IMD-1 Protects SH-SY5Y Cells Against H2O2-Induced Oxidative Injury Through Modulation of Oxidative Stress, Mitochondrial Bioenergetics, Inflammatory Mediator Release, and Apoptosis-Related Responses.

Oxidative stress, mitochondrial dysfunction, inflammation-associated cellular responses, and apoptosis are closely associated with the pathogenesis of neurodegenerative disorders. Therefore, identifying small molecules capable of modulating these interconnected cellular processes is important for the development of potential neuroprotective strategies. The present study investigated the protective effects of the imidazole derivative (IMD)-1 against hydrogen peroxide (H2O2)-induced oxidative injury in SH-SY5Y human neuroblastoma cells using integrated in vitro and in silico approaches. IMD-1 exhibited strong radical scavenging activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, reaching 96.8% inhibition at 1000 µg/mL, which was comparable to the butylated hydroxyl toluene (BHT). IMD-1 pre-treatment significantly restored cell viability, reduced reactive oxygen species (ROS) production, and preserved mitochondrial membrane potential. IMD-1 also attenuated adenosine triphosphate (ATP) depletion. Moreover, IMD-1 reduced H2O2-induced increases in selected inflammation-associated mediators, including interleukin (IL)-2, IL-6, IL-12, vascular endothelial growth factor (VEGF), monocyte chemoattractant protein (MCP)-1, and interferon-gamma (IFN-γ). IMD-1 reduced apoptotic cell death and modulated apoptosis-related cellular and transcriptional responses. Molecular docking suggested a possible interaction between IMD-1 and caspase-8, providing hypothesis-generating support for the apoptosis-related findings. Overall, these findings suggest that IMD-1 attenuates H2O2-induced oxidative injury in SH-SY5Y cells as evidenced by changes in oxidative stress, mitochondrial dysfunction, ATP-associated bioenergetic impairment, inflammatory mediator release, and apoptosis-related responses. However, further protein-level, biochemical, and in vivo studies are required to determine the broader neurobiological and translational relevance of these findings.