Dietary Curcumin Attenuates Arsenic-Induced Oxidative Stress and Neurobehavioral Impairments in Drosophila melanogaster: Mechanistic Insights from In Vivo and In Silico Analyses

Arsenic toxicity remains a critical environmental and public health issue due to its association with oxidative stress, neurodegeneration, and motor dysfunction. This study investigated the protective efficacy of curcumin, a natural polyphenol derived from Curcuma longa, against arsenic trioxide (As₂O₃)-induced toxicity in Drosophila melanogaster. A sublethal concentration of 0.5 mM As₂O₃ induced a 50% mortality rate, while 0.75 mM resulted in complete lethality, confirming arsenic’s dose-dependent toxicity. Oxidative stress biomarkers, including lipid peroxidation (LPO) and catalase activity, were significantly elevated in arsenic-exposed flies, indicating substantial oxidative damage. Co-administration of 1 mM curcumin markedly improved survivability, reduced malondialdehyde (MDA) levels, and restored catalase activity, underscoring its potent antioxidative properties. Additionally, arsenic exposure impaired climbing ability—a behavioral marker of motor dysfunction—which was effectively ameliorated by curcumin supplementation. Computational analysis using the STRING database revealed that curcumin interacts with key proteins involved in cellular metabolism and redox homeostasis, including cytochrome P450 enzymes, glutathione S-transferases, and peroxisome proliferator-activated receptors. Gene ontology (GO) enrichment further highlighted curcumin’s role in modulating oxidative stress and metabolic pathways. These findings suggest that curcumin mitigates arsenic toxicity by enhancing antioxidant defenses and restoring metabolic equilibrium. The integration of in vivo experiments with bioinformatics tools provides mechanistic insights into curcumin’s neuroprotective effects, supporting its potential as a dietary intervention in arsenic-exposed populations. Future studies should explore its efficacy in mammalian models and clinical applications to validate its therapeutic utility.