Neuroprotective Effect of Jobelyn® on Ketamine-Induced Schizophrenia-Like Behaviors and Oxidative Damage in Mice Brain

Background and

Purpose: Schizophrenia is a chronic, debilitating psychiatric disorder affecting many young adult populations worldwide. Evidence from studies of central changes in the oxidative defense system suggests the involvement of oxidative stress in the pathophysiology of schizophrenia. Jobelyn® (JB) is a commercial polyherbal formulation that has been documented to show beneficial effects on psychosis. Preliminary evidence from animal studies suggests that JB is efficacious in animal models of schizophrenia. This study investigated the effects of JB in the prevention and reversal of ketamine-induced schizophrenia-like behaviors and oxidative damage in mice.

Methods: In the reversal protocol, mice received ketamine (20 mg/kg, i.p.) or saline for 14 days, and JB (5, 10, or 50 mg/kg), risperidone (0.5 mg/kg, i.p.), or vehicle from days 8 to 14. In the prevention protocol, mice were pretreated with JB (5, 10, or 50 mg/kg daily), risperidone, or vehicle prior to ketamine. Behaviors related to positive (locomotor activity) and cognitive (Y-maze test) symptoms of schizophrenia were also assessed. Oxidative stress markers, including superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and thiobarbituric acid-reactive substances (TBARS) levels, were measured in the whole brain.

Results: JB and risperidone significantly (P<0.05) prevented and reversed ketamine-induced hyperlocomotion and memory impairment. Ketamine-induced reductions (P<0.05) in SOD, CAT, and GSH levels, alongside increased TBARS content, were ameliorated by JB (P<0.05). These data provide a rationale for evaluating JB as a novel antipsychotic agent and suggest that its mechanism of action includes a neuroprotective antioxidant mechanism.

Conclusion: Our findings showed that Jobelyn® prevented and reversed schizophrenia-like behavioral and oxidative alterations induced by ketamine.