Ficus deltoidea preserves neuronal-glial ultrastructure and attenuates neuroinflammation in an Alzheimer's disease-like rat model.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by β-amyloid (Aβ) plaques, hyperphosphorylated tau tangles, cognitive decline, neuroinflammation, and neuronal-glial dysfunction, yet effective disease-modifying therapies remain unavailable. Increasing evidence suggests that preservation of neuronal and glial integrity is critical for mitigating disease progression. In the present study, we investigated the neuroprotective effects of Ficus deltoidea Jack (FD) in a D-galactose and aluminum chloride (D-gal/AlCl₃)-induced rat model of AD-like neurodegeneration. Adult male Wistar rats were treated with FD (50, 100, and 200 mg/kg) for ten weeks and assessed for cognitive performance, cortical neuronal integrity, hippocampal ultrastructure, and neuroinflammatory signaling. FD treatment significantly improved spatial learning and memory in the Morris water maze without affecting locomotor activity. Histopathological analysis demonstrated dose-dependent preservation of pyramidal neurons in prefrontal cortex and hippocampal layers II (p < 0.0001), III (p < 0.0001), and V (p < 0.0001), with the highest dose of FD producing neuronal viability comparable to donepezil. Importantly, transmission electron microscopy demonstrated that FD markedly preserved the ultrastructural integrity of hippocampal microglia and astrocytes, maintaining mitochondrial morphology, rough endoplasmic reticulum organization, and myelin integrity. Consistent with these structural effects, FD significantly suppressed neuroinflammatory cytokine expression (IL-1β, IL-6, and TNF-α) in the prefrontal cortex. Collectively, this study provides the first integrated ultrastructural and molecular evidence that FD confers multi-level neuroprotection across the cortical-hippocampal axis by preserving neuronal-glial architecture and attenuating neuroinflammation. These findings highlight FD as a promising multi-target natural candidate for mitigating neurodegenerative processes associated with AD.