Neuroprotective role of Curcuma amada evidenced from pesticide-induced stressed Drosophila melanogaster: insights from RNAseq and gut microbiome analyses.

Prolonged exposure to pesticides is linked to neurodegenerative disorders through mechanisms involving oxidative stress, inflammation, and neuronal signaling. Therapeutic plants may offer a promising and natural alternative for protecting against such damage. Hence, the present study aims to understand the role of Curcuma amada in mitigating pesticide-induced neurotoxicity and its molecular mechanism in Drosophila. The pesticidal stress was induced in Drosophila through oral feed of ethion and its action was confirmed through behavioural assay. The stressed flies were treated with C. amada rhizome and the effect of both ethion and ethion +  C. amada was assessed through RNA profiling and gut microbiome analysis. Decrease in locomotory activity on exposure to ethion represents the induced neuronal stress and an increase was seen after C. amada was fed to the stressed flies. Many DEGs were identified through RNAseq results of stressed and C. amada treated which were further analysed using Cytoscape. In ethion and ethion + C. amada treated flies, the upregulated and downregulated genes were found to be associated with neuronal signal processing and mitochondrial function [MRPs, Dop2R, 5-HT1A, aminoacyl-tRNA synthetase (AARs), ND-B17]. A significant change in the gut microbial population (especially decrease in Lactiplantibacillus species) was observed in stressed flies. But the restoration of healthy bacterial population such as Lactiplantibacillus in C. amada treated flies evidencing the crucial role of gut microbiome in neuronal health. This study highlights the beneficial effects of C. amada from pesticidal stress which needs to be further researched to understand the underlying molecular mechanisms.