title: Selective inhibition of the cytochrome P450 isoform by hyperoside and its potent inhibition of CYP2D6.
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 μM after 0 and 15 min of preincubation, and a Ki value of 2.01 μM 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 μM. 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.
authors.affiliation: College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, South Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Song
authors.forename: Miri
authors.initials: M
authors.lastname: Hong
authors.forename: Min Young
authors.initials: MY
authors.lastname: Lee
authors.forename: Jun-Goo
authors.initials: JG
authors.lastname: Jee
authors.forename: You Mie
authors.initials: YM
authors.lastname: Lee
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
authors.forename: Tae Cheon
authors.initials: TC
authors.lastname: Jeong
authors.forename: Sangkyu
authors.initials: S
authors.lastname: Lee
mesh_terms: D001667:Binding, Competitive; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D003915:Dextromethorphan / Q000378:metabolism; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D005697:Galactosides / Q000378:metabolism / Q000494:pharmacology; D041743:Herb-Drug Interactions; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D008745:Methylation / Q000187:drug effects; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D031050:Oenanthe / Q000737:chemistry; D011794:Quercetin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D065690:Cytochrome P-450 CYP2D6 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D005697:Galactosides; D007527:Isoenzymes; D011994:Recombinant Proteins; C581364:isorhamnetin-3-O-galactoside; D003915:Dextromethorphan; C021304:hyperoside; D003577:Cytochrome P-450 Enzyme System; D011794:Quercetin; D019389:Cytochrome P-450 CYP2D6
keywords: CYP; CYP2D6; HLMs; Herb–drug interaction; Human liver microsomes; Hyperoside; Inhibitor; cytochrome P450; human liver microsomes