Mangiferin ameliorates intracerebroventricular-quinolinic acid-induced cognitive deficits, oxidative stress, and neuroinflammation in Wistar rats.

INTRODUCTION: Mangiferin (MGF), a xanthonoid polyphenol, confers neuroprotection via combating oxidative stress and inflammation. The current investigation aimed to assess the neuroprotective potential of MGF on behavioral and neurochemical anomalies evoked by administration of quinolinic acid (QA) through intrastriatal injection in male Wistar rats and to reveal the associated mechanisms. MATERIALS AND METHODS: QA (300 nm/4 μl saline) was administered intracerebroventricular in the striatum (unilaterally) once. Thereafter, MGF 20 and 40 mg/kg (peroral) was administered to the animals for 21 days. RESULTS: QA administration caused marked alteration in motor activity (rotatod), footprint analysis, and cognitive function (Morris water maze test, and novel object recognition test). Furthermore, oxido-nitrosative stress (increased nitrite content, lipid peroxidation, with reduction of GSH), cholinergic dysfunction, and mitochondrial complex (I, II, and IV) dysfunction were observed in hippocampus and striatal region of QA-treated rats in comparison to normal control. Pro inflammatory mediators (tumor necrosis factor-alpha TNF-α and interleukin-1β) were noted to increase in the hippocampus and striatum of QA-treated rats. In addition, we observed BDNF depletion in both the hippocampus and striatum of QA-treated animals. MGF treatment significantly ameliorated memory and motor deficits in QA-administered rats. Moreover, MGF treatment (40 mg/kg) restored the GSH level and reduced the MDA, nitrite level, and pro-inflammatory cytokines in striatum and hippocampus. Furthermore, QA-induced cholinergic dysfunction (AChE), BDNF depletion and mitochondrial impairment were found to be ameliorated by MGF treatment. CONCLUSION: The results suggest that MGF offers the neuroprotective potential that may be a promising pharmacological approach to ameliorate cognitive deficits associated with neurodegeneration.