7,8-dihydroxycoumarin may promote sciatic nerve regeneration by suppressing NF-κB expression in mice.Mol Med Rep 2013; 8(5):1525-30MM
Nuclear factor (NF)-κB expression occurs during sciatic injury. In addition, 7,8-dihydroxycoumarin exhibits a neurotrophic effect on peripheral nerve regeneration. To investigate the effects of 7,8-dihydroxycoumarin on the expression levels of NF-κB in L4-6 spinal cord segments of the injured sciatic nerve in mice and on the functional recovery and regeneration following nerve injury, a total of 160 healthy adult male BALB/c mice underwent unilateral sciatic nerve interruption and anastomosis. The mice were separated into groups and subsequently treated with physiological saline (control) or high, medium or low doses of 7,8-dihydroxycoumarin. NF-κB levels were detected by western blot analysis and quantitative polymerase chain reaction (qPCR), and the sciatic functional index (SFI) was measured. Neuronal apoptosis was detected by terminal-deoxynucleotidyl transferase dUTP-mediated nick-end labeling (TUNEL) staining. The results revealed that NF-κB was activated in the L4-6 spinal cord connected to the injured sciatic nerve. qPCR and western-blot analysis results showed that the expression levels of NF-κB in the high- and medium-dose groups were significantly lower compared with the low-dose and control groups at 12 h, one day, three days, five days and one week (P<0.05 for each). SFI and TUNEL results demonstrated that the high- and medium-dose groups exhibited improved functional nerve regeneration and reduced apoptosis compared with the low-dose and control groups. In conclusion, 7,8-dihydroxycoumarin is capable of suppressing the immune activation of NF-κB in the neurons of the L4-6 spinal cord connected with the injured sciatic nerve, thereby reducing the focal filtration of inflammatory cells, producing the optimum environment for nerve regeneration.