Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of ginseol k-g3, an Rg3-enriched fraction, on scopolamine-induced memory impairment and learning deficit in mice

  • Pena, Ike Dela (Uimyung Research Institute for Neuroscience, Sahmyook University) ;
  • Yoon, Seo Young (Uimyung Research Institute for Neuroscience, Sahmyook University) ;
  • Kim, Hee Jin (Uimyung Research Institute for Neuroscience, Sahmyook University) ;
  • Park, Sejin (Department of Oriental Pharmaceutical Science, Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University) ;
  • Hong, Eun Young (Nutraceuticals and Functional Food Research & Development, Cheil Jedang (CJ) Corporation) ;
  • Ryu, Jong Hoon (Department of Oriental Pharmaceutical Science, Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University) ;
  • Park, Il Ho (Uimyung Research Institute for Neuroscience, Sahmyook University) ;
  • Cheong, Jae Hoon (Uimyung Research Institute for Neuroscience, Sahmyook University)
  • Received : 2013.05.03
  • Accepted : 2013.08.28
  • Published : 2014.01.15
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Although ginsenosides such as Rg1, Rb1 and Rg3 have shown promise as potential nutraceuticals for cognitive impairment, their use has been limited due to high production cost and low potency. In particular, the process of extracting pure Rg3 from ginseng is laborious and expensive. Methods: We described the methods in preparing ginseol k-g3, an Rg3-enriched fraction, and evaluated its effects on scopolamine-induced memory impairment in mice. Results: Ginseol k-g3 (25-200 mg/kg) significantly reversed scopolamine-induced cognitive impairment in the passive avoidance, but not in Y-maze testing. Ginseol k-g3 (50 and 200 mg/kg) improved escape latency in training trials and increased swimming times within the target zone of the Morris water maze. The effect of ginseol k-g3 on the water maze task was more potent than that of Rg3 or Red ginseng. Acute or subchronic (6 d) treatment of ginseol k-g3 did not alter normal locomotor activity of mice in an open field. Ginseol k-g3 did not inhibit acetylcholinesterase activity, unlike donezepil, an acetylcholinesterase inhibitor. Rg3 enrichment through the ginseol k-g3 fraction enhanced the efficacy of Rg3 in scopolamine-induced memory impairment in mice as demonstrated in the Morris water maze task. Conclusion: The effects of ginseol k-g3 in ameliorating scopolamine-induced memory impairment in the passive avoidance and Morris water maze tests indicate its specific influence on reference or long-term memory. The mechanism underlying the reversal of scopolamine-induced amnesia by ginseol k-g3 is not yet known, but is not related to anticholinesterase-like activity.

Keywords

References

  1. Koo EH, Lansbury PT, Kelly JW. Amyloid diseases: abnormal protein aggregation in neurodegeneration. Proc Natl Acad Sci USA 1999;96:9989-90. https://doi.org/10.1073/pnas.96.18.9989
  2. Terry RD. The fine structure of neurofibrillary tangles in Alzheimer's disease. J Neuropathol Exp Neurol 1963;22:629-42. https://doi.org/10.1097/00005072-196310000-00005
  3. Braak H, Braak E. Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol Aging 1997;18:351-7. https://doi.org/10.1016/S0197-4580(97)00056-0
  4. Bartus RT, Dean 3rd RL, Beer B, Lippa A. The cholinergic hypothesis of geriatric memory dysfunction. Science 1982;217:408-17. https://doi.org/10.1126/science.7046051
  5. Francis PT, Palmer AM, Snape M, Wilcock GK. The cholinergic hypothesis of Alzheimer's disease: a review of progress. J Neurol Neurosurg Psychiatry 1999;66:137-47. https://doi.org/10.1136/jnnp.66.2.137
  6. Mufson EJ, Counts SE, Perez SE, Ginsberg SD. Cholinergic system during the progression of Alzheimer's disease: therapeutic implications. Expert Rev Neurother 2008;8:1703-18. https://doi.org/10.1586/14737175.8.11.1703
  7. Terry Jr AV, Buccafusco JJ. 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 2003;306:821-7. https://doi.org/10.1124/jpet.102.041616
  8. Rountree SD, Chan W, Pavlik VN, Darby EJ, Siddiqui S, Doody RS. Persistent treatment with cholinesterase inhibitors and/or memantine shows clinical progression of Alzheimer disease. Alzheimers Res Ther 2009;1:7. https://doi.org/10.1186/alzrt7
  9. Jeong SM, Nah SY. Ginseng and ion channels: are ginsensosides, active component of Panax ginseng, differential modulator of ion channels? J Ginseng Res 2005;29:19-26. https://doi.org/10.5142/JGR.2005.29.1.019
  10. ParkJD,KimDS,KwonHY,SonSK,LeeYH,BaekNI,KimSI,RheeDK.Effectsofginseng saponin on modulation of multidrug resistance. Arch Pharm Res 1996;19:213-8. https://doi.org/10.1007/BF02976892
  11. Mook JI, Hong HS, Boo JH, Lee KH, Yun SH, Cheong MY, Joo I, Huh K, Jung MW. Ginsenoside Rb1 and Rg1 improve spatial learning and increase hippocampal synaptophysin level in mice. J Neurosci Res 2001;63:509-15. https://doi.org/10.1002/jnr.1045
  12. Saito H. Effects of ginsenoside Rb1 and ginsenoside Rg1 on learning and memory. In: Shibata S, Ohtsuka Y, Saito H, editors. Recent advances in ginseng study. Tokyo: Hirokawa Publishing; 1990. p. 99.
  13. Yamaguchi Y, Haruta K, Kobayashi H. Effects of ginsenosides on impaired performance induced in the rat by scopolamine in a radial-arm maze. Psychoneuroendocrinology 1995;20:645-53. https://doi.org/10.1016/0306-4530(95)00008-C
  14. Tohda C, Matsumoto N, Zou K, Meselhy MR, Komatsu K. Ab(25-35)- induced memory impairment, axonal atrophy, and synaptic loss are ameliorated by M1, a metabolite of protopanaxadiol-type saponins. Neuropsychopharmacology 2004;29:860-8. https://doi.org/10.1038/sj.npp.1300388
  15. Zhang JT, Qu ZW, Liu Y, Deng HL. Preliminary study on antiamnesic mechanism of Rg1 and Rb1. Chin Med J 1990;103:932-8.
  16. Liao B, Newmark H, Zhou R. Neuroprotective effects of ginseng total saponin and ginsenosides Rb1 and Rg1 on spinal cord neurons in vitro. Experiment Neurol 2002;173:224-34. https://doi.org/10.1006/exnr.2001.7841
  17. Nishiyama N, Cho SI, Kitagawa I, Saito H. Malonyl-ginsenoside Rb1 potentiates nerve growth factor (NGF)-induced neurite outgrowth of cultured chick embryonic dorsal root ganglia. Biol Pharmacol Bull 1994;17:509-13. https://doi.org/10.1248/bpb.17.509
  18. Bao HY, Zhang J, Yeo SJ, Myung CS, Kim HM, Kim JM, Park JH, Cho JS, Kang JS. Memory enhancing and neuroprotective effects of selected ginsenosides. Arch Pharm Res 2005;28:335-42. https://doi.org/10.1007/BF02977802
  19. Fang F, Chen X, Huang T, Lue LF, Luddy JS, Yan SS. Multi-faced neuroprotective effects of Ginsenoside Rg1 in an Alzheimer mouse model. Biochim Biophys Acta 2012;1822:286-92. https://doi.org/10.1016/j.bbadis.2011.10.004
  20. Yang JH, Han SJ, Ryu JH, Kang IS, Kim DH. Ginsenoside Rh2 ameliorates scopolamine-induced learning deficit in mice. Biol Pharm Bull 2009;32: 1710-5. https://doi.org/10.1248/bpb.32.1710
  21. Klinkenberg I, Blokland A. The validity of scopolamine as a pharmacological model for cognitive impairment: a review of animal behavioral studies. Neurosci Biobehav Rev 2010;34:1307-50. https://doi.org/10.1016/j.neubiorev.2010.04.001
  22. Kim S, Rhim H. Ginsenosides inhibit NMDA receptor-mediated epileptic discharges in cultured hippocampal neurons. Arch Pharm Res 2004;27:524-30. https://doi.org/10.1007/BF02980126
  23. Kim JH, Kim S, Yoon IS, Lee JH, Jang BJ, Jeong SM, Lee JH, Lee BH, Han JS, Oh S, et al. Protective effects of ginseng saponins on 3-nitropropionic acid-induced striatal degeneration in rats. Neuropharmacology 2005;48:743-56. https://doi.org/10.1016/j.neuropharm.2004.12.013
  24. Roh YS, Kim HB, Kang CW, Kim BS, Nah SY, Kim JH. Neuroprotective effects of ginsenoside Rg3 against 24-OH-cholesterol-induced cytotoxicity in cortical neurons. J Ginseng Res 2010;34:246-53. https://doi.org/10.5142/jgr.2010.34.3.246
  25. Tian J, Fu F, Geng M, Jiang Y, Yang J, Jiang W, Wang C, Liu K. Neuroprotective effect of 20(S)-ginsenoside Rg3 on cerebral ischemia in rats. Neurosci Lett 2005;374:92-7. https://doi.org/10.1016/j.neulet.2004.10.030
  26. Kim S, Ahn K, Oh TH, Nah SY, Rhim H. Inhibitory effect of ginsenosides on NMDA receptor-mediated signals in rat hippocampal neurons. Biochem Biophys Res Commun 2002;296:247-54. https://doi.org/10.1016/S0006-291X(02)00870-7
  27. Chen F, Eckman E, Eckman C. Reductions in levels of the Alzheimer's amyloid b peptide after oral administration of ginsenosides. FASEB J 2006;20:1269-71. https://doi.org/10.1096/fj.05-5530fje
  28. In JG, Lee BS, Kim EJ, Park MH, Yang DC. Increase of functional saponin by acidic treatment and temperature of red ginseng extract. Korea J Plant Res 2006;19:139-43.
  29. Kim DH, Jeon SJ, Son KH, Jung JW, Lee SJ, Yoon BH, Lee JJ, Cho YW, Cheong JH, Ko KH, et al. The ameliorating effect of oroxylin A on scopolamine-induced memory impairment in mice. Neurobiol Learn Mem 2007;87:536-46. https://doi.org/10.1016/j.nlm.2006.11.005
  30. Lee YJ, Choi DY, Han SB, Kim YH, Kim KH, Seong YH, Oh KW, Hong TJ. A comparison between extract products of Magnolia officinalis on memory impairment and amyloidogenesis in a transgenic mouse model of Alzheimer's disease. Biomol Ther 2012;20:332-9. https://doi.org/10.4062/biomolther.2012.20.3.332
  31. Kim SR, Kang SY, Lee KY, Kim SH, Markeloni GJ, Oh TH, Kim CK. Anti-amnesic activity of E-p-methoxycinnamic acid from Scrophularia buergeriana. Brain Res Cog Brain Res 2003;17:454-61. https://doi.org/10.1016/S0926-6410(03)00161-7
  32. Ellman GL, Courtney KD, Andres V, Feather-Stone RM. A new and rapid colormetric determination of cholinesterase activity. Biochem Pharmacol 1961;7:88-95. https://doi.org/10.1016/0006-2952(61)90145-9
  33. Park SJ, Jung JM, Lee HE, Lee YW, Kim DH, Kim JM, Hong JG, Lee CH, Jung IH, Cho YB, et al. The memory ameliorating effects of INM-176, an ethanolic extract of Angelica gigas, against scopolamine- or Ab1-42-induced cognitive dysfunction in mice. J Ethnopharmacology 2012;143:611-20. https://doi.org/10.1016/j.jep.2012.07.019
  34. Olton DS, Papas BC. Spatial memory and hippocampal function. Neuropsychologia 1979;17:669-82. https://doi.org/10.1016/0028-3932(79)90042-3
  35. Lorenzini CA, Baldi E, Bucherelli C, Sacchetti B, Tassoni G. Role of dorsal hippocampus in acquisition, consolidation and retrieval of rat's passive avoidance response: a tetrodotoxin functional inactivation study. Brain Res 1996;730: 32-9. https://doi.org/10.1016/0006-8993(96)00427-1
  36. Barnes CA, Danysz W, Parsons CG. Effects of the uncompetitive NMDA receptor antagonist memantine on hippocampal long-term potentiation, shortterm exploratory modulation and spatial memory in awake, freely moving rats. Eur J Neurosci 1996;8:565-71. https://doi.org/10.1111/j.1460-9568.1996.tb01241.x
  37. Morris RG. Development of a water maze procedure for studying spatial learning in the rat. J Neurosci Methods 1984;11:47-60. https://doi.org/10.1016/0165-0270(84)90007-4
  38. Buccafusco JJ. The revival of scopolamine reversal for the assessment of cognition-enhancing drugs. In: Buccafusco JJ, editor. Methods of behavior analysis in neuroscience. 2nd ed. Florida: CRC Press; 2009. Ch. 17:329-43.
  39. Rossor M, Iversen LL. Non-cholinergic neurotransmitter abnormalities in Alzheimer's disease. Brit Med Bull 1986;42:70-4. https://doi.org/10.1093/oxfordjournals.bmb.a072101
  40. Takada Y, Yonezawa A, Kume T, Katsuki H, Kaneko S, Sugimoto H, et al. Nicotinic acetylcholine receptor-mediated neuroprotection by donezepil against glutamate neurotoxicity in rat cortical neurons. J Pharmacol Exp Ther 2003;306:772-7. https://doi.org/10.1124/jpet.103.050104
  41. Fan Y, Hu J, Li J, Yang Z, Xin X, Wang J, Ding J, Geng M. Effect of acidic oligosaccharide sugar chain on scopolamine-induced memory impairment in rats and its related mechanisms. Neurosci Lett 2005;374:222-6. https://doi.org/10.1016/j.neulet.2004.10.063
  42. Kim EJ, Jung IH, Van Le TK, Jeong JJ, Kim NJ, Kim DH. Ginsenoside Rg5 and Rh3 protect scopolamine-induced memory deficits in mice. J Ethnopharmacol 2013;146:294-9. https://doi.org/10.1016/j.jep.2012.12.047

Cited by

  1. Phytochemical Analysis, Antioxidant, Antistress, and Nootropic Activities of Aqueous and Methanolic Seed Extracts of Ladies Finger ( Abelmoschus esculentus L.) in Mice vol.2014, pp.None, 2014, https://doi.org/10.1155/2014/519848
  2. ginsenoside Rg3에 의한 B16F10 흑색종 세포의 세포사멸 유도 vol.24, pp.9, 2014, https://doi.org/10.5352/jls.2014.24.9.1001
  3. Improvement in Long-Term Memory following Chronic Administration of Eryngium planum Root Extract in Scopolamine Model: Behavioral and Molecular Study vol.2015, pp.None, 2014, https://doi.org/10.1155/2015/145140
  4. Effects of the Methanolic Extract of Vitellaria paradoxa Stem Bark Against Scopolamine-Induced Cognitive Dysfunction and Oxidative Stress in the Rat Hippocampus vol.36, pp.7, 2014, https://doi.org/10.1007/s10571-015-0310-7
  5. Changes in ginsenoside patterns of red ginseng extracts according to manufacturing and storage conditions vol.26, pp.6, 2017, https://doi.org/10.1007/s10068-017-0149-4
  6. Neuroprotective and Antiamnesic Effects of Mitragyna inermis Willd (Rubiaceae) on Scopolamine-Induced Memory Impairment in Mice vol.2017, pp.None, 2017, https://doi.org/10.1155/2017/5952897
  7. Ascorbic acid tethered polymeric nanoparticles enable efficient brain delivery of galantamine: An in vitro - in vivo study vol.7, pp.None, 2014, https://doi.org/10.1038/s41598-017-11611-4
  8. Protective effects of cultured and fermented ginseng extracts against scopolamine-induced memory loss in a mouse model vol.34, pp.1, 2014, https://doi.org/10.5625/lar.2018.34.1.37
  9. Active ginseng components in cognitive impairment: Therapeutic potential and prospects for delivery and clinical study vol.9, pp.71, 2018, https://doi.org/10.18632/oncotarget.26035
  10. Neuroprotective Effects of Ginseng Phytochemicals: Recent Perspectives vol.24, pp.16, 2014, https://doi.org/10.3390/molecules24162939
  11. Evaluation of Anticonvulsant Effect of Aqueous and Methanolic Extracts of Seven Inula Species vol.18, pp.suppl1, 2014, https://doi.org/10.22037/ijpr.2019.15509.13151
  12. Neuroprotective Effect and Antioxidant Potency of Fermented Cultured Wild Ginseng Root Extracts of Panax ginseng C.A. Meyer in Mice vol.26, pp.10, 2021, https://doi.org/10.3390/molecules26103001