The Benzopyrone Biochanin-A as a reversible, competitive, and selective monoamine oxidase B inhibitor

• Published in: BMC complementary and alternative medicine Vol. 17; no. 1; p. 34
• Main Authors: Zarmouh, Najla O, Eyunni, Suresh K, Soliman, Karam F A
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 10-01-2017; BioMed Central
• Subjects: Benzoquinones - chemistry; Binding, Competitive; Chemical properties; Genistein - chemistry; Health aspects; Humans; Isoenzymes; Kinetics; Molecular Docking Simulation; Molecular Structure; Monoamine Oxidase - chemistry; Monoamine Oxidase - metabolism; Monoamine oxidase inhibitors; Monoamine Oxidase Inhibitors - chemistry; Plant Extracts - chemistry; Psoralea - chemistry; Biochanin-A; Docking studies; Flavonoids; Coumarins; Human monoamine oxidase-A; Benzopyrone; Human monoamine oxidase-B; Psoralea corylifolia ethanolic extract; Reversible competitive inhibition
• ISSN: 1472-6882; 1472-6882
• DOI: 10.1186/s12906-016-1525-y

Monoamine oxidase-B (MAO-B) inhibitors are widely used in the treatment of Parkinson's disease. They increase vital monoamine neurotransmitters in the brain. However, there is a need for safer natural reversible MAO inhibitors with MAO-B selectivity. Our previous studies showed that Psoralea corylifolia seeds (PCS) extract contains compounds that inhibit monoamine oxidase-B.
In this study, six of PCS constituents sharing a benzopyrone structure were investigated. The compounds Biochanin-A (BIO-A), isopsoralen, 6-prenylnaringenin, neobavaisoflavone, psoralen, and psoralidin, were tested for their ability to inhibit recombinant human MAO-A and B (hMAO-A and hMAO-B) isozymes. The ability of these compounds to inhibit MAO-A and MAO-B were compared to that of PCS ethanolic extract (PCSEE) using spectrophotometric assays and confirmed by luminescence assays. The highly potent and selective MAO-B inhibitor, BIO-A, was further investigated for both isozymes reversibility and enzyme kinetics. Molecular docking studies were used to predict the bioactive conformation and molecular interactions of BIO-A with both isozymes.
The data obtained indicate that benzopyrones inhibited hMAO-A and hMAO-B with different degrees as confirmed with the luminescence assay. BIO-A inhibited hMAO-B with high potency and selectivity in the present study (IC
 = 0.003 μg/mL) and showing 38-fold more selectivity than PCSEE (hMAO-B IC
 = 3.03 μg/mL, 17-fold selectivity) without affecting hydrogen peroxide. Furthermore, BIO-A reversibly and competitively inhibited both hMAOs with significantly lower inhibitory constant (K
) in hMAO-B (3.8 nM) than hMAO-A (99.3 nM). Our docking studies indicated that the H-bonds and hydrophobic interactions at the human MAO-A and MAO-B active sites contributed to the reversibility and selectivity of BIO-A.
The data obtained indicate that BIO-A is a potent, reversible and selective MAO-B inhibitor and may be recommended for further investigation in its possible use in the therapeutic management of Parkinson's and Alzheimer's diseases.