Monoamine oxidase inhibition is an important therapeutic approach for various neurodegenerative disorders.
Reversible MAO inhibitors selectively targeting only one isoform possess substantial merit in
terms of safety, efficacy, and side effect profile. This study aimed to isolate the secondary metabolites
of Zanthoxylum flavum stems and evaluate their recombinant human MAO inhibition, antimicrobial,
and antiprotozoal activities. As a result, fourteen compounds were isolated and identified (nine of them
were reported from Z. flavum for the first time). Compound 3 (sesamin) exhibited potent selective MAO-B
inhibition (IC50 value of 1.45 ± 0.05 mM) which reported herein for the first time. Compound 2 showed
selective MAO-A inhibition activity, compound 5 exhibited good trypanocidal activity, and compound
7 displayed moderate antibacterial activity. The promising MAO-B inhibitory activity of sesamin provoked
us to further explore the kinetic properties, the binding mode, and the underlying mechanism
of MAO-B inhibition by this lignan. This detailed investigation substantiated a reversible binding and
mixed MAO-B catalytic function inhibition via sesamin (Ki: 0.473 ± 0.076 lM). Selectivity and reversibility
of sesamin on MAO-B provide exciting prerequisites for further in vivo investigation to confirm its
therapeutic potentiality.