Kaempferol exerts a neuroprotective effect to reduce neuropathic pain through TLR4/NF-ĸB signaling pathway

Switching microglial polarization from the M1 to M2 phenotype is a promising therapeutic strategy for neuropathic pain (NP). Toll-like receptor 4 (TLR4) is activated by lipopolysaccharide (LPS). Uncontrolled activation of TLR4 has been proven to trigger chronic inflammation. Kaempferol, a dietary flavonoid, is known to have anti-inflammatory properties. This study is aimed to investigate the analgesic and anti-inflammatory effects and the underlying mechanisms of kaempferol, which were explored with an NP model in vivo and LPS-induced injury in microglial BV2 cells in vitro. The levels of proinflammatory cytokines were evaluated. H&E staining and immunohistochemistry were used to assess the sciatic nerve condition after chronic constriction injury surgery. Western blotting and immunofluorescence were used to determine whether TLR4/NF-ĸB signaling pathway plays a major role in kaempferol-mediated alleviation of neuroinflammation. Quantitative real-time polymerase chain reaction and flow cytometry were used to examine the modulator effect of kaempferol on microglial M1/M2 polarization. We found that kaempferol treatment can significantly reduce NP and proinflammatory cytokine production. Kaempferol attenuated the activation of TLR4/NF-κB pathways in LPS-activated BV2 cells. The analgesic effects of kaempferol on NP may be due to inhibition of microglia activation and switching the M1 to M2 phenotype.