β-Sitosterol Alleviates Neuropathic Pain by Affect Microglia Polarization through Inhibiting TLR4/NF-κB Signaling Pathway.

Abstract

The etiology of neuropathic pain is mostly caused by mechanical deformation and neuroinflammation, of which neuroinflammation is the main cause of chronic neuropathic pain. Activation of the TLR4/NF-κB signaling pathway mediates elevated levels of inflammatory cytokines, and we clearly demonstrated by in vivo and in vitro Western blot experiments that β-sitosterol significantly inhibited the elevated Toll-like receptor 4 (TLR4) expression levels and nuclear factor-kappa B (NF-κB) activation associated with inflammatory responses. In cellular experiments, we clearly saw that both β-sitosterol and TLR4/NF-κB signaling pathway inhibitors could inhibit M1 proinflammatory phenotype expression and promote M2 anti-inflammatory phenotype expression in GMI-R1 microglia by flow cytometry and immunofluorescence assays. Therefore, we suggest that β-sitosterol can affect microglial polarization by inhibiting the TLR4/NF-κB signaling pathway thereby reducing neuroinflammation and thus alleviating neuropathic pain.