Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay

• Published in: Molecules (Basel, Switzerland) Switzerland), 2011-08, Vol.16 (9), p.7344-7356
• Main Authors: Kong, Wai Mun, Chik, Zamri, Ramachandra, Murali, Subramaniam, Umarani, Aziddin, Raja Elina Raja, Mohamed, Zahurin
• Format: Article
• Language: English
• Subjects: alkaloids; Alkaloids - chemistry; Aryl Hydrocarbon Hydroxylases - antagonists & inhibitors; Aryl Hydrocarbon Hydroxylases - chemistry; Chromatography; Cytochrome; cytochrome P450 (CYP); Drug interactions; Drug withdrawal; Enzyme Assays; Enzymes; herb-drug interactions; High-Throughput Screening Assays; Humans; in vitro; Kinetics; Mass spectrometry; Measurement techniques; Metabolism; Metabolites; Mitragyna - chemistry; Mitragyna speciosa; Morphine; Narcotics; Plant Extracts - chemistry; Plant Leaves - chemistry; Recombinant Proteins - antagonists & inhibitors; Recombinant Proteins - chemistry; Scientific imaging; Toxicity
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules16097344

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 (IC(50)) values of 0.78 µg/mL and 0.636 µg/mL, respectively. In addition, moderate inhibition was observed for CYP1A2, with an IC(50) of 39 µg/mL, and weak inhibition was detected for CYP2C19. The IC(50) of CYP2C19 could not be determined, however, because inhibition was