title: 7,8-dihydroxycoumarin may promote sciatic nerve regeneration by suppressing NF-κB expression in mice.
abstract: 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.
authors.affiliation: Department of Neurology, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.
authors.forename: Jian-Shi
authors.initials: JS
authors.lastname: Du
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhao
authors.forename: Ying-Li
authors.initials: YL
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Ma
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D009416:Nerve Regeneration / Q000187:drug effects*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D014468:Umbelliferones / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D012333:RNA, Messenger; D014468:Umbelliferones; C039952:daphnetin