The interaction potential of herbal medicinal products: a luminescence-based screening platform assessing effects on cytochrome P450 and its use with devil's claw (Harpagophyti radix) preparations

作者: Maryam Modarai , Andy Suter , Andreas Kortenkamp , Michael Heinrich

DOI: 10.1111/J.2042-7158.2010.01235.X

关键词:

摘要: Objectives  Potential interactions between herbal medicinal products and the cytochrome (CYP) P450 system are an important safety concern. We set out to develop a screening panel for assessing such use it evaluate interaction potential of devil's claw. Methods  The consisted luminescence-based inhibition assays CYP1A2, 2C9, 2C19, 2D6 3A4, reporter gene (luciferase) assay pregnane X receptor (PXR) activation CYP3A4 induction. Caftaric acid chlorogenic acid, two compounds with strong fluorescence quenching properties, were used demonstrate assay's resistance interference. tested 10 commercial claw preparations as well harpagoside harpagide, constituents claw. Key findings  Five found weakly inhibit (IC50 124.2–327.6 µg/ml) five activate PXR (EC50 10.21–169.3 µg/ml). Harpagoside harpagide did not CYP3A4. In agreement published data, bergamottin, natural product known interact CYP3A4, was shown IC50 13.63 µm EC50 6.7 µm. Conclusions  Devil's unlikely have clinically relevant effect on CYP function. proved effective in preparations, demonstrating its suitability plant extracts. It showed superior sensitivity

参考文章(28)
Victoria A. Eagling, John F. Tjia, David J. Back, Differential selectivity of cytochrome P450 inhibitors against probe substrates in human and rat liver microsomes British Journal of Clinical Pharmacology. ,vol. 45, pp. 107- 114 ,(1998) , 10.1046/J.1365-2125.1998.00679.X
B.L. Fiebich, B.L. Fiebich, M. Heinrich, K.O. Hiller, N. Kammerer, Inhibition of TNF-alpha synthesis in LPS-stimulated primary human monocytes by Harpagophytum extract SteiHap 69. Phytomedicine. ,vol. 8, pp. 28- 30 ,(2001) , 10.1078/0944-7113-00002
Basavaraj Girennavar, Shibu M. Poulose, Guddadarangavvanahally K. Jayaprakasha, Narayan G. Bhat, Bhimanagouda S. Patil, Furocoumarins from grapefruit juice and their effect on human CYP 3A4 and CYP 1B1 isoenzymes Bioorganic & Medicinal Chemistry. ,vol. 14, pp. 2606- 2612 ,(2006) , 10.1016/J.BMC.2005.11.039
Maryam Modarai, Elisabete Silva, Andy Suter, Michael Heinrich, Andreas Kortenkamp, Safety of Herbal Medicinal Products: Echinacea and Selected Alkylamides Do Not Induce CYP3A4 mRNA Expression Evidence-based Complementary and Alternative Medicine. ,vol. 2011, pp. 213021- 213021 ,(2011) , 10.1093/ECAM/NEP174
Kan He, Krishna R. Iyer, Roger N. Hayes, Michael W. Sinz, Thomas F. Woolf, Paul F. Hollenberg, Inactivation of Cytochrome P450 3A4 by Bergamottin, a Component of Grapefruit Juice Chemical Research in Toxicology. ,vol. 11, pp. 252- 259 ,(1998) , 10.1021/TX970192K
Maryam Modarai, Min Yang, Andy Suter, Andreas Kortenkamp, Michael Heinrich, Metabolomic Profiling of Liquid Echinacea Medicinal Products with In Vitro Inhibitory Effects on Cytochrome P450 3A4 (CYP3A4) Planta Medica. ,vol. 76, pp. 378- 385 ,(2010) , 10.1055/S-0029-1186152
Charles L. Crespi, Vaughn P. Miller, Bruce W. Penman, Microtiter plate assays for inhibition of human, drug-metabolizing cytochromes P450 Analytical Biochemistry. ,vol. 248, pp. 188- 190 ,(1997) , 10.1006/ABIO.1997.2145
S. Chrubasik, Addendum to the ESCOP monograph on Harpagophytum procumbens. Phytomedicine. ,vol. 11, pp. 691- 695 ,(2004) , 10.1016/J.PHYMED.2004.03.003