Synergistic neuroprotection of chitosan-cannabidiol nanoparticles in a rat model of Alzheimer's disease: Amelioration of cognitive deficits and neuroinflammation

BackgroundAlzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, neuroinflammation, and oxidative stress. Current treatments are largely symptomatic, necessitating novel neuroprotective strategies.ObjectiveThis study aimed to investigate the anti-inflammatory and antioxidant effects of chitosan-cannabidiol (CS-CBD) nanoparticles in a streptozotocin (STZ)-induced rat model of AD.MethodsSixty male Wistar rats were randomly divided into five groups: control, AD model (STZ-induced), chitosan-treated, cannabidiol-treated, and CS-CBD-treated. AD was induced by intracerebroventricular injection of STZ (3 mg/kg). Treatments were administered intranasally for 21 days. Cognitive performance was assessed using the Morris water maze. After treatment, oxidative stress markers (NO, FRAP), liver enzymes (ALT, AST), and the expression of inflammatory and neuroprotective genes (IL1β, IL6, IL10, iNOS, PPARγ, BDNF) were evaluated by real-time PCR. Histological analysis of the hippocampus was also performed. Data were analyzed using one-way ANOVA and Tukey's post hoc test (p < 0.05).ResultsThe AD group showed significant impairments in memory and learning (p < 0.0001), increased oxidative stress, and upregulation of pro-inflammatory genes (IL1β, iNOS), with decreased neuroprotective markers (BDNF, PPARγ). CS-CBD treatment significantly improved cognitive function (p < 0.001), restored oxidative balance, reduced IL1β and iNOS expression, and elevated BDNF and PPARγ expression (p < 0.05). Histological analysis confirmed reduced neuronal degeneration and increased neuronal density in the CS-CBD group.ConclusionsCS-CBD nanoparticles exerted potent neuroprotective, antioxidant, and anti-inflammatory effects in an STZ-induced rat model of AD. These findings support the potential of CS-CBD nanoparticles as a promising adjunctive therapy for AD, warranting further investigation.