Advances in Traditional Medicine

Kyung Hee Oriental Medicine Research Center (경희대학교 융합한의과학연구소)
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Effect of Allium sativum on cytochrome P450 and possible drug interactions

  • Janil, Ashutosh (Department of Pharmacology, K.B. Institute of Pharmaceutical Education and Research) ;
  • Mehta, Anita A (Department of Pharmacology, L.M. College of Pharmacology)
  • Published : 2006.12.31
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Abstract

Allium sativum (Family Amaryllidaceae or Liliaceae) is used worldwide for various clinical uses like hypertension, cholesterol lowering effect, antiplatelets and fibrinolytic activity etc. Due to these common house hold uses of Allium sativum, as a herbal supplements, and failure of patients to inform their physician of the over-the-counter supplements they consume leads to drugnutrient interactions with components in herbal supplements. Today these types of interactions between a herbal supplement and clinically prescribed drugs are an increasing concern. In vitro studies indicated that garlic constituents modulated various CYP (cytochrome P450) enzymes. CYP 3A4 is abundantly present in human liver and small intestine and contributes to the metabolism of more than 50% of commonly used drugs including nifedipine, cyclosporine, erythromycin, midazolam, alprazolam, and triazolam. Extracts from fresh and aged garlic inhibited CYP 3A4 in human liver microsomes. The in vivo effects of garlic constituents are found to be species depended and the dosing regimen of garlic constituents appeared to influence the modulation of various CYP isoforms. Studies have indicated that the inhibition of various CYPs by organosulfur compounds from garlic was related to their structure also. Studies using in vitro, in vivo, animal and human models have indicated that various garlic constituents can be the substrates, inhibitors and or inducers of various CYP enzymes. The modulation of CYP enzyme activity and expression are dependent on the type and chemical structure of garlic constituents, dose regime, animal species and tissue, and source of garlic thus this review throws light on the possible herb drug interaction with the use of garlic.

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References

  1. Ameer B, Weintraub RA. (1997) Drug interactions with grapefruit juice. Clin. Pharmacokinet. 33, 103-121. https://doi.org/10.2165/00003088-199733020-00003
  2. Barnes J, Anderson LA, Philipson JD. (2001) St. John’s wort (Hypericum perforatum L.): a review of its chemistry, pharmacology and clinical properties. J. Pharm. Pharmacol. 53, 583-600. https://doi.org/10.1211/0022357011775910
  3. Block E, Ahmad S, Cataltamo JL, Jain MK, Apitz Castro R. (1986) Antithrombotic organosulfur compounds from garlic, structural mechanistic and synthetic studies. J. Am. Chem. Soc. 108, 7045-7055. https://doi.org/10.1021/ja00282a033
  4. Brady JF, Ishizaki H, Fukuto JM, Lin MC, Fadel A, Gapac JM, Yang CS. (1991b) Inhibition of cytochrome P-450 2El by diallyl sulfide and its metabolites Chem. Res. Toxicol, 4, 642-647. https://doi.org/10.1021/tx00024a008
  5. Brady JF, Wang MH , Hong JY , Xiao F, LiY, YooJ S, Ning SM, Fukuto JM, Gapac JM, Yang CS. (1991a) Modulation of rat hepatic microsomal monooxygenase activities and cytotoxicity by diallyl sulfide. Toxicol. Appl. Pharm. 108, 342 -354. https://doi.org/10.1016/0041-008X(91)90123-V
  6. Brigelius Flohe R. (2003) Vitamin E and drug metabolism. Biochem. Biophys. Res. Commun. 305, 737-740. https://doi.org/10.1016/S0006-291X(03)00811-8
  7. Budzinski JW, Arnason JT, Trudeau V, Krantis A, Foster BC. (2001) Effects of Goldenseal and milk thistle on the modulation of cytochrome P450 3A4 and Pglycoprotein. Drug Metab. Rev. 33, 86.
  8. Calvey EM, Matusik JE, White KD, DeOrazio R, Sha D, Block E. (2000) Allium chemistry: Supercritical fluid extraction and LC-APCI-MS of thiosulfinates and related compounds from Prostaglandins, Leukotrienes and Essential Fatty Acids 62, 55-73. https://doi.org/10.1054/plef.1999.0124
  9. Chan K. (2003) Some aspects of toxic contaminants in herbal medicines. Chemosphere. 52, 1361-1371. https://doi.org/10.1016/S0045-6535(03)00471-5
  10. Chatterjee P, Franklin MR. (2003) Human cytochrome P450 inhibition and metabolicintermediate complex formation by goldenseal extract and its methylenedioxyphenyl components. Drug Metab. Dispos. 31, 1391-1397. https://doi.org/10.1124/dmd.31.11.1391
  11. Choi SU, Park SH, Kim KH, Choi EJ, Kim S et al. (1998) The bisbenzylisoquinoline alkaloids, tetrandine and fangchinoline, enhance the cytotoxicity of multidrug resistancerelated drugs via modulation of P-glycoprotein. Anti-Cancer Drugs 9, 255-261. https://doi.org/10.1097/00001813-199803000-00008
  12. Choudhri SH, Gallicano K, Fosterm B. (2000) A study of pharmacokinetic interaction between garlic supplements and ritonavir in healthy volunteers (abstract 1637). The 40th Interscience Conference on Antimicrobial agents and chemotherapy, Toronto, Washington, DC: American Society for microbiology.
  13. Chun YJ, Kim S. (2003) Discovery of cytochrome P450 1B1 inhibitors as new promising anti-cancer agents. Med. Res. Rev 23, 657-668. https://doi.org/10.1002/med.10050
  14. Chutani SK, Bordia A. (1981) The effect of fried versus raw garlic on fibrinolytic activity in man. Atherosclerosis 38, 417-421. https://doi.org/10.1016/0021-9150(81)90058-7
  15. Dalvi RR. (1992) Alteration in hepatic phase I and phase II biotransformation enzymes by garlic oil in rats. Toxicol. Lett. 60, 299-305. https://doi.org/10.1016/0378-4274(92)90288-U
  16. Deferme S, Kamuhabwa A, Nshimo C, de Witte P, Augustijns P. (2003) Screening of Tanzanian plant extracts for their potential inhibitory effect on P-glycoprotein mediated efflux. Phytother. Res. 17, 459-464. https://doi.org/10.1002/ptr.1173
  17. Deferme S, Van Gelder J, Augustijns P. (2002) Inhibitory effect of fruit extracts on P- glycoprotein-related efflux carriers: an in-vitro screening. J. Pharm. Pharmacol. 54, 1213-1219. https://doi.org/10.1211/002235702320402053
  18. Dragnev KH, Nims RW, Lubet RA. (1995) The chemopreventive agent dia1lyl sul fide A structurally atypical Phenobarbital-type inducer. Biochem. Pharmacol. 50, 2099 -2104. https://doi.org/10.1016/0006-2952(95)02117-5
  19. Dresser GK, Schwarz UI, Wilkinson GR, Kim RB. (2003) Coordinate induction of both cytochrome P4503A and MDR1 by St John’s wort in healthy subjects. Clin. Pharmacol. Ther. 73, 41-50. https://doi.org/10.1067/mcp.2003.10
  20. Edwards SJ, Musker D, Collin HA, Britton G. (1994) The analysis of S-alk(en)yl-L- cysteine sulphoxides (flavour precursors) from species of Allium by high performance liquid chromatography. Phytochem. Anal. 5, 4-9. https://doi.org/10.1002/pca.2800050103
  21. Egen Schwind C, Eckard R and Kempe FH. (1992a) Metabolism of garlic constituents in the isolated perfused rat liver. Planta Med. 58, 301-305. https://doi.org/10.1055/s-2006-961471
  22. Ernst E. (1987) Cardiovascular effects of garlic (Allium sativum): a review. Pharmatherapeutica 5, 83-89.
  23. Ferreira T, Drouin CE, Krantis A, Amason JT, Foster BC. (2003) Effect of a natural health product containing Echinacea on human N-acetyltransferase expression. Can. J. Infect. Dis. 14, 20A.
  24. Fitzsimmons ME, Collins JM. (1997) Selective biotransformation of the human deficiency virus protease inhibitor saquinavir by human small-intestinal cytochromeP450 3A4: Potential contribution to high first pass metabolism. Drug Metab. Dispos. 25, 256-266.
  25. Foster BC, Foster MS, Vandenhoek S, Budzinski JW, Gallicano KD et al. (2001a) An in vitro evaluation of human cytochrome P450 3A4 and P-glycoprotein inhibition by garlic. J. Pharm. Pharma. Sci. 4, 176-184.
  26. Foster BC, Sockovie ER, Bellefeuille NC, Vandenhoek S, Krantis A et al. (2001b). Effect of St. John's wort on cytochrome P- 450 and flavin monooxygenase enzymes and on P- glycoprotein. Can. J. Infect. Dis. 12, 132P
  27. Foster BC, Vandenhoek S, Hanna J, Budzinski JW, Akhtar MH et al. (2003) Effects of natural health products on cytochrome P-450 drug metabolism. Phytomedicine 10, 334-342. https://doi.org/10.1078/094471103322004839
  28. Foster BC, Vandenhoek S, Li KY, Tang R, Krantis A. (2002) Effect of Chinese herbal products on cytochrome P-450 drug metabolism. J. Pharm. Pharm. Sci. 5, 185-189.
  29. Foster MS, Vandenhoek S, Drouin CE, Budzinski JW, Krantis A et al. (2001c) In vitro evaluation of human cytochrome P450, P-glycoprotein and antibiotic interactions by garlic (Allium sativum). Can. J. Infect. Dis. 12, 131.
  30. Foushee DB, Ruffin J, and Baneerjee U. (1982) Garlic as a natural agent for the treatment of hypertension: A preliminary report. Cytobios 34, 145-162.
  31. Fujita K, Kamataki T. (2001) Screening of organosulfur compounds as inhibitors of human CYP2A6. Drug Metab. Dispos. 29, 983-989.
  32. Gorski JC, Huang SM, Pinto A, Hamman MA, Hilligoss JK et al. (2004) The effect of Echinacea (Echinacea purpurearoot) on cytochrome P450 activity in vivo. Clin. Pharmacol. Ther. 75, 89-100. https://doi.org/10.1016/j.clpt.2003.09.013
  33. Guengerich FP. (1999) Cytochrome P-450 3A4: Regulation and role in drug metabolism. Annu. Reν . Pharmacol. Toxicol. 39, 1-17. https://doi.org/10.1146/annurev.pharmtox.39.1.1
  34. Guerra MC, Speroni E, Broccoli M, Cangini M, Pasini P et al. (2000) Comparison between Chinese medical herb Pueraria lobata crude extract and its main isoflavone puerarin antioxidant properties and effects on rat liver CYP-catalysed drug metabolism. Life Sci. 67, 2997-3006. https://doi.org/10.1016/S0024-3205(00)00885-7
  35. Guo LQ, Yamazoe Y. (2004) Inhibition of cytochrome P450 by furanocoumarins in grapefruit juice and herbal medicines. Acta. Pharmacol. Sin. 25, 129-136.
  36. Guo Z, Miller D, Pentz R, Kress G, Siegers CP. (1990) Biology and chemistry of active natural substances. International symposium. Bonn, Proceedings. Planta Med. 56, 692.
  37. Guyonnet D, Belloir C, Suscetet M, Siess MH, Le Bon AM. (2000) Liver subcellular fractions from rats treated by organosulfur compounds from Allium modulate mutagen activation. Mutat. Res. 466, 17-26.
  38. Guyonnet D, Siess MH, Le Bon AM, Suscetet M. (1999) Modulation of phase II enzymes by organosulfur compounds form Allium vegetables in rat tissues. Toxicol. Appl. Pharmacol. 154, 50 -58. https://doi.org/10.1006/taap.1998.8574
  39. Haber D, Siess MH, Canivenc Lavier MC, Le Bon AM, Suschetet M. (1995) Differiential effects of dietary diallyl sulfide and diallyl disulfide on rat intestinal and hepatic drug metabolizing enzymes. J. Toxicol. Environ. Health 44, 423-434. https://doi.org/10.1080/15287399509531971
  40. Haber D, Siess MH, De Waziers I, Beaune P, Suschetet M. (1994) Modification of hepatic drug-metabolizing enzymes in rats fed naturally occurring allyl sulphides. Xenobiotica 24, 169 -182. https://doi.org/10.3109/00498259409043230
  41. Harris R, Jang G, Tsunoda S. (2003) Dietary effects on drug metabolism and transport. Clin. Pharmacokinet. 2, 1071-1088.
  42. Hodek P, Trefil P, Stiborova M. (2002) Flavonoids potent and versatile biologically active compounds interacting with cytochromes P450. Chem. Biol. Interact. 139, 1-21. https://doi.org/10.1016/S0009-2797(01)00285-X
  43. Huang SM, Hall SD, Watkins P, Love LA, Serabjit Singh C et al. (2004) Drug interactions with herbal products and grapefruit juice: a conference report. Clin. Pharmacol. Ther. 75, 1-12. https://doi.org/10.1016/j.clpt.2003.07.002
  44. Imai J, Ide N, Nagae S, Moriguchi T, Matsuura H, Itakura Y. (1994) Antioxidant and radical scavenging effects of aged garlic extract and its constituents. Planta Med. 60, 417-420. https://doi.org/10.1055/s-2006-959522
  45. Ioannides C. (2002) Pharmacokinetic interactions between herbal remedies and medicinal drugs. Xenobiotica 32, 451-478. https://doi.org/10.1080/00498250210124147
  46. Izzo AA. (2004) Drug interactions with St. John’s Wort (Hypericum perforatum): a reviewof the clinical evidence. Int. J. Clin. Pharmacol. Ther. 42, 139-148.
  47. Jin L, Baillie TA. (1997) Metabolism of the chemopreventive agent diallyl sulphide to glutathione conjugates in rats Chem. Res. Toxicol. 10, 318 -327. https://doi.org/10.1021/tx9601768
  48. Kendler BS. (1987) Garlic (Allium sativum) and onion (Allium cepa). A review of their relationship to cardiovascular disease. Prev. Med. 16, 670-685. https://doi.org/10.1016/0091-7435(87)90050-8
  49. Kiesewetter H et al. (1991) Effect of garlic on thrombocyte aggregation, microcirculation, and other risk factors. Int. J. Clin. Pharmacol. Ther. Toxicol. 29, 151-155.
  50. Kim AE, Dintaman JM, Waddell DS. (1998) Saqunavir, an HIV protease inhibitor, is transported by P-glycoprotein. J. Pharmacol. Exp. Ther. 286, 143-149.
  51. Kishimoto R, Ueda M, Yoshinga H, Goda K, Park SS. (1999) Combined effects of ethanol and garlic on hepatic ethanol metabolism in mice. J. Nutr. Sci. Vitaminol. 45, 275-286.
  52. Kubec R, Krihove V, Velisek J. (1999) Volatile compounds thermally generated from S- propylcysteine and S-propylcysteine sulfoxide-Aroma precursors of Allium vegetables. J. Agric. Food Chem. 47, 1132-1138. https://doi.org/10.1021/jf980974z
  53. Kwak MK, Kim SG, Kim ND. (1995) Effects of garlic oil on rat hepatic P4502E1 expression. Xenobiotica 25, 1021-1029. https://doi.org/10.3109/00498259509061902
  54. Kwak MK, Kim SG, Kwak JY, Novak RF, Kim ND. (1994) Inhibition of cytochrome P4502E1 expression by organosulfur compounds allylsulfide, allylmercaptan and allyl methylsul fide in rats. Biochem. Pharmacol. 47, 531 -539. https://doi.org/10.1016/0006-2952(94)90185-6
  55. Lau BH, Adetumbi MA, Sanchez A. (1983) Allium sativum (garlic) and atherosclerosis: A review. Nutr. Res. 3, 119-128. https://doi.org/10.1016/S0271-5317(83)80128-6
  56. Lawson LD. (1992) Allicin and other thiosulfinates and their precursors and transformation products from garlic and garlic products In: Kinghorn A D, Balandrin M F, eds Human Medicinal Agents from Plants Washington, DC: American Chemical Society 306-320.
  57. Lawson LD, Wang ZJ. (1993) Pre-hepatic fate of the organosulfur compounds derived from garlic (Allium sativum). Planta Med. 59, A688-A689.
  58. Legnani C et al. (1993) Effects of dried garlic preparation on fibrinolysis and platelet aggregation in healthy subjects. Arzneimitteforschung 43, 119-121.
  59. Lin HL, Liu TY, Wu CW, Chi CW. (1999) Berberine modulates expression of mdr1 gene product and the responses of digestive track cancer cells to Paclitaxel. Br. J. Cancer 81, 416-422. https://doi.org/10.1038/sj.bjc.6690710
  60. Lin RD, Hou WC, Yen KY, Lee MH. (2003)Inhibition of monoamine oxidase B (MAO-B) by Chinese herbal medicines. Phytomedicine 10, 650-656. https://doi.org/10.1078/0944-7113-00324
  61. Loizou GD, CockerJ. (2001) The effect of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazone. Hum. Exp. Toxicol. 20, 321-327. https://doi.org/10.1191/096032701680350587
  62. Maliakal PP, Wanwimolruk S. (2001) Effect of herbal teas on hepatic drug metabolizing enzymes in rats. J. Pharm. Pharmacol. 53, 1323-1329. https://doi.org/10.1211/0022357011777819
  63. Markowitz JS, Devane CL, Chavin KD, Taylor RM, Ruan Y, Donovan JL. (2003) Effects of garlic (Allium sativumL.) supplementation on cytochrome P450 2D6 and 3A4 activity in healthy volunteers. Clin. Pharmacol. Ther. 74, 170-177. https://doi.org/10.1016/S0009-9236(03)00148-6
  64. Mathews JM, Etheridge AS, Black SR. (2002) Inhibition of human cytochrome P450 activities by kava extract and kavalactones. Drug Metab. Dispos. 30, 1153-1157. https://doi.org/10.1124/dmd.30.11.1153
  65. Mitchell SC. (1988) Biological consequences of drug sulphoxidation. Drug Metab. Dispos. 6, 245 -252.
  66. Mori H, Tanaka T and Hirono I. (1998) Toxicants in food: naturally occurring. In C. Ioannides (ed.), Nutrition and Chemical Toxicity (Chichester: Wiley), pp. 1-27.
  67. Munday R, Mundsay CM. (1999) Low doses of diallyl sul fide, a compound derived from garlic,increase tissue activities of quinone reductase and glutathione transferase in the gastrointestinal tract of the rat. Nutr. Cancer 34, 42-48. https://doi.org/10.1207/S15327914NC340106
  68. Norwell DY, Tarr RS. (1983) Garlic, vampires, and CHD. Osteopathic Annals 11, 546-549.
  69. Petkov V. (1979) Plants with hypotensive, antiatheromatous and coronary dilating action. Am. J. Chin. Med. 7, 197-236. https://doi.org/10.1142/S0192415X79000180
  70. Piscitelli SC, Burstein AH, Welden N,Gallicano KD, Falloon J. (2001) The effect of garlic supplements on pharmacokinetics of saquinavir. Clin. Infect. Dis. 34, 234-238. https://doi.org/10.1086/324351
  71. Premdas PD, Bowers RJ, Forkert PK. (2000) Inactivation of hepatic CYP2E1 by an epoxide of diallyl sulfone. J. Pharmacol. Exp. Ther. 293, 1112 -1120.
  72. Pushpendran CK, Devasagayam TP, Chintalwar GJ, Banerji A, Eapen J. (1980) The metabolic fate of [35S]-diallyl disulphide in mice. Experientia 36, 1000-1001. https://doi.org/10.1007/BF01953845
  73. Reicks MM, Crankshaw DL. (1996) Modulation of rat hepatic cytochrome P-450 activity by garlic organosulfur compounds. Nutr. Cancer 25, 241-248. https://doi.org/10.1080/01635589609514448
  74. Rendic S, Di Carlo FJ. (1997) Human cy-tochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab. Rev. 29, 413-580. https://doi.org/10.3109/03602539709037591
  75. Sainani GS et al. (1979) Effect of dietary garlic and onion on serum lipid profile in the Jain community. Ind. J. Med. Res. 69, 776-780.
  76. Sainani GS et al. (1979) Dietary garlic, onion and some coagulation parameters in Jain community. J. Assoc. Phys. Ind. 27, 707-712.
  77. Sheen LY, Chen HW, Kung YL, Liu CT, Lii CK. (1999) Effect of garlic oil and its organosulfur compounds on the activities of hepatic drug metabolizing and antioxidant enzymes in rats fed high and low fat diets. Nutr. Cancer 35, 160-166. https://doi.org/10.1207/S15327914NC352_10
  78. Sheen LY, Sheu SF, Tsai SJ, Meng RHC, Lii CK. (1999) Effect of garlic active principle, diallyl disulphide, on cell viability, lipid peroxidation, glutathione concentration and its related enzyme activities in primary rat hepatocytes. Am. J. chin. Med. 27, 95-106. https://doi.org/10.1142/S0192415X99000124
  79. Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP. (1994) Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J. Pharmacol. Exp. Ther. 270, 414-423.
  80. Siess MH, LeBon AM, Canivenc Lavier MC, Suschetet M. (1997) Modification of hepatic drug metabolizing enzymes in rats treated with alkyl sulfides. Cancer Lett. 120, 195-201. https://doi.org/10.1016/S0304-3835(97)00309-1
  81. Silagy CA, Neil AW. (1994) A meta-analysis of the effect of garlic on blood pressure. J. Hypertens. 12, 463-468.
  82. Soons PA, Schellens JHM, Breimer DD. (1992) Variability in pharmacokinetics and metabolism of nifedipine and dihydropy-ridine calcium entry blockers. In Pharmacogenetics of Drug Metabolism, ed. W Kalow, New York: Pergaman 769-89.
  83. Sun M, Sakakibara H, Ashida H, Danno G, Kanazawa K. (2000) Cytochrome P4501A1- inhibitory action of antimutagenic anthraquinones in medicinal plants and the structureactivity relationship. Biosci. Biotechnol. Biochem. 64, 1373-1378. https://doi.org/10.1271/bbb.64.1373
  84. Teyssier C, Guenotl, Suschetet M, Siess MH. (1999) Metabolism of diallyl disulfide by human liver microsomal cytochromes P-450 and flavin containing monooxygenases. Drug Metab. Dispos. 27, 835-841.
  85. Teyssier C, Siess MH. (2000) Metabolism of dipropyl disulfide by rat liver phase I and phase II enzymes and by isolated perfused rat liver. Drug Metab. Dispos. 28, 648 -654.
  86. Teyssier C, Guenot L, Suschetet M, Siess MH. (1999) Metabolism of diallyl disulfideby human liver microsomal cytochromes P-450 and Flavin-containing monooxygenases. Drug Metab. Dispos. 27, 835-841.
  87. Thummel KE, Wilkinson GR. (1998) In vitro and in vivo drug interactions involving human CYP3A. Annu. Rev. Pharmacol. Toxicol. 38, 389-430. https://doi.org/10.1146/annurev.pharmtox.38.1.389
  88. Turner M. (1994) Garlic and circulatory disorders. J. R. Soc. Health 110, 390.
  89. Ueng YF, Ko He, Chen CF, Wang JJ, Chen KT. (2002) Modulation of drugmetabolizing enzymes by extracts of a herbal medicine Evodia rutaecarpa in C57BL/6J. mice. Life Sci. 71, 1267-1277. https://doi.org/10.1016/S0024-3205(02)01854-4
  90. Van Zanden JJ, Ben Hamman O, van Iersel ML, Boeren S, Cnubben NH et al. (2003) Inhibition of human glutathione S-transferase P1-1 by the flavonoid quercetin. Chem. Biol. Interact. 145, 139-148. https://doi.org/10.1016/S0009-2797(02)00250-8
  91. Venkataramanan R, Ramachandran V, Komoroski BJ, Zhang S, Schiff PL, Strom SC. (2000) Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures. Drug Metab. Dispos. 28, 1270-1273.
  92. Wacher VJ, Wu CY, Benet LZ. (1995) Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein: implications for drug delivery and activity in cancer therapy. Mol. Carcinog. 13, 129-134. https://doi.org/10.1002/mc.2940130302
  93. Wang LS, Zhou G, Zhu B, Wu J, Wang JG et al. (2004) St John’s wort induces both cytochrome P450 3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omeprazole. Clin. Pharmacol. Ther. 75, 191-197. https://doi.org/10.1016/j.clpt.2003.09.014
  94. Ward PM, Fasitsas S, Katz SE. (2002) Inhibition, resistance development, and increased antibiotic and antimicrobial resistance caused by nutraceuticals. J. Food Prot. 65, 528-533.
  95. Wargovich, MJ, Imada O, Stephen LC. (1992) Initiation and post-initiation chemopreventive effects of diallyl sulfide in esophageal carcinogenesis. Cancer Lett. 64, 39-42. https://doi.org/10.1016/0304-3835(92)90019-R
  96. Watkins PB. (1994) Non-invasive tests of CYP3A enzymes. Pharmacogenetics 4, 171-184. https://doi.org/10.1097/00008571-199408000-00001
  97. Wentworth JM, Agostini M, Love J, Schwabe JW, Chatterjee VK. (2000) St John’s wort, a herbal antidepressant, activates the steroidXreceptor. J. Endocrinol. 166, R11-16. https://doi.org/10.1677/joe.0.166R011
  98. Wortelboer HM, Usta M, van der Velde AE, Boersma MG, Spenkelink B et al. (2003) Interplay between MRP inhibition and metabolism of MRP inhibitors: the case of curcumin. Chem. Res. Toxicol. 16, 1642-1651. https://doi.org/10.1021/tx034101x
  99. Wu D, Nair MG, DeWitt DL. (2002) Novel compounds from Piper methysticum Forst (Kava Kava) roots and their effect on cyclooxygenase enzyme. J. Agric. Food Chem. 50, 701-705. https://doi.org/10.1021/jf010963x
  100. Wu WL, Sheen LY, Chen HW, Kuo WW, Tsai SJ, Lii CK. (2002) Differential effects of garlic oil and its three major organosulfur components on hepatic detoxification system in rats. J Agric. Food Chem. 50, 378-383. https://doi.org/10.1021/jf010937z
  101. Yang CS, Chhabra SK, Hong JY, Smith TJ. (2001) Mechanisms of inhibition of chemical toxicity and carcinogenesis by diallyl sul fide (DAS) and related compounds. J. Nutr. 131, 1041S -1045S.
  102. Zhou S, Gao Y, Jiang W, Huang M, Xu A, Paxton JW. (2003) Interactions of herbs with cytochrome P450. Drug Metab. Rev. 35, 35-98. https://doi.org/10.1081/DMR-120018248
  103. Zieger SJ, Stitcher P. (1989) HPLC of S-alk(en)yl-L-cysteine derivatives in garlic including quantitative determination of (+)-S-allyl-L-cystein sulfoxide(alliin). Planta Med. 55, 372-378. https://doi.org/10.1055/s-2006-962031
  104. Zuber R, Modriansky M, Dvorak Z, Rohovsky P, Ulrichova J et al. (2002) Effect of silybin and its congeners on human liver microsomal cytochrome P450 activities. Phytother. Res. 16, 632-638. https://doi.org/10.1002/ptr.1000