Ameliorative potential of metformin in LPS and glutamate-induced neurotoxicity in N2a cell-line.

The study aims to explore the potential of metformin to counteract the lethal effects of glutamate and lipopolysaccharide (LPS)- induced neurotoxicity in Neuro2a (N2a) cells, resembling CNS-comorbidities generally associated with metabolic disorders. Glutamate and LPS-induced N2a cell models were used to conduct the in-vitro study to evaluate the beneficial effect of metformin. Cell viability assay, biochemical parameter viz. cytokines level, superoxide dismutase (SOD) was performed. Further, reactive oxygen species (ROS) were also staged using the Fluorescence-Activated Cell Sorting (FACS) technique to evaluate the beneficial effect of metformin on oxidative stress. Metformin treatments during the study revealed neuroprotective effects and abridged neurotoxicity by significantly reducing the levels of cytokines (viz. IL-1β, IL-6, and TNF-α), raising SOD enzyme activities and declining the ROS levels in LPS and glutamate-treated N2a cells. Based on experimental observation, in an in-vitro study, the effective dose of Met was 50 µM. The results showed that metformin had a neuroprotective effect by enhancing cell viability, diminishing the cytokine storm, and reducing various oxidative stressors. These findings imply that due to the anti-inflammatory, diminishing reactive oxidative species, and antioxidant properties of metformin, it can be considered a therapeutic drug candidate for treating and managing neurological disorders and CNS complications associated with metabolic abnormalities. Further, an in-vivo mechanistic study is warranted to validate the safety and efficacy of metformin for neurological disorders associated with metabolic abnormalities and neurodegenerative disorders.