Mangiferin Mitigates Ketamine-Induced Dopaminergic and Glial Dysregulation and Modulates Nrf2 Expression in a Rat Schizophrenia-Like Model
Journal of Experimental Pharmacology April 1, 2026 V. A. Chukwu, G. Anyanwu, N. Nto et al.
In a rat model of schizophrenia-like symptoms induced by ketamine, the natural compound mangiferin (from mango) reduced behavioral abnormalities, oxidative stress, inflammation, and glial activation in brain regions involved in motor and cognitive function. Ketamine caused reduced exploratory activity, hyperlocomotion, anxiety, elevated dopamine, and disrupted antioxidant defenses. Mangiferin at 50–75 mg/kg restored locomotor activity, antioxidant enzymes, and reduced inflammatory markers and astrocytosis, while increasing Nrf2, a key antioxidant regulator. The antipsychotic risperidone improved behavior and inflammation but was less effective at normalizing redox markers. The findings suggest mangiferin may be a candidate for adjunctive therapy targeting redox–glial dysfunction in schizophrenia.