Chitosan-curcumin nanoparticles: a potential nano-therapeutic for cognitive restoration in a streptozotocin-induced rat model of Alzheimer's disease.

BACKGROUND

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory impairment, with no definitive cure currently available. Neuroinflammation, oxidative stress, and amyloid-beta accumulation play central roles in disease progression. While curcumin shows therapeutic promise, its clinical efficacy is limited due to poor bioavailability. This study investigates the neuroprotective effects of chitosan-curcumin nanoparticles in a streptozotocin (STZ)-induced rat model of AD, focusing on cognitive performance, hippocampal integrity, and molecular markers of neurodegeneration.

METHODS

Sixty male Wistar rats were randomly divided into five groups: control, AD, AD + chitosan, AD + curcumin, and AD + chitosan-curcumin. AD was induced via intraventricular injection of STZ (3 mg/kg). Two weeks' post-induction, cognitive function was assessed using the Morris water maze (MWM). At the end of the treatment period, oxidative stress parameters, inflammatory cytokines, and gene expression levels (IL-1β, IL-6, IL-10, NRF2, PPARγ, BDNF) were measured via real-time PCR. Data were analyzed using one-way ANOVA with Tukey's post hoc test (p < 0.05).

RESULTS

Rats treated with chitosan-curcumin nanoparticles exhibited significantly improved memory and learning compared to all other groups (p < 0.001). There was a marked downregulation of IL-1β and IL-6, along with increased expression of NRF2, PPARγ, and BDNF (p < 0.05). Histological analysis confirmed reduced neuronal damage and increased neuronal density. Chitosan-curcumin nanoparticles demonstrated potent neuroprotective effects, enhancing cognitive performance, reducing inflammation and oxidative stress, and preserving neuronal structure.

CONCLUSION

These multifaceted effects highlight the therapeutic potential of CS-CUR nanoparticles in targeting the core pathological mechanisms of AD. Future studies should focus on long-term safety and efficacy assessments, dose-response optimization, and mechanistic pathway analyses to further elucidate the neuroprotective actions of CS-CUR nanoparticles. Additionally, translational and clinical investigations are warranted to validate the therapeutic potential of this nanocarrier system for Alzheimer's disease management.