Your browser doesn't support javascript.
loading
Effects of Jiawei Foshou San capsule on rat hepatic cytochrome P450 enzymes invitro and invivo / 药学学报
Acta Pharmaceutica Sinica ; (12): 1101-1107, 2019.
Article in Chinese | WPRIM | ID: wpr-780176
ABSTRACT
This study aimed to evaluate the effects of Jiawei Foshou San capsule (JWFSSC) on CYP1A2, CYP2C6, CYP2D2, CYP2E1 and CYP3A1/2 enzyme activities in rat liver microsomes in vitro and in vivo, and to provide pharmacokinetic data for its combined use with other medicines. After incubating liver microsomes with a cocktail of probe drugs, the metabolites were quantitated with LC-MS/MS to assess the CYP enzyme activity. The hepatic pathological changes were evaluated by histology after hematoxylin and eosin (HE) staining. With the dose range up to 3 200 mg·L-1, the IC50 of JWFSSC for CYP2D2, CYP2E1 and CYP3A1/2 in vitro was 229.3 mg·L-1, 361.9 mg·L-1 and 274.6 mg·L-1 respectively. Compared with the vehicle control group, the enzyme activities of CYP1A2, CYP2C6 and CYP3A1/2 showed a significant increase in animals given JWFSSC 180 mg·kg-1·d-1 (P<0.01). Based on histology, several pathological changes were observed in JWFSSC groups there was less inflammatory infiltration compared to the tetrahydropalmatine (THP) group. These results of inhibition in vitro and induction in vivo suggest a strengthened efficacy and a prolonged effective time of drugs metabolized by CYP2D2 and CYP2E1 enzymes when combined with JWFSSC in use. The dosage of parent drugs should be appropriately reduced when used in combination with JWFSSC. However, if a drug is metabolized by CYP1A2 and CYP2C6 when used in combination with JWFSSC, the effect of the drug is likely reduced and the dosage should be increased appropriately. In addition, the combination of ferulic acid (FA), ligustrazine (LZ) and THP can significantly reduce the toxicity of THP in rat livers. In this study, the program of animal testing had been approved by Committee on the management and usage of experimental animal in the College of Pharmaceutical Sciences, Southwest University.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Acta Pharmaceutica Sinica Year: 2019 Type: Article

Similar

MEDLINE

...
LILACS

LIS

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Acta Pharmaceutica Sinica Year: 2019 Type: Article