中药与临床2025，Vol.16Issue(4)：37-43,7.
氢溴酸樟柳碱及氢溴酸山莨菪碱对体外人肝微粒体CYP450酶活性的影响
The effects of anisodine hydrobromide and anisodamine hydrobromide on the activity of CYP450 enzymes in human liver microsomes in vitro
摘要
Abstract
Objective:To investigate the effects of anisodine hydrobromide and anisodamine hydrobromide on the activity of cytochrome P450(CYP450)enzymes in human liver microsomes.Methods:An analytical method was established based on high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)to simultaneously determine the content of me-tabolites of various subtypes of CYP450 enzyme probes in human liver microsomes.An in vitro incubation system for human liver microsomes was established to preliminarily investigate the effects of anisodine hydrobromide and anisodamine hydrobromide on the activities of several major subtypes of CYP450 enzymes in vitro,which provided reference for clinical medication.Results:The established analytical method had a good linear relationship with accuracy and precision within±10%.The concentration of human liver microsomal protein in the incubation system was 0.5 mg·mL-1,and the incubation time was 90 minutes.The Km values of the probe substrates including phenacetin,bupropion,testosterone,terfenadine,amodiaquine,diclofenac,and dextro-methorphan were 57 570,516.30,4 187,8.78,240.50,650.40 and 277.10 μm·L-1,respectively.The in vitro experimental results showed that both anisodine hydrobromide and anisodamine hydrobromide had significant induction effects on CYP3A4,but had no significant effect on other metabolic enzyme subtypes.Conclusion:The study successfully established the HPLC-MS/MS analysis method,which can be used for the rapid evaluation of the effect of drugs on CYP450 isoform enzyme activity in vitro,and prelim-inarily verified that both anisodine hydrobromide and anisodamine hydrobromide had a significant inducing effect on CYP3A4 in vitro,which can provide certain experimental bases for the in vitro validation study and clinical application.关键词
氢溴酸樟柳碱/氢溴酸山莨菪碱/高效液相色谱-质谱联用法/细胞色素P450酶/人肝微粒体Key words
Anisodine hydrobromide/anisodamine hydrobromide/HPLC-MS/MS/cytochrome P450 enzyme/human liver microsomes分类
医药卫生引用本文复制引用
张建兰,万峰,刘艳芳,吴瑞,余宇洁,张传涛,谢晓芳,何瑶,魏伯平,李芸霞..氢溴酸樟柳碱及氢溴酸山莨菪碱对体外人肝微粒体CYP450酶活性的影响[J].中药与临床,2025,16(4):37-43,7.基金项目
成都市卫生健康委员会与高等院校创新基金(WXLH202402028) （WXLH202402028）
四川省中医药管理局科学技术研究专项(2024ZD02) （2024ZD02）
