title: Metabolism of the hepatotoxic compound sophoraflavanone G in rat liver microsomes.
abstract: Our study aimed at investigating the metabolic characteristics of sophoraflavanone G (SFG), one of the hepatotoxic constituents of Sophora flavescens, in rat liver microsomes (RLMs). SFG was metabolized to 3 phase I metabolites, di-hydroxylated SFG (M1), mono-hydroxylated SFG (M2), dehydrogenated product of mono-hydroxylated SFG (M3) and 3 SFG glucuronides (M4, M5, and M6) by RLMs. The formation kinetics of M2 conformed to biphasic kinetics in RLMs. The formation kinetics of M4 and M5 best-fitted the Hill equation kinetics. Chemical inhibition studies found that CYP1A2 and CYP2E1 were the major enzymes responsible for the formation of M2, and the formation of M4 and M5 may be catalyzed by multiple UGT1A isoforms.
authors.affiliation: School of Pharmacy, Fudan Univ, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Xiuwen
authors.initials: X
authors.lastname: Zhang
authors.forename: Taomin
authors.initials: T
authors.lastname: Huang
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Yu
authors.forename: Nengneng
authors.initials: N
authors.lastname: Cheng
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D044950:Flavanones / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D015971:Gene Expression Regulation, Enzymologic; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D018517:Plant Roots / Q000737:chemistry; D051381:Rats; D029909:Sophora / Q000737:chemistry
chemical_list: D044950:Flavanones; D003577:Cytochrome P-450 Enzyme System; C064849:vexibinol
keywords: RLMs; hepatotoxicity; metabolism; sophoraflavanone G