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学科主题物理化学
Characterization Of In Vitro Metabolism of Brucine Using Human Liver Microsomes
Mao YX(毛玉玺); Fang ZZ(房中则); Ge GB(葛广波); Yang L(杨凌); Ling Yang
会议名称18th International Symposium on Microsomes and Drug Oxidations
会议日期2010-5-16
2010-05-16
会议地点中国
页码278/1
部门归属十八室
主办者Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College
英文摘要Background. Brucine, one of the bitter alkaloids isolated from Chinese folk medicine Strychnos nux-vomica L. (Loganiaceae), is known as an effective analgesic and anti- inflammatory agent for relieving arthritic and traumatic pain. However, therapeutic application of brucine is limited by its high incidence of side-effects, such as violent convulsion and even lethal poisoning. Thus, it is imperative to investigate the brucine’s metabolic profile in human which is helpful for understanding the pharmacology and toxicology of brucine. Method. In the present study, characterization of the metabolites and cytochrome P450 isoforms involved in the metabolism of brucine were investigated in vitro incubation systems by using human liver microsomes(HLMs) and recombinant human CYP isoforms (rhCYPs). Results. Two major metabolites (M-1 and M-2) and one minor metabolite (M-3) were detected when brucine was incubated with HLM in the presence of NADPH. M1 and M2 were tentatively identified as mono-oxygenated metabolites and the minor metabolite (M-3) was assigned as demethylated metabolite by using liquid chromatography /mass spectrometry (LC/MS). CYP3A4 was identified as the major CYP isoforms involved in the formation of the two major metabolites(M-1 and M-2) by a series of studies including inhibition with specific P450 inhibitors, metabolism by rhCYP isoforms, and correlation analysis. In human liver microsomes, the Km values were 111.3±3.4 and 94.5±3.9 μM, and the Vmax values were 62.9±0.7 and 117.0±1.6 pmol/min/mg for M-1 and M-2, respectively. Conclusion. This study clarified the metabolite profile and kinetic properties of brucine in human and provided important information relevant to the pharmacology and toxicology of brucine and brucine-containing Chinese Traditional Medicines.
语种中文
文献类型会议论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/114056
专题中国科学院大连化学物理研究所
通讯作者Ling Yang
推荐引用方式
GB/T 7714
Mao YX,Fang ZZ,Ge GB,et al. Characterization Of In Vitro Metabolism of Brucine Using Human Liver Microsomes[C],2010:278/1.
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