β-Sitosterol alleviates neuropathic pain by affect microglia polarization through inhibiting TLR4/NF-κB signaling pathway

Abstract The etiology of neuropathic pain is mostly due to 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 TLR4 expression levels and NF-κB activation associated with inflammatory responses. In cellular experiments, we could clearly see that both β-sitosterol and TLR4/NF-κB signaling pathway inhibitor could inhibit M1 pro-inflammatory phenotype expression and promote M2 anti-inflammatory phenotype expression in microglia GMI-R1 by flow cytometry and immunofluorescence assays. Therefore, we suggest that β-sitosterol can affect microglia polarization by inhibiting TLR4/NF-κB signaling pathway thereby reducing neuroinflammation and thus alleviating neuropathic pain.