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Metabolism of the Hepatotoxic Compound Sophoraflavanone G in Rat Liver Microsomes
Author(s) -
Chen Ping,
Zhang Xiuwen,
Huang Taomin,
Yu Qianqian,
Cheng Nengneng
Publication year - 2014
Publication title -
journal of food science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.772
H-Index - 150
eISSN - 1750-3841
pISSN - 0022-1147
DOI - 10.1111/1750-3841.12501
Subject(s) - chemistry , kinetics , cyp1a2 , microsome , metabolism , cyp2e1 , product inhibition , biochemistry , metabolic pathway , cytochrome p450 , enzyme , non competitive inhibition , physics , quantum mechanics
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.