Polyphenols and Alzheimer's Disease: A Review on Molecular and Therapeutic Insights With In Silico Support

Alzheimer's disease (AD), a progressive neurodegenerative disorder, characterized by amyloid-beta (Aβ) aggregation, tau hyperphosphorylation, oxidative stress, and neuroinflammation resulted the cognitive memory loss. Despite extensive research, effective therapeutic treatment remains elusive. Polyphenols, naturally occurring bioactive compounds, have emerged as promising neuroprotective agents due to their potent antioxidant, anti-inflammatory, and amyloid-modulating properties. Research indicated that these bioactive compounds have potent antioxidant and anti-inflammatory properties, have garnered significant attention for their potential role in combating AD by targeting its key pathological mechanisms. Preclinical studies highlight the efficacy of various polyphenols, such as resveratrol, curcumin, and epigallocatechin gallate, in improving cognitive function and reducing neurodegeneration. Moreover, in silico approaches, displayed polyphenols mechanistic interactions with key AD targets to reduce pathogenesis. These computational models accelerate drug discovery by predicting binding affinities, optimizing structural modifications, and identifying novel polyphenol derivatives with enhanced therapeutic potential. This review explores the multifaceted role of polyphenols in AD mitigation, emphasizing their impact on oxidative stress and neuroinflammation while integrating in silico evidence to reinforce their therapeutic relevance. Convincingly, through the suppression of key mediators of AD, including oxidative stress, neuroinflammation, amyloid-beta and tau proteins, polyphenols exhibited outstanding therapeutic potential to treat AD.