title: High-throughput screening of inhibitory effects of Bo-yang-hwan-o-tang on human cytochrome P450 isoforms in vitro using UPLC/MS/MS.
abstract: Bo-yang-hwan-o-tang (BHT) is an oriental herbal medicine for treating brain disorders such as cerebral ischemia.  The objective of this study was to develop an economically feasible and time-saving high-throughput screening method to monitor the potential inhibitory effects of BHT on human cytochrome P450 (CYP) enzymes in vitro.  Two cocktail sets were used for incubation of human liver microsomes: Cocktail A: 6 probe substrates for CYP1A2, CYP2A6, CYP2C8, CYP2C19, CYP2D6, CYP3A4; Cocktail B: 3 for CYP2B6, CYP2C9, CYP2E1.  The concentrations of the substrate metabolites were simultaneously analyzed using UPLC/MS/MS.  The BHT extract had almost negligible inhibitory effects on the nine human CYP isoforms tested, with the half-maximal inhibitory concentration value ranged from 3624.99 to 45412.44 μg/ml.  The results suggest that BHT extract has no inhibitory effects on CYP isoforms within the clinically recommended dosage range.  We conclude that BHT might be free of drug-herb interactions when co-administered with other medicines.  However, more in vivo human studies are needed to confirm these results.  The high-throughput screening method can be a useful tool for drug discovery and for understanding drug interactions.
authors.affiliation: Department of Molecular Medicine, Kyungpook National University School of Medicine, Daegu 700-412, South Korea.
authors.forename: Miran
authors.initials: M
authors.lastname: Lee
authors.forename: Jeonghyeon
authors.initials: J
authors.lastname: Park
authors.forename: Mi-sun
authors.initials: MS
authors.lastname: Lim
authors.forename: Sook Jin
authors.initials: SJ
authors.lastname: Seong
authors.forename: Joomi
authors.initials: J
authors.lastname: Lee
authors.forename: Jeong Ju
authors.initials: JJ
authors.lastname: Seo
authors.forename: Yong-Ki
authors.initials: YK
authors.lastname: Park
authors.forename: Hae Won
authors.initials: HW
authors.lastname: Lee
authors.forename: Young-Ran
authors.initials: YR
authors.lastname: Yoon
mesh_terms: D002851:Chromatography, High Pressure Liquid; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000032:analysis / Q000494:pharmacology*; D057166:High-Throughput Screening Assays; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007723:Korea; D055670:Medicine, Korean Traditional; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D013329:Structure-Activity Relationship; D053719:Tandem Mass Spectrometry
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010936:Plant Extracts; D003577:Cytochrome P-450 Enzyme System