Affiliation:
1. Division of Biomedical Sciences, School of Pharmacy, Faculty of Science and Engineering, University of Nottingham,
Semenyih, 43000, Malaysia
2. Department of Pharmacy, Taylor's University, Subang Jaya, Malaysia
Abstract
Background:
Mangiferin has been identified as one of the major active constituents of Aquilaria
plants. It was reported to have several promising chemotherapeutic potentials. Our preliminary data
suggested that Aquilaria plant water extracts inhibited several cytochrome P450 (CYP) isoenzymes in
vitro.
Objective:
This study aimed to investigate the modulatory effects of mangiferin on six major drug metabolizing
CYP enzymes including CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP3A4, and CYP3A5.
Methods:
The enzyme activities were measured using fluorescence-based assays and enzyme kinetic such
as IC50 parameters and Ki values were calculated to evaluate inhibitory potencies and mechanisms. Moreover,
for potent inhibitions, molecular docking studies were carried out to explore potential interactions of
residues between mangiferin and CYP enzymes.
Results:
Our findings suggested that mangiferin could inhibit CYP2D6, CYP3A4, and CYP3A5 in vitro
with IC50 values of 9.2, 8.7, and 4.3 μM, and Ki values of 3.8, 10.8, and 9.6 μM, in a non-competitive
inhibition pattern. Molecular docking studies using AutoDock 4.2 identified potential residues contained
in mangiferin that interacted with CYP2D6, CYP3A4, and CYP3A5, resulting in the observed inhibitory
effects.
Conclusion:
Mangiferin should be used carefully, in particular, with conventional drugs metabolized
mainly by CYP2D6, CYP3A4, and CYP3A5. Further in vivo studies are recommended to evaluate the
clinical relevance of these inhibitions.
Funder
University of Nottingham Malaysia
Publisher
Bentham Science Publishers Ltd.
Subject
Organic Chemistry,Biochemistry