Subject Area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
Conference Name18th International Symposium on Microsomes and Drug Oxidations
Conference Date2010-5-16
Conference Place中国
Funding OrganizationInstitute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College
AbstractBackground. 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.
Document Type会议论文
Corresponding AuthorLing Yang
Recommended Citation
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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