MOLECULAR EVALUATION OF A SENOLYTIC PHYTOCHEMICAL NANOFORMULATION IN EXPERIMENTAL COGNITIVE DYSFUNCTION THROUGH BDNF, SIRT1, AND NEUROINFLAMMATORY GENE EXPRESSION ANALYSIS

Abstract

Cognitive dysfunction is a major consequence of aging and neurodegenerative disorders, primarily driven by oxidative stress, neuroinflammation, and impaired neurotrophic signaling. The present study aimed to develop and evaluate a quercetin-loaded chitosan nanoformulation for its neuroprotective efficacy in a scopolamine-induced experimental model of cognitive dysfunction. The prepared nanoparticles exhibited desirable physicochemical characteristics, including nanoscale particle size, high entrapment efficiency, and good colloidal stability. Behavioral assessment using the Morris Water Maze demonstrated significant improvement in learning and memory following treatment with the quercetin nanoformulation. Biochemical analysis revealed restoration of endogenous antioxidant enzymes and reduction of lipid peroxidation and acetylcholinesterase activity. Molecular studies further demonstrated significant upregulation of BDNF and SIRT1 gene expression, accompanied by downregulation of TNF-α, IL-1β, IL-6, and NF-κB. Histopathological examination confirmed preservation of hippocampal neuronal architecture. These findings indicate that quercetin-loaded nanoparticles possess significant neuroprotective potential and may represent a promising senolytic nanotherapeutic strategy for the management of age-related cognitive dysfunction and neurodegenerative diseases.