Inhibitory Effects of Water Extract of Mitragyna Speciosa (Korth.) Havil. on Human Cytochrome P450 Enzymes

Author

Norizah A., Mohd isa W, Noral ‘Ashikin Y and Zakiah, I
Herba Medicine Research Centre,  Institute for Medical Research, Kuala Lumpur
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Language

English

Title

Inhibitory Effects of Water Extract of Mitragyna Speciosa (Korth.) Havil. on Human Cytochrome P450 Enzymes

Proceeding

Medicinal and Aromatic Plants Seminar (MAPS 2010)

Date

3rd August - 4th August (2010)

Place Held

Forest Research Institute Malaysia(FRIM)

Abstract

Cytochromes P450 (CYPs), a group of more than 50 different proteins, are the principal enzymes for the oxidative metabolism of drugs and other xenobiotics. Among the xenobiotic metabolizing cytochromes P450, five forms, i.e., CYPIA2, CYP2C19, CYP2C9, CYP2D6 and CYP3A4, appear to be the most commonly responsible for drug metabolism. Inhibition of one of them often results in unexpected and sometimes severe adverse drug interactions, as the metabolic clearance of co- administered drugs can be altered dramatically. Mitragyna speciosa (Korth.) Havil. (family Rubiaceae) is an indigenous tree found in Southeast Asia particularly in Thailand and Malaysia. This plant is known as ‘ketum’ in Malaysia and one of the most popular plant extract being highlighted in the mass media for opium substitute. The leaf of M. speciosa has been used traditionally for alleviating pain from wounds, reduce coughing, stopping diarrhoea and its coca-like stimulant ability to combat fatigue and enhance tolerance to hard work under a hot sun. With an increasing consumption of this plant, and sometimes administered in combination with conventional therapeutic drugs, it is likely that constituents in its preparations may be substrates, inhibitors or inducers of CYPs and have impact on the pharmacokinetics of any co-administered drugs metabolized by the system. The aim of this study is to assess the drug inhibition potentials of ketum extract in vitro and to assess the cytochromes P450 enzymes responsible for the metabolism as well as to generate initial data for justifying further studies. The inhibitory effect of ketum extract on four selected human cytochromes P450 enzymes (CYP 3A4, CYP 1A2, CYP 2D6 and CYP 2C9) were investigated. Increasing concentration of extract was incubated with individual, recombinant CYP isoforms and their effect on the conversion of substrate was measured flourometrically. Percentage inhibition was calculated relative to the substrate without inhibitor, Ketum extract demonstrated minor inhibition toward CYP 2D6, CYP 3A4 and CYP 1A2 with 40% inhibition for CYP 2D6 and CYP 3A4 while only 20% inhibition for CYP 1A2 at concentration of 0.5 µg/mI. No activity was detected against CYP 2C9. In conclusion, although there was only small activity, this preliminary data suggested that ketum extract could have the potential to inhibit the metabolism of certain co-administered drugs and further investigation would be required to clarify its clinical relevance.

Keywords

Cytochrome P450; ketum: Mitragyna speciosa; in vitro

Session

Poster Abstracts: P30

Topic

Harnessing the Tropical heritage: Recent Advances in R&D and commercialization