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Studies on metabolites and metabolic pathways of bulleyaconitine A in rat liver microsomes using LC‐MS n combined with specific inhibitors
Author(s) -
Bi Yunfeng,
Zhuang Xiaoyu,
Zhu Hongbin,
Song Fengrui,
Liu Zhiqiang,
Liu Shuying
Publication year - 2015
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.3388
Subject(s) - microsome , chemistry , metabolic pathway , cyp1a2 , hydroxylation , metabolism , cytochrome p450 , biochemistry , cyp3a , metabolite , demethylation , gene isoform , high performance liquid chromatography , cyp3a4 , drug metabolism , enzyme , pharmacology , chromatography , biology , gene , gene expression , dna methylation
Bulleyaconitine A (BLA) from Aconitum bulleyanum plants is usually used as anti‐inflammatory drug in some Asian countries. It has a variety of bioactivities, and at the same time some toxicities. Since the bioactivities and toxicities of BLA are closely related to its metabolism, the metabolites and the metabolic pathways of BLA in rat liver microsomes were investigated by HPLC–MS n . In this research, the 12 metabolites of BLA were identified according to the results of HPLC‐MS n data and the relevant literature. The results showed that there are multiple metabolites of BLA in rat liver microsomes, including demethylation, deacetylation, dehydrogenation deacetylation and hydroxylation. The major metabolic pathways of BLA in rat liver microsomes were clarified by HPLC‐MS combined with specific inhibitors of CYP450 isoforms. As a result, CYP3A and 2C were found to be the principal CYP isoforms contributing to the metabolism of BLA. Moreover, CYP2D6 and 2E1 are also more important CYP isoforms for the metabolism of BLA. While CYP1A2 only affected the formation rate of M11, its effect on the metabolism of BLA is very small. Copyright © 2014 John Wiley & Sons, Ltd.