Abstract：
OBJECTIVE:To investigate the propensity of plumbagin to inhibit the three isoforms of human cytochrome P450 (CYP), i.e., CYP1A2, CYP2C19, and CYP3A4 using human liver microsomes in vitro. METHODS:Inhibitory effects of plumbagin on the three human CYP isoforms were investigated using pooled human liver microsomes. Phenacetin O-deethylation, omeprazole hydroxylation and nifedipine oxidation were used as selective substrates for CYP1A2, CYP2C19 and CYP3A4 activities, respectively. Concentrations of paracetamol, 5-hydroxyomeprazole, and oxidized nifedipine were determined in microsomal incubation mixture using high-performance liquid chromatography. RESULTS:Plumbagin showed significant inhibitory effects on all CYP isoforms, but with the most potent activity on CYP2C19-mediated omeprazole hydroxylation. The IC50 (concentration that inhibits enzyme activity by 50%) values of plumbagin and nootkatone (selective inhibitor) for CYP2C19 were (0.78 ± 0.01) and (27.31 ± 0.66) μM, respectively. The inhibitory activities on CYP1A2-mediated phenacetin O-deethylation and CYP3A4-mediated nifedipine oxidation were moderate. The IC50 values of plumbagin and α-naphthoflavone (selective inhibitor) for CYP1A2 were (1.39 ± 0.01) and (0.02 ± 0.36) μM, respectively. The corresponding IC50 values of plumbagin and ketoconazole (selective inhibitor) for CYP3A4 were (2.37 ± 0.10) and (0.18 ± 0.06) μM, respectively. CONCLUSIONS:Clinical relevance of the interference of human drug metabolizing enzymes should be aware of for further development scheme of plumbagin as antimalarial drug when used in combination with other antimalarial drugs which are metabolized by these CYP isoforms.
journal_name
Asian Pac J Trop Medjournal_title
Asian Pacific journal of tropical medicineauthors
Sumsakul W,Chaijaroenkul W,Na-Bangchang Kdoi
10.1016/j.apjtm.2015.10.016subject
Has Abstractpub_date
2015-11-01 00:00:00pages
914-918issue
11eissn
1995-7645issn
2352-4146pii
S1995-7645(15)00173-Xjournal_volume
8pub_type
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journal_title：Asian Pacific journal of tropical medicine
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更新日期：2012-12-01 00:00:00
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更新日期：2011-06-01 00:00:00
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更新日期：2014-06-01 00:00:00
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更新日期：2011-11-01 00:00:00
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更新日期：2015-10-01 00:00:00
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更新日期：2016-02-01 00:00:00
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