Anti-Neuroinflammatory Effects of Safinamide on Lipopolysaccharide-Stimulated BV-2 Microglia

Background: Parkinson's disease (PD) is a neurodegenerative disease that affects the dopaminergic pathway, leading to both motor and non-motor symptoms. Neuroinflammation is a critical component of PD pathophysiology. The first-line medication for PD, levodopa, is used to alleviate motor symptoms but is often associated with significant side effects, especially with chronic use. Safinamide, a monoamine oxidase (MAO) inhibitor, has shown promise in mitigating these side effects. Given the accumulating evidence that neuroinflammation plays a pivotal role in the progression of neurodegenerative diseases, elucidating safinamide’s potential therapeutic effects in this context has become increasingly critical. This study investigates the anti-neuroinflammatory effects of safinamide on lipopolysaccharide (LPS)-stimulated BV-2 microglia. Objective: The aim of this study was to evaluate the anti-neuroinflammatory effects of safinamide in LPS-stimulated BV-2 microglia. Specific objectives include assessing the effects of safinamide on cell viability, cytokines level, and nitric oxide (NO) production in the LPS-induced BV-2 microglia. Methodology: The 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used to determine the maximum non-toxic dose (MNTD) of safinamide and the optimum LPS concentration in BV-2 cells. Additionally, the cell rescue effect of safinamide in LPS-induced BV-2 cells was investigated. Enzyme-linked immunosorbent (ELISA) assays were used to measure the levels of interleukin (IL)-6, tumour necrosis factor (TNF)-α, and IL-10 in both safinamide-treated and non-treated LPS- induced BV-2 cells. The Griess assay was used to evaluate the anti-oxidative effect of safinamide by measuring NO levels in LPS-induced BV-2 cells. Results: The MNTD of safinamide in BV-2 cells was determined to be 18 μM, and the optimum LPS concentration to activate microglia was 1 μg/mL. Safinamide significantly increased the cell viability of LPS-induced BV-2 cells. It significantly decreased IL-6 production, modestly decreased TNF-α production, and significantly increased IL-10 production. However, safinamide at the MNTD did not reduce NO levels; instead, it increased them in the LPS-induced BV-2 microglia. Conclusion: Safinamide attenuated LPS-induced BV-2 microglial cell death, likely due to its anti- inflammatory effects. It suppressed the LPS-induced increases in proinflammatory cytokines IL-6 and TNF-α production while reversing the suppression of the anti-inflammatory cytokine IL-10 production. However, safinamide increased nitric oxide production at the MNTD, indicating a complex role in oxidative stress responses. These findings suggest that safinamide may provide therapeutic benefits in managing PD-associated neuroinflammation. Further studies are warranted to elucidate the mechanisms underlying its effects on oxidative stress responses and to explore its clinical implications in PD therapy towards good health and well-being.