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.