Memory Enhancing Effect of Longanae Arillus against Scopolamine-induced Amnesia in C57BL/6 Mice

스코폴라민으로 유도한 기억 손상 모델에서 용안육(龍眼肉)의 보호 효과 연구

  • Jung, Tae-Young (Department of Diagnostics, College of Oriental Medicine, Daeguhaany University) ;
  • Lee, Heui-Woong (Department of Pathology, College of Oriental Medicine, Daeguhaany University) ;
  • Park, Jong-Hyun (Department of Pathology, College of Oriental Medicine, Daeguhaany University)
  • 정태영 (대구한의대학교 한의과대학 진단학교실) ;
  • 이희웅 (대구한의대학교 한의과대학 병리학교실) ;
  • 박종현 (대구한의대학교 한의과대학 병리학교실)
  • Received : 2011.03.28
  • Accepted : 2011.05.26
  • Published : 2011.06.25

Abstract

In this study, we have verified the memory and cognitive enhancing effect of Longanae Arillus, the fruit of Euphoria longana Lamarck, which has been used as a tonic and for the treatment of amnesia, insomnia, and palpitations in oriental medicine. To investigate the effect of Longanae Arillus water extract(LAE) on the memory and cognitive dysfunction, scopolamine (1 mg/kg, i.p.) was injected in C57BL/6 mice and several behavior tests including Y-maze, Morris water-maze, passive avoidance and fear conditioning tests were conducted. Administration of LAE (100 or 200 mg/kg/day, p.o.) effectively improved scopolamine-induced memory impairment and dysfunction. To further determine the possible molecule mechanism of LAE, we have examined the activity and/or mRNA expression of diverse proteins involved in the acetylcholine metabolism. LAE particularly increased the amount of acetylcholine in the cortex which was mediated by suppression of acetylcholine esterase (AchE) activity. In addition, LAE elevated the mRNA expression of muscarinic acetylcholine receptors (mAchRs) without affecting the mRNA levels of choline acetyltransferase (ChAT) and acetylcholine esterase (AchE). In another experiment, LAE effectively inhibited mRNA expression of pro-inflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-$1{\beta}$ (IL1-${\beta}$), which seemed to be mediated by inhibition of upstream transcription factor NF-${\kappa}B$ and extracellular-regulated kinase 1/2 (ERK1/2). These results demonstrate that Longanae Arillus can increase acetylcholine amount the cortex via regulation of AchE activity as well as mAchRs expression and decrease pro-inflammatory responses via inhibition of NF-${\kappa}B$ signaling pathway, thereby having therapeutic potential to improve memory and cognitive deficit in amnesia.

Keywords

References

  1. 이부영 역. ICD-10 정신 및 생동장애 분류. 서울, 일조각, pp 63-66, 1994.
  2. 김지혁, 황의완. 동의정신의학. 서울, 현대의학서적사, pp 256-271, 327-330, 1992. : 이근후. 최신임상정신의학. 하나의학사, p 138, 1998.
  3. 이근후. 최신임상정신의학. 하나의학사, p 138, 1998.
  4. Kumar, V., Abbas, A.K., Fausto, N. Robbins and Cotran Pathologic Basis of Disease. San Diego, USA. Elsevier Saunders. pp 1386-1388, 2004.
  5. 조추용, 최현자 역저. 치매 예방과 케어. 창지사, p 49, 2002.
  6. Pakaski, M., Kalman, J. Interactions between the amyloid and cholinergic mechanism in Alzheimer's disease. Neurochem Int. 53(5):103-111, 2008. https://doi.org/10.1016/j.neuint.2008.06.005
  7. 張介賓. 景岳全書. 서울, 한미의학, p 1549, 2006.
  8. 錢鏡湖. 辨證奇問全書. 台北, 甘地出版社, pp 222-225, 1990.
  9. 洪元植. 精校黃帝內經素問. 서울, 東洋醫學硏究院, p 218, 1981.
  10. 대한한방신경정신과학회편. 한방신경정신의학. 파주, 집문당, 125: 311-316, 432-435, 451, 2005.
  11. 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.
  12. 류기준, 김지형, 안건상, 이제균, 권승로. 최근 10년간 치매에 대한 한의학적 연구 동향 고찰. 동의신경정신과학회지 18(3):135-145, 2007.
  13. 최성열, 김대현, 김상태, 김태헌, 강형원, 류영수. 치매에 대한 최신 실험적 연구 동향 (2000년 이후 한의학 학술지를 중심으로). 동의신경정신과학회지 19(1):125-146, 2008.
  14. 전국한의과대학 공동교재편찬위원회. 본초학. 서울, 영림사, p 642, 2004.
  15. 하연귀. 龍眼肉이 구속스트레스 생쥐 뇌의 Noepinephrine 함량에 미치는 영향. 경원대 석사학위논문. 2002.
  16. 황선미. 龍眼肉과 백복신이 구속스트레스 생쥐의 뇌 부위별 serotonin 함량에 미치는 영향. 대구한의대 석사학위논문. 2002.
  17. Small, G.W., Rabins, P.V., Barry, P.P., Buckholtz, N.S., DeKosky, S.T., Ferris, S.H., Finkel, S.I., Gwyther, L.P., Khachaturian, Z.S., Lebowitz, B.D., McRae, T.D., Morris, J.C., Oakley, F., Schneider, L.S., Streim, J.E., Sunderland, T., Teri, L.A., Tune, L.E. Diagnosis and treatment of Alzheimer disease and related disorders. JAMA 278(16):1363-1371, 1997. https://doi.org/10.1001/jama.1997.03550160083043
  18. 서순규. 성인병 노인병학. 서울, 고려의학, pp 225-228, 1992.
  19. Buxbaum, J.D., Greengard, P. Regulation of APP processing by intra and intercellur signals. Ann. NY Acad. Sci. 17(777):327-331, 1996.
  20. Lee, M.C., Kim, D.L., Woo, Y.J., Kim, S.U., McGeer, P.L., Tai, T. Gangliosiders expression in normal and alzheimer brain. 대한의학회, 37(3):285-292, 2001.
  21. Baddeley, A.D., Bressi, S., Sala, S.D., Logie, R., Soinnler, H. The decline of working memory in Alzheimer' disease. Brain 114: 2521-2542, 1991. https://doi.org/10.1093/brain/114.6.2521
  22. 龔廷賢. 增補萬病回春. 서울, 一中社, pp 229-230, 1994.
  23. 杜英杰. 中醫內科學. 四川, 四川科學技術出版社, pp 141-142, 1985.
  24. 동양학연구소. 동의내과학. 서울, 여강출판사, pp 179-181, 1994.
  25. 전국한의과대학 신경정신과 교과서편찬위원회 편. 한의신경정신과학. 파주, 집문당, p 235, 2007.
  26. 程國彭. 醫學心悟. 경희대학교 한의과대학 제50기 졸업준비 위원회. pp 478-499, 2002.
  27. 허 준. 동의보감. 서울, 법인문화사, p 340, 2005.
  28. Pepeu, G., Giovannini, M.G. Cholinesterase inhibitors and memory. Chem. Biol. Interact. 187: 403-408, 2010. https://doi.org/10.1016/j.cbi.2009.11.018
  29. Fuller, S., Münch, G., Steele, M. Activated astrocytes: a therapeutic target in Alzheimer's disease? Expert. Rev. Neurother. 9: 1585-1594, 2009. https://doi.org/10.1586/ern.09.111
  30. Varvel, N.H., Bhaskar, K., Kounnas, M.Z., Wagner, S.L., Yang, Y., Lamb, B.T., Herrup, K. NSAIDs prevent, but do not reverse, neuronal cell cycle reentry in a mouse model of Alzheimer disease. J. Clin. Invest. 119: 3692-3702, 2009. https://doi.org/10.1172/JCI39716
  31. Lee, M., Sparatore, A., Del Soldato, P., McGeer, E., McGeer, P.L. Hydrogen sulfide-releasing NSAIDs attenuate neuroinflammation induced by microglial and astrocytic activation. Glia 58: 103-113, 2010. https://doi.org/10.1002/glia.20905
  32. Flirski, M., Sobow, T. Biochemical markers and risk factors of Alzheimer's disease. Curr. Alzheimer Res. 2: 47-64, 2005 https://doi.org/10.2174/1567205052772704
  33. Giovannini, M.G., Scali, C., Prosperi, C., Bellucci, A., Vannucchi, M.G., Rosi, S., Pepeu, G., Casamenti, F. Beta-amyloid-induced inflammation and cholinergic hypofunction in the rat brain in vivo: involvement of the p38APK pathway. Neurobiol. Dis. 11: 257-264, 2002. https://doi.org/10.1006/nbdi.2002.0538
  34. McGeer, E.G., McGeer, P.L. Neuroinflammation in Alzheimer's disease and mild cognitive impairment: a field in its infancy. J. Alzheimers Dis. 19: 355-361, 2010. https://doi.org/10.3233/JAD-2010-1219
  35. Heneka, M.T., O'Banion, M.K., Terwel, D., Kummer, M.P. Neuroinflammatory processes in Alzheimer's disease. J. Neural. Transm. 117: 919-947, 2010. https://doi.org/10.1007/s00702-010-0438-z
  36. Lee, B., Jung, K., Kim, D.H. Timosaponin AIII, a saponin isolated from Anemarrhena asphodeloides, ameliorates learning and memory deficits in mice. Pharmacol. Biochem. Behav. 93: 121-127, 2009. https://doi.org/10.1016/j.pbb.2009.04.021
  37. Jung, K., Lee, B., Han, S.J., Ryu, J.H., Kim, D.H. Mangiferin ameliorates scopolamine-induced learning deficits in mice. Biol. Pharm. Bull. 32: 242-246, 2009. https://doi.org/10.1248/bpb.32.242
  38. Zhong, K., Wang, Q., He, Y., He, X. Evaluation of radicals scavenging, immunity-modulatory and antitumor activities of longan polysaccharides with ultrasonic extraction on in S180 tumor mice models. Int. J. Biol. Macromol. 47: 356-360, 2010. https://doi.org/10.1016/j.ijbiomac.2010.05.022
  39. Ho, S.C., Hwang, L.S., Shen, Y.J., Lin, C.C. Suppressive effect of a proanthocyanidin-rich extract from longan (Dimocarpus longan Lour.) flowers on nitric oxide production in LPS-stimulated macrophage cells. J. Agric. Food Chem. 55: 10664-10670, 2007. https://doi.org/10.1021/jf0721186
  40. Aktan F. iNOS-mediated nitric oxide production and its regulation. Life Sci. 75: 639-653, 2004. https://doi.org/10.1016/j.lfs.2003.10.042
  41. Vallabhapurapu, S. and Karin, M. Regulation and function of NF-kappaB transcription factors in the immune system. Annu. Rev. Immunol. 27: 693-733, 2009. https://doi.org/10.1146/annurev.immunol.021908.132641
  42. Hwang, M.H., Damte, D., Lee, J.S., Gebru, E., Chang, Z.Q., Cheng, H., Jung, B.Y., Rhee, M.H., Park, S.C. Mycoplasma hyopneumoniae induces pro-inflammatory cytokine and nitric oxide production through NF-$\kappa$B and MAPK pathways in RAW264.7 cells. Vet. Res. Commun. 35: 21-34, 2011. https://doi.org/10.1007/s11259-010-9447-5
  43. Lee, J.W., Lee, Y.K., Ban, J.O., Ha, T.Y., Yun, Y.P., Han, S.B., Oh, K.W., Hong, J.T. Green tea (-)-epigallocatechin-3-gallate inhibits $\beta$-amyloid-induced cognitive dysfunction through modification of secretase activity via inhibition of ERK and NF-$\kappa$B pathways in mice. J. Nutr. 139: 1987-1993, 2009. https://doi.org/10.3945/jn.109.109785
  44. Kim, T.I., Lee, Y.K., Park, S.G., Choi, I.S., Ban, J.O., Park, H.K., Nam, S.Y., Yun, Y.W., Han, S.B., Oh, K.W., Hong, J.T. I-Theanine, an amino acid in green tea, attenuates beta-amyloid-induced cognitive dysfunction and neurotoxicity: reduction in oxidative damage and inactivation of ERK/p38 kinase and NF-$\kappa$B pathways. Free Radic. Biol. Med. 47: 1601-1610, 2009. https://doi.org/10.1016/j.freeradbiomed.2009.09.008