Anu RANI, Pritam Babu SHARMA, Saurabh BHATIA, Arun K. SHARMA
Journal of Research in Pharmacy - 2025;29(6):2587-2601
Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by progressive cognitive decline, memory loss, and behavioral changes, driven by cholinergic dysfunction and amyloid-beta (Abeta) accumulation. Building on our prior findings, Ficus racemosa exhibits exceptional potential to target AD by modulating ACh, AChE, and Abeta protein pathophysiology. The current study validates the therapeutic potential of ethanolic extracts of Ficus racemosa leaves (EEFRL) and fruits (EEFRF) targeting AD-related molecular pathologies. Behavioral and cognitive functions were assessed using the Morris water maze, Y-maze, novel object recognition, Barnes maze, and passive avoidance tasks in scopolamine-induced AD mice models. The therapeutic potential of EEFRL and EEFRF were accessed by evaluating antioxidant enzymes (SOD and GSH), oxidative stress (TBARS), and pro-inflammatory cytokines (IL-6, TNF-alpha, NFkappaB) diseases model. The architecture of brain tissue was evaluated for the hippocampal CA1 region, neuronal integrity, and Abeta accumulation using histological analysis and immunohistochemistry. EEFRL and EEFRF pre-treatments (300 mg/kg/p.o dose of each per day) significantly improved cognitive performance and memory retention, comparable to the standard AD treatment, donepezil. Biochemical assessments indicated that both extracts reduced oxidative stress and neuroinflammation, restoring antioxidant enzyme levels and reducing ROS and pro-inflammatory cytokines. Histological analysis revealed preserved hippocampal structure, with uniform cortical layers and healthier neurons. Immunohistochemistry showed decreased Abeta accumulation and enhanced neuronal integrity in EEFRL and EEFRF-treated groups. The study substantiates the significant neuroprotective and anti-inflammatory properties of EEFRL and EEFRF, demonstrating their potential as multi-target therapeutic agents in mitigating cholinergic dysfunction and Abeta pathology in AD.
