Selective inhibition of the cytochrome P450 isoform by hyperoside and its potent inhibition of CYP2D6

Title
Selective inhibition of the cytochrome P450 isoform by hyperoside and its potent inhibition of CYP2D6
Author(s)
정태천송민[송민]홍미리[홍미리]지준구[지준구]이유미[이유미]배종섭[배종섭]이상규[이상규]이민영[이민영]
Keywords
METABOLISM; ENZYMES
Issue Date
201309
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Citation
FOOD AND CHEMICAL TOXICOLOGY, v.59, pp.549 - 553
Abstract
Hyperoside, quercetin-3-O-galactoside, is a flavonoid isolated from Oenanthe javanica. In the present study, we investigated potential herb-drug inhibitory effects of hyperoside on nine cytochrome P450 (CYP) isoforms in pooled human liver microsomes (HLMs) and human recombinant cDNA expressed CYP using a cocktail probe assay. Hyperoside strongly inhibited CYP2D6-catalyzed dextromethorphan O-demethylation, with IC50 values of 1.2 and 0.81 mu M after 0 and 15 min of preincubation, and a Ki value of 2.01 mu M in HLMs, respectively. Hyperoside strongly decreased CYP2D6 activity dose-, but not time-, dependently in HLMs. In addition, the Lineweaver-Burk and Secondary plots for the inhibition of CYP2D6 in HLMs fitted a competitive inhibition mode. Furthermore, hyperoside decreased CYP2D6-catalyzed dextromethorphan O-demethylation activity of human recombinant cDNA-expressed CYP2D6, with an IC50 value of 3.87 mu M. However, other CYPs were not inhibited significantly by hyperoside. In conclusion, our data demonstrate that hyperoside is a potent selective CYP2D6 inhibitor in HLMs, and suggest that hyperoside might cause herb-drug interactions when co-administrated with CYP2D substrates. (C) 2013 Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/28974http://dx.doi.org/10.1016/j.fct.2013.06.055
ISSN
0278-6915
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약학대학 > 약학부 > Articles
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