Therapeutic Potential of Jeongjihwan for the Prevention and Treatment of Amnesia

정지환(定志丸)의 기억 및 인지기능 향상에 대한 효능 연구

  • Jung, Tae-Young (Department of Diagnostics, College of Oriental Medicine, Daeguhaany University) ;
  • Jeong, Won-Choon (Department of Diagnostics, College of Oriental Medicine, Daeguhaany University) ;
  • Park, Jong-Hyun (Department of Pathology, College of Oriental Medicine, Daeguhaany University)
  • 정태영 (대구한의대학교 한의과대학 진단학교실) ;
  • 정원춘 (대구한의대학교 한의과대학 진단학교실) ;
  • 박종현 (대구한의대학교 한의과대학 병리학교실)
  • Received : 2010.12.23
  • Accepted : 2011.01.25
  • Published : 2011.02.25

Abstract

This study was aimed to investigate the memory enhancing effect of Jeongjihwan against scopolamine-induced amnesia in C57BL/6 mice. To determine the effect of Jeongjihwan on the memory and cognitive function, we have injected scopolamine (1 mg/kg, i.p.) into C57BL/6 mice 30 min before beginning of behavior tests. We have conducted Y-maze, Morris water-maze, passive avoidance and fear conditioning tests to compare learning and memory functions. Scopolamine-induced behavior changes of memory impairment were significantly restored by oral administration of Jeongjihwan (100 or 200 mg/kg/day). To elucidate the molecular mechanism underlying the memory enhancing effect of Jeongjihwan, we have examined the antioxidant defense system and neurotrophic factors. Jeongjihwan treatment attenuated intracellular accumulation of reactive oxygen species and up-regulated mRNA and protein expression of antioxidant enzymes as assessed by RT-PCR and western blot analysis, respectively. Jeongjihwan also increased protein levels of brain-derived neurotrophic factor (BDNF) compared with those in the scopolamine-treated group. Furthermore, as an upstream regulator, the activation of cAMP response element-binding protein (CREB) via phosphorylation was assessed by Western blot analysis. Jeongjihwan elevated the phosphorylation of CREB (p-CREB), which seemed to be mediated partly by extracellular signal-regulated kinase1/2 (ERK1/2) and protein kinase B/Akt. These findings suggest that Jeongjihwan may have preventive and therapeutic potential in the management of amnesia.

Keywords

References

  1. 김지혁, 황의완. 동의정신의학. 서울, 현대의학서적사, pp 256-271, 327-333, 1992.
  2. 이근후. 최신임상정신의학. 서울, 하나의학사, pp 138, 216-228, 1988.
  3. 서울대학교병원. 치매 노인 유병률 조사. 보건복지가족부. 2008.
  4. Frank, B., Gupta, S. A review of antioxidants and Alzheimer's disease. Ann. Clin. Psychiatry. 17: 269-286, 2005. https://doi.org/10.1080/10401230500296428
  5. Hermona, S., Shlomo, S. Acetylcholinesterase-new roles for an old actor. Nature 2: 294-302, 2001.
  6. 張介賓. 景岳全書. 서울, 한미의학, p 1549, 2006.
  7. 錢鏡湖. 辨證奇問全書. 台北, 甘地出版社, pp 222-225, 1990.
  8. 洪元植. 精校黃帝內經素問. 서울, 東洋醫學硏究院, p 218, 1981.
  9. 孫思邈. 備急千金要方. 서울, 大星文化社, p 265, 1984.
  10. 하재원. 定志丸이 老化에 미치는 영향 : 학습, 기억능력, 항산 화력, 혈액 생화학치. 대전대학교 석사학위논문, 1996.
  11. 최용준, 성강경, 문병순. 定志丸이 腦組織의 生化學的變化와 神經細胞의 損傷에 미치는 實驗的硏究. 대한한의학회지 19(1):392-409, 1998.
  12. 신학수, 이선우, 이민구, 윤종민, 이 인, 신선호, 문병순. 定志丸과 시스플라틴의 신경교아세포종에 대한 세포고사 기전연구. 대한한의학회지 26(2):1-12, 2005.
  13. 민성길 외 편저. 최신정신의학. 서울, 일조각, p 203, 2006.
  14. 대한정신의학회. 신경정신의학. 서울, 중앙문화사, pp 507-509, 2007.
  15. Talesa, V.N. Acetylcholine esterase in Alzheimer's disease. Mech. Ageing Dev. 122(16):1961-1969, 2001. https://doi.org/10.1016/S0047-6374(01)00309-8
  16. Kasa, P., Rakonczay, Z., Gulya, K. The cholinergic system in Alzheimer's disease. Prog. Neurobiol. 52(6):511-535, 1997. https://doi.org/10.1016/S0301-0082(97)00028-2
  17. 杜英杰. 中醫內科學. 四川:四川科學技術出版社, pp 141-142, 1985.
  18. 東洋學硏究所. 東醫內科學. 서울:麗江出版社, pp 179-181, 1994.
  19. 柳熙英. 東醫精神科學. 서울, 남산당, p 57, 1988.
  20. 허 준. 동의보감. 서울, 남산당, p 98, 1976.
  21. 李 仟. 醫學入門. 서울, 大星文化社, p 514, 1980.
  22. 林佩琴. 類證治裁. 臺北, 旋風出版社, pp 255-257, 1978.
  23. 中國中醫硏究院. 中醫症狀鑑別診斷學. 北京, 人民衛生出版社, pp 106-107, 2000.
  24. 전국한의과대학 공동교재편찬위원회. 본초학. 서울, 영림사, 2004.
  25. Zulli, R., Nicosia, F., Borroni, B., Agosti, C., Prometti, P., Donati, P., De Vecchi, M., Turini, D., Romanelli, G., Grassi, V., Padovani, A. Increased prevalence of silent myocardial ischaemia and severe ventricular arrhythmias in untreated patients with Alzheimer's disease and mild cognitive impairment without overt coronary artery disease. Clin. Neurol. Neurosurg. 110: 791-796, 2008. https://doi.org/10.1016/j.clineuro.2008.05.002
  26. 김회영, 손현수, 강지홍, 최우정, 이진석, 양재훈, 설재균, 이언정. 국소 전뇌 허혈 모델 백서에서 가감정지환과 오수유가 기억증진과 신경세포보호에 미치는 효과. 동의생리병리학회지. 22: 1488-1494, 2008.
  27. Diaz Vivancos, P., Wolff, T., Markovic, J., Pallardo, F.V., Foyer, C.H. A nuclear glutathione cycle within the cell cycle. Biochem. J. 431: 169-178, 2010. https://doi.org/10.1042/BJ20100409
  28. Hsieh, H.M., Wu, W.M., Hu, M.L. Genistein attenuates D-galactose-induced oxidative damage through decreased reactive oxygen species and NF-$\kappa$B binding activity in neuronal PC12 cells. Life Sci. 2010, in press.
  29. Gundacker, C., Gencik, M., Hengstschlager, M. The relevance of the individual genetic background fir the toxicokinetics of two significant nurodevelopmental toxicants: mercury and lead. Mutat. Res. 705: 130-140, 2010. https://doi.org/10.1016/j.mrrev.2010.06.003
  30. Shimizu, S., Saito, M., Dimitriadis, F., Kinoshita, Y., Shomori, K., Satoh, I., Satoh, K. Protective effect of ischaemic post-conditioning on ipsilateral and contralateral teates after unilateral testicular ischaemia-reperfusion injury. Int. J. Androl. 2010, in press.
  31. Jaiswal, A.K. Nrf2 signaling in coordinated activation of antioxidant gene expression. Free Radic. Biol. Med. 36: 1199-1207, 2004. https://doi.org/10.1016/j.freeradbiomed.2004.02.074
  32. Shin, M.K., Kim, H.G., Kim, K.L. A novel trimeric peptide, Neuropep-1 stimulating brain-derived neurotrophic factor expression in rat brain improves spatial learning and memory as measured by the Y-maze and Morris water maze. J. Neurochem. 2010, in press.
  33. French, S.J., Humby, T., Horner, C.H., Sofroniew, M.V., Rattray, M. Hippocampal neurotrophin and trk receptor mRNA levels are altered by local administration of nicotine, carbachol and pilocarpine. Brain Res. Mol. Brain Res. 67: 124-136, 1999. https://doi.org/10.1016/S0169-328X(99)00048-0
  34. Blurton-Jones, M., Kitazawa, M., Martinez-Coria, H., Castello, N.A., Müller, F.J., Loring, J.F., Yamasaki, T.R., Poon, W.W., Green, K.N., LaFerla, F.M. Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proc. Natl. Acad. Sci. USA 106: 13594-13599, 2009. https://doi.org/10.1073/pnas.0901402106
  35. Barnes, P., Kirtley, A., Thomas, K.L. Quantitatively and qualitatively different cellular processes are engaged in CA1 during the consolidation and reconsolidation of contextual fear memory. Hippocampus 2010, in press.
  36. Beste, C., Schneider, D., Epplen, J.T., Arning, L. The functional BDNF Val66Met polymorphism affects functions of pre-attentive visual sensory memory processes. Neuropharmacology 2010, in press.
  37. Liu, R., Gao, M., Qiang, G.F., Zhang, T.T., Lan, X., Ying, J., Du, G.H. The anti-amnestive effects of luteolin against amyloid $\beta$25-35 peptide-induced toxicity involve the protection of neurovascular unit. Neuroscience 162: 1232-1243, 2009. https://doi.org/10.1016/j.neuroscience.2009.05.009
  38. Kwon, J., Wang, Y.L., Setsuie, R., Sekiguchi, S., Sato, Y., Sakurai, M., Noda, M., Aoki, S., Yoshikawa, Y., Wada, K. Two closely related ubiquitin C-terminal hydrolase isozymes function as reciprocal modulators of germ cell apoptosis in cryptorchid testis. Am. J. Pathol. 165: 1367-1374, 2004. https://doi.org/10.1016/S0002-9440(10)63394-9
  39. Chun, H., Hao, W., Honghai, Z., Ning, L., Yasong, W., Chen, D. CCL3L1 prevents gp120-induced neuron death via the CREB cell signaling pathway. Brain Res. 1257: 75-88, 2009.
  40. Sands, W.A., Palmer, T.M. Regulating gene transcription in response to cyclic AMP elevation. Cell Signal. 20(3):460-466, 2008. https://doi.org/10.1016/j.cellsig.2007.10.005
  41. Xue, W., Hu, J.F., Yuan, Y.H., Sun, J.D., Li, B.Y., Zhang, D.M., Li, C.J., Chen, N.H. Polygalasaponin XXXII from Polygala tenuifolia root improves hippocampal-dependent learning and memory. Acta Pharmacol. Sin. 30: 1211-1129, 2009. https://doi.org/10.1038/aps.2009.112