Therapeutic Targets for Depression Caused by Oxidative Stress
Author(s): M Ganga Raju*, Ankitha G, and NVL Suvarchala Reddy V
Abstract
Depression is a mood disorder that involves a persistent feeling of sadness and loss of interest which stops you doing your normal activities. The present study is focused on the evaluation of Leaves of Catharanthus roseus extract as antidepressant and anti-oxidant and to scientifically validate the claim by in silico docking studies of natural compounds present in the extract for their respective sites against selected proteins. The preliminary phytochemical investigation of methanolic extract of leaves of Catharanthus roseus revealed the presence of bioactive compounds of which phenolic acids, flavonoids, alkaloids, steroids, terpenoids, carbohydrates and tannins were the most prominent. In vivo evaluation of antidepressant activity of the extract of Catharanthus roseus was carried out by using Forced swim test and Tail suspension test. Imipramine was used as standard. The animal brains were subjected for histopathological studies and brain dopamine levels were also estimated in FST model. In vitro evaluation of antioxidant activity of the extract of Catharanthus roseus was carried out using Lipid peroxidation assay and Hydroxyl radical scavenging assay. Upon treatment with extract at 200 mg/kg. bd. wt, 400 mg/kg. bd. wt. & imipramine (5 mg/kg), the duration of immobility was found to be reduced when compared with the control group. Histopathological results clearly showed improvement in thickness of granule cell layer, increase in count of glial cells, no shrinkage of hippocampal volume and no visible atrophy was observed. This clearly shows that the extract possesses anti-depressant activity. Improved brain dopamine levels were observed in groups treated with extract and standard drug. The anti-oxidant results clearly showed the ability of the extract to scavenge the free radicals in both the assays. In the present study docking studies were performed for natural compounds present in the extract such as yohimbine, chlorogenic acid, catharanthine, kameferol, quercetin, vindolinine, gallic acid, serpentine, vindoline, lurasidone and standard drug imipramine against PDB ID: 5I6X, PDB ID: 4UH5, PDB ID: 1HD2, PDB ID: 1RVL using Schrödinger software. The statistical verification of the model was evaluated with PROCHEK; a structure verification program relies on Ramachandran plot which determines the quality of the predicted structures. The results revealed that yohimbine, chlorgenic acid, catharanthine, quercetin, vindolinine, lurasidone and standard drug imipramine had shown highest glide scores which indicates a stronger receptor-ligand binding affinity among the various phytochemical constituents present in the extract. From the above it is concluded that the extract possess anti-depressant and anti-oxidant activity.