Pumpkin seed oil exerted antidepressant effects through ameliorating the oxidative stress and neuroinflammation in the hippocampus of depressed rats

Abstract

We hypothesized that pumpkin seed oil (PSO) exhibits antidepressant activity by modulating oxidative and neuroinflammatory pathways. This would be the first study to report the antidepressant effect of PSO in the hippocampus. Sixty adult male rats were divided into six groups. The first group served as the control. Groups two and three received venlafaxine (20 mg/kg) or PSO (40 mg/kg), respectively. Groups 4-6 were subjected to chronic mild stress (CMS); group four remained untreated, while groups five and six received venlafaxine or PSO, respectively. CMS induced a redox imbalance evidenced by elevated malondialdehyde and nitric oxide levels, and reduced activity of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) in the hippocampus. CMS increased neuroinflammation, decreased neurotransmitter levels and downregulated the expression of histamine-N-methyl transferase and tyrosine hydroxylase. These changes were associated with behavioral alterations, including reduced sucrose preference, body weight, and coat state score, alongside increased immobility time in the tail suspension test and freezing time in the open field test, and decreased rearing activity. Administration of PSO reversed all neurochemical and behavioral changes induced by CMS by attenuating oxidative stress and neuroinflammation induced by depression. PSO demonstrated efficacy comparable to or better than venlafaxine in mitigating these effects.