Abstract

(1) Background: Neosaxitoxin (NeoSTX) has been used as a local anesthetic, but its anti-inflammatory effects have not been well defined. In the present study, we investigate the effects of NeoSTX on lipopolysaccharide (LPS)-activated macrophages. (2) Methods: Raw 264.7 and equine PBMC cells were incubated with or without 100 ng/mL LPS in the presence or absence of NeoSTX (1 mu M). The expression of inflammatory mediators was assessed: nitric oxide (NO) content using the Griess assay, TNF-alpha content using the ELISA assay, and mRNA of inducible nitric oxide synthase (iNOS), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) using a real-time polymerase chain reaction. (3) Results: NeoSTX (1 mu M) significantly inhibited the release of NO, TNF-alpha, and expression of iNOS, IL-1 beta, and TNF-alpha in LPS-activated macrophages of both species studied. Furthermore, our study shows that the LPS-induced release of inflammatory mediators was suppressed by NeoSTX. Additionally, NeoSTX deactivated polarized macrophages to M1 by LPS without compromising its polarization towards M2. (4) Conclusions: NeoSTX inhibits LPS-induced release of inflammatory mediators from macrophages, and these effects may be mediated by the blockade of voltage-gated sodium channels (VGSC).