Kaempferol counteracts bupivacaine‐induced neurotoxicity in mouse dorsal root ganglia neurons by regulating TRAF6‐dependent NF‐κB signaling

Abstract Kaempferol (KA), a widely recognized anti‐oxidation and anti‐inflammation agent, has been reported to have neuroprotective effects. This work aimed to investigate whether KA protects mouse dorsal root ganglia (DRG) neurons against bupivacaine (BU)‐stimulated neurotoxicity and explore the underlying mechanisms. In this study, BU treatment suppressed DRG neuron viability and promoted LDH leakage, which was partially abated by KA. Besides, BU‐triggered DRG neuron apoptosis, and changes in Bax and Bcl‐2 levels were attenuated by KA treatment. In addition, pretreatment with KA substantially reduced interleukin (IL)‐6, IL‐1β, and tumor necrosis factor (TNF)‐α levels in BU‐treated DRG neurons. In addition, KA administration abrogated BU‐induced decline in CAT, SOD, and GSH‐Px levels, as well as the increase in the malondialdehyde level. Interestingly, we found that KA significantly attenuated BU‐induced TNF receptor‐associated factor 6 (TRAF6) upregulation as well as NF‐κB activation. Furthermore, oe‐TRAF6‐mediated TRAF6 overexpression promoted NF‐κB activation and partly abolished KA‐induced protection against BU‐triggered neurotoxic effects on DRG neurons. Our results revealed that KA mitigated BU‐induced neurotoxic effects on DRG neurons by deactivating the TRAF6/NF‐κB signaling.