DOI QR코드

DOI QR Code

Rubus coreanus Miquel Improves on Impairment of Memory in Senescence-Accelerated Mouse (SAM)

노화촉진마우스를 이용한 복분자의 기억력 감퇴 개선 효과

  • Choi, Mi-Ran (Center for Efficacy Assessment and Development of Functional Foods and Drugs) ;
  • Lee, Min-Young (Center for Efficacy Assessment and Development of Functional Foods and Drugs) ;
  • Kim, Jeong-Eun (Center for Efficacy Assessment and Development of Functional Foods and Drugs) ;
  • Hong, Ji-Eun (Center for Efficacy Assessment and Development of Functional Foods and Drugs) ;
  • Jang, Kuen-Hye (Center for Efficacy Assessment and Development of Functional Foods and Drugs) ;
  • Lee, Jae-Yong (Center for Efficacy Assessment and Development of Functional Foods and Drugs) ;
  • Chun, Jang-Woo (Research and Development Center, Hitejinro Co., Ltd.) ;
  • Kim, Tae-Hwan (Research and Development Center, Hitejinro Co., Ltd.) ;
  • Shin, Hyun-Kyung (Center for Efficacy Assessment and Development of Functional Foods and Drugs) ;
  • Kim, Eun-Ji (Center for Efficacy Assessment and Development of Functional Foods and Drugs)
  • 최미란 (한림대학교 식의약품의 효능평가 및 기능성소재개발센터) ;
  • 이민영 (한림대학교 식의약품의 효능평가 및 기능성소재개발센터) ;
  • 김정은 (한림대학교 식의약품의 효능평가 및 기능성소재개발센터) ;
  • 홍지은 (한림대학교 식의약품의 효능평가 및 기능성소재개발센터) ;
  • 장근혜 (한림대학교 식의약품의 효능평가 및 기능성소재개발센터) ;
  • 이재용 (한림대학교 식의약품의 효능평가 및 기능성소재개발센터) ;
  • 전장우 (하이트진로주식회사 중앙연구소) ;
  • 김태환 (하이트진로주식회사 중앙연구소) ;
  • 신현경 (한림대학교 식의약품의 효능평가 및 기능성소재개발센터) ;
  • 김은지 (한림대학교 식의약품의 효능평가 및 기능성소재개발센터)
  • Received : 2012.05.11
  • Accepted : 2012.07.16
  • Published : 2012.09.30

Abstract

In the present study, we investigated the effects of Rubus coreanus Miquel (RCM) on memory ability of senescence-accelerated mice (SAM). Prone 8 strains of SAM mice (SAMP8), which is a useful animal for investigating the mechanism of brain aging and senile dementia, were fed a diet containing 100 mg/kg body weight/day of RCM for 8 weeks. Memory ability of mice was examined by using passive avoidance test and Morris water maze test. SAMP8 mice showed remarkable memory impairment compared with senescence-resistant 1 strains of SAM (SAMR1). RCM significantly improved memory ability of SAMP8 mice. In addition, acetylcholineasterase activities decreased in the brain of SAMP8 mice treated with RCM. Taken together, these results suggest that RCM may act as an acetylcholineasterase inhibitor, thereby improving senescence-related memory impairment.

본 연구에서는 복분자 섭취가 노화에 의한 기억력 감퇴에 개선 효과를 나타내는지 조사하기 위해 노화촉진마우스 (SAM)를 사용하여 평가하였다. 28주령 SAMP8 마우스에 복분자 시료를 100 mg/kg body weight/day로 8주간 투여한 후 수동회피시험과 수중미로시험을 실시하여 기억력 개선효과를 평가하였다. 수동회피시험에서 노화 촉진 동물(SAMP8)은 대조동물(SAMR1)에 비해 밝은 방에서 체류시간이 현저히 감소하였다. 복분자를 섭취한 노화 촉진 동물의 밝은 방에서의 체류 시간은 복분자를 섭취하지 않은 동물에 비해 현저히 증가하였다. 수중미로실험에서 대조 동물에 비해 노화 촉진 동물의 평균 탈출잠복기는 길었고, 복분자를 섭취한 경우 평균 탈출잠복기가 유의적으로 감소하였다. 뇌의 대뇌피질과 해마 조직에서 대조군에 비해 노화 촉진 동물의 acetylcholinesterase 활성이 증가하였다. 복분자를 섭취한 노화 촉진 동물의 해마 조직 내 acetylcholinesterase는 복분자를 섭취하지 않은 동물에 비해 유의적으로 감소하였다. 이 결과들은 복분자가 노화촉진마우스에서 노화에 의한 기억력 감퇴에 대한 개선 효과를 나타내며, 이는 콜린성 신경전달에 중요한 역할을 하는 acetylcholinesterase 활성 감소를 통해 이루어짐을 나타낸다. 향후 더 많은 연구가 수행 되어야 하나, 본 연구는 복분자가 노인의 기억력 개선제 개발에 좋은 기능성 소재로 활용할 수 있음을 제시한다.

Keywords

References

  1. Oh SK. 2005. Neurotransmetters and Brain Disease. Shinil Books company, Seoul, Korea. p 345-364.
  2. Coyle JT, Puttfarcken P. 1993. Oxidative stress, glutamate, and neurodegenerative disorders. Science 262: 689-695. https://doi.org/10.1126/science.7901908
  3. Mecocci P, MacGarvery U, Kaufman AE, Koontz D, Shoffner JM, Wallace DC, Beal MF. 1993. Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain. Ann Neurol 34: 609-616. https://doi.org/10.1002/ana.410340416
  4. Hof PR, Morrison JH. 2004. The aging brain: morphomolecular senescence of cortical circuits. Trends Neurosci 27: 607-613. https://doi.org/10.1016/j.tins.2004.07.013
  5. Tang Y, Janssen WG, Hao J, Rpberts JA, McKay H, Lasley B, Allen PB, Greenard P, Rapp PR, Kordower JH, Hof PR, Morrison JH. 2004. Estrogen replacement increases spinophilin- immunoreactive spine numbers in the prefrontal cortex of female rhesus monkeys. Cereb Cortex 14: 215-223. https://doi.org/10.1093/cercor/bhg121
  6. Gorini A, Ghingini B, Villa RF. 1996. Acetylcholinesterase activity of synaptic plasma membranes during aging: effect of L-acetylcarnitine. Dementia 7: 147-154.
  7. Terry AV Jr, Buccafusco JJ. 2003. The cholinergic hypothesis of age and Alzheimer's disease-related cognitive deficits: recent challenges and their implications for novel drug development. J Pharmacol Exp Ther 306: 821-827. https://doi.org/10.1124/jpet.102.041616
  8. Kuhl DE, Koeppe RA, Minoshima S, Snyder SE, Ficaro EP, Foster NL, Frey KA, Kibourn MR. 1999. In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer's disease. Neurology 52: 691-699. https://doi.org/10.1212/WNL.52.4.691
  9. Kasa P, Papp H, Kasa P Jr, Torok I. 2000. Donepezil dosedependently inhibits acetylcholinesterase activity in various areas and in the presynaptic cholinergic and the postsynaptic cholinoceptive enzyme-positive structures in the human and rat brain. Neuroscience 101: 89-100. https://doi.org/10.1016/S0306-4522(00)00335-3
  10. Dawson GR, Iversen SD. 1993. The effects of novel cholinesterase inhibitors and selective muscarinic receptor agonists in tests of reference and working memory. Behav Brain Res 57: 143-153. https://doi.org/10.1016/0166-4328(93)90130-I
  11. Dennes RP, Barnes JC. 1993. Attenuation of scopolamineinduced spatial memory deficits in the rat by cholinomimetic and non-cholinomimetic drugs using a novel task in the 12-arm radial maze. Psychopharmacology (Berl) 111: 435-441. https://doi.org/10.1007/BF02253533
  12. Perry E, Howes MJ. 2011. Medicinal plants and dementia therapy: herbal hopes for brain aging? CNS Neurosci Ther 17: 683-698. https://doi.org/10.1111/j.1755-5949.2010.00202.x
  13. Cha HS, Lee MK, Hwang JB, Park MS, Park KM. 2001. Physicochemical characteristics of Rubus coreanus Miquel. J Korean Soc Food Sci Nutr 30: 1021-1025.
  14. Kim KH, Lee YA, Kim JS, Lee DI, Choi YW, Kim HH, Lee MW. 2000. Antioxidative activity of tannins from Rubus coreanum. Yakhak Hoeji 44: 354-357.
  15. Lee JW, Do YH. 2000. Determination of total phenolic compounds from the fruit of Rubus coreanum and antioxidantive activity. J Korean Soc Food Sci Nutr 29: 943-947.
  16. Kim E, Kim YC. 1987. A triterpene glycoside in berries of Rubus coreanus. Kor J Pharmacogn 18: 188-190.
  17. Choe M, Shin GJ, Choi GP, Do JH, Kim JD. 2003. Synergistic effects of extracts from Korean red ginseng, Saururus chinensis (Lour.) Baill. and Rubus coreanus Miq. on antioxidative activities in rats. Korean J Medicinal Crop Sci 11: 148-154.
  18. Won KS, Lee TW, Eun JS, Song JM. 2003. Effect of Rubus coreanus Miquel on the specific immune response in mice. Korean J Oriental Physiology & Pathology 17: 656-661.
  19. Yang HM, Lim YS, Lee YS, Shin HK, Oh YS, Kim JK. 2007. Comparision of the anti-inflammatory effects of the extracts from Rubus coreanus and Rubus occidentalis. Korean J Food Sci Technol 39: 342-347.
  20. Kim EJ, Lee YJ, Shin HK, Park JH. 2005. Induction of apoptosis by the aqueous extract of Rubus coreanum in HT-29 human colon cancer cells. Nutrition 21: 1141-1148. https://doi.org/10.1016/j.nut.2005.02.012
  21. Jeon YH, Choi SW, Kim MR. 2009. Antimutagenic and cytotoxic activity of ethanol and water extracts from Rubus coreanum. Korean J Food Cookery Sci 25: 379-386.
  22. Choi MR, Lee MY, Hong JE, Lee JY, Chun JW, Kim TH, Shin HK, Kim EJ. 2012. The aqueous extract of Rubus coreanus Miquel improves scopolamine-induced memory impairment in ICR mice. J Korean Soc Food Sci Nutr 41: 192-196. https://doi.org/10.3746/jkfn.2012.41.2.192
  23. Takeda T, Hosokawa M, Takeshita S, Irino M, Higuchi K, Matsushita T, Tomite Y, Yasuhira K, Hamamoto H, Shimizu K, Ishii M, Yamamuro T. 1981. A new murine model of accelerated senescence. Mech Ageing Dev 17: 183-194. https://doi.org/10.1016/0047-6374(81)90084-1
  24. Takeshita S, Hosokawa M, Irino M, Higuchi K, Shimizu K, Yasuhira K, Takeda T. 1982. Spontaneous age-associated amyloidosis in senescence-accelerated mouse (SAM). Mech Ageing Dev 20: 13-23. https://doi.org/10.1016/0047-6374(82)90070-7
  25. Ohta A, Hirano T, Yagi H, Tanaka S, Hosokawa M, Takeda T. 1989. Behavioral characteristics of the SAM-P/8 strain in Sidman active avoidance task. Brain Res 498: 195-198. https://doi.org/10.1016/0006-8993(89)90421-6
  26. Yagi H, Katoh S, Akiguchi I, Takeda T. 1988. Age-related deterioration of ability of acquisition in memory and learning in senescence accelerated mouse; SAM-P/8 as an animal model of disturbances in recent memory. Brain Res 474: 86-93. https://doi.org/10.1016/0006-8993(88)90671-3
  27. 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
  28. Ellman GL, Courtney KD, Andres V Jr, Feather-stone RM. 1961. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7: 88-95. https://doi.org/10.1016/0006-2952(61)90145-9
  29. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. 1951. Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265-275.
  30. Kim JM, Kim DH, Park SJ, Jung JW, Ryu JH. 2010. Memory enhancing properties of the ethanolic extract of black sesame and its ameliorating properties on memory impairments in mice. Kor J Pharmacogn 41: 196-203.
  31. Park SJ, Park DS, Kim SS, He X, Ahn JH, Yoon WB, Lee HY. 2010. The effect of fermented Codonopsis lanceolata on the memory impairment of mice. J Korean Soc Food Sci Nutr 39: 1691-1694. https://doi.org/10.3746/jkfn.2010.39.11.1691
  32. Lee HM, Park EJ, Jeon IS, Kang YS, Jin DI, Chung HJ. 2010. Effect of maca supplementation on scopolamine-induced memory impairment of mice. Korean J Food & Nutr 23: 485-491.
  33. Um MY, Choi WH, An JY, Kim SR, Ha TY. 2004. Effect of defatted sesame and perilla methanol extracts on congnitive function and antioxidant activity in SAMP8 mice. Korean J Food Sci Technol 35: 637-642.
  34. Choi JH, Kim DW, Kim JI, Han SS, Shim CS. 1996. Effect of aloe on leaning and memory impairments in dementia animal model SAMP8 strain III. Feeding effect of aloe on neurotransmitters and their metabolites in SAMP8. Korean J Life Sci 6: 142-148.
  35. Yoo JK, Choi SJ, Kang JK, Han SS. 1999. Effects of Ganoderma lucidum extract on memory and oxidative stress of senescence-accelerated mouse. Korean J Life Sci 9: 548-555.
  36. Suganuma H, Hirano T, Kaburagi S, Hayakawa K, Inakuma T. 2004. Ameliorative effects of dietary carotenoids on memory deficits in senescence-accelerated mice (SAMP8). Int Congr Series 1260: 129-135. https://doi.org/10.1016/S0531-5131(03)01601-7
  37. Yang H, Jin G, Ren D, Luo S, Zhou T. 2011. Mechanism of isoflavone aglycone's effect on cognitive performance of senescence-accelerated mice. Brain Cogn 76: 206-210. https://doi.org/10.1016/j.bandc.2010.10.008
  38. Kang SY, Lee KY, Koo KA, Yoon JS, Lim SW, Kim YC, Sung SH. 2005. EPS-102, a standardized combined extract of Angelica gigas, Saururus chinensis and Schizandra chinensis, significantly improved scopolamine-induced memory impairment in mice. Life Sci 76: 1691-1705. https://doi.org/10.1016/j.lfs.2004.07.029
  39. Wang R, Yan H, Tang XC. 2006. Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacol Sin 27: 1-26. https://doi.org/10.1111/j.1745-7254.2006.00255.x

Cited by

  1. Establishment of a Comprehensive List of Candidate Antiaging Medicinal Herb Used in Korean Medicine by Text Mining of the Classical Korean Medical Literature, “Dongeuibogam,” and Preliminary Evaluation of the Antiaging Effects of These Herbs vol.2015, 2015, https://doi.org/10.1155/2015/873185
  2. Reduction of Plasma Triglycerides and Cholesterol in High Fat Diet-Induced Hyper-Lipidemic Mice by n-3 Fatty Acid from Bokbunja (Rubus coreanus Miquel) Seed Oil vol.44, pp.7, 2015, https://doi.org/10.3746/jkfn.2015.44.7.961