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Evidence-Based Complementary and Alternative Medicine
Volume 2016 (2016), Article ID 1423052, 12 pages
http://dx.doi.org/10.1155/2016/1423052
Research Article

Evaluation of the Isoflavone Genistein as Reversible Human Monoamine Oxidase-A and -B Inhibitor

College of Pharmacy & Pharmaceutical Sciences, Florida A & M University, Tallahassee, FL 32307, USA

Received 21 December 2015; Revised 8 March 2016; Accepted 10 March 2016

Academic Editor: Michele Navarra

Copyright © 2016 Najla O. Zarmouh et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Monoamine oxidases inhibitors (MAOIs) are effective therapeutic drugs for managing Parkinson’s disease (PD) and depression. However, their irreversibility may lead to rare but serious side effects. As finding safer and reversible MAOIs is our target, we characterized the recombinant human (h) MAO-A and MAO-B inhibition potentials of two common natural isoflavones, genistein (GST) and daidzein (DZ) using luminescence assay. The results obtained showed that DZ exhibits partial to no inhibition of the isozymes examined while GST inhibited hMAO-B (IC50 of 6.81 μM), and its hMAO-A inhibition was more potent than the standard deprenyl. Furthermore, the reversibility, mode of inhibition kinetics, and tyramine oxidation of GST were examined. GST was a time-independent reversible and competitive hMAO-A and hMAO-B inhibitor with a lower of hMAO-B (1.45 μM) than hMAO-A (4.31 μM). GST also inhibited hMAO-B tyramine oxidation and hydrogen peroxide production more than hMAO-A. Docking studies conducted indicated that the GST reversibility and hMAO-B selectivity of inhibition may relate to C5-OH effects on its orientation and its interactions with the threonine 201 residue of the active site. It was concluded from this study that the natural product GST has competitive and reversible MAOs inhibitions and may be recommended for further investigations as a useful therapeutic agent for Parkinson’s disease.