Safinamide prevents lipopolysaccharide (LPS)-induced inflammation in macrophages by suppressing TLR4/NF-κB signaling

•Safinamide reduced LPS-induced expression of IL-1α, IL-6, TNF-α, CXCL1, CCL2, MMP-2, and MMP-9 in U937 macrophages;•Safinamide prevented LPS-induced expression of COX-2, iNOS, and the production of PGE2 and NO;•Safinamide prevented activation of NF-κB mediated by Nrf2 in U937 macrophages. Inflammation is a basal host defense response that eliminates the causes and consequences of infection and tissue injury. Macrophages are the primary immune cells involved in the inflammatory response. When activated by LPS, macrophages release various pro-inflammatory cytokines, chemokines, inflammatory mediators, and MMPs. However, unbridled inflammation causes further damage to tissues. Safinamide is a selective and reversible monoamine oxidase B (MAOB) inhibitor that has been used for the treatment of Parkinson's disease. In this study, we aimed to investigate whether safinamide has effects on LPS-treated macrophages. Our results show that safinamide inhibited the expression of pro-inflammatory cytokines such as IL-1α, TNF-α, and IL-6. Furthermore, safinamide suppressed the production of CXCL1 and CCL2, thereby preventing leukocyte migration. In addition, safinamide reduced iNOS-derived NO, COX-2-derived PGE2, MMP-2, and MMP-9. Importantly, the functions of safinamide mentioned above were found to be dependent on its inhibitory effect on the TLR4/NF-κB signaling pathway. Our data indicates that safinamide may exert a protective effect against inflammatory response.