Inhibitory effects of water extract of Mitragyna speciosa Korth. Havil. on human cytochrome P450 enzymes.

Norizah A., . and Mohd Isa W., . and Noral ;Ashikin Y., . and Zakiah I., . (2010) Inhibitory effects of water extract of Mitragyna speciosa Korth. Havil. on human cytochrome P450 enzymes. [Proceedings Paper]

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 Le. CYP1A2 CYP2C19 CYP2C9 CYP206 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 206 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 206 CYP 3A4 and CYP 1A2 with 40 inhibition for CYP 206 and CYP 3A4 while only 20 inhibition for CYP 1A2 at concentration of 0.5 ug/ml. 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.

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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 Le. CYP1A2 CYP2C19 CYP2C9 CYP206 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 206 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 206 CYP 3A4 and CYP 1A2 with 40 inhibition for CYP 206 and CYP 3A4 while only 20 inhibition for CYP 1A2 at concentration of 0.5 ug/ml. 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.

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Item Type:	Proceedings Paper
Additional Information:	2 tables; 8 refs. SB 293 S471 2010
AGROVOC Term:	Water
AGROVOC Term:	Proteins
AGROVOC Term:	Extracts
AGROVOC Term:	Cytochromes
AGROVOC Term:	Xenobiotics
AGROVOC Term:	Cytochrome P-450
AGROVOC Term:	In vitro
AGROVOC Term:	INHIBITORY
Geographical Term:	MALAYSIA
Depositing User:	Ms. Suzila Mohamad Kasim
Last Modified:	24 Apr 2025 05:14
URI:	http://webagris.upm.edu.my/id/eprint/11537

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