Effect of panaxytriol on cytochrome P450 3A4 via the pregnane X receptor regulatory pathway.
Cytochrome P-450 CYP3A
/ drug effects
Drug Combinations
Drugs, Chinese Herbal
/ pharmacology
Enediynes
/ pharmacology
Fatty Alcohols
/ pharmacology
Gene Expression Regulation, Enzymologic
/ drug effects
Hep G2 Cells
Humans
Pregnane X Receptor
/ physiology
Receptors, Steroid
/ metabolism
Transcriptional Activation
/ drug effects
Up-Regulation
/ drug effects
CYP3A4
molecular mechanism
panaxytriol
pregnane X receptor
regulatory pathway
Journal
Phytotherapy research : PTR
ISSN: 1099-1573
Titre abrégé: Phytother Res
Pays: England
ID NLM: 8904486
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
received:
14
08
2018
revised:
17
12
2018
accepted:
20
12
2018
pubmed:
18
1
2019
medline:
14
6
2019
entrez:
18
1
2019
Statut:
ppublish
Résumé
Panaxytriol (PXT) is one of the major effective components of red ginseng and Shenmai injection. The present study aimed to explore the effect of PXT on cytochrome P450 3A4 (CYP3A4) based on the pregnane X receptor (PXR)-CYP3A4 regulatory pathway in HepG2 cells and hPXR-overexpressing HepG2 cells treated with PXT for different time periods using quantitative polymerase chain reaction, Western blot, and dual-luciferase reporter gene assays. PXT could upregulate the levels of PXR and CYP3A4 mRNA in HepG2 cells treated with PXT for 1 hr, with no impact on the expression of their protein levels. The expression levels of both PXR and CYP3A4 mRNA and protein in HepG2 cells treated with PXT for 24 hr increased in a concentration-dependent manner. The effects of PXT on the expression of PXR and CYP3A4 mRNA and protein in hPXR-overexpressing HepG2 cells were similar to those in HepG2 cells. Moreover, the influence trend of PXT on CYP3A4 was consistent with that of PXR in HepG2 cells and hPXR-overexpressing HepG2 cells. The dual-luciferase reporter gene assay in HepG2 cells further demonstrated that PXT treatment for specific time periods could significantly induce the expression of CYP3A4 mediated by the PXR regulatory pathway.
Substances chimiques
Drug Combinations
0
Drugs, Chinese Herbal
0
Enediynes
0
Fatty Alcohols
0
Pregnane X Receptor
0
Receptors, Steroid
0
fructus schizandrae, radix ginseng, radix ophiopogonis drug combination
0
panaxytriol
87005-03-6
Cytochrome P-450 CYP3A
EC 1.14.14.1
CYP3A4 protein, human
EC 1.14.14.55
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
968-975Subventions
Organisme : China National Nature Science Fund
ID : 81560606 and 81760672
Informations de copyright
© 2019 John Wiley & Sons, Ltd.