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Black ginseng-enriched Chong-Myung-Tang extracts improve spatial learning behavior in rats and elicit anti-inflammatory effects in vitro

  • Saba, Evelyn (Laboratory of Physiology and Cell Signaling, College of Veterinary Medicine, Kyungpook National University) ;
  • Jeong, Da-Hye (Laboratory of Physiology and Cell Signaling, College of Veterinary Medicine, Kyungpook National University) ;
  • Roh, Seong-Soo (College of Korean Medicine, Daegu Haany University) ;
  • Kim, Seung-Hyung (Institute of Traditional Medicine and Bioscience, Daejeon University) ;
  • Kim, Sung-Dae (Laboratory of Physiology and Cell Signaling, College of Veterinary Medicine, Kyungpook National University) ;
  • Kim, Hyun-Kyoung (Department of Food Science and Engineering, Seowon University) ;
  • Rhee, Man-Hee (Laboratory of Physiology and Cell Signaling, College of Veterinary Medicine, Kyungpook National University)
  • Received : 2015.12.30
  • Accepted : 2016.02.22
  • Published : 2017.04.15

Abstract

Background: Chong-Myung-Tang (CMT) extract is widely used in Korea as a traditional herbal tonic for increasing memory capacity in high-school students and also for numerous body ailments since centuries. The use of CMT to improve the learning capacity has been attributed to various plant constituents, especially black ginseng, in it. Therefore, in this study, we have first investigated whether black ginseng-enriched CMT extracts affected spatial learning using the Morris water maze (MWM) test. Their molecular mechanism of action underlying improvement of learning and memory was examined in vitro. Methods: We used two types of black ginseng-enriched CMT extracts, designated as CM-1 and CM-2, and evaluated their efficacy in the MWM test for spatial learning behavior and their anti-inflammatory effects in BV2 microglial cells. Results: Our results show that both black ginseng-enriched CMT extracts improved the learning behavior in scopolamine-induced impairment in the water maze test. Moreover, these extracts also inhibited nitric oxide production in BV2 cells, with significant suppression of expression of proinflammatory cytokines, especially inducible nitric oxide synthase, cyclooxygenase-2, and $interleukin-1{\beta}$. The protein expression of mitogen-activated protein kinase and nuclear $factor-{\kappa}B$ pathway factors was also diminished by black ginseng-enriched CMT extracts, indicating that it not only improves the memory impairment, but also acts a potent anti-inflammatory agent for neuroinflammatory diseases. Conclusion: Our research for the first time provides the scientific evidence that consumption of black ginseng-enriched CMT extract as a brain tonic improves memory impairment. Thus, our study results can be taken as a reference for future neurobehavioral studies.

Keywords

References

  1. Oh YJ, Kim BK. A study of ChongMyungTang (CMT) and HyangbujaChongMyungTang (HCMT) on dementiadextract & nano powder drug types. J Orien Neuropsychiatry 2006;17:79-105.
  2. Lee MR, Yun BS, Park SY, Ly SY, Kim SN, Han BH, Sung CK. Anti-amnesic effect of Chong-Myung-Tang on scopolamine-induced memory impairments in mice. J Ethnopharmacol 2010;132:70-4. https://doi.org/10.1016/j.jep.2010.07.041
  3. Jeon J, Jo C. Editing style of Imwon-Gyeongjeji, Inje-ji and inclusion of the medicinal knowledge of the late period of Joseon - Comparing mainly with Dongui-Bogam. Uisahak 2012;21:403-48 [Article in Korean].
  4. Gonzalez-Burgos E, Fernandez-Moriano C, Gomez-Serranillos MP. Potential neuroprotective activity of Ginseng in Parkinson's disease: a review. J Neuroimmune Pharmacol 2015;10:14-29. https://doi.org/10.1007/s11481-014-9569-6
  5. Nitta H, Matsumoto K, Shimizu M, Ni XH, Watanabe H. Panax ginseng extract improves the scopolamine-induced disruption of 8-arm radial maze performance in rats. Biol Pharm Bull 1995;18:1439-42. https://doi.org/10.1248/bpb.18.1439
  6. Ong WY, Farooqui T, Koh HL, Farooqui AA, Ling EA. Protective effects of ginseng on neurological disorders. Front Aging Neurosci 2015;7:129.
  7. Ryuk JA, Kim YS, Lee HW, Ko BS. Identification of Acorus gramineus, A. calamus, and A. tatarinowii using sequence characterized amplified regions (SCAR) primers for monitoring of Acori graminei rhizoma in Korean markets. Int J Clin Exp Med 2014;7:2488-96.
  8. Lee KY, Jeon YJ. Polysaccharide isolated from Poria cocos sclerotium induces NF-kappaB/Rel activation and iNOS expression in murine macrophages. Int Immunopharmacol 2003;3:1353-62. https://doi.org/10.1016/S1567-5769(03)00113-9
  9. Park CH, Choi SH, Koo JW, Seo JH, Kim HS, Jeong SJ, Suh YH. Novel cognitive improving and neuroprotective activities of Polygala tenuifolia Willdenow extract, BT-11. J Neurosci Res 2002;70:484-92. https://doi.org/10.1002/jnr.10429
  10. Zhang J, Li L, Jiang C, Xing C, Kim SH, Lu J. Anti-cancer and other bioactivities of Korean Angelica gigas Nakai (AGN) and its major pyranocoumarin compounds. Anticancer Agents Med Chem 2012;12:1239-54. https://doi.org/10.2174/187152012803833071
  11. Oh TW, Park KH, Jung HW, Park YK. Neuroprotective effect of the hairy root extract of Angelica gigas NAKAI on transient focal cerebral ischemia in rats through the regulation of angiogenesis. BMC Complement Altern Med 2015;15:101. https://doi.org/10.1186/s12906-015-0589-4
  12. Peng WH, Hsieh MT, Lee YS, Lin YC, Liao J. Anxiolytic effect of seed of Ziziphus jujuba in mouse models of anxiety. J Ethnopharmacol 2000;72:435-41. https://doi.org/10.1016/S0378-8741(00)00255-5
  13. Choi SB, Wha JD, Park S. The insulin sensitizing effect of homoisoflavoneenriched fraction in Liriope platyphylla Wang et Tang via PI3-kinase pathway. Life Sci 2004;75:2653-64. https://doi.org/10.1016/j.lfs.2004.04.039
  14. Jo EH, Hong HD, Ahn NC, Jung JW, Yang SR, Park JS, Kim SH, Lee YS, Kang KS. Modulations of the Bcl-2/Bax family were involved in the chemopreventive effects of licorice root (Glycyrrhiza uralensis Fisch) in MCF-7 human breast cancer cell. J Agric Food Chem 2004;52:1715-9. https://doi.org/10.1021/jf035012t
  15. Chung WT, Lee SH, Kim JD, Sung NS, Hwang B, Lee SY, Yu CY, Lee HY. Effect of the extracts from Glycyrrhiza uralensis Fisch on the growth characteristics of human cell lines: anti-tumor and immune activation activities. Cytotechnology 2001;37:55-64. https://doi.org/10.1023/A:1016111713056
  16. Lee KP, Kang S, Park SJ, Kim JM, Lee JM, Lee AY, Chung HY, Choi YW, Lee YG, Im DS. Anti-allergic effect of alpha-cubebenoate isolated from Schisandra chinensis using in vivo and in vitro experiments. J Ethnopharmacol 2015;173:361-9. https://doi.org/10.1016/j.jep.2015.07.049
  17. Panossian A, Wikman G. Pharmacology of Schisandra chinensis Bail.: an overview of Russian research and uses in medicine. J Ethnopharmacol 2008;118:183-212. https://doi.org/10.1016/j.jep.2008.04.020
  18. Yeh YC, Hahm TS, Sabliov CM, Lo YM. Effects of Chinese wolfberry (Lycium chinense P. Mill.) leaf hydrolysates on the growth of Pediococcus acidilactici. Bioresour Technol 2008;99:1383-93. https://doi.org/10.1016/j.biortech.2007.01.058
  19. dela Pena IJ, Hong E, Kim HJ, de la Pena JB, Woo TS, Lee YS, Cheong JH. Artemisia capillaris Thunberg produces sedative-hypnotic effects in mice, which are probably mediated through potentiation of the GABAA receptor. Am J Chin Med 2015;43:667-9. https://doi.org/10.1142/S0192415X1550041X
  20. Mahady GB, Pendland SL, Yun GS, Lu ZZ, Stoia A. Ginger (Zingiber officinale Roscoe) and the gingerols inhibit the growth of Cag A+ strains of Helicobacter pylori. Anticancer Res 2003;23:3699-702.
  21. Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc 2006;1:848-58. https://doi.org/10.1038/nprot.2006.116
  22. Saba E, Jeon BR, Jeong DH, Lee K, Goo YK, Kwak D, Kim S, Roh SS, Kim SD, Nah SY, et al. A novel Korean Red Ginseng compound gintonin inhibited inflammation by MAPK and NF-B pathways and recovered the levels of MIR-34a and MIR-93 in RAW 264.7 cells. Evid Based Complement Alternat Med 2015;2015:624132.
  23. Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol 2014;5:461.
  24. Moynagh PN. The NF-kappaB pathway. J Cell Sci 2005;118:4589-92. https://doi.org/10.1242/jcs.02579
  25. Wang DS, Zurek AA, Lecker I, Yu J, Abramian AM, Avramescu S, Davies PA, Moss SJ, Lu WY, Orser BA. Memory deficits induced by inflammation are regulated by alpha5-subunit-containing GABAA receptors. Cell Rep 2012;2:488-96. https://doi.org/10.1016/j.celrep.2012.08.022
  26. Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 2008;9:46-56. https://doi.org/10.1038/nrn2297
  27. Khakpai F, Nasehi M, Haeri-Rohani A, Eidi A, Zarrindast MR. Scopolamine induced memory impairment; possible involvement of NMDA receptor mechanisms of dorsal hippocampus and/or septum. Behav Brain Res 2012;231:1-10. https://doi.org/10.1016/j.bbr.2012.02.049
  28. Portero-Tresserra M, Del Olmo N, Marti-Nicolovius M, Guillazo-Blanch G, Vale-Martinez A. d-Cycloserine prevents relational memory deficits and suppression of long-term potentiation induced by scopolamine in the hippocampus. Eur Neuropsychopharmacol 2014;24:1798-807. https://doi.org/10.1016/j.euroneuro.2014.10.002
  29. Stellwagen D, Beattie EC, Seo JY, Malenka RC. Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-alpha. J Neurosci 2005;25:3219-28. https://doi.org/10.1523/JNEUROSCI.4486-04.2005
  30. Yirmiya R, Goshen I. Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain Behav Immun 2011;25:181-213. https://doi.org/10.1016/j.bbi.2010.10.015
  31. Wilson CJ, Finch CE, Cohen HJ. Cytokines and cognitiondthe case for a headto-toe inflammatory paradigm. J Am Geriatr Soc 2002;50:2041-56. https://doi.org/10.1046/j.1532-5415.2002.50619.x
  32. Pickering M, Cumiskey D, O'Connor JJ. Actions of TNF-alpha on glutamatergic synaptic transmission in the central nervous system. Exp Physiol 2005;90:663-70. https://doi.org/10.1113/expphysiol.2005.030734
  33. Aravalli RN, Hu S, Rowen TN, Palmquist JM, Lokensgard JR. Cutting edge: TLR2-mediated proinflammatory cytokine and chemokine production by microglial cells in response to herpes simplex virus. J Immunol 2005;175:4189-93. https://doi.org/10.4049/jimmunol.175.7.4189
  34. Jang S, Dilger RN, Johnson RW. Luteolin inhibits microglia and alters hippocampal-dependent spatial working memory in aged mice. J Nutr 2010;140:1892-8. https://doi.org/10.3945/jn.110.123273
  35. Ben Menachem-Zidon O, Goshen I, Kreisel T, Ben Menahem Y, Reinhartz E, Ben Hur T, Yirmiya R. Intrahippocampal transplantation of transgenic neural precursor cells overexpressing interleukin-1 receptor antagonist blocks chronic isolation-induced impairment in memory and neurogenesis. Neuropsychopharmacology 2008;33:2251-62. https://doi.org/10.1038/sj.npp.1301606
  36. Kang G, Kong PJ, Yuh YJ, Lim SY, Yim SV, Chun W, Kim SS. Curcumin suppresses lipopolysaccharide-induced cyclooxygenase-2 expression by inhibiting activator protein 1 and nuclear factor kappab bindings in BV2 microglial cells. J Pharmacol Sci 2004;94:325-8. https://doi.org/10.1254/jphs.94.325
  37. Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol 2009;1:a001651.
  38. Sethi G, Sung B, Aggarwal BB. Nuclear factor-kappaB activation: from bench to bedside. Exp Biol Med (Maywood) 2008;233:21-31. https://doi.org/10.3181/0707-MR-196
  39. Hommes DW, Peppelenbosch MP, van Deventer SJ. Mitogen activated protein (MAP) kinase signal transduction pathways and novel anti-inflammatory targets. Gut 2003;52:144-51. https://doi.org/10.1136/gut.52.1.144
  40. Arthur JS, Ley SC. Mitogen-activated protein kinases in innate immunity. Nat Rev Immunol 2013;13:679-92. https://doi.org/10.1038/nri3495

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