文章基本信息

标题：Mechanism-Based Inhibition of CYP3A4 by Constituents of Zingiber aromaticum
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作者：Tepy Usia ; Tadashi Watabe ; Shigetoshi Kadota 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2005
卷号：28
期号：3
页码：495-499
DOI：10.1248/bpb.28.495
出版社：The Pharmaceutical Society of Japan
摘要：Sixteen compounds isolated from Zingiber aromaticum and showing concentration-dependent inhibition with IC₅₀ values less than 100 μ M , were analyzed for their possibility of time-, concentration-, and NADPH-dependent inhibition of CYP3A4 and four were analyzed for CYP2D6. All seven kaempferol glycosides and two kaempferol derivatives (4, 5, 8—14) appear to be the mechanism-based inhibitors of CYP3A4 enzyme in which the inhibition is irreversible and driven by the catalytic process. The other compounds showed no NADPH-dependent inhibition or reversible inhibition, and thus do not appear to be mechanism-based inhibitors. K _I values for compounds 4, 5, 8—14 were in the range of 2.21—27.01 μ M , whereas the k _inact values were 0.23—0.65 min⁻¹. Kaempferol-3- O -(2,3,4-tri- O -acetyl-α- L -rhamnopyranoside) (5) was found to be the most potent CYP3A4 inactivator with K _I and k _inact values of 2.21 μ M and 0.45 min⁻¹, respectively.
关键词：Indonesian medicinal plant;mechanism-based inhibition;CYP3A4;CYP2D6;Zingiber aromaticum