The circadian clock regulates vital aspects of physiology including protein synthesis and oxidative stress response. In this investigation, we performed a proteome-wide scrutiny of rhythmic protein accrual in Drosophila melanogaster on exposure to rotenone, rotenone + hesperidin and hesperidin in D. melanogaster. Total protein from fly samples collected at 6 h intervals over the 24 h period was subjected to two-dimensional gel electrophoresis and mass spectrometry. Bioinformatics tool, Protein ANalysis THrough Evolutionary Relationships classification system was used to the determine the biological processes of the proteins of altered abundance. Conspicuous variations in the proteome (151 proteins) of the flies exposed to oxidative stress (by rotenone treatment) and after alleviating oxidative stress (by hesperidin treatment) were observed during the 24 h cycle. Significantly altered levels of abundance of a wide variety of proteins under oxidative stress (rotenone treatment) and under alleviation of oxidative stress (rotenone + hesperidin treatment) and hesperidin (alone) treatment were observed. These proteins are involved in metabolism, muscle activity, heat shock response, redox homeostasis, protein synthesis/folding/degradation, development, ion-channel/cellular transport, and gustatory and olfactory function of the flies. Our data indicates that

Objective: To assess the dose-dependent effect of vanillic acid on cognitive behavior and indices of redox homeostasis in the fruit fly, Drosophila melanogaster. Methods: In this study, flies were divided into five groups-group 1 control, group 2-treated with 0.01% NDEA through drinking water for 15 w, group 3-treated with NDEA and vanillic acid (VA) (0.005%) in culture medium, group 4-treated with NDEA and VA (0.01%) and group 5-treated with NDEA and VA (0.05%). Cognitive-behavioral assays and assessment of redox homeostasis indices were performed. Results: Behavioural abnormalities (negative geotaxis, phototaxis, smell and taste chemotaxis, hypotaxis and thermotaxis) were quantitatively deviated in NDEA treated flies compared to control but were tend to be normalized in VA treated flies. The contents of protein carbonyl, thiobarbituric acid reactive substance (TBARS), protein thiol and lipid peroxides were noticeably augmented in NDEA treated flies than control flies and correspondingly tend to normalize in VA (0.01%) treated groups. Further, superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione peroxidise (GPX) and reduced glutathione (GSH) were decreased in NDEA treated group and were significantly increased (p<0.05) in VA treated (0.01%) groups. Conclusion: Vanillic acid, a bioactive phytochemical could act as a potent antioxidant and as well exhibit antiproliferative characteristics. The dose lower than 0.01% could not be effective as the dose is low. Nevertheless, at 0.01% the maximum benefits could have been achieved, and beyond this saturation point, higher doses, such as 0.05% could not be effective.