药学学报, 2017, 52(1): 66-70
引用本文:
杜佐, 陈大为, 付志伟, 房中则, 杨昆. 白花前胡丙素、丁素、E素对羧酸酯酶的抑制作用[J]. 药学学报, 2017, 52(1): 66-70.
DU Zuo, CHEN Da-wei, FU Zhi-wei, FANG Zhong-ze, YANG Kun. The inhibition of carboxylesterases by praeruptorin C, D and E[J]. Acta Pharmaceutica Sinica, 2017, 52(1): 66-70.

白花前胡丙素、丁素、E素对羧酸酯酶的抑制作用
杜佐, 陈大为, 付志伟, 房中则, 杨昆
天津医科大学公共卫生学院, 天津 300070
摘要:
白花前胡丙素、丁素、E素是从中药白花前胡中提取的重要成分,具有多种药理学活性。本研究通过体外人肝微粒体孵育体系,检测白花前胡丙素、丁素及E素对人体重要的Ⅰ相代谢酶-羧酸酯酶1和羧酸酯酶2活性的抑制作用,同时进行抑制动力学评价和体外-体内外推。结果显示,100 μmol·L-1白花前胡丁素对羧酸酯酶1有很强的抑制作用,抑制率达到81.7%。白花前胡丁素对羧酸酯酶1抑制作用类型为非竞争性抑制,抑制动力学参数(Ki)为122.2 μmol·L-1,提示白花前胡丁素可能影响在体内对羧酸酯酶1产生影响,从而引发内源性代谢障碍或药物-药物相互作用。
关键词:    白花前胡丙素      白花前胡丁素      白花前胡E素      羧酸酯酶1      羧酸酯酶2      药物-药物相互作用     
The inhibition of carboxylesterases by praeruptorin C, D and E
DU Zuo, CHEN Da-wei, FU Zhi-wei, FANG Zhong-ze, YANG Kun
School of Public Health, Tianjin Medical University, Tianjin 300070, China
Abstract:
Praeruptorin C (PC), D (PD) and E (PE) are important compounds extracted from Peucedanum praeruptorum DUNN and have been reported to exert multiple pharmacological activities. The present study is purposed to determine the inhibition of PC, PD and PE on the activity of important phase I metabolic enzymes-carboxylesterases (CES). In vitro human liver microsomes (HLM) incubation system was used to determine the inhibition potential of PC, PD and PE on the activity of CES1 and CES2. Inhibition behaviour was determined, and in vitro-in vivo extrapolation was performed by using the combination of in vitro inhibition kinetic parameter (Ki) and in vivo exposure level of PD. PD exhibited the strongest inhibition on the activity of CES1, with 81.7% activity inhibited by 100 μmol·L-1 of PD. PD noncompetitively inhibited the activity of CES1 with the Ki to be 122.2 μmol·L-1, indicating inhibition potential of PD towards CES1 in vivo. Therefore, closely monitoring the endogenous metabolic disorders caused by PD and interaction between PD and drugs mainly undergoing CES1-catalyzed metabolism is very necessary.
Key words:    praeruptorin C    praeruptorin D    praeruptorin E    carboxylesterase 1    carboxylesterase 2    herbdrug interaction   
收稿日期: 2016-10-17
DOI: 10.16438/j.0513-4870.2016-1024
基金项目: 天津市千人计划青年项目;天津市应用基础与前沿技术研究计划一般项目(15JCYBJC54700);中国博士后科学基金(2016M590210).
通讯作者: 房中则,Tel:18322513076,Fax:86-22-83336637,E-mail:fangzhongze@tmu.edu.cn;杨昆,E-mail:yangkun@tijmu.edu.cn
Email: fangzhongze@tmu.edu.cn;yangkun@tijmu.edu.cn
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