Effects of Nicotine on SH-SY5Y Cells: An NMR-Based Metabolomic Study

Background/Objectives: Nicotine is a naturally occurring alkaloid primarily found in Nicotiana tabacum. This phytochemical is well known for its addictive properties, and its consumption-particularly through tobacco smoking-is strongly associated with an increased risk of malignancies, metabolic dysfunctions, and cardiovascular as well as respiratory diseases. Despite these adverse effects, several studies have also reported beneficial actions of nicotine, including the enhancement of cognitive functions in several neurodegenerative diseases. Methods: To better elucidate the multiple effects of nicotine and clarify their underlying mechanisms, we performed an NMR-based metabolomic analysis of SH-SY5Y neuroblastoma cells exposed to nicotine action. Results: Our results indicate that nicotine modulates mitochondrial function and membrane turnover, thereby influencing mitochondrial bioenergetics, synaptic plasticity, and connectivity. Conclusions: Collectively, these findings may contribute, at least in part, to explaining the neuroprotective effects of nicotine described in preclinical models of neurodegenerative disease.