细胞色素P450
谷胱甘肽
生物化学
微粒体
代谢物
CYP3A4型
新陈代谢
药物代谢
酶
CYP1A2
化学
代谢途径
生物碱
生物
药理学
立体化学
作者
Yaoyao Guo,Huanhuan Lv,Jidong Lv,Zenghong Jiang
出处
期刊:Xenobiotica
[Informa]
日期:2023-07-03
卷期号:53 (6-7): 474-483
标识
DOI:10.1080/00498254.2023.2269417
摘要
The in vitro metabolism of hirsutine was determined using liver microsomes and human recombinant cytochrome P450 enzymes. Under the current conditions, a total of 14 phase I metabolites were tentatively identified.Ketoconazole showed significant inhibitory effect on the metabolism of hirsutine. Human recombinant cytochrome P450 enzyme analysis revealed that metabolism of hirsutine was mainly catalysed by CYP3A4.Our data revealed that hirsutine was metabolised via mono-oxygenation, di-oxygenation, N-oxygenation, dehydrogenation, demethylation and hydrolysis.In glutathione (GSH)-supplemented liver microsomes, four GSH adducts were identified. Hirsutine underwent facile P450-mediated metabolic activation, forming reactive 3-methyleneindolenine and iminoquinone intermediates.This study provided valuable information on the metabolic fates of hirsutine in liver microsomes, which would aid in understanding the hepatotoxicity caused by hirsutine or hirsutine-containing herb preparation.
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