Multifaceted Computational Approach to Explore Nardostachys Jatamansi Neuroprotective Phytochemicals as Potential MAO-B Inhibitors for Parkinson’s Disease

Parkinson’s disease is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons and motor dysfunction, in which MAO-B plays a crucial role by catalyzing the breakdown of dopamine and generating oxidative stress. MAO-B inhibition is a well-established strategy for managing Parkinson’s disease symptoms and slowing disease progression. Given its traditional claims in Ayurvedic medicine for the treatment of neurological disorders, Nardostachys jatamansi was selected for in silico screening to explore its neuroprotective potential. A total of 25 phytochemicals were evaluated using computational tools. All compounds satisfied Lipinski’s Rule of Five and Jorgensen’s Rule of Three, indicating favorable oral bioavailability and drug likeness. Molecular docking studies revealed that the phytochemicals jatamansinone (-9.729 kcal/mol), eselin (-9.138 kcal/mol), and jatamansinol (-8.979 kcal/mol) exhibited strong binding affinities with MAO-B, comparable to the reference inhibitor safinamide (-10.66 kcal/mol). These phytochemicals effectively occupied the active site, interacting with key residues such as Tyr326, and extended into both the entrance and substrate cavities, suggesting a mechanism of inhibition similar to that of safinamide. Furthermore, 100 ns molecular dynamics simulations demonstrated stable interactions and minimal structural changes in the MAO-B-ligand complexes throughout the simulation trajectory. Prediction of Activity Spectra for Substances (PASS) analysis predicted a wide range of neuroprotective properties of these phytochemicals, including antioxidant, anti-inflammatory, neurotransmitter-modulating, and motor-stabilizing activities. Their predicted ability to influence the serotonin and GABA pathways further highlights their potential as promising natural agents for the treatment or prevention of Parkinson’s disease and related neurodegenerative disorders.