치매병태(癡呆病態)모델에서 천마(天麻)의 신경세포(神經細胞) 손상(損傷) 보호효과(保護效果)

Protective Effect of Gastrodia Elata on Neuronal Cell Damage in Alzheimer's Disease

  • 정영수 (동국대학교 한의과대학 신경정신과학교실) ;
  • 강재현 (동국대학교 한의과대학 신경정신과학교실) ;
  • 박세환 (동국대학교 한의과대학 신경정신과학교실) ;
  • 권영미 (원광대학교 한의과대학 영상의학과) ;
  • 김근우 (동국대학교 한의과대학 신경정신과학교실) ;
  • 구병수 (동국대학교 한의과대학 신경정신과학교실)
  • Jung, Young-Su (Dept. of Neuropsychiatry, College of Korean Medicine, Dong-Guk University) ;
  • Kang, Jae-Hyun (Dept. of Neuropsychiatry, College of Korean Medicine, Dong-Guk University) ;
  • Prak, Se-Hwan (Dept. of Neuropsychiatry, College of Korean Medicine, Dong-Guk University) ;
  • Kwon, Young-Mi (Dept. of Diagnostic Radiology, College of Oriental Medicine, Won-Kwang University) ;
  • Kim, Geun-Woo (Dept. of Neuropsychiatry, College of Korean Medicine, Dong-Guk University) ;
  • Koo, Byung-Soo (Dept. of Neuropsychiatry, College of Korean Medicine, Dong-Guk University)
  • 투고 : 2010.05.10
  • 심사 : 2010.06.04
  • 발행 : 2010.06.30

초록

Objectives : The purpose of this study is to examine from various angles the protective effect of Gastrodia elata Blume (GEB) against nerve cell death induced by $\beta$-amyloid by using the cell line SH-SY5Y, which is commonly utilized for toxicity testing in nerve cells, and to find out its mechanism of action. Methods : To begin with, as a result of assessing the rate of cell survival by employing MTT reduction assay, the treatment with $\beta$-amyloid at different concentrations caused cytotoxicity, which was inhibited by preprocessing GEB extract. In addition, after $\beta$-amyloid was processed with the cell SH-SY5Y, apoptosis progressed, which was reduced effectively by processing GEB extract. Results : When cytotoxicity was caused by using hydrogen peroxide, a representative ROS, in order to examine the antioxidant effect of GEB, its protective effect was also observed. Apart from ROS, reactive nitrogen species (RNS) are also known to play a crucial role in nerve cell death. The treatment with the NO donor SNAP increased the production of nitric oxide and the expression of iNOS, which was also inhibited by GEB extract. Meanwhile, as an attempt to find out the mechanism of action explaining the antioxidant effect, the intracellular antioxidant enzyme expressions were measured by RT-PCR, which showed that GEB extract increased the expressions of heme oxygenase-1, GAPDH and $\gamma$-glutamate cysteine ligase. Lastly, GEB extract had a protective effect against impaired memory induced by scopolamine in animal models (in vivo). Conclusions : These findings indicate that GEB has a protective effect against the death of cranial nerve cells, suggesting possibilities for the prevention and treatment of AD.

키워드

참고문헌

  1. Jooghan Park. Causes and Management of Dementia. Korean J Psychophamacol. 1992; 3(1):33-42.
  2. 대한한방신경정신과학회. 한방신경정신의학. 경기:집문당. 2005:311-9, 454-5, 700-1.
  3. 대한노인정신의학회. 노인정신의학. 서울:중앙문화사. 2004:141-75.
  4. 장상근. 치매. 서울:(주)신원문화사. 2004:21-2, 120-3.
  5. Kim Sang-Tae, Kim Jeong-Do, Lyu Yeoung -Su, Lee Min-Yung, Kang Hyung-won. Neuroprotective Effect of Some Plat Extracts in Cultured CT105-Induced PC12 Cells. Bio. Pharm. Bull. 2006;29(10):2021-4. https://doi.org/10.1248/bpb.29.2021
  6. Hsieh MT, Peng WH, Wu CR, Wang WH. The Ameliorating Effects of Cognitive-Enhancing Chinese Herbs on Scopolamine-Induced Amnesia in Rats. Phytother. Res. 2000;14:375-7. https://doi.org/10.1002/1099-1573(200008)14:5<375::AID-PTR593>3.0.CO;2-5
  7. Kim Ho-Cheol, Ahn Duk-Kyun. Neuroprotective Effect of Gastrodiae Rhizoma on Global Ischemia Induced by 4-Vessel Occlusion in Rats. Kor. J. Herbology. 1999;14(1):121-9.
  8. 全國韓醫科大學 本草學敎授 共編著. 本草學. 서 울:永林社. 1999:504-5.
  9. Freshney RI. Culture of animal cells. A manual of basic technique. 3rd ed. Wiley-Liss. 1994.
  10. 대한진단검사의학회. 진단검사의학(임상병리학). 서울:고려의학. 2001:21, 27, 54-5, 595.
  11. 김경환. 이우주의 약리학강의. 서울:의학문화사. 2001:143, 151, 237.
  12. 사망원인 통계결과. 통계청. 2001.
  13. 임달오, 김종석. 노령인구의 평균여명 개선에 관한 연구. 인구의학연구논집. 2005.
  14. Jin-Soo Kim. Alzheimer's Dementia-General Concepts and Recent Advances-. Korean J Psychophamacol. 1991;2(1):30-42.
  15. 대한신경정신의학회. 신경정신의학. 서울:중앙 문화사. 2005:497-520, 534-5.
  16. Frank H. Netter. CIBA원색도해의학총서. 서울:정담. 2000:145.
  17. William Rodman Shankle․Daniel G. Amen. 알츠하이머 치매의 예방과 치료. 서울:고려의 학. 2005:5, 9-10, 37-8, 41-2, 215-8, 292.
  18. Aspey BS, Cohen S, Patel Y. Middle cerebral artery occlusion in the rat: consistent protocol for a model or stroke. Neuropathol Appl Neurobiol. 1998;24:487-97. https://doi.org/10.1046/j.1365-2990.1998.00146.x
  19. Benveniste H, Drejer J, Schousboe A. Elevation of the extracellular concentration of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebra microdialysis. J Neurochem. 1984; 43(5):1369-74, 1984. https://doi.org/10.1111/j.1471-4159.1984.tb05396.x
  20. 권중돈. 치매환자를 위한 프로그램의 실제. 경기:현학사. 2004:66-74.
  21. 張介賓. 景岳全書. 서울:정담. 1999:640, 846.
  22. 陣士鐸. 石室秘錄(下). 서울:書苑堂. 1984:316-7.
  23. 황의완, 김지혁. 동의정신의학. 서울:현대의학 서적사. 1987:269-71.
  24. 周 康, 黃躍東. 중서의학 결합 정신병치료. 서울:정담. 2004:25-7.
  25. 金完熙, 崔達永. 臟腑辨證論治. 서울:성보사. 1996:146-66.
  26. 전통의학연구소. 한의학사전. 서울:성보사. 1994: 112-3, 154-5, 243.
  27. 김창민, 신민교, 안덕균, 이경순. 중약대사전. 서울:정담. 1999:4105-10.
  28. 許浚. 對譯 東醫寶鑑. 경남:동의보감 출판사. 2005:102, 103, 105, 110, 194, 446, 449, 453, 456, 457, 461, 500, 528, 559, 708, 710, 731, 732, 781, 790, 835, 836, 895, 985, 993, 1001-4, 1006, 1007, 1010-3, 1015, 1018, 1019, 1026, 1027, 1029, 1030, 1035, 1037, 1040, 1072, 1307, 1308, 1340, 1350, 1513, 1569, 1601, 1602, 1612, 1622, 1635, 1644, 1652, 1858, 1860, 1862, 1864-7, 1869-71, 1873-1875, 1890, 1900, 1915, 1934, 1977, 2148, 2149, 2154, 2183.
  29. Kim HJ, Moon KD, Oh SY. 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. 2001; 314:65-8. https://doi.org/10.1016/S0304-3940(01)02296-0
  30. Sun XF, Wang W, Wang DQ, Du GY. Research progress of neuroprotective mechanisms of Gastrodia elata and its preparation. Zhongguo Zhong Yao Za Zhi. 2004;29(4):292-5.
  31. Hu JF, Li GZ, Li MJ. Protective effect of Gastrodia elata and E-gelatin on lead-induced damage to the structure and function of rat hippocampus. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2003;21(2):124-7.
  32. Xie L, Wu HQ, Jin XN, Ge Q, Jin H, Liu GQ. The effect of vanillin on the fully amygdala-kindled seizures in the rat. Yao Xue Xue Bao. 1989;24(7):482-6.
  33. Hsieh CL, Lin JJ, Chiang SY, Su SY, Tang NY, Lin GG, Lin IH, Liu CH, Hsiang CY, Chen JC, Ho TY. Gastrodia elata modulated activator protein 1 via c-Jun N-terminal kinase signaling pathway in kainic acid-induced epilepsy in rats. J Ethnopharmacol. 2007; 109(2):241-7. https://doi.org/10.1016/j.jep.2006.07.024
  34. Zhou BH, Li XJ, Liu M, Wu Z, Ming Hu X. Antidepressant-like activity of the Gastrodia elata ethanol extract in mice. Fitoterapia. 2006;77(7-8):592-4. https://doi.org/10.1016/j.fitote.2006.06.016
  35. 백영숙, 송재경, 윤춘희, 정교순, 유혜숙. 천마(Gastrodia elata Blume)의 항혈소판, 항혈 전활성. 생약학회지. 1996;26(4):385-9.
  36. 허근. 천마 성분인 4-히드록시-3-메톡시벤즈 알데히드 및 파라-히드록시벤즈알데히드의 흰 쥐에서의 약물동태. 약제학회지. 1999;29(1): 47-53.
  37. Guix FX, Uribesalgo I, Coma M, Munoz FJ. The physiology and pathophysiology of nitric oxide in the brain. Prog. Neurobiol. 2005;76:126-52. https://doi.org/10.1016/j.pneurobio.2005.06.001