Ficus deltoidea preserves dentate gyrus microarchitecture and modulates cholinergic dysfunction in a D-galactose and aluminium chloride–induced Alzheimer's disease–like model

Alzheimer’s disease (AD)–related cognitive impairment is characterized by progressive hippocampal dysfunction, neuronal vulnerability, and cholinergic imbalance. Ficus deltoidea (FD), a flavonoid-rich medicinal plant traditionally used in Southeast Asia, has demonstrated antioxidant and neuroprotective properties; however, its effects on hippocampal subregional integrity and cholinergic modulation in AD–like models remain insufficiently characterized. Male Wistar rats were subjected to D-galactose and aluminium chloride (AlCl 3 )–induced neurodegeneration to model AD–like cognitive impairment. FD ethanol extract (50, 100, and 200 mg/kg) was administered orally for 70 days. Recognition memory was evaluated using the novel object recognition (NOR) test, hippocampal dentate gyrus morphology was assessed via hematoxylin and eosin (H&E) staining, and acetylcholinesterase (AChE) levels in the hippocampus were quantified using enzyme-linked immunosorbent assay (ELISA). FD treatment significantly improved recognition memory performance during the retention phase and increased discrimination index values compared with untreated AD-like rats. Histological analysis revealed preservation of dentate gyrus granule cell morphology in FD-treated groups, while biochemical analysis demonstrated a significant reduction in hippocampal AChE levels. Notably, the most pronounced effects were observed at lower FD doses, suggesting a non-linear dose–response relationship. Collectively, these findings suggest that FD exhibits neuroprotective and anticholinesterase effects that may support cognitive function in a chemically induced AD–like model. Nevertheless, further studies incorporating amyloid- and tau-related pathology, synaptic and oxidative stress markers, and direct assessment of cholinergic neurotransmission are warranted to clarify its mechanistic and translational relevance. • Ficus deltoidea (FD) preserves dentate gyrus microarchitecture in an Alzheimer’s disease–like model • FD significantly improves recognition memory and discrimination index • FD reduces hippocampal acetylcholinesterase, indicating cholinergic modulation • Neuroprotective effects exhibit a non-linear dose–response (hormetic pattern) • Findings support FD as a potential multi-target therapy for hippocampal neurodegeneration