Possible neuroprotective mechanisms of action involved in the neurobehavioral property of naringin in mice

Flavonoids are naturally occurring bioactive phytochemical metabolites widely known to prevent and suppress several human diseases, and are important sources of therapeutic compounds from plants. Evidence derived from previous studies suggests that naringin, a neuroactive flavonoid possess functional beneficial neurobehavioral effects including anxiolytic, antidepressant and memory enhancing properties. However, literature search revealed that no studies have been carried out to evaluate the possible biochemical mechanisms involved in the neurobehavioral property of naringin alone following repeated treatment. Hence, this study was designed to evaluate the possible neuro-biochemical mechanisms involved in the neurobehavioral property of naringin following repeated administration in mice. The effects of naringin (2.5, 5 and 10 mg/kg), diazepam (2 mg/kg), imipramine (15 mg/kg) and donepezil (1 mg/kg) or vehicle on neurobehavioral and biochemical effects were evaluated in mice following repeated intraperitoneal injection for 7 consecutive days. Neurobehavioral activities consisting of open-field (locomotor), elevated-plus maze (anxiolytic), forced swim and social interaction (antidepressant and social preference), and Y-maze (memory enhancing) tests were assessed. Thereafter, brains levels of biomarkers of oxidative, nitrosative and cholinergic parameters were determined. Repeated treatment with naringin produced increased locomotor activity, and demonstrated antidepressant-like effects evidenced by decreased immobility time in forced swim test and increased % social preference in the social interaction test relative to controls. Also, naringin induced anxiolytic-like effect and increased cognitive performance in mice. Mechanistically, naringin significantly increased the activities of superoxide dismutase and catalase, and glutathione concentration relative to vehicle-controls. However, naringin significantly decreased malondialdehyde and nitrite contents, and reduced brain acetylcholinesterase activity in mice brains in a significant manner relative to controls. Taken together, these findings suggest that treatment with naringin might be useful to produce functional behavioral effects via mechanisms related to enhancement of cholinergic transmission, antioxidant defense systems, inhibition of lipid peroxidation and nitrosative processes.