7,8-dihydroxycoumarin may promote sciatic nerve regeneration by suppressing NF-κB expression in mice

Du,Jian-Shi; Zhao,Qing; Zhang,Ying-Li; Wang,Yu; Ma,Ming

doi:10.3892/mmr.2013.1682

7,8-dihydroxycoumarin may promote sciatic nerve regeneration by suppressing NF-κB expression in mice

Authors:
- Jian-Shi Du
- Qing Zhao
- Ying-Li Zhang
- Yu Wang
- Ming Ma
View Affiliations

Affiliations: Department of Neurology, China-Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China
Published online on: September 13, 2013 https://doi.org/10.3892/mmr.2013.1682
Pages: 1525-1530

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View References

1	Iwatsuki K, Arai T, Ota H, Kato S, Natsume T, Kurimoto S, Yamamoto M and Hirata H: Targeting anti-inflammatory treatment can ameliorate injury-induced neuropathic pain. PLoS One. 8:e577212013. View Article : Google Scholar : PubMed/NCBI
2	Camara-Lemarroy CR, Gonzalez-Moreno EI, Guzman-de la Garza FJ and Fernandez-Garza NE: Arachidonic acid derivatives and their role in peripheral nerve degeneration and regeneration. ScientificWolrdJournal. 2012:1689532012.PubMed/NCBI
3	Stern S, Sinske D and Knöll B: Serum response factor modulates neuron survival during peripheral axon injury. J Neuroinflammation. 9:782012. View Article : Google Scholar : PubMed/NCBI
4	Que J, Cao Q, Sui T, Du S, Kong D and Cao X: Effect of FK506 in reducing scar formation by inducing fibroblast apoptosis after sciatic nerve injury in rats. Cell Death Dis. 4:e5262013. View Article : Google Scholar : PubMed/NCBI
5	Azizi S, Mohammadi R, Amini K and Fallah R: Effects of topically administered FK506 on sciatic nerve regeneration and reinnervation after vein graft repair of short nerve gaps. Neurosurg Focus. 32:E52012. View Article : Google Scholar : PubMed/NCBI
6	Yan Y, Sun HH, Hunter DA, Mackinnon SE and Johnson PJ: Efficacy of short-term FK506 administration on accelerating nerve regeneration. Neurorehabil Neural Repair. 26:570–580. 2012. View Article : Google Scholar : PubMed/NCBI
7	Li X, Wang W, Wei G, Wang G, Zhang W and Ma X: Immunophilin FK506 loaded in chitosan guide promotes peripheral nerve regeneration. Biotechnol Lett. 32:1333–1337. 2010. View Article : Google Scholar : PubMed/NCBI
8	Wang MS and Gold BG: FK506 increase the regeneration of spinal cord axons in a predegenerated peripheral nerve autograft. J Spinal Cord Med. 22:287–296. 1999.PubMed/NCBI
9	Jost SC, Doolabh VB, Mackinnon SE, Lee M and Hunter D: Acceleration of peripheral nerve regeneration following FK506 administration. Restor Neurol Neurosci. 17:39–44. 2000.PubMed/NCBI
10	Phan DQ and Schuind F: Tolerance and effects of FK506 (tacrolimus) on nerve regeneration: a pilot study. J Hand Surg Eur Vol. 37:537–543. 2012. View Article : Google Scholar : PubMed/NCBI
11	Jifeng H, Dezhong L, Qiongjiao Y, Huayong Z and Shipu L: Evaluation of PRGD/FK506/NGF conduits for peripheral nerve regeneration in rats. Neurol India. 58:384–391. 2010. View Article : Google Scholar : PubMed/NCBI
12	Rustemeyer J and Dicke U: Allografting combined with systemic FK506 produces greater functional recovery than conduit implantation in a rat model of sciatic nerve injury. J Reconstr Microsurg. 26:123–129. 2010. View Article : Google Scholar : PubMed/NCBI
13	Sibilia J and Griscelli C: Immunotherapy of inflammatory diseases, 2005. Expert Opin Biol Ther. (Suppl 1): S1–13. 2005. View Article : Google Scholar : PubMed/NCBI
14	Zheng BR, Shen JP, Zhuang HF, Lin SY, Shen YP and Zhou YH: Treatment of severe aplastic anemia by immunosuppressor anti-lymphocyte globulin/anti-thymus globulin as the chief medicine in combination with Chinese drugs. Chin J Integr Med. 15:145–148. 2009. View Article : Google Scholar : PubMed/NCBI
15	Xue B, Jiao J, Zhang L, Li KR, Gong YT, Xie JX and Wang XM: Triptolide upregulates NGF synthesis in rat astrocyte cultures. Neurochem Res. 32:1113–1119. 2007. View Article : Google Scholar : PubMed/NCBI
16	Yang G: Trends of research on immunology of Chinese materia medica. Zhongguo Chong Xi Yi Jie He Za Zhi. 19:259–260. 1999.(In Chinese).
17	Cao J, Niu Z, Wang Y, Jiang Y, et al: Immune reactions and nerve repair in mice with sciatic nerve injury 14 days after intraperitoneal injection of Brazil. Neural Regen Res. 7:675–679. 2012.PubMed/NCBI
18	Yan L, Zhou X, Zhou X, Zhang Z and Luo HM: Neurotrophic effects of 7,8-dihydroxycoumarin in primary cultured rat cortical neurons. Neurosci Bull. 28:493–498. 2012. View Article : Google Scholar : PubMed/NCBI
19	Du J, Zhao Q, Zhang Y, Wang Y and Ma M: 7,8-dihydroxycoumarin improves neurological function in a mouse model of sciatic nerve injury. Neural Regen Res. 7:445–450. 2012.PubMed/NCBI
20	Ojala T, Remes S, Haansuu P, Vuorela H, Hiltunen R, Haahtela K and Vuorela P: Antimicrobial activity of some coumarin containing herbal plants growing in Finland. J Ethnopharmacol. 73:299–305. 2000. View Article : Google Scholar : PubMed/NCBI
21	Wang CH, Wang B, Wendu RL, Bi HE, Cao GF, Ji C, Jiang Q and Yao J: Protective role of Wallerian degeneration slow (Wlds) gene against retinal ganglion cell body damage in a Wallerian degeneration model. Exp Ther Med. 5:621–625. 2013.PubMed/NCBI
22	Li M, Guo W, Zhang P, Li H, Gu X and Yao D: Signal flow and pathways in response to early Wallerian degeneration after rat sciatic nerve injury. Neurosci Lett. 536:56–63. 2013. View Article : Google Scholar : PubMed/NCBI
23	Sun SC, Ganchi PA, Ballard DW and Greene WC: NF-kappa B controls expression of inhibitor I kappa B alpha: evidence for an inducible autoregulatory pathway. Science. 259:1912–1915. 1993. View Article : Google Scholar : PubMed/NCBI
24	Chen F, Castranova V and Shi X: New insights into the role of nuclear factor-kappa B in cell growth regulation. Am J Pathol. 159:387–397. 2001. View Article : Google Scholar : PubMed/NCBI
25	Meffert MK, Chang JM, Wiltgen BJ, Fanselow MS and Baltimore D: NF-kappa B functions in synaptic signaling and behavior. Nat Neurosci. 6:1072–1078. 2003. View Article : Google Scholar : PubMed/NCBI
26	Brambilla R, Bracchi-Ricard V, Hu WH, Frydel B, Bramwell A, Karmally S, Green EJ and Bethea JR: Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves functional recovery after spinal cord injury. J Exp Med. 202:145–156. 2005. View Article : Google Scholar : PubMed/NCBI
27	The Ministry of Science and Technology of the People’s Republic of China. Guidance suggestions for the care and use of Laboratory Animals. 2006.
28	Huang JH, Huang XZ, Chen ZY, Zheng QS and Sun RY: Dose conversion among different animals and healthy volunteers in pharmacological study. Chin J Clin Pharmacol Therapeut. 9:1069–1072. 2004.(In Chinese).
29	Chen G, Gong M, Yan M and Zhang X: Sevoflurane induces endoplasmic reticulum stress mediated apoptosis in hippocampal neurons of aging rats. PLoS One. 8:e578702013. View Article : Google Scholar : PubMed/NCBI