北京大学学报（医学版）2012，Vol.44Issue(3)：431-436,6.DOI:10.3969/j.issn.1671-167X.2012.03.021
细胞色素P450介导的补骨脂酚代谢减毒
Metabolic detoxification of bakuchiol is mediated by cytochrome P450 enzymes in human liver microsomes
摘要
Abstract
Objective:To analyze cytochrome P450 (CYP) phenotyping for bakuchiol metabolism and study the mechanism of detoxification of bakuchiol by human liver microsomes ( HLM) in vitro. Methods; The CYP phenolyping for bakuchiol metabolism was determined using HLM combined with CYP specific inhibitors and recombinant human CYP isoforms. The relative activities of CYP isoforms were determined by analyzing the formation of the substrate metabolites using HPLC-MS/MS, in presence or absence of 1 -aminobenzotriazole (ABT) which was CYP enzymes' broad spectrum inhibitor. The residual concentrations of bakuchiol in microsomal incubates were determined using HPLC to investigate ABT' s effect on the metabolism of bakuchiol. The effects of CYP enzymes on the nephrotoxicity of bakuchiol were investigated using human kidney-2( HK-2) by MTT assay, in presence or absence of ABT. Results: CYP1A2, CYP2C9, CYP2C19 and CYP3A4 in HLM were involved in bakuchiol metabolism, among which CYP2C19 showed the highest metabolic rate. Co-incubation with ABT (2.5 mmol/L) could inhibit more than 90% of the enzyme activities for CYP1A2, CYP2C9, CYP2C19 and CYP3A4. ABT (2.5 mmol/L) could inhibit the HLM metabolism of bakuchiol with inhibition ratio 83. 24%±2. 13%. When preincubated with ABT, the metabolic detoxification of bakuchiol by HLM was significantly reduced ( P < 0. 05). Conclusion; The mechanism of metabolic detoxification of bakuchiol by HLM is associated with bakuchiol metabolism by CYP enzymes to form non toxic or lower toxic metabolites. The broad spectrum inhibitor of CYP could inverse the detoxification of HLM.关键词
补骨脂酚/细胞色素P450酶系统/微粒体,肝Key words
Bakuchiol/Cytochrome P-450 enzyme system/Microsomes, liver分类
医药卫生引用本文复制引用
李艾芳,沈国林,焦士勇,李桦,王旗..细胞色素P450介导的补骨脂酚代谢减毒[J].北京大学学报（医学版）,2012,44(3):431-436,6.基金项目
北京大学985项目基金(BMU20100119)资助 （BMU20100119）
