title: Studies on metabolites and metabolic pathways of bulleyaconitine A in rat liver microsomes using LC-MS(n) combined with specific inhibitors.
abstract: 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.
authors.affiliation: National Centre of Mass Spectrometry in Changchun, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022, People's Republic of China.|College of Food Science and Engineering, Jilin Agricultural University, Changchun, 130118, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Bi
authors.affiliation: National Centre of Mass Spectrometry in Changchun, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022, People's Republic of China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: National Centre of Mass Spectrometry in Changchun, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022, People's Republic of China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Zhu
authors.affiliation: National Centre of Mass Spectrometry in Changchun, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022, People's Republic of China.
authors.forename: Fengrui
authors.initials: F
authors.lastname: Song
authors.affiliation: National Centre of Mass Spectrometry in Changchun, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022, People's Republic of China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: National Centre of Mass Spectrometry in Changchun, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, 130022, People's Republic of China.
authors.forename: Shuying
authors.initials: S
authors.lastname: Liu
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D003577:Cytochrome P-450 Enzyme System; D008297:Male; D053858:Metabolic Networks and Pathways; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C052509:bulleyaconitine A; D003577:Cytochrome P-450 Enzyme System; D000157:Aconitine
keywords: Cytochrome P450; LC-MSn; bulleyaconitine A; metabolites; specific inhibitor