title: Inhibitory effects of polyphenols on human cytochrome P450 3A4 and 2C9 activity.
abstract: Polyphenols present in foods and supplements may contribute to human health by preventing cardiovascular diseases and cancer. Drug-food or drug-herb interactions have recently come into focus but, except for some phytochemicals, few components of food or herbs participate in such interactions. In this study, we systematically evaluated the inhibitory effects of 60 polyphenols and related compounds on human cytochrome P450 (CYP) 3A4 and CYP2C9 activity by in vitro assay to investigate whether some polyphenols induce drug interactions. In addition, the kinetics of potent CYP inhibitors was investigated by Lineweaver-Burk plot analysis. Three coumarins and 12 flavonoids significantly suppressed CYP3A4 or CYP2C9 activities. Lineweaver-Burk plot analysis indicated that apigenin and its dimer amentoflavone and imperatorin displayed a mixed type of inhibition on CYP3A4 or CYP2C9. Among the inhibitors, amentoflavone was the most potent inhibitor of CYP3A4 and CYP2C9 activities with IC(50) values of 0.07 and 0.03 microM, respectively. The K(i) value of amentoflavone was significantly lower than that of the CYP2C9 inhibition positive control sulfaphenazole. These findings suggest that some dietary polyphenols may have the potential to inhibit the metabolism of clinical drugs.
authors.affiliation: Division of Pharmaceutical Sciences, Okayama University, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kimura
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ito
authors.forename: Ryoko
authors.initials: R
authors.lastname: Ohnishi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hatano
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D044946:Biflavonoids / Q000737:chemistry / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D065729:Cytochrome P-450 CYP2C9; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D044946:Biflavonoids; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D005419:Flavonoids; D004364:Pharmaceutical Preparations; D010636:Phenols; D059808:Polyphenols; C011164:amentoflavone; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human