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Molecules 2011, 16(9), 7344-7356; doi:10.3390/molecules16097344

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

1,2,* , 1
1 Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia 2 Aurigene Discovery Technologies (M) Sdn. Bhd, Malaysia, 57000 Bukit Jalil, Kuala Lumpur, Malaysia 3 Aurigene Discovery Technologies Limited, Bangalore 560100, Karnataka, India 4 Department of Pathology, Hospital Kuala Lumpur, 50586 Kuala Lumpur, Malaysia
* Author to whom correspondence should be addressed.
Received: 4 July 2011 / Revised: 8 August 2011 / Accepted: 19 August 2011 / Published: 29 August 2011
(This article belongs to the Special Issue Alkaloids: Novel Therapeutic Perspectives)
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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 determined, however, because inhibition was < 50%. Competitive inhibition was found for the MSE-treated CYP2D6 inhibition assay, whereas non-competitive inhibition was shown in inhibition assays using CYP3A4, CYP1A2 and CYP2C19. Quinidine (CYP2D6), ketoconazole (CYP3A4), tranylcypromine (CYP2C19) and furafylline (CYP1A2) were used as positive controls throughout the experiments. This study shows that MSE may contribute to an herb-drug interaction if administered concomitantly with drugs that are substrates for CYP3A4, CYP2D6 and CYP1A2.
Keywords: herb-drug interactions; cytochrome P450 (CYP); Mitragyna speciosa; in vitro; alkaloids herb-drug interactions; cytochrome P450 (CYP); Mitragyna speciosa; in vitro; alkaloids
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Kong, W.M.; Chik, Z.; Ramachandra, M.; Subramaniam, U.; Aziddin, R.E.R.; Mohamed, Z. Evaluation of the Effects of Mitragyna speciosa Alkaloid Extract on Cytochrome P450 Enzymes Using a High Throughput Assay. Molecules 2011, 16, 7344-7356.

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