Modulatory Effects of Mangiferin Isolated from Aquilaria Plants on Human Cytochrome P450 Enzyme (CYP) Activities In vitro and In silico Studies

被引:1
作者
Pan, Yan [1 ]
Jagadish, Premika [1 ]
Tze, Ung Yee [1 ]
Ming, Sharoen Lim Yu [1 ]
Hon, Lim Kuan [1 ]
Ee, Jason Loo Siau [2 ]
Pung, Yuh Fen [1 ]
Chowdhury, Lamia Noushin Sadeque [1 ]
Tao, Shang [1 ]
机构
[1] Univ Nottingham, Fac Sci & Engn, Sch Pharm, Div Biomed Sci, Semenyih 43000, Malaysia
[2] Taylors Univ, Dept Pharm, Subang Jaya, Malaysia
关键词
Mangiferin; cytochrome P450; inhibition; drug-herb interactions; molecular docking; in vitro; P450; ENZYMES; INHIBITION; METABOLISM; AGARWOOD; RAT;
D O I
10.2174/2210315513666230307115348
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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 K-i 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 mu M, and K-i values of 3.8, 10.8, and 9.6 mu M, 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.
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页数:10
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