In Silico Pharmacological Evaluation of Berry Polyphenols Targeting Monoamine Oxidase‐B in Parkinson's Disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder marked by the selective loss of dopaminergic neurons, resulting in a severe deficiency of dopamine. Monoamine oxidase‐B (MAO‐B), a key enzyme involved in dopamine catabolism, is an important therapeutic target in PD management. Although berry‐derived polyphenols are well known for their antioxidant and neuroprotective properties, their MAO‐B inhibitory potential remains inadequately explored. In this study, an integrated in silico approach was employed to investigate 15 major polyphenolic compounds derived from berries as potential MAO‐B inhibitors. Molecular docking, density functional theory‐based quantum chemical calculations, molecular dynamics (MD) simulations, and binding free energy analyses were performed to elucidate binding affinity, interaction stability, and inhibition mechanisms. In addition, pharmacokinetic profiling, ADMET prediction, and toxicity assessments, including cardiotoxicity, carcinogenicity, and cytochrome P450 isoform inhibition, were conducted to evaluate drug‐likeness and safety profiles. While most polyphenols exhibited favorable interactions with MAO‐B, kaempferol, ellagic acid, quercetin, and pelargonidin demonstrated superior binding affinities and stable active‐site interactions during MD simulations. These findings were further supported by favorable quantum chemical descriptors and lower binding free energy values. Overall, this computational study identifies berry‐derived polyphenols as promising MAO‐B inhibitors for PD.