The inhibition of carboxylesterases by praeruptorin C, D and E
10.16438/j.0513-4870.2016-1024
- VernacularTitle:白花前胡丙素、丁素、E素对羧酸酯酶的抑制作用
- Author:
Zuo DU
1
;
Da-wei CHEN
1
;
Zhi-wei FU
1
;
Zhong-ze FANG
1
;
Kun YANG
1
Author Information
1. School of Public Health, Tianjin Medical University, Tianjin 300070, China
- Publication Type:SPECIAL REPORTS
- Keywords:
praeruptorin C;
praeruptorin D;
praeruptorin E;
carboxylesterase 1;
carboxylesterase 2;
herbdrug interaction
- From:
Acta Pharmaceutica Sinica
2017;52(1):66-70
- CountryChina
- Language:Chinese
-
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.
