Stress is a state of mental or emotional strain of an individual.  In recent years nutritional antioxidants study have gain more attention in minimizing the stress like oxidative stress. The stress resistant ability in an organism can be increased by the supplementation of herbal resources. However, few plant extracts are known to have stress resistant ability and increases the tolerance capacity. Plants containing high antioxidant and other bioactive compounds promote tolerance capacity. An antioxidant rich plant has been proved to decreases the   lipid peroxidation. Here, we investigated the potential protective effect of ethanolic extract of Withania somnifera (WS), against Paraquat toxicity on stress tolerance capacity using Drosophila melanogaster. Wild-type fruit flies of Oregon-K strain were fed with standard food media with 1mg/ml and 10 mg/ml of WS.  The oxidative stress was induced by exposing the extract supplemented flies to Paraquat (20 mM).  The stress tolerance capacity of flies was measured by subjecting to desiccation and oxidative stresses. Further, locomotor activity, lipid peroxidation were also studied along with the quantification of triglycerides, glycogen in WS fed flies under stress conditions. Our result reveals that PQ induced WS fed flies showed greater survivability, better locomotor ability when compared to PQ induced flies.WS fed flies increases about 73.55% of resistance ability under oxidative conditions and increased by 59.15% under desiccation than PQ induced flies. WS was more effective in protecting against Paraquat toxicity. The flies fed with high dose of WS (10mg/ml) showed greater improvement of the tolerance ability when subjected to desiccation and oxidative stresses. Further, the data on biochemical analysis reveals that lipid peroxidation activities were found to be significantly low and the triglyceride as well as glycogen quantities were found to be significantly high in WS fed flies compare to –ve control under both desiccation and oxidative stress conditions.  Together, these findings suggest that WS promotes stress resistant ability by modulating metabolism and reducing oxidative damage. Keywords: Drosophila melanogaster, Withania somnifera, Oxidative stress assay, Desiccation Assay, Negative Geotaxis,

Amyotrophic Lateral Sclerosis is a progressive, incurable amyloid aggregating neurodegenerative disease involving the motor neurons. Identification of potential biomarkers and therapeutic targets can assist in the better management of the disease. We used an integrative approach encompassing analysis of transcriptomic datasets of human and mice from GEO database. Our analysis of ALS patient datasets showed deregulation in Non-alcoholic fatty acid liver disease and oxidative phosphorylation. Transgenic mice datasets pertaining to SOD1, FUS and TDP-43 showed deregulation in oxidative phosphorylation and ribosome associated pathways. Commonality analysis between the human and mice datasets showed oxidative phosphorylation as a major deregulated pathway among the different datasets. Further, gene expression analysis of mitochondrial electron transport chain show downregulation of genes belonging to Complex I and IV. The results were then validated using the yeast model system. Inhibitor studies using metformin (complex-I inhibitor) and malonate (complex-II inhibitor) did not have any effect in mitigating the amyloids while antimycin (complex-III inhibitor) and azide (complex-IV inhibitor) reduced amyloidogenesis. Knock-out of QCR8 (complex-III) or COX8 (complex–IV) completely cleared the amyloids. Taken together, our results show a critical role for mitochondrial oxidative phosphorylation in amyloidogenesis and as a potential therapeutic target in ALS.