Unveiling the Multi-Target Therapeutic Potential of Resveratrol Against Alzheimer’s Disease: An Integrative Network Pharmacology and Molecular Simulation Approach

Abstract

This study investigates the multi-target therapeutic potential of Resveratrol against Alzheimer's disease (AD) through an integrative network pharmacology and computational framework. Predicted targets of Resveratrol were identified using multiple databases and cross-referenced with Alzheimer's-associated genes, yielding 11 overlapping targets implicated in apoptosis regulation, mitochondrial function, and neuronal survival. Core proteins, including TP53, BCL2, BAX, and BDNF, formed a tightly connected protein–protein interaction network enriched in apoptotic and neuroinflammatory pathways. Molecular docking revealed strong binding affinities of Resveratrol with key targets, such as 1B8M, BCL2, and TP53, which were further validated by 100-nanosecond molecular dynamics simulations. Key structural metrics, such as RMSD, RMSF, Rg, and SASA, indicated stable protein–ligand complexes with significant hydrogen bonding, particularly in the BCL2 and TP53 systems. Collectively, the findings demonstrate Resveratrol’s potential as a multitarget neuroprotective agent in Alzheimer's disease, offering a mechanistic rationale for its repositioning in neurodegenerative therapeutics.