Effect of Gyehyuldeung Treatments in Peripheral Nerve Regeneration of Rat

계혈등(鷄血藤)이 Rat의 말초신경 재생에 미치는 효과

  • Lim, Seung-Min (Dept. of Internal Medicine, College of Oriental Medicine, Dae-jeon Univers) ;
  • Ahn, Jung-Jo (Dept. of Internal Medicine, College of Oriental Medicine, Dae-jeon Univers) ;
  • Jo, Hyun-Kyung (Dept. of Internal Medicine, College of Oriental Medicine, Dae-jeon Univers) ;
  • Yoo, Ho-Ryong (Dept. of Internal Medicine, College of Oriental Medicine, Dae-jeon Univers) ;
  • Kim, Yoon-Sik (Dept. of Internal Medicine, College of Oriental Medicine, Dae-jeon Univers) ;
  • Seol, In-Chan (Dept. of Internal Medicine, College of Oriental Medicine, Dae-jeon Univers)
  • 임승민 (대전대학교 한의과대학 심계내과학교실) ;
  • 안정조 (대전대학교 한의과대학 심계내과학교실) ;
  • 조현경 (대전대학교 한의과대학 심계내과학교실) ;
  • 유호룡 (대전대학교 한의과대학 심계내과학교실) ;
  • 김윤식 (대전대학교 한의과대학 심계내과학교실) ;
  • 설인찬 (대전대학교 한의과대학 심계내과학교실)
  • Published : 2009.06.30

Abstract

Objective : Gyehyuldeung (GHD) has been widely used in oriental medicine for the treatments of cardiovascular and neurological disorders. Thus, its potential facilitatory activity on axonal regeneration was investigated in the rats. Methods: Sprague-Dawley rats were given crush injury at the sciatic nerve and the changes of axon growth after nerve injury on each nerve injury model were investigated with anti-NF-200 antibody, DiI, GAP-43 protein and Cdc2 protein Results : GHD-mediated enhancement of axonal regeneration after crush injury was measured in both qualitative and quantitative ways by immunofluorescence staining with anti-NF-200 antibody and retrograde tracing of fluorescence dye DiI. GAP-43 protein levels were elevated by GHD treatments in the distal injured sciatic nerve and DRG sensory neurons. The neurite outgrowth of DRG sensory neurons was facilitated by GHD treatment when co-cultured with Schwann cells and astrocytes prepared from injured sciatic nerves and injured spinal cord tissues, respectively. It was observed that Cdc2 protein was up-regulated in co-cultured Schwann cells or astrocytes and Cdc2 protein signals were co-localized to a certain extent with those of phospho-vimentin protein. Conclusions : These results suggest that GHD may play a facilitatory role in axonal regeneration by acting on the injured axons and adjacent non-neuronal cells. The current findings may be useful for the development of therapeutic targets through more specific explorations on molecular interactions between herbal components and endogenous factors.

Keywords

References

  1. David S, Aguayo AJ. Axonal regeneration after crush injury of rat central nervous system fibers innervating peripheral nerve grafts. J Neurocytol. 1985;14(1):1. https://doi.org/10.1007/BF01150259
  2. Fawcett. Peripheral nerve regeneration in Brain damage, Brain repair, edited by JW Fawcett, AE Rosser, SB Dunnett, Oxford University Press(NY)2001:145-54.
  3. Chen YS. Wu CH. Yao CH. Chen CT. Ginsenoside Rb1 enhances peripheral nerve regeneration across wide gaps in silicone rubber chambers. Int J Artif Organs. 2002 Nov;25(11):1103-8.
  4. 전국한의과대학 심계내과학교실. 심계내과학. 서울: 군자출판사;2006, p. 343-58.
  5. Jo HK, NamGung U, Seol IC, Kim YS. Growth Promotiong Effects of Oriental Medical Drugs on Sciactic Nerve Regeneration in the Rat. Korean J. Oriental Physiology& Pathology. 2005;19(6): 1666-72.
  6. Han KS, Seol IC, Ryu HR, Jo HK, An, JJ, NamGung, U, Kim YS. Improved Regenerative Responses of Injured Spinal Cord Nerve Fibers by the Treatment of Sukjihwang(Rehmanniae radix preparat). Korean J. Oriental Physiology&Pathology. 2007;21(6):1569-75.
  7. Kim JH, Seol IC, Ryu HR, Jo HK, An JJ, Namgung U, Kim YS. Facilitated Axonal Regeneration of Injured Sciactic Nerves by Yukmijihwang-tang Treatment, Korean J. Oriental Physiology&Pathology. 2008;22(4):896-902.
  8. Baek KM, Kim YS, Ryu HR, Jo HK, An JJ, Namgung U, Seol IC. Sengmaek-san-mediated Enhancement of Axonal Regeneration after Sciatic Nerve Injury in the Rat. Korean J. Oriental Physiology&Pathology. 2008;22(2):431-7.
  9. 趙學敏. 本草綱目拾遺. 북경:중국중의학출판사; 1998, p. 230-3.
  10. 전국한의과대학 본초학교수 공편저. 본초학. 서울: 영림사;1994, p. 445-6.
  11. 이상록, 정현우. 鷄血藤이 뇌혈류량 및 Lactate Dehydrogenase활성에 미치는 실험적 효과. 동의생리병리학회지. 2006;20(1):25-30.
  12. 서해경, 오민석, 김동희. 류마토이드 關節炎 患者 滑膜細胞에 대한 鷄血藤의 免疫反應. 동의생리병리학회지. 2003;17(3):780-6.
  13. 권용수, 이진훈, 김창민. 계혈등(Mucuna birdwoodiana) 의 3$\alpha$-Hydroxysteroid dehydrogenase 억제 성분. 생약학회지. 1999;30(2):216-21.
  14. 李宇彬. 抗癌中藥藥理與應用. 黑龍江:黑龍江科學技術出版社;1999, p. 745-7.
  15. 차배천, 이은희, 노미애. 계혈등의 항산화 활성. 생약학회지. 2005;36(1):50-5.
  16. Liao B, Newmark H, Zhou R. Neuroprotective effects of ginseng total saponin and ginsenosides Rb1 and Rg1 on spinal cord neurons in vitro. Exp Neurol. 2002;173(2):224-34. https://doi.org/10.1006/exnr.2001.7841
  17. Hafidi A, Romand R. First appearance of type II neurons during ontogenesis in the spiral ganglion of the rat. An immunocytochemical study. Brain Res Dev Brain Res. 1989;48(1):143-9. https://doi.org/10.1016/0165-3806(89)90098-9
  18. Skene JH. Axonal growth-associated proteins. Annu Rev Neurosci. 1989;12:127-56. https://doi.org/10.1146/annurev.ne.12.030189.001015
  19. Benowitz, L.I., Routenberg, A. A membrane phosphorylation associated with neuronal development, axonal regulation, phospholipid metabolism and synaptic plasticity. Trends Neurosci. 1987;10:527-31. https://doi.org/10.1016/0166-2236(87)90135-4
  20. Perrone-Bizzozero NI, Cansino VV, Kohn DT. Posttranscriptional regulation of GAP-43 gene expression in PC12 cells through protein kinase C-dependent stabilization of the mRNA. J Cell Biol. 1993 Mar;120(5):1263-70. https://doi.org/10.1083/jcb.120.5.1263
  21. Curtis R, Stewart HJ, Hall SM, Wilkin GP, Mirsky R, Jessen KR. GAP-43 is expressed by nonmyelin -forming Schwann cells of the peripheral nervous system. J Cell Biol. 1992 Mar;116(6):1455-64. https://doi.org/10.1083/jcb.116.6.1455
  22. Aigner L, Arber S, Kapfhammer JP, Laux T, Schneider C, Botteri F, Brenner HR, Caroni P. Overexpression of the neural growth-associated protein GAP-43 induces nerve sprouting in the adult nervous system of transgenic mice. Cell. 1995 Oct 20;83(2):269-78. https://doi.org/10.1016/0092-8674(95)90168-X
  23. Strittmatter SM, Fankhauser C, Huang PL, Mashimo H, Fishman MC. Neuronal pathfinding is abnormal in mice lacking the neuronal growth cone protein GAP-43. Cell. 1995 Feb 10;80(3):445-52. https://doi.org/10.1016/0092-8674(95)90495-6
  24. Apel ED, Byford MF, Au D, Walsh KA, Storm DR. Identification of the protein kinase C phosphorylation site inneuromodulin. Biochemistry. 1990 Mar 6;29(9):2330-5. https://doi.org/10.1021/bi00461a017
  25. Smith DS, Skene JH. A transcription-dependent switch controls competence of adult neurons for distinct modes of axon growth. J Neurosci. 1997 Jan 15;17(2):646-58.
  26. Bomze HM, Bulsara KR, Iskandar BJ, Caroni P, Skene JH. Spinal axon regeneration evoked by replacing two growth cone proteins in adult neurons. Nat Neurosci. 2001 Jan ;4(1):38-43. https://doi.org/10.1038/82881
  27. Liu RY, Snider WD. Different signaling pathways mediate regenerative versus developmental sensory axon growth. J Neurosci. 2001 Sep 1;21(17):RC164.
  28. Snider WD, Zhou FQ, Zhong J, Markus A. Signaling the pathway to regeneration. Neuron. 2002 Jul 3;35(1):13-6. https://doi.org/10.1016/S0896-6273(02)00762-6
  29. Morgenstern DA, Asher RA, Fawcett JW. Chondroitin sulphate proteoglycans in the CNS injury response. Prog Brain Res. 2002;137:313-32. https://doi.org/10.1016/S0079-6123(02)37024-9
  30. Grandpre T, Strittmatter SM. Nogo: a molecular determinant of axonal growth and regeneration. Neuroscientist. 2001 Oct ;7(5):377-86. https://doi.org/10.1177/107385840100700507