Berberine Selectively Inhibits Human Monoamine Oxidase B: Kinetics And Mechanism Of Inhibition

Berberine is a prominent constituent of several medicinal plants used in Indian and Chinese traditional/indigenous systems of medicine. Berberine has shown broad spectrum of pharmacological activities and therapeutic applications. Earlier studies have shown promising antidepressant actions of berberine in animal models. Preliminary computational analysis suggested monoamine oxidases (MAO) as potential targets. MAOs are involved in numerous neurophysiological functions that are affected by the neurological disorders such as depression, Alzheimer's disease and Parkinson's disease. Berberine was evaluated in vitro as an inhibitor of human monoamine oxidase A and B to explore its potential applications for the treatment of neurological disorders. Interaction and binding characteristics of berberine with MAO-A and -B were determined by substrate-kinetics assays, enzyme-inhibitor complex formation and equilibrium-dialysis dissociation analysis. Berberine showed significant inhibition of MAO-A and -B with IC₅₀ values of 43.7 ± 1.1 and 7.4 ± 1.0µM respectively. Berberine showed > 11 fold selectivity for inhibition of MAO-B (Ki 1.92 ± 0.28µM) than MAO-A (Ki 22.38 ± 3.45µM) with mixed-type inhibition kinetics. Binding of berberine with MAO-A and -B was not time-dependent and reversible, as determined by enzyme-inhibitor binding and dissociation-dialysis assays. The study shows berberine as a selective inhibitor of MAO-B. Berberine interacts with the MAO-B through reversible-binding mechanism. Selective MAO-B inhibitory properties of the berberine suggest its potential for eliciting selective pharmacological effects that might be useful in treatment of neurological disorders.

Acknowledgements: USDA-ARS Cooperative Scientific Agreement # 58 – 6408 – 2-0009: NCRR Grant Number P20GM104932 from the National Institute of General Medical Sciences (NIGMS), a component of the National Institutes of Health (NIH), (CORE C- CORE-NPN).