Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2011, 155(3):253-257 | DOI: 10.5507/bp.2011.047

THE EFFECT OF ST JOHN’S WORT (HYPERICUM PERFORATUM) ON CYTOCHROME P450 1A2 ACTIVITY IN PERFUSED RAT LIVER

Miroslav Dostaleka,d, Jana Pistovcakovab, Jan Juricab, Alexandra Sulcovab, Josef Tomandlc
a Department of Pharmacology, Faculty of Medicine, Masaryk University Brno, Czech Republic
b Masaryk University, Central European Institute of Technology (CEITEC), c/o Masaryk University Brno
c Department of Biochemistry, Faculty of Medicine, Masaryk University Brno
d Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA

Aims: We previously reported the effect of St John's wort (Hypericum perforatum) standardised extract LI 160 on the activities of cytochrome P450 2C6, 2D2 and 3As (Dostalek et al., Life Sciences 2005;78(3):239-44). In this study, we aimed to assess the effect of St John's wort on the activity of cytochrome P450 1A2.

Methods: The isolated perfused rat liver model was used in our experiments with phenacetin as a marker substrate for cytochrome P450 1A2. Male Wistar rats were treated with St John's wort extract (100 mg/kg, once daily for 10 days); comparative inhibitor (alpha-naphthoflavone, 100 mg/kg) or comparative inducer (omeprazole, 30 mg/kg).

Results: The rate of formation of acetaminophen was significantly inhibited by the use of St John's wort (P<0.001). In addition, St John's wort extract inhibited cytochrome P450 1A2 activity significantly more than the control inhibitor (P<0.001).

Conclusions: St John's wort significantly inhibited cytochrome P450 1A2 enzyme activity. It remains to be determined whether the co-administration of St John's wort extract and other medications or substrates for cytochrome P450 1A2 could result in significant drug interactions.

Keywords: St John‘s wort, Hypericum perforatum, Cytochrome P450, Liver, isolated perfused, Rat

Received: April 21, 2011; Accepted: August 18, 2011; Published: September 1, 2011  Show citation

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Dostalek, M., Pistovcakova, J., Jurica, J., Sulcova, A., & Tomandl, J. (2011). THE EFFECT OF ST JOHN’S WORT (HYPERICUM PERFORATUM) ON CYTOCHROME P450 1A2 ACTIVITY IN PERFUSED RAT LIVER. Biomedical papers, 155(3), 253-257. doi: 10.5507/bp.2011.047
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    References

    1. Gurley BJ, Gar d n e r SF, Hubbard MA, Williams DK, Gentry WB, Cui Y, Ang CY. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther 2002;72(3):276-87. Go to original source... Go to PubMed...
    2. Borrelli F, Izzo AA. Herb-drug interactions with St John's wort (Hypericum perforatum): an update on clinical observations. AAPS J 2009;11(4):710-27. Go to original source... Go to PubMed...
    3. 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 John's wort, garlic oil, Panax ginseng and Ginkgo biloba. Drugs Aging 2005;22(6):525-39. Go to original source... Go to PubMed...
    4. Gurley BJ, Swain A, Hubbard MA, Williams DK, Barone G, Hartsfield F, Tong Y, Carrier DJ, Cheboyina S, Battu SK. Clinical assessment of P4502D6-mediated herb-drug interactions in humans: effects of milk thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea. Mol Nutr Food Res 2008;52(7):755-63. Go to original source... Go to PubMed...
    5. Mai I, Bauer S, Perloff ES, Johne A, Uehleke B, Frank B, Budde K, Roots I. Hyperforin content determines the magnitude of the St John's wort-cyclosporine drug interaction. Clin Pharmacol Ther 2004;76(4):330-40. Go to original source... Go to PubMed...
    6. Nebel A, Schneider BJ, Baker RK, Kroll DJ. Potential metabolic interaction between St. John's wort and theophylline. Ann Pharmacother 1999;33(4):502. Go to original source... Go to PubMed...
    7. Wang Z, Gorski JC, Hamman MA, Huang SM, Lesko LJ, Hall SD. The effects of St. John's wort (Hypericum perforatum) on human cytochrome P450 activity. Clin Pharmacol Ther 2001;70(4):317-26. Go to original source... Go to PubMed...
    8. Shibayama Y, Ikeda R, Motoya T, Yamada K. St John's wort (Hypericum perforatum) induces overexpression of multidrug resistance protein 2 (MRP2) in rats: a 30-day ingestion study. Food Chem Toxicol 2004;42(6):995-1002. Go to original source... Go to PubMed...
    9. Wenk M, Todesco L, Krahenbuhl S. Effect of St John's wort on the activities of P4501A2, P4503A4, P4502D6, N-acetyltransferase 2, and xanthine oxidase in healthy males and females. Br J Clin Pharmacol 2004;57(4):495-9. Go to original source... Go to PubMed...
    10. Arold G, Donath F, Maurer A, Diefenbach K, Bauer S, Henneickevon Zepelin HH, Friede M, Roots I. No relevant interaction with alprazolam, caffeine, tolbutamide, and digoxin by treatment with a low-hyperforin St John's wort extract. Planta Med 2005;71(4):331- 7. Go to original source... Go to PubMed...
    11. Obach RS. 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 2000;294(1):88-95. Go to PubMed...
    12. Dostalek M, Pistovcakova J, Jurica J, Tomandl J, Linhart I, Sulcova A, Hadasova E. Effect of St John's wort (Hypericum perforatum) on cytochrome P-450 activity in perfused rat liver. Life Sci 2005;78(3):239-44. Go to original source... Go to PubMed...
    13. Jurica J, Konecny J, Zahradnikova LZ, Tomandl J. Simultaneous HPLC determination of tolbutamide, phenacetin and their metabolites as markers of cytochromes 1A2 and 2C6/11 in rat liver perfusate. J Pharm Biomed Anal 2010;52(4):557-64. Go to original source... Go to PubMed...
    14. Butterweck V, Schmidt M. St. John's wort: role of active compounds for its mechanism of action and efficacy. Wien Med Wochenschr 2007;157(1314):356-61. Go to original source... Go to PubMed...
    15. Brantner A, Grein E. Antibacterial activity of plant extracts used externally in traditional medicine. J Ethnopharmacol 1994;44(1):35- 40. Go to original source... Go to PubMed...
    16. Lasker JM, Huang MT, Conney AH. In vitro and in vivo activation of oxidative drug metabolism by flavonoids. J Pharmacol Exp Ther 1984;229(1):162-70. Go to PubMed...
    17. Ito K, Iwatsubo T, Kanamitsu S, Ueda K, Suzuki H, Sugiyama Y. Prediction of pharmacokinetic alterations caused by drug-drug interactions: metabolic interaction in the liver. Pharmacol Rev 1998;50(3):387-412. Go to PubMed...
    18. Barbenel DM, Yusufi B, O'Shea D, Bench CJ. Mania in a patient receiving testosterone replacement postorchidectomy taking St John's wort and sertraline. J Psychopharmacol 2000;14(1):84-6. Go to original source... Go to PubMed...
    19. Breidenbach T, Kliem V, Burg M, Radermacher J, Hoffmann MW, Klempnauer J. Profound drop of cyclosporin A whole blood trough levels caused by St. John's wort (Hypericum perforatum). Transplantation 2000;69(10):2229-30. Go to original source... Go to PubMed...
    20. Bock K W, Forster A, Gschaidmeier H, Bruck M, Munzel P, Schareck W, Fournel-Gigleux S, Burchell B. Paracetamol glucuronidation by recombinant rat and human phenol UDPglucuronosyltransferases. Biochem Pharmacol 1993;45(9):1809-14. Go to original source... Go to PubMed...
    21. Munzel P A, Lehmkoster T, Bruck M, Ritter J K, Bock K W. Aryl hydrocarbon receptor-inducible or constitutive expression of human UDP glucuronosyltransferase UGT1A6. Arch Biochem Biophys 1998;350(1):72-8. Go to original source... Go to PubMed...
    22. Fisher MB, Vandenbranden M, Findlay K, Burchell B, Thummel KE, Hall SD, Wrighton SA. Tissue distribution and interindividual variation in human UDP-glucuronosyltransferase activity: relationship between UGT1A1 promoter genotype and variability in a liver bank. Pharmacogenetics 2000;10(8):727-39. Go to original source... Go to PubMed...
    23. Court MH, Duan SX, von Moltke LL, Greenblatt DJ, Patten CJ, Miners JO, Mackenzie PI. Interindividual variability in acetaminophen glucuronidation by human liver microsomes: identification of relevant acetaminophen UDP-glucuronosyltransferase isoforms. J Pharmacol Exp Ther 2001;299(3):998-1006. Go to PubMed...

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