Journal of Pharmacopuncture (대한약침학회지)

KOREAN PHARMACOPUNCTURE INSTITUTE (대한약침학회)
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The Effect of the Uncariae Ramulus et Uncus on the Regeneration Following CNS Injury

중추신경계 손상 회복에 미치는 대한 조구등의 영향

  • Lee, Jin-Goo (Department of Internal Medicine, Wonkwang University Oriental Medical School) ;
  • Park, Hyoung-Jin (Department of Internal Medicine, Wonkwang University Oriental Medical School) ;
  • Kim, Dong-Woong (Department of Internal Medicine, Wonkwang University Oriental Medical School) ;
  • Song, Bong-Keun (Department of Internal Medicine, Wonkwang University Oriental Medical School)
  • 이진구 (원광대학교 한의과대학 내과학교실) ;
  • 박형진 (원광대학교 한의과대학 내과학교실) ;
  • 김동웅 (원광대학교 한의과대학 내과학교실) ;
  • 송봉근 (원광대학교 한의과대학 내과학교실)
  • Published : 2009.03.30
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Abstract

Objective : Following central nervous system(CNS) injury, inhibitory influences at the site of axonal damage occur. Glial cells become reactive and form a glial scar, gliosis. Also myelin debris such as MAG inhibits axonal regeneration. Astrocyte-rich gliosis relates with up-regulation of GFAP and CD81, and eventually becomes physical and mechanical barrier to axonal regeneration. MAG is one of several endogenous axon regeneration inhibitors that limit recovery from CNS injury and disease. It was reported that molecules that block such inhibitors enhanced axon regeneration and functional recovery. Recently it was reported that treatment with anti-CD81 antibodies enhanced functional recovery in the rat with spinal cord injury. So in this current study, the author investigated the effect of the water extract of Uncariae Ramulus et Uncus on the regulation of CD81, GFAP and MAG that increase when gliosis occurs. Methods : MTT assay was performed to examine cell viability, and cell-based ELISA, western blot and PCR were used to detect the expression of CD81, GFAP and MAG. Then also immunohistochemistry was performed to confirm in vivo. Results : Water extract of Uncariae Ramulus et Uncus showed relatively high cell viability at the concentration of 0.05%, 0.1% and 0.5%. The expression of CD81, GFAP and MAG in astrocytes was decreased after the administration of Uncariae Ramulus et Uncus water extract. These results was confirmed in the brain sections following cortical stab injury by immunohistochemistry. Conclusion : The authors observed that Uncariae Ramulus et Uncus significantly down-regulates the expression of CD81, GFAP and MAG. These results suggest that Uncariae Ramulus et Uncus can be a candidate to regenerate CNS injury.

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References

  1. McKeon RJ, Schreiber RC, Rudge JS, Silver J. Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes. J Neurosci. 1991;11(11):3398-3411 https://doi.org/10.1523/JNEUROSCI.11-11-03398.1991
  2. Eng LF, Reier PJ, Houle JD. Astrocyte activation and fibrous gliosis: glial fibrillary acidic protein immunostaining of astrocytes following intraspinal cord grafting of fetal CNS tissue. Prog Brain Res. 1987;71:439-455 https://doi.org/10.1016/S0079-6123(08)61845-2
  3. Fawcett JW, Asher RA. The glial scar and central nervous system repair. Brain Res Bull. 1999;49(6):377-391 https://doi.org/10.1016/S0361-9230(99)00072-6
  4. Geisert EE, Jr, Yang L, Irwin MH. Astrocyte growth, reactivity, and the target of the antiproliferative antibody, TAPA. J Neurosci. 1996;16:5478-5487
  5. Song BK, Geisert GR, Vazquez-Chona F, Geisert EE Jr. Temporal regulation of CD81 following retinal injury in the rat. Neurosci Lett. 2003;338(1):29-32 https://doi.org/10.1016/S0304-3940(02)01364-2
  6. Geisert EE Jr, Abel HJ, Fan L, Geisert GR. Retinal pigment epithelium of the rat express CD81, the target of the anti-proliferative antibody (TAPA). Invest Ophthalmol Vis Sci. 2002;43(1):274-280
  7. Berditchevski, F, Tolias, KF, Wong, K, Carpenter, CL, Hemler, ME. A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and CD81), and phosphatidylinositol 4-kinase J Biol Chem. 1997;272:2595-2598 https://doi.org/10.1074/jbc.272.5.2595
  8. Hemler ME. Specific tetraspanin functions. J Cell Biol. 2001;155(7):1103-1107 https://doi.org/10.1083/jcb.200108061
  9. Cai D, Shen Y, De Bellard M, Tang S, Filbin MT. Prior exposure to neurotrophins blocks inhibition of axonal regeneration by MAG and myelin via a cAMP-dependent mechanism. Neuron. 1999;22(1):89-101 https://doi.org/10.1016/S0896-6273(00)80681-9
  10. Kim ST, Kim JD, Lyu YS, Lee MY, Kang HW. Neuroprotective effect of some plant extracts in cultured CT105-induced PC12 cells. Biol Pharm Bull. 2006;29(10):2021-2024 https://doi.org/10.1248/bpb.29.2021
  11. Suk K, Kim SY, Leem K, Kim YO, Park SY, Hur J, Baek J, Lee KJ, Zheng HZ, Kim H. Neuroprotection by methanol extract of Uncaria rhynchophylla against global cerebral ischemia in rats. Life Sci. 2002;70(21):2467-2480 https://doi.org/10.1016/S0024-3205(02)01534-5
  12. Lee B, Choi Y, Kim H, Kim SY, Hahm DH, Lee HJ, Shim I. Protective effects of methanol extract of Acori graminei rhizoma and Uncariae Ramulus et Uncus on ischemiainduced neuronal death and cognitive impairments in the rat. Life Sci. 2003;74(4):435-450 https://doi.org/10.1016/j.lfs.2003.06.034
  13. Kim JH, Chung JY, Lee YJ, Park S, Kim JH, Hahm DH, Lee HJ, Shim I. Effects of methanol extract of Uncariae Ramulus et Uncus on ibotenic acid-induced amnesia in the rat. J Pharmacol Sci. 2004;96(3):314-323 https://doi.org/10.1254/jphs.FP0040179
  14. Xu XM, Guenard V, Kleitman N, Aebischer P, Bunge MB. A combination of BDNF and NT-3 promotes supraspinal axonal regeneration into Schwann cell grafts in adult rat thoracic spinal cord. Exp Neurol. 1995;134(2):261-272 https://doi.org/10.1006/exnr.1995.1056
  15. Ye JH, Houle JD. Treatment of the chronically injured spinal cord with neurotrophic factors can promote axonal regeneration from supraspinal neurons. Exp Neurol. 1997;143(1):70-81 https://doi.org/10.1006/exnr.1996.6353
  16. Broude E, McAtee M, Kelley MS, Bregman BS. Fetal spinal cord transplants and exoge-nous neurotrophic support enhance c-Jun expression in mature axotomized neurons after spinal cord injury. Exp Neurol. 1999;155(1):65-78 https://doi.org/10.1006/exnr.1998.6964
  17. Menet V, Gimenez Y Ribotta M, Sandillon F, Privat A. GFAP null astrocytes are a favorable substrate for neuronal survival and neurite growth. Glia. 2000;31(3):267-272 https://doi.org/10.1002/1098-1136(200009)31:3<267::AID-GLIA80>3.0.CO;2-N
  18. Dijkstra S, Duis S, Pans IM, Lankhorst AJ, Hamers FP, Veldman H, Bar PR, Gispen WH, Joosten EA, Geisert EE Jr. Intraspinal administration of an antibody against CD81 enhances functional recovery and tissue sparing after experimental spinal cord injury. Exp Neurol. 2006;202(1):57-66 https://doi.org/10.1016/j.expneurol.2006.05.011
  19. Fawcett JW, Housden E, Smith-Thomas L, Meyer RL. The growth of axons in threedimensional astrocyte cultures. Dev Biol. 1989;135(2):449-458 https://doi.org/10.1016/0012-1606(89)90193-0
  20. McKeon RJ, Hoke A, Silver J. Injury-induced proteoglycans inhibit the potential for lamininmediated axon growth on astrocytic scars. Exp Neurol. 1995;136(1):32-43 https://doi.org/10.1006/exnr.1995.1081
  21. Levy S, Todd SC, Maecker HT. CD81 (TAPA-1): a molecule involved in signal transduction and cell adhesion in the immune system. Annu Rev Immunol. 1998;16:89-109 https://doi.org/10.1146/annurev.immunol.16.1.89
  22. Boucheix C, Rubinstein E. Tetraspanins. Cell Mol Life Sci. 2001;58(9):1189-1205 https://doi.org/10.1007/PL00000933
  23. Schick MR, Nguyen VQ, Levy S. Anti-TAPA-1 antibodies induce protein tyrosine phosphorylation that is prevented by increasing intracellular thiol levels. J Immunol. 1993;151(4):1918-1925
  24. Oren R, Takahashi S, Doss C, Levy R, Levy S. TAPA-1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins Mol Cell Biol 1990;10:4007-4015 https://doi.org/10.1128/MCB.10.8.4007
  25. Geisert EE Jr, Williams RW, Geisert GR, Fan L, Asbury AM, Maecker HT, Deng J, Levy S. Increased brain size and glial cell number in CD81-null mice. J Comp Neurol 20024;453(1):22-32 https://doi.org/10.1002/cne.10364
  26. Mukhopadhyay G, Doherty P, Walsh FS, Crocker PR, Filbin MT. A novel role for myelin-associated glycoprotein as an inhibitor of axonal regeneration. Neuron. 1994;13(3):757-767 https://doi.org/10.1016/0896-6273(94)90042-6
  27. Arquint M, Roder J, Chia LS, Down J, Wilkinson D, Bayley H, Braun P, Dunn R. Molecular cloning and primary structure of myelin-associated glycoprotein. Proc Natl Acad Sci U S A. 1987;84(2):600-604 https://doi.org/10.1073/pnas.84.2.600
  28. Owens GC, Bunge RP. Schwann cells infected with a recombinant retrovirus expressing myelin-associated glycoprotein antisense RNA do not form myelin. Neuron. 1991;7(4):565-575 https://doi.org/10.1016/0896-6273(91)90369-B
  29. Ozaki Y. Pharmacological studies of indole alkaloids obtained from domestic plants, Uncaria rhynchophylla Miq. and Amsonia elliptica Roem. et Schult. Yakurigaku Zasshi. 1989;94(1):17-26 https://doi.org/10.1254/fpj.94.17
  30. Chang P, Koh YK, Geh SL, Soepadmo E, Goh SH, Wong AK. Cardiovascular effects in the rat of dihydrocorynantheine isolated from Uncaria callophylla. J Ethnopharmacol. 1989;25(2):213-215 https://doi.org/10.1016/0378-8741(89)90023-8
  31. Goto H, Sakakibara I, Shimada Y, Kasahara Y, Terasawa K. Vasodilator effect of extract prepared from Uncariae ramulus on isolated rat aorta. Am J Chin Med. 2000;28(2):197-203 https://doi.org/10.1142/S0192415X00000246
  32. Shi JS, Yu JX, Chen XP, Xu RX. Pharmacological actions of Uncaria alkaloids, rhynchophylline and isorhynchophylline. Acta Pharmacol Sin. 2003;24(2):97-101
  33. Hsieh CL, Chen MF, Li TC, Li SC, Tang NY, Hsieh CT, Pon CZ, Lin JG. Anticonvulsant effect of Uncaria rhynchophylla (Miq) Jack. in rats with kainic acid-induced epileptic seizure. Am J Chin Med. 1999;27(2):257-264 https://doi.org/10.1142/S0192415X9900029X
  34. Itoh T, Shimada Y, Terasawa K. Efficacy of Choto-san on vascular dementia and the protective effect of the hooks and stems of Uncaria sinensis on glutamate-induced neuronal death. Mech Ageing Dev. 1999;111(2-3):155-173 https://doi.org/10.1016/S0047-6374(99)00062-7
  35. Shimada Y, Goto H, Itoh T, Sakakibara I, Kubo M, Sasaki H, Terasawa K. Evaluation of the protective effects of alkaloids isolated from the hooks and stems of Uncaria sinensis on glutamate-induced neuronal death in cultured cerebellar granule cells from rats. J Pharm Pharmacol. 1999;51(6):715-722 https://doi.org/10.1211/0022357991772853
  36. Shimada Y, Goto H, Kogure T, Shibahara N, Sakakibara I, Sasaki H, Terasawa K. Protective effect of phenolic compounds isolated from the hooks and stems of Uncaria sinensis on glutamate-induced neuronal death. Am J Chin Med. 2001;29(1):173-180 https://doi.org/10.1142/S0192415X01000198
  37. Kang HW, Park JS, Ryu YS, Chung JM, Lee GM. A study on the effect of Ramulus et Uncus uncareae (REUU) on the cultured spinal dorsal root ganglion neurons damaged by onygen free radicals. J Oriental Neuropsychiatry 2000;11(1):1-18
  38. Lee BC, Lee JK, Lee KC, Jeong JG, Lee GM, Shin MK, Song HJ. Effect of Ramulus et Uncus Uncariae on the oxidative stress in culutred mouse cerebral neurons. The Korea J Herbology 2003;18(3):27-31