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황금(黃芩), 석창포(石菖蒲), 천마(天麻) 물추출액 혼합물이 배양한 흰쥐 대뇌신경세포의 활성과 학습능력 증진 효능

Effects of Water-extract Mixture of Scutellariae baicalensis GEORGI, Acarus gramineus SOLAND and Gastrodia elata BLUME on Cultured Rat Cortical Neurons and Enhancement of Learning and Memory Power

  • 배철환 (동국대학교 한의과대학 내과학 교실) ;
  • 정현정 (동국대학교 한의과대학 내과학 교실) ;
  • 정승현 (동국대학교 한의과대학 내과학 교실) ;
  • 문일수 (동국대학교 의과대학 해부학교실) ;
  • 이원철 (부산대학교 한의학전문대학원) ;
  • 신길조 (동국대학교 한의과대학 내과학 교실)
  • 발행 : 2009.06.30

초록

Scutellariae baicalensis GEORGt Acorus gramineus SOLAND and Gastrodia elata BLUME are traditional medicines used in the treatment of incipient stoke. In this study we investigated their effects on various aspects of neuronal differentiation in single or composite forms. Water-extracts of these medicines showed neuroprotective effects on cultured rat cortical neurons in normoxia and hypoxia. To understand the mechanism for neuroprotection we carried out various cell biological assays. They stimulated initial differentiation of neuronal development (transition from stage 1 to 2), and increased the number of spines and the length and number of dendritic processes. These effects were best manifested in the experimental group, which were given a mixture of the three kinds of extracts (p<0.01). To assess improvement of brain functions we carried out Morris water-maze tests for the mice that were fed on these extracts instead of water for 4 weeks. The experimental groups, especially those which were given the mixture of the three kinds of extract, showed significant (p<0.01) enhancement in memory as early as one day after the learning trial. These results indicate that these three kinds of extracts have synergistic effects on neuronal protection and improvement of brain functions.

키워드

참고문헌

  1. Abbott, L. F. and S. B. Nelson. 2000. Synaptic plasticity: taming the beast. Nat. Neurosci. 3, 1178-1183 https://doi.org/10.1038/81453
  2. Bliss, T. V. and G. L. Collingridge. 1993. A synaptic model of memory: long term potentiation in the hippocampus. Nature 361, 31-39 https://doi.org/10.1038/361031a0
  3. Brewer, G. J., J. R. Torricelli, E. K. Evege, and P. J Price. 1993. Optimized survival of hippocampal neurons in B27-supplemented Neurobasal, a new serum-free medium combination. J. Neurosci. Res. 35, 567-576 https://doi.org/10.1002/jnr.490350513
  4. Cajal, S. R. 1991. Degeneration and Regeneration of the Nervous System. pp. 1928, Oxford University Press, London
  5. Chang, F. and W. T. Greenough. 1994. Transient and enduring morphological correlates of synaptic activity and efficacy change in the rat hippocampal slice. Brain Res. 309, 35-46 https://doi.org/10.1016/0006-8993(84)91008-4
  6. Chklovskii, D. B., B. W. Mel, and K. Svoboda. 2004. Cortical rewiring and information storage. Nature 431, 782-788 https://doi.org/10.1038/nature03012
  7. Cho, J., J. Y. Kong, D. Y. Jeong, K. D. Lee, D. U. Lee, and B. S. Kang. 2001. NMDA receptor-mediated neuroprotection by essential oils from the rhizomes of Acorus gramineus. Life Sci. 68, 1567-1573 https://doi.org/10.1016/S0024-3205(01)00944-4
  8. Cho, J., Y. H. Kim, J. Y. Kong, C. H. Yang, and C. G. Park. 2002. Protection of cultured rat cortical neurons from excitotoxicity by asarone, a major essential oil component in the rhizomes of Acorus gramineus. Life Sci. 71, 591-599 https://doi.org/10.1016/S0024-3205(02)01729-0
  9. Choe, S. Y. 2003. Synaptic plasticity and critical period in cerebrum cortex. Biochemistry and Molecular Biology News 23, 288-295
  10. Davis, G. W. and I. Bezprozvanny. 2001. Maintaining the stability of neural function: a homeostatic hypothesis. Annu. Rev. Physiol. 63, 847-869 https://doi.org/10.1146/annurev.physiol.63.1.847
  11. Doubell, T. P. and M. G. Stewart. 1993. Short-term changes in the numerical density of synapses in the intermediate and medial hyperstriatum ventrale following one-trial passive avoidance training in the chick. J. Neurosci. 13, 2230-2235
  12. Gibbs, R. B. and R. Gabor. 2003. Estrogen and cognition: applying preclinical findings to clinical perspectives. J. Neurosci Res. 74, 637-643 https://doi.org/10.1002/jnr.10811
  13. Hao, J., W. G. Janssen, Y. Tang, J. A. Roberts, H. McKay, B. Lasley, P. B. Allen, P. Greengard, P. R. Rapp, J. H. Kordower, P. R. Hof, and J. H. Morrison. 2003. Estrogen increases the number of spinophilin-immunoreactive spines in the hippocampus of young and aged female rhesus monkeys. J. Comp Neurol. 465, 540-550
  14. Hoe, J. 1999. Dong-Eui-Bo-Gam. pp. 367, 961, 965, 1024, 1937, 1955, 1938, 1st eds., Byuinmoonhwasa, Seoul
  15. Hof, P. R. and J. H. Morrison. 2004. The aging brain: morphomolecular senescence of cortical circuits. Trends Neurosci. 27, 607-613 https://doi.org/10.1016/j.tins.2004.07.013
  16. Hsieh, M. T., C. R. Wu and C. F. Chen. 1997. Gastrodin and p-hydroxybenzyl alcohol facilitate memory consolidation and retrieval, but not acquisition, on the passive avoidance task in rats. J. Ethnopharmacol. 56, 45-54.(=2) https://doi.org/10.1016/S0378-8741(96)01501-2
  17. Huang, N. K., Y. L. Lin, J. J. Cheng, and W. L. Lai. 2004. Gastrodia elata prevents rat pheochromocytoma cells from serum-deprived apoptosis: the role of the MAPK family. Life Sci. 75, 1649-1657 https://doi.org/10.1016/j.lfs.2004.05.008
  18. Jeong, H. W., S. Y. Kang, and S. W. Bak. 1999. Effect of Rhizoma Acori Graminei extract on blood pressure and regional cerebral blood flow in rats. Kor. J. Herbology 14, 81-88
  19. Ji, H. J. and S. I. Lee. 1988. Hanyack-Gyugyuk-Juhea. pp. 219, 361, 638, Korean index Co., Seoul
  20. Kang, S. J., H. S. Keum, Y. Y. Joen, E. J. Lee, C. S. Park, C. G. Park, J. H. Heo, C. H. Yang, and J. S. Cho. 2001. The neuroprotective effect of Acori graminei rhizoma extract cerebral ischemia in rats. Korean J. Oriental Int. Med. 22, 341-351
  21. Kenneth, W. L. 2006. Neurology and neurosurgery illustrated. pp. 34, 4th eds., e-public. Seoul
  22. Kim, H. J., K. D. Moon, D. S. Lee, and S. H Lee. 2003. Ethyl ether fraction of Gastrodia elata Blume protects amyloid beta peptide-induced cell death. J. Ethnopharmacol. 84, 95-98.(=3) https://doi.org/10.1016/S0378-8741(02)00290-8
  23. Kim, H. J., K. D. Moon, S. Y. Oh, S. P. Kim, and S. R. Lee. 2001. Ether fraction of methanol extracts of Gastrodia elata, a traditional medicinal herb, protects against kainic acid-induced neuronal damage in the mouse hippocampus. Neurosci. Lett. 314, 65-68 https://doi.org/10.1016/S0304-3940(01)02296-0
  24. Kim, H. J., S. R. Lee, and K. D. Moon. 2003. Ether fraction of methanol extracts of Gastrodia elata, medicinal herb protects against neuronal cell damage after transient global ischemia in gerbils. Phytother. Res. 17, 909-912 https://doi.org/10.1002/ptr.1246
  25. Kim, K. H., S. H. Jeong, J. W. Kim, H. S. Eum, S. H. Chung, G. G. Shin, W. C. Lee, and I. S. Moon. 2002. The effect of HwangGum (Scutellariae Radix) for delayed neuronal death on hypoxia. Korean J. Oriental Int. Med. 23, 396-405
  26. Kim, Y. O., K. Leem, J. Park, P. Lee, D. Ahn, B. C. Lee, H. K. Park, K. Suk, S. Y. Kim, and H. Kim. 2001. Cytoprotective effect of Scutellaria baicalensis in CA1 hippocampal neurons of rats after global cerebral ischemia. J. Ethnopharmacol. 77, 183-188 https://doi.org/10.1016/S0378-8741(01)00283-5
  27. Knott, G. W., C. Quairiaux, C. Genoud, and E. Welker. 2002. Formation of dendritic spines with GABAergic synapses induced by whisker stimulation in adult mice. Neuron 34, 265-273 https://doi.org/10.1016/S0896-6273(02)00663-3
  28. Kretz, O., L. Fester, U. Wehrenberg, L. Zhou, S. Brauckmann, S. Zhao, J. Prange-Kiel, T. Naumann, H. Jarry, M. Frotscher, and G. M Rune. 2004. Hippocampal synapses depend on hippocampal estrogen synthesis. J. Neurosci. 24, 5913-5921 https://doi.org/10.1523/JNEUROSCI.5186-03.2004
  29. Kullmann, D. M. and S. A. Siegelbaum. 1995. The site of expression of NMDA receptor-dependent LTP: new fuel for an old fire. Neuron 15, 997-1002 https://doi.org/10.1016/0896-6273(95)90089-6
  30. Lamour, Y., M. H. Bassant, B. Potier, J. M. Billard, and P. Dutar. 1994. Aging of memory mechanisms. C R Seances Soc. Biol. Fil. 188, 469-486
  31. Lee, B. C., K. H. Leem, Y. O. Kim, S. Y. Kim, D. K. Ahn, H. K. Park, and H. C. Kim. 1999. Neuroprotective effects of Scutellariae Radix on the brain ischemia induced by four - vessel occlusion in rats. Kor. J. Herbology 14, 89-96
  32. Martin, S. J., P. D. Grimwood, and R. G Morris. 2000. Synaptic plasticity and memory: an evaluation of the hypothesis. Annu. Rev. Neurosci. 23, 649-711 https://doi.org/10.1146/annurev.neuro.23.1.649
  33. Morrison, J. H. and P. R Hof. 1997. Life and death of neurons in the aging brain. Science 278, 412-419 https://doi.org/10.1126/science.278.5337.412
  34. Moser, M. B., M. Trommald, and P. Andersen. 1994. An increase in dendritic spine density on hippocampal CA1 pyramidal cells following spatial-learning in adult rats suggests the formation of new synapses. Proc. natn. Acad. Sci. USA 91, 12673-12675 https://doi.org/10.1073/pnas.91.26.12673
  35. Nikonenko, I., P. Jourdain, and D. Muller. 2003. Presynaptic remodeling contributes to activity-dependent synaptogenesis. J. Neurosci. 23, 8498-8505
  36. Park, M. S. 1997. Molecular Biology of mind science. pp. 23, Jisik-Sanup Publications Co., Seoul
  37. Park, T. J. 2004. Cognitive Neural Mechanisms of Aging. The Korean Journal of Experimental Psychology 16, 317-336
  38. Rapp, P. R., J. H. Morrison, and J. A. Roberts. 2003. Cyclic estrogen replacement improves cognitive function in aged ovariectomized rhesus monkeys. J. Neurosci. 23, 5708-5714
  39. Richard, F. T. 1996. Brain. pp. 35, 75, Sung-Won-Sa, Seoul
  40. Rusakov, D. A., H. A Davies, I. M. Krivko, M. G. Stewart, and M. Schachner. 1994. Training in chicks alters PSA-NCAM distribution in forebrain cell membranes. NeuroReport 5, 2469-2473 https://doi.org/10.1097/00001756-199412000-00016
  41. Suh, K. S, Y. H. Nam, Y. M. Ahn, N. J. Kim, C. Y. Park, G. Koh, S. Oh, J. T. Woo, S. W. Kim, J. W. Kim, and Y. S. Kim. Effect of Scutellariae radix extract on the high glucose-induced apoptosis in cultured vascular endothelial cells. Biol. Pharm. Bull. 26, 1629-1632 https://doi.org/10.1248/bpb.26.1629
  42. Spires, T. L. and B. T. Hyman. 2004. Neuronal structure is altered by amyloid plaques. Rev. Neurosci. 15, 267-278 https://doi.org/10.1515/REVNEURO.2004.15.4.267
  43. Stent, G. S. 1973. A physiological mechanism for Hebb's postulate of learning. Proc. Natl. Acad. Sci. USA 70, 997-1001 https://doi.org/10.1073/pnas.70.4.997
  44. Turner, A. M. and W. T. Greenough. 1985. Differential rearing effects on rat visual cortex synapses. I. Synaptic and neuronal density and synapses per neuron. Brain Res. 329, 195-203 https://doi.org/10.1016/0006-8993(85)90525-6
  45. Unal, B., P. M. Bradley, B. Sahin, S. Canan, H. Aslan, and S. Kaplan. 2002. Estimation of numerical density and mean synaptic height in chick hippocampus 24 and 48 hours after passive avoidance training. Brain Res. Dev. Brain Res. 136, 135-144 https://doi.org/10.1016/S0165-3806(02)00357-7
  46. Wang, A. 1989. Bon-cho-bi-yo. pp. 44-45, 177-180, Komoonsa. Seoul
  47. Wang, H. and H. Tiedge. 2004. Translational control at the synapse. Neuroscientist 10, 456-466 https://doi.org/10.1177/1073858404265866