Diosmin attenuates schizophrenia-like behavior, oxidative stress, and acetylcholinesterase activity in mice

Abstract

Abstract Objectives Diosmin (DSM), commonly isolated from various plants, is a citrus nutrient that has been shown to increase intracellular antioxidant capacity and assuage symptoms associated with neurological disorders. Deficiency in the antioxidant system has been implicated in the pathogenesis of schizophrenia. The use of antioxidants as neuroprotectants to suppress schizophrenia pathology is increasingly being sought. Hence, this study investigated the effects of DSM on schizophrenia-like behavior and the underlying changes in biomarkers of oxidative stress and acetylcholinesterase (AChE) activity in mice. Methods The acute antipsychotic effect of DSM (25, 50, and 100 mg/kg, intraperitoneally [i.p.]), haloperidol (1 mg/kg, i.p.), and risperidone (RIS) (0.5 mg/kg, i.p.) was investigated on stereotyped behaviors induced by apomorphine (2 mg/kg, i.p.) and ketamine (10 mg/kg, i.p.). The effect of DSM on ketamine-induced hyperlocomotion, immobility enhancement, and its woodblock cataleptogenic potential was evaluated. Also, the subacute antipsychotic potential of DSM was assessed following intraperitoneal injection of DSM (25–100 mg/kg, i.p.) alone and in combination with ketamine (20 mg/kg, i.p.) for 10 days. The behaviors of the animals were assessed in the open-field, Y-maze, and forced swim tests. Brains of the animals were afterward processed for spectrophotometric assay of oxidative stress and AChE contents. Results DSM (25, 50, and 100 mg/kg) attenuated apormorphine-induced stereotypy and devoid of cataleptogenic effect. DSM and RIS reversed acute and subacute ketamine-induced schizophrenia-like behaviors. Disomin alone increased cognitive function and reduced despair-like phenotype. Furthermore, DSM increased superoxide dismutase and glutathione and decreased malondialdehyde and AChE levels in naïve and ketamine schizophrenic mice. Conclusions DSM prevents schizophrenia-like behavior, attenuates oxidative stress, and AChE activity in naïve and ketamine schizophrenic mice.