Restraint stress-induced central monoaminergic & oxidative changes in rats & their prevention by novel Ocimum sanctum compounds
Ausaf Ahmad1, Naila Rasheed2, Kailash Chand3, Rakesh Maurya3, Naheed Banu4, Gautam Palit5
1 Division of Pharmacology, CSIR-Central Drug Research Institute; Present address: Amity Institute of Biotechnology, Amity University, Lucknow campus, Lucknow 226 010, India
2 Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, India; Present address: College of Medicine, Qassim University, P.O. Box 6655, Buraidah 51452, KSA
3 Division of Medicinal Chemistry, CSIR-Central Drug Research Institute, Lucknow, India
4 Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, India
5 Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, India
Scientist G, Sr. Dy. Director & Head, Neuropharmacology Unit, Division of Pharmacology, CSIR-Central Drug Research Institute (CDRI), Lucknow 226 001, India
Source of Support: None, Conflict of Interest: None
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.