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The Effects of Korean Ginseng on Memory Loss in a Rat Models

Scopolamine 유도 치매동물모델에서 고려인삼(백삼, 홍삼 및 흑삼)의 기억력 개선 효과

  • Kang, Shin-Jyung (Dept. of Medicines Resources, Joongbu University) ;
  • Woo, Jeong-Hwa (Dept. of Research Institute of Medical Nutrition, Kyung Hee University) ;
  • Kim, Ae-Jung (The Graduate School of Alternative Medicine, Kyonggi University)
  • 강신정 (중부대학교 한약자원학과) ;
  • 우정화 (경희대학교 임상영양연구소) ;
  • 김애정 (경기대학교 대체의학대학원)
  • Received : 2013.04.11
  • Accepted : 2013.05.07
  • Published : 2013.08.31

Abstract

The purpose of this study was to investigate the mechanism and effects of different types of ginseng on memory improvement in an experimental rat model. In this study, SD rats were induced for memory deficits through scopolamine treatment (1 mg/kg, i.p.) then administrated with ginseng extract for 7 weeks. The rats were divided into five groups: saline (1 mL/kg, NC: negative control), white ginseng (300 mg/kg, WG), red ginseng (300 mg/kg, RG), black ginseng (300 mg/kg, BG), and scopolamine (1 mg/kg, PC: positive control). The step through latency of the BG and RG groups was significantly longer than the PC group in the retention trial of multiple trial passive avoidance test. In the spatial reference memory triads of the Morris water maze test, the latency time of BG and RG was significantly lower than the PC group. In addition, in the prove test, the time spent in the platform quadrant of BG and RG groups were significantly longer than the PC group. Brain choline acetyltransferase (ChAT) activities BG and RG groups significantly increased compared to other groups. On the other hand, the levels of malondialdehyde (MDA) were significantly lower in the BG and RG groups compared to other groups. These result suggested that black ginseng could be useful to enhance learning memory and cognitive function by regulation of cholinergic enzymes.

연구에서는 백삼이나 홍삼의 기억력 개선 효과 연구를 기초로 흑삼의 기억력 개선효과 여부를 판단하고자 scopolamine으로 유도된 시험동물에게 7주간 시료 물질(백삼, WG; 홍삼, RG; 흑삼, BG) 추출액을 투여한 후, 행동학적인 평가 및 뇌 조직 내 malondialdehyde 농도, ChAT 활성 변화를 비교 분석하여 기억력 및 학습능력 손상에 대한 개선효과를 알아보고자 하였다. 수동회피시험에서 BG군과 RG군의 latency time이 scopolamine 투여한 PC군(positive control)에 비해서 유의적으로 길어지는 결과를 나타냈다. 수중미로시험에서도 BG군과 RG군의 scopolamine에 의한 기억 손상이 유의적으로 개선되어 NC군의 escape latency 수준 정도로 낮아짐을 확인할 수 있었다. 또한 probe test에서도 BG군과 RG군에서 장기 기억력 손상이 유의적으로 개선됨이 확인되었다. BG군과 RG군의 뇌조직 ChAT 효소 활성은 PC군에 비해 각각 42%, 71% 수준의 유의성 있는 활성증가를 보였다. 지질 과산화도 malondialdehyde 측정 결과에서 PC군 대비 RG군과 BG군에서 각각 37%, 33% 수준의 유의성 있는 감소를 보였다. 이상의 결과를 요약하면 시험물질 가운데 흑삼의 반복 경구투여는 scopolamine으로 유도된 흰쥐에서 기억력 감퇴를 개선하는 데 가장 효과적인 것으로 사료된다.

Keywords

References

  1. Oh SK. 2005. Neurotransmetters and brain disease. Shinil Books Company, Seoul, Korea. p 345-364.
  2. Kuhl DE, Koeppe RA, Minoshima S, Snyder SE, Ficaro EP, Foster NL, Frey KA, Kilbourn MR. 1999. In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer' disease. Neurology 52: 691-699. https://doi.org/10.1212/WNL.52.4.691
  3. Evans DA, Funkenstein HH, Albert MS, Scherr PA, Cook NR, Chown MJ, Hebert LE, Hennekens CH, Taylor JO. 1989. Prevalence of Alzheimer's disease in a community population of older persons. Higher than previously reported. JAMA 262: 2551-2556. https://doi.org/10.1001/jama.1989.03430180093036
  4. Bartus RT, Dean RL, Beer B, Lipas AS. 1982. The cholinergic hyphothesis of geriatic memory dysfuntion. Science 217: 408-414. https://doi.org/10.1126/science.7046051
  5. Colye JT, Price DL, DeLong MR. 1983. Alzheimer's disease: a disorder of cortical cholinergic innervation. Science 219:1184-1190. https://doi.org/10.1126/science.6338589
  6. Shudo K, Kagechike H, Yamazaki N, Igarashi M, Tateda C. 2004. A synthetic retnoid am80 (tamibarotene) rescues the memory deficit caused by scopolamine in a passive avoidance paradigm. Biol Pharm Bull 27: 1887-1899. https://doi.org/10.1248/bpb.27.1887
  7. Tanabe F, Miyasaka N, Kubota T, Aso T. 2004. Estrogen and progesterone improve scopolamine-induced impairment of spartial memory. J Med Dent Sci 51: 89-98.
  8. Davies P, Maloney AJ. 1976. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet 2: 1403.
  9. Davis KL, Thal LJ, Gamzu ER, Davis CS, Woolson RF, Gracon SI, Drachman DA, Schneider LS, Whitehouse PJ, Hoover TM. 1992. A double-blind placebo-controlled multicenter study of tacrine for Alzheimer's disease. N Engl J Med 327: 1253-1259. https://doi.org/10.1056/NEJM199210293271801
  10. Rogers SL, Farlow MR, Doody RS, Mohs R, Friedhoff LT. 1998. A 24-week, double-blind, pacebo-cotrolled trial of donepezil in patients with Alzheimer' disease. Neurology 50:136-145. https://doi.org/10.1212/WNL.50.1.136
  11. Rosler M, Anand R, Cicin-Sain A, Gauthier S, Agid Y, Dal-Bianco P. 1999. Efficacy and safety of rivastigmine in patients with Alzheimer' disease, international randomized controlled trial. BMJ 318: 633-638.
  12. Tariot PN, Solomon PR, Morris JC, Kershaw P, Lilienfeld S, Ding C. 2000. A 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-10 Study Group. Neurology 54: 2269-2276. https://doi.org/10.1212/WNL.54.12.2269
  13. Lawrence CH, Wang BW, Lee TF 2006. Effects of ginseng saponins on ${\beta}$-amyloid-imduced amnesia in rats. J Ethnopharmacol 103: 103-108. https://doi.org/10.1016/j.jep.2005.07.010
  14. LeDoux JE. 1993. Emotional memory system in the brain. Behav Brain Res 20: 69-79.
  15. Morris R. 1984. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11: 47-60. https://doi.org/10.1016/0165-0270(84)90007-4
  16. Lee MR, Yun BS, Park SY, Lym SY, Kim SN, Han BH, Sung CK. 2010. Anti-amnesic effect of Chong-Myung-Tang on scopolamine-induced memory impairments in mice. J Ethnopharmacol 132: 70-74. https://doi.org/10.1016/j.jep.2010.07.041
  17. Villa-Caballero L, Nava-Ocampo AA, Frati-Munari AC, Ponce-Monter H. 2000. Oxidative stress should it be measured in the diabetic patient? Gac med Mex 136: 249-256.
  18. Van der Zee EA, Biemans BA, Gekema MP, Daan S. 2004. Habitutation to a test apparatus during associative learning is sufficient to enhance muscarinic acetycholine receptorimmunoreactivity in rat suprachiasmatic nucleus. J Neurosci Res 78: 508-519. https://doi.org/10.1002/jnr.20300
  19. Lozenzini CA, Bal E, Bucherelli C, Sacchetti B, Tassoni G. 1996. Role of dorsal hippocampus in acquisition, consolidation and retrieval of rat's passive avoidance response: a tetrodotoxin functional inactivation study. Brain Research 730: 32-39. https://doi.org/10.1016/0006-8993(96)00427-1
  20. Seo JH, Woo SY, Kim YT, Kim MY, Park YM, Jin ZH, Bu YM, Kim HC. 2007. Enhancing effect of multiherb extracts HT008-1 on memory and cognitive function. Kor J Herbology 22: 51-58.
  21. Kim EJ, Jung IH, Le TKV, Jeong JJ, Kim NJ, Kim DH. 2013. Ginsenosides Rg5 and Rh3 protect scopolamine-induced memory deficits in mice. J Ethnopharmacol 146:294-299. https://doi.org/10.1016/j.jep.2012.12.047
  22. Zhao H, Li Q, Pei X, Zhang Z, Yang R, Wang J, Li Y. 2009. Long-term ginsenoside administration prevents memory impairment in aged C57BL/6J mice by up-regulating the synaptic-related proteins in hippocampus. Behav Brain Res 201: 311-317. https://doi.org/10.1016/j.bbr.2009.03.002
  23. Yamaguchi Y, Higashi M, Kobayashi H. 1997. Effects of ginsenosides on maze performance and brain choline acetyltransferase activity in scopolamine-treated young rats and aged rats. Eur J Pharmacol 329: 37-41. https://doi.org/10.1016/S0014-2999(97)10115-7
  24. Lee ML, Yun BS, Liu L, Zhang DL, Wang Z, Wang CL, Gu LJ, Wang CY, Mo EK, Sung CK. 2010. Effect of black ginseng on memory improvement in the amnesic mice induced by scopolamine. J Ginseng Res 34: 51-58. https://doi.org/10.5142/JGR.2010.34.1.051
  25. Lee ML, Sun BS, Gu LJ, Wang CY, Mo EK, Yang SA, Ly SY, Sung CK. 2008. Effects of white ginseng and red ginseng extract on learning performance and acetylcholinesterase activity inhibition. J Ginseng Res 4: 341-346. https://doi.org/10.5142/JGR.2008.32.4.341
  26. Saito H, Suba K, Schwab M, Thonen H. 1977. Potentiation of the NGF-mediated nerve fiber outgrowth by ginsenoside Rb1 in organ cultures of chick dorsal root ganglia. Jpn J Pharmacol 27: 445-451. https://doi.org/10.1254/jjp.27.445
  27. Benishin CG. 1992. Actions of ginsenoside Rb1 on cholin uptake in central cholinergic nerve ending. Neurochem Int 21: 1-5. https://doi.org/10.1016/0197-0186(92)90061-U
  28. Choi X, Saji H, Iida Y, Magata Y, Yokoyma A. 1996. Ginseng pretreatment protects against transient global cerebral ischemia in the rat: measurement of local cerebral glucose utilization by deoxyglucose autoradiography. Biol Pharm Bull 19: 644-646. https://doi.org/10.1248/bpb.19.644
  29. Chu GX, Chen X. 1989. Protective effect of ginsenosides on acute cerebral ischemia-reperfusion injury of rats. China J Pharmacol Toxicol 3: 18-23.
  30. Sloley BD, Pang PK, Huang BH, Ba F, Li FL, Benishin CG. 1999. American ginseng extract reduces scopolamine induced amnesia in spatial learning task. J Psychiatry Neurosci 24: 442-452.
  31. Zang JT, Qu ZW, Liu Y, Deng HL. 1990. Preliminary study on antiamnestic mechanism of ginsenoside Rg1 and Rb1. Clin Med J 103: 932-938.
  32. Salim KN, McEwen BS, Chao HM. 1997. Ginsenoside Rb1 regulates ChAT, NGF and tr kA mRNA expression in the rat brain. Brain Res Mol Brain Res 47: 177-182. https://doi.org/10.1016/S0169-328X(97)00042-9
  33. Bassett CN, Montine TJ. 2003. Lipoproteins and lipid peroxidation in Alzhimer's disease. J Nutr Health Aging 7:446-451.
  34. Yokozawa T, Satoh A, Cho EJ. 2004. Ginsenoside Rd attenuates oxidative damage related to aging in senescenceaccelerated mice. J Pharm Pharmacol 56: 107-113. https://doi.org/10.1211/0022357022449
  35. Chun H, David DK. 2001. Free radical scavenging capacity as related to antioxidant activity and ginsenoside composition of Asian and North American ginseng extracts. JAOCS 78: 249-255.
  36. Tian J, Fu F, Geng M, Jang Y, Yang J, Jiang W, Wang C, Liu K. 2005. Neuroprotective effect of 20(S)-ginsenoside Rg3 on cerebral ischemia in rats. Neurosci Lett 374: 92-97. https://doi.org/10.1016/j.neulet.2004.10.030
  37. Liu ZQ, Luo XY, Liu GZ, Chen YP, Wang ZC, Sun YX. 2003. In vitro study of the relationship between the structure of ginsenoside and its antioxidative or prooxidative activity in free radical induced hemolysis of human erythrocytes. J Agric Food Chem 51: 2555-2558. https://doi.org/10.1021/jf026228i
  38. Kang KS, Kim HY, Beak SH, Yoo HH, Park JH, Yokozawa T. 2007. Study on the hydroxyl radical scavenging activity changes of ginseng and ginsenoside-Rb2 by heat processing. Biol Pharm Bull 30: 724-728. https://doi.org/10.1248/bpb.30.724
  39. Lee SY, Kim DH, Woo WH. 2011. Antioxidant activity of black Panax ginseng. Korean J Oriental Physiology & Pathology 25: 115-121.

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