摘要
目的 考察常春藤皂苷元对人肝微粒体中的5种细胞色素P450(CYP450)酶的抑制作用。方法 采用Cocktail探针药物法,在肝微粒体中加入常春藤皂苷元与混合探针底物[包含非那西丁(CYP1A2探针底物)、双氯芬酸钠(CYP2C9探针底物)、苯乙妥英(CYP2C19探针底物)、右美沙芬(CYP2D6探针底物)和咪达唑仑(CYP3A4探针底物)]共同孵育60 min。采用超高效液相色谱-质谱联用法(UPLC-MS/MS),以甲苯磺丁酰胺为内标,定量检测底物的代谢物含量,并计算常春藤皂苷元和特异性抑制药对人肝微粒体中CYP1A2、CYP2D6、CYP2C19、CYP2C9和CYP3A4的半数抑制浓度(IC_(50))。结果 常春藤皂苷元对人肝微粒体中CYP1A2、CYP2D6与CYP3A4的IC;值均大于50μmol·L^(-1),对CYP2C9及CYP2C19的IC_(50)值分别为4.94μmol·L^(-1)和18.00μmol·L^(-1)。结论 常春藤皂苷元对肝微粒体中CYP1A2、CYP2D6与CYP3A4无明显抑制作用,对CYP2C9和CYP2C19有一定的抑制作用。
Objective To evaluate the inhibitory effects of hederagenin on five cytochrome P450(CYP) enzymes in human liver microsomes. Methods Through cocktail approach, hederagenin was incubated for 60 min with mixed probe substrates [phenacetin(a probe substrate of CYP1 A2), diclofenac sodium(a probe substrate of CYP2 C9), ethotoin(a probe substrate of CYP2 C19), dextromethorphan(a probe substrate of CYP2 D6), midazolam(a probe substrate of CYP3 A4)] in the liver microsome incubation system, respectively. Ultra-high performance liquid chromatography coupled with mass spectrometry method was used to quantify the metabolites of substrates(toluene sulfonamide as internal standard), and then the half inhibitory concentration(IC_(50)) values of hederagenin and specific inhibitors on CYP1 A2, CYP2 D6, CYP2 C19, CYP2 C9 and CYP3 A4 in human liver microsomes were calculated. Results The IC_(50)values of hederagenin on CYP1 A2, CYP2 D6 and CYP3 A4 in human liver microsomes were all greater than 50 μmol·L^(-1), but on CYP2 C9 and CYP2 C19 were 4.94 and 18.00 μmol·L^(-1), respectively. Conclusion Hederagenin has no obvious inhibitory effects on CYP1 A2, CYP2 D6 and CYP3 A4 in human liver microsomes, but showed a certain inhibitory effect on CYP2C9 and CYP2C19.
作者
黄静
陈瑞
班玉娟
刘婉霞
朱高峰
方翼
汤磊
HUANG Jing;CHEN Rui;BAN Yu-juan;LIU Wan-xia;ZHU Gao-feng;FANG Yi;TANG Lei(Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D,Guizhou Medical University,Guiyang 550004,Guizhou Province,China;School of Pharmacy,Guizhou Medical University,Guiyang 550004,Guizhou Province,China;Department of Pharmacy,Peking University People’s Hospital,Beijing 100044,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2022年第9期993-997,共5页
The Chinese Journal of Clinical Pharmacology
基金
国家自然科学基金资助项目(82060323)。
关键词
常春藤皂苷元
人肝微粒体
细胞色素P450酶
超高效液相色谱-质谱联用法
酶抑制
hederagenin
human liver microsomes
cytochrome P450 enzyme
ultra-high performance liquid chromatography coupled with mass spectrometry
enzyme inhibition
