Al-Azhar International Medical Journal /Al-Azhar International Medical Journal · Feb 25, 2026

Evaluating the neuroprotective effect of Metformin on experimentally induced Parkinsonism by Rotenone in both diabetic and non-diabetic rats

By zaffan M, Alkafee ALA, Saief AMIA

Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by progressive dopaminergic neuron degeneration. Diabetes mellitus increases PD risk, suggesting potential therapeutic targets for dual neuroprotection. Aim: Using both diabetic and non-diabetic rats, we will study metformin's neuroprotective effects on rotenone-induced Parkinsonism and look for any synergistic effects with selegiline. Patients and methods: 72 male rats were divided into 9 groups (n=8 each): control, rotenone, diabetic (alloxan-induced), and various treatment combinations with metformin (250mg/kg) and/or selegiline (0.25mg/kg) for 21 days. Behavioral assessments included the Morris water maze, the hang wire test, and the forced swim test. Biochemical markers measured dopamine, MDA, GSH, and α-synuclein levels. Results: Rotenone and diabetes significantly impaired cognitive and motor functions while increasing oxidative stress. Metformin treatment improved performance in both models. Selegiline showed superior neuroprotection, with combination therapy (selegiline+metformin) achieving optimal results. Combined treatment restored dopamine levels to near-normal (99.68pg/ml vs 115pg/ml control), normalized oxidative stress markers, and reduced α-synuclein accumulation. Conclusion: Metformin demonstrates significant neuroprotective effects against rotenone-induced Parkinsonism. Combination with selegiline provides superior therapeutic benefits through synergistic mechanisms targeting oxidative stress, dopamine preservation, and protein aggregation.

doi.org/10.21608/aimj.2026.413463.2759 Open access Interventions