Selective Inhibitory Effect of Osthenol on Human Cytochrome 2C8

Osthenol is a furanocoumarin with anti‐tumor, anti‐inflammatory, and anti‐viral activity. It is present in various citrus juices and fruits; however, its inhibitory effects on cytochrome P450 (CYP) enzyme activity, in the context of herb–drug interaction (HDI) prediction, have not been previously st...

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Bibliographic Details
Published in:Bulletin of the Korean Chemical Society 2018, 39(6), , pp.801-805
Main Authors: Cho, Pil Joung, Nam, WoongShik, Lee, Doohyun, Lee, Taeho, Lee, Sangkyu
Format: Article
Language:English
Subjects:
CYP2C8
Furanocoumarin
Human liver microsomes
Osthenol
Paclitaxel
화학
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Summary:Osthenol is a furanocoumarin with anti‐tumor, anti‐inflammatory, and anti‐viral activity. It is present in various citrus juices and fruits; however, its inhibitory effects on cytochrome P450 (CYP) enzyme activity, in the context of herb–drug interaction (HDI) prediction, have not been previously studied. In this study, osthenol was chemically synthesized in order to identify potential HDIs. Its inhibitory effect on eight CYP isoforms and the underlying mechanism of inhibition were investigated by using cocktail assays and liquid chromatography‐tandem mass spectrometry in pooled human liver microsomes. The inhibitory effect of osthenol on CYP2C8‐catalyzed paclitaxel hydroxylation was selective and dose‐dependent, but not time‐dependent. The IC50 value was 2.8 μM. Additionally, osthenol displayed mixed mode inhibition with a relatively low Ki value of 0.96 μM, which is indicative of the potential for HDIs with co‐administered CYP2C8 substrates. To the best of our knowledge, this is the first report of selective inhibition of CYP2C8 by osthenol.
ISSN:1229-5949
0253-2964
1229-5949
DOI:10.1002/bkcs.11479