Neuroprotective Effect of Imeglimin Hydrochloride on H2O2-Induced SH-SY5Y Cells.

Abstract

Introduction: Alzheimer's disease is characterized by cognitive decline accompanied by the degeneration of cholinergic neurons. Notably, ROS make neurons more vulnerable to oxidative stress-induced damage and functional impairment in the brain. Hence, this research aimed to explore the antioxidant and neuroprotective activities of Imeglimin HCl in the SH-SY5Y cell line.

Methods: Initially, the cytotoxic effect of Imeglimin HCl at 6.25 and 12.5 μg/mL was determined using the MTT assay. Subsequently, the inhibitory effect of Imeglimin HCl on H2O2-induced Reactive Oxygen Species (ROS) in SH-SY5Y cells was carried out.

Results: The study demonstrated that 70% of cells were viable up to 12.5 μg/mL. The ROS inhibition assay showed that Imeglimin HCl inhibited the H2O2-induced ROS production in SH-SY5Y cells. It was concluded from the study that Imeglimin HCl has a neuroprotective effect.

Discussion: In SH-SY5Y cells, HⁿOⁿ exposure mimics AD-related oxidative damage by elevating ROS and impairing mitochondrial function. Excessive ROS generation induced by H2O2 compromises mitochondrial membrane stability, which in turn activates the intrinsic apoptotic pathway. In the present study, Imeglimin hydrochloride significantly attenuated HⁿOⁿ-induced ROS generation, indicating a protective effect against oxidative stress.

Conclusion: It was concluded from the study that Imeglimin hydrochloride acts on GABA-A and M2 Muscarinic acetylcholine receptors, which play a prominent role in AD, since it has a better binding affinity. In addition, Imeglimin HCl exhibited antioxidant properties in SH-SY5Y cell lines by reducing reactive oxygen species production.