Restraint stress-induced central monoaminergic & oxidative changes in rats & their prevention by novel Ocimum sanctum compounds.

Background & objectives: Ocimum sanctum (OS) is known to possess various therapeutic properties. We have earlier isolated and characterized three OS compounds; Ocimarin, Ocimumoside A and Ocimumoside B. However, their role in modulating stress-induced central changes is unexplored. Thus, the present study was aimed to investigate the effect of these OS compounds on restraint stress (RS)-induced changes in the monoaminergic and antioxidant systems in the frontal cortex, striatum and hippocampus of rats. Methods: RS was produced by immobilizing (restraining) the Sprague Dawley rats for a period of 2.5 h inside cylindrical steel tubes. The monoamine levels and the in vivo antioxidant status in brain regions were evaluated by HPLC-EC and spectrophotometric assays, respectively. Results: RS significantly increased the dopamine levels in the frontal cortex and decreased in the striatum and hippocampus, and accompanied with selective increase of dopamine metabolites compared to the NS control group. The serotonin and its metabolite levels were significantly increased, while noradrenaline levels were decreased by RS in the three brain regions studied. The activities of superoxide dismutase and glutathione peroxidase in the frontal cortex and striatum were significantly increased by RS with decreased glutathione levels and increased lipid peroxidation. Pre-treatment with Ocimumoside A and B (40 mg/kg po) for a period of 3 days prevented the RS-induced changes with an efficacy similar to that of standard anti-stress (Panax quinquefolium; 100 mg/kg po) and antioxidant (Melatonin; 20 mg/kg ip) drugs, while, Ocimarin failed to modulate these changes. OS compounds per se had no effect on these parameters. Interpretation & conclusions: The present findings showed the anti-stress potential of Ocimumoside A and B in relation to their simultaneous modulatory effects on the central monoaminergic and antioxidant systems implicating their therapeutic importance in stress-related disorders. Further studies are required to understand the mechanism of action of these compounds.

Induction of oxidative stress by restraint stress and corticosterone treatments in rats.

Chronic exposure to psychological stress in humans and restraint stress in experimental animals results in increased oxidative stress and resultant tissue damage. To study the contribution of stress hormones towards stress-induced oxidative processes in the brain, we investigated the response of important free-radical scavenging enzymes toward chronic administration of two doses of corticosterone (low dose: 10 mg/kg/day, high dose: 40 mg/kg/day) in rodents. After a 21-day experimental period, a significant decline in both superoxide dismutase and catalase was observed in both stressed and stress hormone-treated animals. The brain levels of glutathione as well as the activities of glutathione-S-transferase and glutathione reductase were also significantly decreased, while lipid peroxidation levels were significantly increased in comparison to controls. A direct pro-oxidant effect of stress hormones in the brain during physical and psychological stress was observed, indicating important implications for oxidative stress as a major pathological mechanism during chronic stress and a consequent target option for anti-stress therapeutic interventions.