title: [Identification of metabolites of epiberberine in rat liver microsomes and its inhibiting effects on CYP2D6].
abstract: Epiberberine, one of the most important isoquinoline alkaloid in Coptidis Rhizoma, possesses extensive pharmacological activities. In this paper, the liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to study phase I and phase II metabolites. A Thermo HPLC system (including Surveyor AS, Surveyor LC Pump, Surveyor PDA. USA) was used. The cocktail probe drugs method was imposed to determine the content change of metoprolol, dapsone, phenacetin, chlorzoxazone and tolbutamide simultaneously for evaluating the activity of CYP2D6, CYP3A4, CYP1A2, CYP2E1 and CYP2C9 under different concentrations of epiberberine in rat liver microsomes. The result showed that epiberberine may have phase I and phase II metabolism in the rat liver and two metabolites in phase I and three metabolites in phase II are identified in the temperature incubation system of in vitro liver microsomes. Epiberberine showed significant inhibition on CYP2D6 with IC50 value of 35.22 μmol L(-1), but had no obvious inhibiting effect on the activities of CYP3A4, CYP1A2, CYP2E1 and CYP2C9. The results indicated that epiberberine may be caused drug interactions based on CYP2D6 enzyme. This study aims to provide a reliable experimental basis for its further research and development of epiberberine.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Ye
authors.forename: Gui-Xia
authors.initials: GX
authors.lastname: Sun
authors.forename: Bao-Juan
authors.initials: BJ
authors.lastname: Xue
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhao
authors.forename: Pei-Pei
authors.initials: PP
authors.lastname: Miao
authors.forename: Jin
authors.initials: J
authors.lastname: Su
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D065690:Cytochrome P-450 CYP2D6 Inhibitors / Q000737:chemistry / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry
chemical_list: D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004365:Drugs, Chinese Herbal; D001599:Berberine; C061432:epiberberine; D019389:Cytochrome P-450 CYP2D6