Neuroprotective Effects of Ursolic Acid-loaded Dendrimer Conjugates in aRat Model of Scopolamine-induced Dementia

Introduction: Dementia and cognitive impairment are progressive neurodegenerative disorders that significantly affect memory and learning abilities. The blood–brain barrier (BBB) poses a major challenge for drug delivery to the brain. Ursolic acid (UA), a naturally occurring triterpenoid, has potent neuroprotective, antioxidant, and anti-inflammatory properties but suffers from poor solubility and bioavailability. Poly(amidoamine) (PAMAM) dendrimers can enhance UA stability and facilitate targeted brain delivery. This study investigates the neuroprotective efficacy of UA-loaded PAMAM G0 dendrimers in a rat model of scopolamine-induced dementia. Method: Adult SD rats (n = 5 per group, male, 8–10 weeks old, 200–250 g) were divided into four groups: Normal Control (NC), Disease Control (DC), Treatment Control (TC), and Standard Control (SC). The DC, TC, and SC groups received scopolamine hydrobromide (5 mg/kg, i.p.) for three consecutive days. The TC group received UA-loaded PAMAM G0 dendrimers (40 mg/kg, p.o.), and the SC group received donepezil (2.5 mg/kg, p.o.), both administered two hours after scopolamine for 11 days. Behavioral assessments included the Morris Water Maze, Elevated Plus Maze, Rotarod, and Tail Flick tests. Biochemical assays measured GABA, GSH, TBARS, NO, and TNF-α levels. Histopathological analysis of the hippocampus and cortex was performed. Results: UA-loaded dendrimers significantly improved spatial learning and memory performance in the Morris Water Maze and Elevated Plus Maze tests compared to the disease group (p <0.01). Treatment also restored antioxidant enzyme levels, reduced lipid peroxidation, and decreased NO and TNF-α levels. Histopathology revealed preservation of neuronal morphology and reduced neuroinflammation in treated rats. Discussion: The improved cognitive and biochemical outcomes suggest that PAMAM G0 dendrimers enhance UA’s bioavailability and facilitate its targeted delivery across the BBB, thereby attenuating oxidative stress, neuroinflammation, and neuronal degeneration in dementia. Conclusion: UA-loaded PAMAM dendrimers demonstrate potent neuroprotective effects in scopolamine-induced dementia and cognitive impairment in rats, supporting their potential as a promising nanocarrier-based therapeutic approach for neurodegenerative disorders. Further longterm and translational studies are warranted.