Evaluation of the Effects of Mitragyna speciosa Alkaloid Extract on Cytochrome P450 Enzymes Using a High Throughput Assay.docVIP

Molecules 2011, 16, 7344-7356; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Evaluation of the Effects of Mitragyna speciosa Alkaloid Extract on Cytochrome P450 Enzymes Using a High Throughput Assay Wai Mun Kong 1,2,*, Zamri Chik 1, Murali Ramachandra 3, Umarani Subramaniam 2, Raja Elina Raja Aziddin 4 and Zahurin Mohamed 1 1 Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia; E-Mails: zamrichik@.my (Z.C.); zahurin@.my (Z.M.) 2 Aurigene Discovery Technologies (M) Sdn. Bhd, Malaysia, 57000 Bukit Jalil, Kuala Lumpur, Malaysia; E-Mail: umarani_s@ 3 Aurigene Discovery Technologies Limited, Bangalore 560100, Karnataka, India; E-Mail: murali_r@ 4 Department of Pathology, Hospital Kuala Lumpur, 50586 Kuala Lumpur, Malaysia; E-Mail: rajaelina@ * Author to whom correspondence should be addressed; E-Mail: kongwm1214@; Tel.: +60 38996 4577; Fax: +60 38996 4581. Received: 4 July 2011; in revised form: 8 August 2011 / Accepted: 19 August 2011 / Published: 29 August 2011 Abstract: The extract from Mitragyna speciosa has been widely used as an opium substitute, mainly due to its morphine-like pharmacological effects. This study investigated the effects of M. speciosa alkaloid extract (MSE) on human recombinant cytochrome P450 (CYP) enzyme activities using a modified Crespi method. As compared with the liquid chromatography-mass spectrometry method, this method has shown to be a fast and cost- effective way to perform CYP inhibition studies. The results indicated that MSE has the most potent inhibitory effect on CYP3A4 and CYP2D6, with apparent half-maximal inhibitory concentration (IC50) values of 0.78 μg/mL and 0.636 μg/mL, respectively. In addition, moderate inhibition was observed for CYP1A2, with an IC50 of 39 μg/mL, and weak inhibition was detected for CYP2C19. The IC50 of CYP2C19 could not be dete