In vitro inhibitory effects of plumbagin, the promising antimalarial candidate, on human cytochrome P450 enzymes
10.1016/j.apjtm.2015.10.016
- Author:
Wiriyaporn SUMSAKUL
1
;
Wanna CHAIJAROENKUL
2
;
Kesara NA-BANGCHANG
2
Author Information
1. Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University
2. Center of Excellence in Pharmacology and Molecular Biology, Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University
- Publication Type:Journal Article
- Keywords:
Cytochrome P450;
Enzyme inhibition;
Human liver microsomes;
Metabolism;
Plumbagin
- From:
Asian Pacific Journal of Tropical Medicine
2015;8(11):914-918
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the propensity of plumbagin to inhibit the three isoforms of human cytochrome P450 (CYP), i.e., CYP1A2, CYP2C19, and CYP3A4 using human liver microsomes in vitro. Methods: Inhibitory effects of plumbagin on the three human CYP isoforms were investigated using pooled human liver microsomes. Phenacetin O-deethylation, omeprazole hydroxylation and nifedipine oxidation were used as selective substrates for CYP1A2, CYP2C19 and CYP3A4 activities, respectively. Concentrations of paracetamol, 5-hydroxyomeprazole, and oxidized nifedipine were determined in microsomal incubation mixture using high-performance liquid chromatography. Results: Plumbagin showed significant inhibitory effects on all CYP isoforms, but with the most potent activity on CYP2C19-mediated omeprazole hydroxylation. The IC