Enhanced Cognitiveand Memory Functions via Gold Nanoparticle-MediatedDelivery of Afzelin through Synaptic Modulation Pathways in Alzheimer’sDisease Mouse Models

Gold nanoparticles (AuNPs) are valuable tools in pharmacological and biological research, offering unique properties for drug delivery in the treatment of neurodegenerative diseases. This study investigates the potential of gold nanoparticles loaded with afzelin, a natural chemical extracted from Ribes fasciculatum, to enhance its therapeutic effects and overcome the limitations of using natural compounds regarding low productivity. We hypothesized that the combined treatment of AuNPs with afzelin (AuNP–afzelin) would remarkably enforce neuroprotective effects compared with the single treatment of afzelin. Central administration of AuNP–afzelin (10 ng of afzelin) indicated improvements in cognition and memory-involved assessments of behavioral tests, comparing single treatments of afzelin (10 or 100 ng of afzelin) in scopolamine-induced AD mice. AuNP–afzelin also performed superior neuroprotective effects of rescuing mature neuronal cells and recovered cholinergic dysfunction compared to afzelin alone, according to further investigations of BDNF–pCREB–pAkt signaling, long-term potentiation, and doublecortin (DCX) expression in the hippocampus. This study highlights the potential of afzelin with gold nanoparticles as a promising therapeutic approach for mitigating cognitive impairments associated with neurodegenerative diseases and offers a new avenue for future research and drug development.