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Anti-amnesic Effect and Antioxidant Defense Systems of Yukmijihwang-tang on Scopolamine-induced Memory Impairment in Mice

Scopolamine 유발 건망증 마우스 모델에서 육미지황탕(六味地黃湯)의 기억력 개선 및 항산화 효과

  • Seo, Young-Min (Department of Oriental Neuropsychiatry, College of Korean Medicine, Daegu Hanny University) ;
  • Han, Da-young (Department of Oriental Neuropsychiatry, College of Korean Medicine, Daegu Hanny University) ;
  • Kim, Sang-ho (Department of Oriental Neuropsychiatry, College of Korean Medicine, Daegu Hanny University) ;
  • Chung, Dae-kyoo (Department of Oriental Neuropsychiatry, College of Korean Medicine, Daegu Hanny University)
  • 서영민 (대구한의대학교 한의과대학 신경정신과교실) ;
  • 한다영 (대구한의대학교 한의과대학 신경정신과교실) ;
  • 김상호 (대구한의대학교 한의과대학 신경정신과교실) ;
  • 정대규 (대구한의대학교 한의과대학 신경정신과교실)
  • Received : 2018.10.16
  • Accepted : 2018.12.05
  • Published : 2018.12.31

Abstract

Objectives: The objective of this study was to observe the anti-amnesic effects of Yukmijihwang-tang (YMJHT), on the scopolamine (Sco)-induced memory impairment in C57BL/6 mice through its favorable acetylcholine (ACh). Also, to observe acetylcholinesterase (AChE) activity, Choline acetyltransferase (ChAT) mRNA expressions, and antioxidant effect. Methods: Six groups, with a total of 20 normal and 100 Sco treated mice were selected based on their body weights after 1 week of acclimatization, were used in this study as follows. Half of the mice in each group were used for passive avoidance task tests and hippocampus ACh content, AChE activity and ChAT mRNA expression measurement, and the remaining half in each group used for Morris water maze test and measurement of cerebral antioxidant defense system. Results: Amnesia due to AChE activations and destroyed cerebral cortex antioxidant defense systems were markedly and dose-dependently inhibited after 28 days of continuous oral pre-treatment with YMJHT 400, 200 and 100 mg/kg, respectively. The overall effects of YMJHT 400 mg/kg were similar to those of tacrine 10 mg/kg. Conclusions: Based on the results, it was established that oral administration of YMJHT favorably alleviates Sco-induced memory impairment, through preservation of ACh, mediated by up-regulation of ChAT mRNA expressions and related AChE inhibition and augmentation of cerebral antioxidant defense system, at least in a condition of this experiment. The overall effects of YMJHT 400 mg/kg were similar to those of tacrine 10 mg/kg.

Keywords

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Fig. 1. Experimental Design Used in This Study.

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Fig. 1. Experimental Design Used in This Study.

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Fig. 2. Body Weight Changes in Normal Mice and Sco-induced Amnesia Mice.

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Fig. 2. Body Weight Changes in Normal Mice and Sco-induced Amnesia Mice.

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Fig. 3. Changes on the Step-through Latency Times of Passive Avoidance Task Test in Normal Mice and Sco-induced Amnesia Mice.

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Fig. 3. Changes on the Step-through Latency Times of Passive Avoidance Task Test in Normal Mice and Sco-induced Amnesia Mice.

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Fig. 4. Changes on the Escape Latency Times of Morris Water Maze Test in Normal Mice and Sco-induced Amnesia Mice.

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Fig. 4. Changes on the Escape Latency Times of Morris Water Maze Test in Normal Mice and Sco-induced Amnesia Mice.

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Fig. 5. Changes on the Hippocampus ACh Contents in Normal Mice and Sco-induced Amnesia Mice.

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Fig. 5. Changes on the Hippocampus ACh Contents in Normal Mice and Sco-induced Amnesia Mice.

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Fig. 6. Changes on the Hippocampus AChE Activities in Normal Mice and Sco-induced Amnesia Mice.

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Fig. 6. Changes on the Hippocampus AChE Activities in Normal Mice and Sco-induced Amnesia Mice.

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Fig. 7. Changes on the Hippocampus ChAT mRNA Expressions in Normal Mice and Sco-induced Amnesia Mice.

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Fig. 7. Changes on the Hippocampus ChAT mRNA Expressions in Normal Mice and Sco-induced Amnesia Mice.

Table 1. Composition of YMJHT Used in This Study

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Table 1. Composition of YMJHT Used in This Study

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Table 2. The Specific Sequence for Each Primer

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Table 2. The Specific Sequence for Each Primer

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Table 3. Changes on the Body Weight Gains in Normal Mice and Scopolamine-Induced Amnesia Mice

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Table 3. Changes on the Body Weight Gains in Normal Mice and Scopolamine-Induced Amnesia Mice

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Table 4. Cerebral Cortex Antioxidant Defense Systems in Normal Mice and Scopolamine-induced Amnesia Mice

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Table 4. Cerebral Cortex Antioxidant Defense Systems in Normal Mice and Scopolamine-induced Amnesia Mice

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References

  1. Chuong NN, Trung BH, Luan TC, Hung TM, Dang NH, Dat NT. Anti-amnesic effect of alkaloid fraction from Lycopodiella cernua (L.) Pic. Serm. on scopolamine-induced memory impairment in mice. Neurosci Lett. 2014; 575:42-6. https://doi.org/10.1016/j.neulet.2014.05.031
  2. Becker R, Giacobini E, Elble R, McIlhany M, Sherman K. Potential pharmacotherapy of Alzheimer disease. A com - parison of various forms of physostigmine administration. Acta Neurol Scand Suppl. 1988;116:19-32.
  3. Choi WH, Um MY, Ahn JY, Kim SR, Kang MH and Ha TY. Acetylcholinesterase inhibitory activity and protective effect against cytotoxicity of perilla seed methanol extract. J Korean Food Sci Technol. 2004;36:1026-31.
  4. Saxena G, Singh SP, Agrawal R, Nath C. Effect of donepezil and tacrine on oxidative stress in intracerebral streptozotocin-induced model of dementia in mice. Eur J Pharmacol. 2008;581(3):283-9. https://doi.org/10.1016/j.ejphar.2007.12.009
  5. Watkins PB, Zimmerman HJ, Knapp MJ, Gracon SI, Lewis KW. Hepatotoxic effects of tacrine administration in patients with Alzheimer's disease. JAMA. 1994;271(13): 992-8. https://doi.org/10.1001/jama.1994.03510370044030
  6. Xiao J, Li S, Sui Y, Wu Q, Li X, Xie B, Zhang M, Sun Z. Lactobacillus casei-01 facilitates the ameliorative effects of proanthocyanidins extracted from lotus seedpod on learning and memory impairment in scopolamine-induced amnesia mice. PLoS One. 2014;9(11):e112773. https://doi.org/10.1371/journal.pone.0112773
  7. Hasanein P, Mahtaj AK. Ameliorative effect of rosmarinic acid on scopolamine-induced memory impairment in rats. Neurosci Lett. 2015;585:23-7. https://doi.org/10.1016/j.neulet.2014.11.027
  8. Kang M, Kim JH, Cho C, Lee KY, Shin M, Hong M, Shim I, Bae H. Effects of Yukmijihwang-tang derivatives (YMJd) on ibotenic acid-induced amnesia in the rat. Biol Pharm Bull. 2006;29(7):1431-5. https://doi.org/10.1248/bpb.29.1431
  9. Lee S, Kim J, Seo SG, Choi BR, Han JS, Lee KW, Kim J. Sulforaphane alleviates scopolamine-induced memory impairment in mice. Pharmacol Res. 2014;85:23-32. https://doi.org/10.1016/j.phrs.2014.05.003
  10. Nam Y, Lee D. Ameliorating effects of constituents from Cortex Acanthopanacis Radicis on memory impairment in mice induced by scopolamine. J Tradit Chin Med. 2014;34(1):57-62. https://doi.org/10.1016/S0254-6272(14)60055-8
  11. Morris R. Developments 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
  12. Jamall IS, Smith JC. Effects of cadmium on glutathione peroxidase, superoxidase dismutase and lipid peroxidation in the rat heart: a possible mechanism of cadmium cardiotoxicity. Toxicol Appl Pharmacol. 1985;80: 33-42. https://doi.org/10.1016/0041-008X(85)90098-5
  13. Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem. 1968;25(1):192-205. https://doi.org/10.1016/0003-2697(68)90092-4
  14. Aebi H. Catalase. In: Bergmeyer HU (Ed.), Methods in Enzymatic Analysis. New York: Academic Press. 1974; 673-86.
  15. Sun Y, Larry WO, Ying L. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988;34:497-500.
  16. Levene A. Pathological factors influencing excision of tumours in the head and neck. Part I. Clin Otolaryngol Allied Sci. 1981;6(2):145-51. https://doi.org/10.1111/j.1365-2273.1981.tb01800.x
  17. Ludbrook J. Update: microcomputer statistics packages. A personal view. Clin Exp Pharmacol Physiol. 1997; 24(3-4):294-6. https://doi.org/10.1111/j.1440-1681.1997.tb01823.x
  18. Kang SJ, Lee JE, Lee EK, Jung DH, Song CH, Park SJ, Choi SH, Han CH, Ku SK, Lee YJ. Fermentation with Aquilariae Lignum enhances the anti-diabetic activity of green tea in type II diabetic db/db mouse. Nutrients. 2014;6(9):3536-71. https://doi.org/10.3390/nu6093536
  19. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorder. 4th ed. Washington DC. American Psychiatric Association. 1994.
  20. LeDoux JE. Emotional memory systems in the brain. Behav Brain Res. 1993;58:69-79. https://doi.org/10.1016/0166-4328(93)90091-4
  21. Park SM, Ki SH, Han NR, Cho IJ, Ku SK, Kim SC, Zhao RJ, Kim YW. Tacrine, an oral acetylcholinesterase inhibitor, induced hepatic oxidative damage, which was blocked by liquiritigenin through GSK3-beta inhibition. Biol Pharm Bull. 2015;38(2):184-92. https://doi.org/10.1248/bpb.b14-00430
  22. Song XY, Chen Q, Qi XY. Effects of liuwei dihuang pill on erythrocyte aldose reductase activity in early diabetic nephropathy patients. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2004;24(12):1087-90.
  23. Kang DG, Sohn EJ, Moon MK, Mun YJ, Woo WH, Kim MK, Lee HS. Yukmijihwang-tang ameliorates ischemia/reperfusion-induced renal injury in rats. J Ethnopharmacol. 2006;104(1-2):47-53. https://doi.org/10.1016/j.jep.2005.08.044
  24. Ha H, Lee JK, Lee HY, Koh WS, Seo CS, Lee MY, Huang DS, Shin H. Safety evaluation of Yukmijihwang-tang: Assessment of acute and subchronic toxicity in rats. Evid Based Complement Alternat Med. 2011;2011:672136.
  25. Shin IS, Lee MY, Ha HK, Seo CS, Shin HK. Inhibitory effect of Yukmijihwang-tang, a traditional herbal formula against testosterone-induced benign prostatic hyperplasia in rats. BMC Complement Altern Med. 2012;12:48. https://doi.org/10.1186/1472-6882-12-48
  26. Oh MS, Chang MS, Park W, Kim DR, Bae H, Huh Y, Park SK. Yukmijihwangtang protects against cyclophosphamide-induced reproductive toxicity. Reprod Toxicol. 2007;24(3-4):365-70. https://doi.org/10.1016/j.reprotox.2007.05.007
  27. Shim KS, Ma CJ, Kim DS, Ma JY. Yukmijihwang-tang inhibits receptor activator for nuclear Factor-${\kappa}B$ ligand-induced osteoclast differentiation. J Med Food. 2011;14 (11):1439-47. https://doi.org/10.1089/jmf.2010.1502
  28. Shen JJ, Lin CJ, Hiang JL, Hsieh KH, Kuo ml. The effect of liu-wei-di-huang wan on cytokine gene expression from human peripheral blood lymphocytes. Am J Chin Med. 2003;31(2):247-57. https://doi.org/10.1142/S0192415X03000886
  29. Abe E. Reversal effect of DM-9384 on scopolamine-induced acetylcholine depletion in certain regions of the mouse brain. Psychopharmacology. 1991;105(3):310-6. https://doi.org/10.1007/BF02244423
  30. Roof RL, Schielke GP, Ren X, Hall ED. A comparison of long-term functional outcome after 2 middle cerebral artery occlusion models in rats. Stroke. 2001;32(11):2648-57. https://doi.org/10.1161/hs1101.097397
  31. Zambrzycka A, Alberghina M, Strosznajder JB. Effects of aging and amyloid-beta peptides on choline acetyltransferase activity in rat brain. Neurochem Res. 2002;27: 277-81. https://doi.org/10.1023/A:1014951010834
  32. Mohapel P, Leanza G, Kokaia M, Lindvall O. Forebrain acetylcholine regulates adult hippocampal neurogenesis and learning. Neurobiol Aging. 2005;26(6):939-46. https://doi.org/10.1016/j.neurobiolaging.2004.07.015
  33. Eichenbaum H. How does the brain organize memories? Science. 1997;277(5324):330-2. https://doi.org/10.1126/science.277.5324.330
  34. Giacobini E. Cholinesterase inhibitors: new roles and therapeutic alternatives. Pharmacol Res. 2004;50(4): 433-40. https://doi.org/10.1016/j.phrs.2003.11.017
  35. Wattanathorn J, Jittiwat J, Tongun T, Muchimapura S, Ingkaninan K. Zingiber officinale mitigates brain damage and improves memory impairment in focal cerebral ischemic rat. Evid Based Complement Alternat Med. 2011; 2011:429505.
  36. Rao KS. Free radical induced oxidative damage to DNA: relation to brain aging and neurological disorders. Indian J Biochem Biophys. 2009;46(1):9-15.
  37. Ghumatkar PJ, Patil SP, Jain PD, Tambe RM, Sathaye S. Nootropic, neuroprotective and neurotrophic effects of phloretin in scopolamine induced amnesia in mice. Pharmacol Biochem Behav. 2015;135:182-91. https://doi.org/10.1016/j.pbb.2015.06.005
  38. Kumar H, Kim BW, Song SY, Kim JS, Kim IS, Kwon YS, Koppula S, Choi DK. Cognitive enhancing effects of alpha asarone in amnesic mice by influencing cholinergic and antioxidant defense mechanisms. Biosci Biotechnol Biochem. 2012;76(8):1518-22. https://doi.org/10.1271/bbb.120247
  39. Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, Jones PK, Ghanbari H, Wataya T, Shimohama S, Chiba S, Atwood CS, Petersen RB, Smith MA. Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol. 2001;60(8):759-67. https://doi.org/10.1093/jnen/60.8.759
  40. Mattson MP, Pedersen WA, Duan W, Culmsee C, Camandola S. Cellular and molecular mechanisms underlying perturbed energy metabolism and neuronal degeneration in Alzheimer's and Parkinson's diseases. Ann N Y Acad Sci. 1999;893:154-75. https://doi.org/10.1111/j.1749-6632.1999.tb07824.x
  41. Swerdlow RH. Brain aging, Alzheimer's disease, and mitochondria. Biochim Biophys Acta. 2011;1812:1630-9. https://doi.org/10.1016/j.bbadis.2011.08.012
  42. Lee JS, Kim HG, Lee HW, Han JM, Lee SK, Kim DW, Saravanakumar A, Son CG. Hippocampal memory enhancing activity of pine needle extract against scopolamine-induced amnesia in a mouse model. Sci Rep. 2015;5:9651. https://doi.org/10.1038/srep09651
  43. Mansoorali KP, Prakash T, Kotresha D, Prabhu K, Rama Rao N. Cerebroprotective effect of Eclipta alba against global model of cerebral ischemia induced oxidative stress in rats. Phytomedicine. 2012;19(12):1108-16. https://doi.org/10.1016/j.phymed.2012.07.004
  44. Raichle ME. The pathophysiology of brain ischemia. Ann Neurol. 1983;13(1):2-10. https://doi.org/10.1002/ana.410130103
  45. Odabasoglu F, Cakir A, Suleyman H, Aslan A, Bayir Y, Halici M, Kazaz C. Gastroprotective and antioxidant effects of usnic acid on indomethacin-induced gastric ulcer in rats. J Ethnopharmacol. 2006;103(1):59-65. https://doi.org/10.1016/j.jep.2005.06.043
  46. Cheeseman KH, Slater TF. An introduction to free radical biochemistry. Br Med Bull. 1993;49(3):481-93. https://doi.org/10.1093/oxfordjournals.bmb.a072625