Effects Of Mitragyna Speciosa Extracts On Drug Metabolizing Enzymes
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Date
2011-10
Authors
Azizi, Juzaili
Journal Title
Journal ISSN
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Publisher
Universiti Sains Malaysia
Abstract
M. speciosa (ketum) leaves have been employed traditionally in Malaysia and Thailand to wean opium addiction and as a substitute for opium when opium is unavailable. M. speciosa leaves have been abused by drug addicts since some of the alkaloids (mainly mitragynine) from the plant possess opiate and cocaine like effects. These bring to its prohibition in Malaysia in 2004 since consumption of M. speciosa leaves has been perceived to lead to the abuse of other drugs such as cannabis and heroin. In the current study, the in vitro and in vivo effects of M. speciosa methanolic, aqueous and total alkaloid extracts on drug metabolizing enzymes, namely cytochrome P450 (CYP450), UDP-glucuronosyl transferase (UGT) and glutathione S-transferase (GST) had been evaluated in rat liver cytosolic fraction and microsomes. Aminopyrine, p-nitrophenol (pNP) and 1-chloro-2,4-dinitrobenzene (CDNB) were employed as probe substrates in aminopyrine N-demethylase (APND), UDP-glucuronosyl transferase (UGT) and glutathione S-transferase (GST) enzyme assays respectively. In addition, various luciferin derivatives were employed as probe substrates to assay five main human CYP450 isoforms in baculosomes systems in vitro. Furthermore, mitragynine was also tested in vitro for its likelihood to inhibit APND, human CYP450 isoforms, UGT and GST activity. The total phenolics content, total flavonoids content and DPPH scavenging capacity for the three M. speciosa extracts were also evaluated. This is because various publications have implicated the antioxidant content of medicinal herbs to be responsible for the modulation of drug metabolizing enzymes activites. The assessment of the enzyme activity and antioxidant study were conducted using absorbance and luminescent methods. Out of the three M. speciosa extracts, the methanolic extract is the most effective in inhibiting the APND, UGT and GST activity in vitro followed by aqueous and total alkaloid extracts.
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Keywords
Effects of mitragyna speciosa extracts , drug metabolizing enzymes