Pathogenic Mechanism of Monoamine Oxidase-B and Research Progress of Its Natural Inhibitors for Treating Parkinson’s Disease

Dopamine represents an important catecholamine neurotransmitter that controls movement, and monoamine oxidase-B(MAO-B) is the key enzyme responsible for dopamine metabolism. Meanwhile, active oxygen molecules such as H₂O₂ are generated in the process of MAO-B oxidation and deamination, and the metabolism of H₂O₂ results in a large number of strongly oxidizing free radicals. Dopamine deficiency and neurotoxicity triggered by free radicals are closely involved in the pathogenesis of Parkinson's disease(PD), therefore, MAO-B is generally considered as a key target for PD, and inhibition of MAO-B enzymatic activity has been proved to be a powerful means for treating PD. In light of this, two pronged approach for prevention and therapy of PD by MAO-B inhibitors has emerged, on one hand, inhibition of MAO-B enzymatic activity is able to reduce dopamine degradation, further increase the amount of dopamine in the synaptic cleft of neurons, and finally ameliorate Parkinsonian motor defects. On the other hand, MAO-B inhibition could scavenge free radicals, reduce oxidative stress, and protect dopaminergic neurons, thus delay the disease progression of PD. This review summarized the structure-activity relationships, inhibitory potency, inhibition modes and binding sites of highly active MAO-B inhibitors derived from natural medicinal plants including Chinese medicine. From the perspective of MAO-B inhibition, this paper attempted to explore, for the first time, the material basis of currently used single herbs and herbal formulas for preventing and treating PD, and provided a reference for the subsequent development of new MAO-B inhibitors with higher efficiency and lower toxicity.