Mangiferin ameliorates 6-hydroxydopamine induced cytotoxicity and oxidative stress in ketamine model of schizophrenia

Background: accumulating evidence indicates that mangiferin (mgf),a natural xanthone,by virtue of its antioxidant and antiinflammatory properties is neuroprotective. here we sought to verify the cytoprotective role of mgf on cultured rat primary mesencephalic cells exposed to 6-hydroxydopamine (6-ohda) in vitro,and the mgfs anti-inflammatory potential in mouse model of ketamine-induced schizophrenia in vivo. methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (mtt)-assaywas performed tomeasure cell viability inmesencephalic cell cultures exposed to neurotoxin (6-ohda,40 μm). schizophrenia was induced in mice by ketamine (50 mg/kg,ip,twice a day,for 7 days). the treatment effects of mgf (50mg/kg,po,for 7 days)were verified on locomotor behavioral changes in open-field test,and on the oxidant stress-related increase in lipid-peroxidation (malondialdehyde) and interleukin-6 (il-6) levels in brain tissues. results: mgf (10-100 μm) produced no per se effect on cell viability as measured by mtt assay,but significantly prevented the 6-ohda-induced cell death in a concentration- dependent manner. acridine orange/ethidium bromide (ao/etbr) staining confirmed the absence of 6-ohda-induced morphological changes characteristic of apoptosis/necrosis. in open-field test,ketamineinduced impaired locomotor activity and behavioral changes such as grooming and stereotyped but not rearing were effectively ameliorated bymgfpretreatment. also,ketamine-associated increase in brain tissue levels of il-6 and mda were significantly lowered in mgf-pretreated mice. conclusion: mangiferin has a neurocytoprotective role related,at least in part,to an antioxidant and anti-inflammatory mechanism,which could be explored for more effective therapies of schizophrenia and other neurodegenerative diseases. copyright © 2012 by institute of pharmacology polish academy of sciences.