Therapeutic potential of nicotine in modulating oxidative and mitochondrial pathways in a C. elegans Parkinson's disease model.

Parkinson's disease (PD) is one of the most widespread neurodegenerative diseases that affect the central nervous system (CNS) in elderly individuals. As of right now, there is no recognized cure for this illness. Bioactive phytochemicals are a natural alternative that can help older persons postpone age-related cognitive diseases. This study attempts to establish whether nicotine, may diminish Parkinsonism in a model of Caenorhabditis elegans disease. This study analyzes the antioxidant and restorative mitochondrial dysfunction potential of nicotine and its related neuroprotective benefits by utilizing models of Caenorhabditis worm strains that are different from the wild type. We examined the effects of nicotine on oxidative stress tolerance and associated regulatory pathways using a model of Caenorhabditis worms. Our results showed that wild-type C. elegans treated with nicotine had higher survival rates during oxidative stress caused by Juglone than those treated with the control. Nicotine decreased intracellular reactive oxygen species levels in C. elegans. In addition, nicotine increased levels of SOD, CAT, and MDA as well as the expression of genes related to stress response, including gst-4, hsf-6, and hsf-1, and mitochondrial function genes, including mev-1, isp-1, and cox-4. Finally, our molecular analysis indicates that the anti-oxidative effects of nicotine are mediated via skin-1 modulation. After Paraquat was administered, nicotine therapy also resulted in higher levels of ATP and MMP. Our research clarifies the various mechanisms of action and communication pathways that underlie nicotine's antioxidant activity in vivo, offering a solid pharmacological foundation for its potential therapeutic use in neurodegeneration.