188-1194
    CrossrefPubMedGoogle Scholar
  • 106 Tannergren C, Engman H, Knutson L, Hedeland M, Bondesson U, Lennernas H. St Johnʼs wort decreases the bioavailability of R- and S-verapamil through induction of the first-pass metabolism. Clin Pharmacol Ther 2004; 75: 298-309
    CrossrefPubMedGoogle Scholar
  • 107 Kawaguchi A, Ohmori M, Tsuruoka S, Nishiki K, Harada K, Miyamori I, Yano R, Nakamura T, Masada M, Fujimura A. Drug interaction between St Johnʼs Wort and quazepam. Br J Clin Pharmacol 2004; 58: 403-410
    CrossrefPubMedGoogle Scholar
  • 108 Rengelshausen J, Banfield M, Riedel KD, Burhenne J, Weiss J, Thomsen T, Walter-Sack I, Haefeli WE, Mikus G. Opposite effects of short-term and long-term St Johnʼs wort intake on voriconazole pharmacokinetics. Clin Pharmacol Ther 2005; 78: 25-33
    CrossrefPubMedGoogle Scholar
  • 109 Xu H, Williams KM, Liauw WS, Murray M, Day RO, McLachlan AJ. Effects of St Johnʼs wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide. Br J Pharmacol 2008; 153: 1579-1586
    PubMedGoogle Scholar
  • 110 Piscitelli SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J. Indinavir concentrations and St Johnʼs wort. Lancet 2000; 355: 547-548
    CrossrefPubMedGoogle Scholar
  • 111 Kroll DJ, Shaw HS, Oberlies NH. Milk thistle nomenclature: why it matters in cancer research and pharmacokinetic studies. Integr Cancer Ther 2007; 6: 110-119
    CrossrefPubMedGoogle Scholar
  • 112 Hogan FS, Krishnegowda NK, Mikhailova M, Kahlenberg MS. Flavonoid, silibinin, inhibits proliferation and promotes cell-cycle arrest of human colon cancer. J Surg Res 2007; 143: 58-65
    CrossrefPubMedGoogle Scholar
  • 113 Brantley SJ, Oberlies NH, Kroll DJ, Paine MF. Two flavonolignans from milk thistle (Silybum marianum) inhibit CYP2C9-mediated warfarin metabolism at clinically achievable concentrations. J Pharmacol Exp Ther 2010; 332: 1081-1087
    CrossrefPubMedGoogle Scholar
  • 114 van Erp NP, Baker SD, Zhao M, Rudek MA, Guchelaar HJ, Nortier JW, Sparreboom A, Gelderblom H. Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan. Clin Cancer Res 2005; 11: 7800-7806
    CrossrefPubMedGoogle Scholar
  • 115 Lu H, Meng X, Li C, Sang S, Patten C, Sheng S, Hong J, Bai N, Winnik B, Ho CT, Yang CS. Glucuronides of tea catechins: enzymology of biosynthesis and biological activities. Drug Metab Dispos 2003; 31: 452-461
    CrossrefPubMedGoogle Scholar
  • 116 Feng WY. Metabolism of green tea catechins: an overview. Curr Drug Metab 2006; 7: 755-809
    CrossrefPubMedGoogle Scholar
  • 117 Zhang Q, Fu H, Pan J, He J, Ryota S, Hara Y, Wang Y, Lubet RA, You M. Effect of dietary Polyphenon E and EGCG on lung tumorigenesis in A/J Mice. Pharm Res 2010; 27: 1066-1071
    CrossrefPubMedGoogle Scholar
  • 118 Yang CS, Chen L, Lee MJ, Balentine D, Kuo MC, Schantz SP. Blood and urine levels of tea catechins after ingestion of different amounts of green tea by human volunteers. Cancer Epidemiol Biomarkers Prev 1998; 7: 351-354
    PubMedGoogle Scholar
  • 119 Yang TT, Koo MW. Chinese green tea lowers cholesterol level through an increase in fecal lipid excretion. Life Sci 2000; 66: 411-423
    PubMedGoogle Scholar
  • 120 Yang TT, Koo MW. Inhibitory effect of Chinese green tea on endothelial cell-induced LDL oxidation. Atherosclerosis 2000; 148: 67-73
    CrossrefPubMedGoogle Scholar
  • 121 Zhong Z, Froh M, Connor HD, Li X, Conzelmann LO, Mason RP, Lemasters JJ, Thurman RG. Prevention of hepatic ischemia-reperfusion injury by green tea extract. Am J Physiol Gastrointest Liver Physiol 2002; 283: G957-G964
    PubMedGoogle Scholar
  • 122 Oyama J, Maeda T, Kouzuma K, Ochiai R, Tokimitsu I, Higuchi Y, Sugano M, Makino N. Green tea catechins improve human forearm endothelial dysfunction and have antiatherosclerotic effects in smokers. Circ J 2010; 74: 578-588
    CrossrefPubMedGoogle Scholar
  • 123 Oyama J, Maeda T, Sasaki M, Kozuma K, Ochiai R, Tokimitsu I, Taguchi S, Higuchi Y, Makino N. Green tea catechins improve human forearm vascular function and have potent anti-inflammatory and anti-apoptotic effects in smokers. Intern Med 2010; 49: 2553-2559
    CrossrefPubMedGoogle Scholar
  • 124 Persson IA, Persson K, Hagg S, Andersson RG. Effects of green tea, black tea and Rooibos tea on angiotensin-converting enzyme and nitric oxide in healthy volunteers. Public Health Nutr 2010; 13: 730-737
    CrossrefPubMedGoogle Scholar
  • 125 Nantz MP, Rowe CA, Bukowski JF, Percival SS. Standardized capsule of Camellia sinensis lowers cardiovascular risk factors in a randomized, double-blind, placebo-controlled study. Nutrition 2009; 25: 147-154
    CrossrefPubMedGoogle Scholar
  • 126 Donovan JL, Chavin KD, Devane CL, Taylor RM, Wang JS, Ruan Y, Markowitz JS. Green tea (Camellia sinensis) extract does not alter cytochrome p 450 3A4 or 2D6 activity in healthy volunteers. Drug Metab Dispos 2004; 32: 906-908
    CrossrefPubMedGoogle Scholar
  • 127 Chow HH, Hakim IA, Vining DR, Crowell JA, Cordova CA, Chew WM, Xu MJ, Hsu CH, Ranger-Moore J, Alberts DS. Effects of repeated green tea catechin administration on human cytochrome P450 activity. Cancer Epidemiol Biomarkers Prev 2006; 15: 2473-2476
    CrossrefPubMedGoogle Scholar
  • 128 Kennedy DO, Wightman EL. Herbal extracts and phytochemicals: plant secondary metabolites and the enhancement of human brain function. Adv Nutr 2011; 2: 32-50
    CrossrefPubMedGoogle Scholar
  • 129 Houghton PJ. The scientific basis for the reputed activity of Valerian. J Pharm Pharmacol 1999; 51: 505-512
    CrossrefPubMedGoogle Scholar
  • 130 Houghton PJ. The biological activity of Valerian and related plants. J Ethnopharmacol 1988; 22: 121-142
    CrossrefPubMedGoogle Scholar
  • 131 Leathwood PD, Chauffard F, Heck E, Munoz-Box R. Aqueous extract of valerian root (Valeriana officinalis L.) improves sleep quality in man. Pharmacol Biochem Behav 1982; 17: 65-71
    CrossrefPubMedGoogle Scholar
  • 132 Leathwood PD, Chauffard F. Aqueous extract of valerian reduces latency to fall asleep in man. Planta Med 1985; 144-148
    Article in Thieme ConnectPubMedGoogle Scholar
  • 133 Dorn M. [Efficacy and tolerability of Baldrian versus oxazepam in non-organic and non-psychiatric insomniacs: a randomised, double-blind, clinical, comparative study]. Forsch Komplementarmed Klass Naturheilkd 2000; 7: 79-84
    CrossrefPubMedGoogle Scholar
  • 134 Donath F, Quispe S, Diefenbach K, Maurer A, Fietze I, Roots I. Critical evaluation of the effect of valerian extract on sleep structure and sleep quality. Pharmacopsychiatry 2000; 33: 47-53
    Article in Thieme ConnectPubMedGoogle Scholar
  • 135 Donovan JL, DeVane CL, Chavin KD, Wang JS, Gibson BB, Gefroh HA, Markowitz JS. Multiple night-time doses of valerian (Valeriana officinalis) had minimal effects on CYP3A4 activity and no effect on CYP2D6 activity in healthy volunteers. Drug Metab Dispos 2004; 32: 1333-1336
    CrossrefPubMedGoogle Scholar
  • 136 Anke J, Ramzan I. Pharmacokinetic and pharmacodynamic drug interactions with Kava (Piper methysticum Forst. f.). J Ethnopharmacol 2004; 93: 153-160
    CrossrefPubMedGoogle Scholar
  • 137 Thompson R, Ruch W, Hasenohrl RU. Enhanced cognitive performance and cheerful mood by standardized extracts of Piper methysticum (Kava-kava). Hum Psychopharmacol 2004; 19: 243-250
    CrossrefPubMedGoogle Scholar
  • 138 Kennedy DA, Seely D. Clinically based evidence of drug-herb interactions: a systematic review. Expert Opin Drug Saf 2010; 9: 79-124
    CrossrefPubMedGoogle Scholar
  • 139 Gurley BJ, Swain A, Hubbard MA, Hartsfield F, Thaden J, Williams DK, Gentry WB, Tong Y. Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activity in vivo . Clin Pharmacol Ther 2008; 83: 61-69
    CrossrefPubMedGoogle Scholar
  • 140 Brown PN, Roman MC. Determination of hydrastine and berberine in goldenseal raw materials, extracts, and dietary supplements by high-performance liquid chromatography with UV: collaborative study. J AOAC Int 2008; 91: 694-701
    PubMedGoogle Scholar
  • 141 Lancaster HM, Davidson AL. Commercial pharmaceutical preparations: 4. Hydrastis – golden seal. Can Med Assoc J 1927; 17: 1317-1320
    PubMedGoogle Scholar
  • 142 Chatterjee P, Franklin MR. Human cytochrome p 450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components. Drug Metab Dispos 2003; 31: 1391-1397
    CrossrefPubMedGoogle Scholar
  • 143 Yi S, Cho JY, Lim KS, Kim KP, Kim J, Kim BH, Hong JH, Jang IJ, Shin SG, Yu KS. Effects of Angelicae tenuissima radix, Angelicae dahuricae radix and Scutellariae radix extracts on cytochrome P450 activities in healthy volunteers. Basic Clin Pharmacol Toxicol 2009; in press
    PubMedGoogle Scholar
  • 144 Fan L, Wang JC, Jiang F, Tan ZR, Chen Y, Li Q, Zhang W, Wang G, Lei HP, Hu DL, Wang D, Zhou HH. Induction of cytochrome P450 2B6 activity by the herbal medicine baicalin as measured by bupropion hydroxylation. Eur J Clin Pharmacol 2009; 65: 403-409
    CrossrefPubMedGoogle Scholar
  • 145 Ramassamy C. Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracellular targets. Eur J Pharmacol 2006; 545: 51-64
    CrossrefPubMedGoogle Scholar
  • 146 Chow HH, Garland LL, Hsu CH, Vining DR, Chew WM, Miller JA, Perloff M, Crowell JA, Alberts DS. Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study. Cancer Prev Res (Phila) 2010; 3: 1168-1175
    CrossrefPubMedGoogle Scholar
  • 147 Chen Y, Liu WH, Chen BL, Fan L, Han Y, Wang G, Hu DL, Tan ZR, Zhou G, Cao S, Zhou HH. Plant polyphenol curcumin significantly affects CYP1A2 and CYP2A6 activity in healthy, male Chinese volunteers. Ann Pharmacother 2010; 44: 1038-1045
    CrossrefPubMedGoogle Scholar