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Corresponding Author

O. A Bamgbose

Authors ORCID

O. A Bamgbose: https://orcid.org/0009-0009-9910-1488

Abstract

Alzheimer's disease (AD) is increasingly recognized as a multisystem neurodegenerative disorder involving oxidative stress and neuroinflammation beyond classical hippocampal pathology. The hypothalamus, a key regulator of metabolic and neuroendocrine homeostasis, remains comparatively underexplored in experimental AD models. This study investigated the effects of aqueous Annona muricata seed extract (SSE) on hypothalamic oxidative injury in an aluminium chloride (AlCl3)-induced Alzheimer's disease–like model in Wistar rats. Adult Wistar rats of both sexes were randomly assigned to five groups (n = 5): control, AlCl3 (100 mg/kg), SSE alone (200 mg/kg), AlCl3 + SSE, and AlCl3 + donepezil (10 mg/kg). Treatments were administered orally for 28 days with blinded outcome assessment. Spatial learning and memory were assessed using the Morris Water Maze. Hypothalamic tissues were stereotaxically dissected and analyzed for oxidative stress markers (superoxide dismutase, catalase, reduced glutathione, malondialdehyde), pro-inflammatory cytokines (TNF-α , IL-B), and histomorphological integrity using hematoxylin-eosin and Cresyl violet staining with quantitative morphometry. AlCl3 exposure impaired spatial learning, reduced antioxidant defenses, elevated lipid peroxidation and inflammatory cytokines, and induced neuronal degeneration within the hypothalamus. SSE co-administration significantly attenuated these alterations and preserved neuronal architecture, with effects comparable to donepezil. However, classical AD hallmarks such as amyloid-β and tau pathology were not assessed, and findings therefore reflect protection against oxidative and inflammatory neurodegeneration rather than comprehensive AD pathology. These results highlight the hypothalamus as a vulnerable target in experimental Alzheimer-like neurodegeneration and suggest that Annona muricata seed extract warrants further mechanistic and translational investigation.

Digital Object Identifier (DOI)

10.70176/3007-973X.1064

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