Integrative In Silico and In Vivo Evidence of Quercetin as a Multitarget Neuroprotective Agent in Alzheimer's Disease

Alzheimer's disease requires therapeutic strategies targeting multiple pathological mechanisms. This study investigates the neuroprotective potential of quercetin using an integrated approach combining in silico modeling and in vivo validation. Computational analyses examined the binding behavior of quercetin toward three key enzymes implicated in disease pathophysiology: acetylcholinesterase, butyrylcholinesterase, and beta-secretase 1. Molecular dynamics simulations reveal consistent interaction patterns and stable binding profiles across independent trajectories. For experimental validation, Wistar rats with surgically induced Alzheimer's disease were orally treated with quercetin (30 mg/kg) for 5 weeks. Histological and immunohistochemical analyses of the hippocampus and subventricular zone evaluated neuronal density and astrocytic activation using glial fibrillary acidic protein and vimentin markers. Computational results supported the multitarget potential of quercetin through stable enzyme interactions. Consistently, in vivo assays demonstrated increased neuronal density and reduced astrocytic marker expression, suggesting a protective modulation of neuroinflammatory processes. These findings highlight quercetin as a promising scaffold for multitarget therapeutic strategies aimed at mitigating the progression of Alzheimer's disease.