In vitro inhibitory effects of Jiawei Foshou San capsule on activity of cytochrome P450 enzymes in rat and human liver microsomes
10.16438/j.0513-4870.2015-0740
- VernacularTitle:加味佛手散胶囊对大鼠和人肝微粒体CYP450酶活性的抑制作用
- Author:
Fang-hong SHANG
1
;
Shan FENG
1
;
Qian CHEN
1
;
Xian-jin CHEN
1
;
Ji-fen ZHANG
1
;
Xiao-yu XU
1
Author Information
1. College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing 400715, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
Jiawei Foshou San capsule;
endometriosis;
cytochrome P450;
liver microsomes;
ferulic acid;
ligustrazine;
tetrahydropalmatine
- From:
Acta Pharmaceutica Sinica
2016;51(6):926-
- CountryChina
- Language:Chinese
-
Abstract:
This study was designed to investigate the inhibitory effects of Jiawei Foshou San (JWFSS) capsule in vitro on five major human liver microsomes CYP1A2, CYP2C9, CYP2D6, CYP2E1, CYP3A4, as well as on rat liver microsomes CYP1A2, CYP2C9, CYP2D2, CYP2E1, CYP3A1/2. The test groups included a negative control group, an inhibitor positive control group, an ferulic acid (FA) group, a ligustrazine (LZ) group, a tetrahydropalmatine (THP) group, and an JWFSS capsule group. After incubating the liver microsomes with a cocktail of probe drugs, the metabolites were quantitated with LC-MS/MS, and IC 50 values were calculated to assess the inhibitory effect of JWFSS capsule and its components on five rat/human CYP450 enzymes. All of the IC50 values for the FA and the LZ for the five CYPs could not be determined. The IC50 of the THP for rat CYP3A1/2 and for human CYP2D6 was 7.46 and 9.24 μmol·L-1, respectively. The IC50 of the JWFSS capsule for rat CYP2D2, CYP2E1 and CYP3A1/2 was 241.3, 369.8 and 293.0 mg ·L-1, for human CYP2D6, CYP2E1 and CYP3A4 was 123.9, 189.9 and 171.3 mg·L-1 respectively. The results indicated there were little probability that FA and LZ inhibited the activity of rat and human liver five CYPs; THP was identified as moderate-intensity inhibitor of rat liver CYP3A1/2 and human liver CYP2D6; JWFSS capsule might have a inhibitory effect on the activity of rat and human liver CYP2D, CYP2E1 and CYP3A in vitro, showing that there was a strengthened efficacy and a prolonged effective time for drugs metabolized by CYP2D, CYP2E1, CYP3A and combined with JWFSS capsule.
