Background: Aluminum chloride (AlCl₃) is a known environmental neurotoxin implicated in oxidative stress and hypothalamic dysfunction. Natural antioxidants from medicinal plants have shown promise in mitigating heavy metal-induced neurotoxicity.

Objective: This study evaluated the protective effects of ethanol leaf extract of Prunus domestica L. against AlCl₃-induced hypothalamic toxicity in adult male Wistar rats.

Methods: Forty (40) adult male Wistar rats were divided into five groups (n = 8): Control, AlCl₃ (100 mg/kg), AlCl₃ + P. domestica (200 mg/kg), AlCl₃ + P. domestica (400 mg/kg), and AlCl₃ + Vitamin E (100 mg/kg). Treatments were administered orally for 28 days. Oxidative stress biomarkers (MDA, SOD, CAT, GSH), hormonal assays (GnRH, LH, FSH, testosterone), and histopathological examinations of the hypothalamus were conducted.

Results: AlCl₃ significantly increased MDA levels and decreased antioxidant enzyme activities and hormonal concentrations (p < 0.05). Treatment with P. domestica extract significantly reversed these alterations in a dose-dependent manner. Histological analysis showed restoration of neuronal architecture in treated groups compared with severe degeneration in the AlCl₃ group.

Conclusion: Ethanol leaf extract of P. domestica significantly ameliorates aluminum-induced hypothalamic toxicity through antioxidant and neuroendocrine regulatory mechanisms.