Investigation of inductive effect of triptolide on cytochrome P450 s in rat hepatocytes and HepG2 cells and possible mechanism
10.3969/j.issn.1001-1978.2017.03.015
- VernacularTitle:雷公藤内酯醇对肝细胞色素P450的诱导及机制研究
- Author:
Xi YU
;
Zijin WAN
;
Yanping ZHU
;
Hairong XU
;
Kai LIAO
;
Feng LIU
;
Wei LI
- Keywords:
triptolide(TP);
cytochrome P450(CYPs);
nuclear receptor;
p53;
hepatocytes;
HepG2
- From:
Chinese Pharmacological Bulletin
2017;33(3):366-372
- CountryChina
- Language:Chinese
-
Abstract:
Aim Toinvestigatingtheinductionof CYPs in hepatocytes or HepG2 cells by triptolide(TP) andthepossiblemechanism.Methods AfterTPtreat-ment,the expression of CYPs in rat primary hepato-cytes or human HepG2 cells was detected by real-time PCR and Western blot assays.Specific inhibitors or gene knockdown method were employed to analyze the possiblemechanism.Results Theexpressionof CYP1A2,2C7,2C11,2C12,2D2,2E1 and 3A1 in rat primary hepatocytes was induced by TP.The fold was 19,2,31,3,21,88 and 34 at 50 nmol·L-1, respectively while at 100 nmol·L-1 it was 20,5,30,23,61,83 and 38,respectively.In HepG2 cells,the expression of human CYP1A1,2B6,2C9,2C19, 2D6,2E1 and 3A4 was also induced by TP.The ac-tivities of nuclear receptor PXR and CAR were inhibi-ted.TP upregulated p53 expression,and the induction of several CYPs caused by TP was blocked when p53 wasinhibited.Conclusions TPinducesCYPsexpres-sion in rat hepatocytes and HepG2 cells.Nuclear re-ceptors may not be involved in TP induced CYPs, while the mechanism may partly attribute to p53.
