Journal of Oriental Neuropsychiatry (동의신경정신과학회지)

The Korean Society of Oriental Neuropsychiatry (대한한방신경정신과학회)
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Sungshim-san-mediated Recovery of Cognition and Motor Function in the Severe Rat Stroke, Permanent Middle Cerebral Artery Occlusion Model

성심산(醒心散)의 중대뇌동맥 폐쇄로 유발된 허혈성 뇌손상 백서(白鼠)에 대한 인지 및 운동기능 회복 촉진효과

  • Lee, Kyung-Seok (Department of Oriental Neuropsychiatry, College of Oriental Medicine, Daegu Haany University) ;
  • Chung, Dae-Kyoo (Department of Oriental Neuropsychiatry, College of Oriental Medicine, Daegu Haany University)
  • 이경석 (대구한의대학교 한의과대학 신경정신과교실) ;
  • 정대규 (대구한의대학교 한의과대학 신경정신과교실)
  • Received : 2015.09.12
  • Accepted : 2015.09.18
  • Published : 2015.09.30
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Abstract

Objectives: The object of this study was to evaluate the cognition and motor function recovery effects of Sungshim-san (SSS), a traditional Korean cardio-protective polyherbal formula in the severe rat stroke, permanent middle cerebral artery occlusion (pMCAO) model. Methods: The experimental animals were divided into 6 groups. SSS aqueous extracts (yield=16.82%; 400, 200 and 100 mg/kg) were administered orally by using Sonde, once daily, for 28 continuous days from 24 hrs post-pMCAO. Donepezil 10 mg/kg, a representative drug for dementia, was used as a reference drug. The body weight changes, infarct/defect sizes, sensorimotor function and cognitive motor behavior were serially monitored. Limb placing and body-swing test for sensorimotor functions were conducted at 1 day before operation (base line), and 1, 3, 7, 14, 21 and 28 days post-pMCAO; and water maze test for the cognitive motor behavior was conducted at 14 and 28 days post-pMCAO, respectively. Results: Focal cerebral cortex infarct and defects due to pMCAO resulted in marked decreases of body weight, disorders of sensorimotor functions and cognitive motor behaviors. However, the pMCAO-related ischemic damages were markedly and dose-dependently inhibited by treatment with SSS 400 and 200 mg/kg, respectively. Donepezil markedly decreased the body weight and gains, as compared with pMCAO control rats; however, SSS 400 and 200 mg/kg favorably ameliorated the pMCAO-induced decreases in body weight and gains. SSS 100 mg/kg treated rats did not show any favorable effects on the pMCAO-related ischemic damages, as compared with pMCAO control rats. Conclusions: The results of the study indicated that oral administration of SSS 400 and 200 mg/kg accelerated cognition and motor function recovery in the rat pMCAO model. The treatment effect was potentially mediated by neuroprotection via the known augmentation of cerebral antioxidant defense system of SSS itself or its individual herbal components. Especially, the overall effects of SSS 200 mg/kg were similar to those of donepezil 10 mg/kg, but less toxic.

Keywords

References

  1. Feigin VL, Lawes CM, Bennett DA, Anderson CS. Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century. Lancet Neurol. 2003;2:43-53. https://doi.org/10.1016/S1474-4422(03)00266-7
  2. Kim YS. Intergrated clinical approach to stroke. Seoul: Seowondang. 1997:303-8,317-29.
  3. Jang WS, Shin YJ, Ko SJ, Ha YJ, Kwon YM, Shin SH. Effect of Yukgunja-tang on Glutamate-induced Apoptosis in C6 Glial Cells. Journal of korean oriental internal medicine. 2010; 31(3):586-99.
  4. Kirino T, Tamura A, Sano K. Selective vulnerability of the hippocampus to ischemia -reversible and irreversible types of ischemic cell damage. Progress in Brain Res. 1985;63:39-58. https://doi.org/10.1016/S0079-6123(08)61974-3
  5. Jung GS, Kim BH, Hwang WD. Effect of Chungpaesagan-tang on cerebral Ischemic Damage Induced by MCAO in Rats. Korean journal of oriental preventive medicine. 2009;13:13-27.
  6. Kim YT, Woo HJ. Protective Effects of Yinjinchunggantang (YJCGT) on Alcohol-induced Oxidative Stress. Journal of korean oriental internal medicine. 2011;32(4): 550-64.
  7. Watanabe H, Zhao Q, Matsumoto K, Tohda M, Murakami Y, Zhang SH, Kang TH, Mahakunakorn P, Maruyama Y, Sakakibara I, Aimi N, Takayama H. Pharmacological evidence for antidementia effect of Choto-san (Goutengsan), a traditional Kampo medicine. Pharmacol Biochem Behav. 2003;75:635-43 https://doi.org/10.1016/S0091-3057(03)00109-6
  8. McCarty MF, Barroso-Aranda J, Contreras F. Potential complementarity of high-flavanol cocoa powder and spirulina for health protection. Med Hypotheses. 2010; 74:370-3. https://doi.org/10.1016/j.mehy.2008.09.060
  9. Harada S, Hamabe W, Kamiya K, Satake T, Yamamoto J, Tokuyama S. Preventive effect of Morinda citrifolia fruit juice on neuronal damage induced by focal ischemia. Biol Pharm Bull. 2009;32:405-9. https://doi.org/10.1248/bpb.32.405
  10. Birks J, Harvey RJ. Donepezil for dementia due to Alzheimer's disease. Cochrane Database Syst Rev. 2006; (1):CD001190.
  11. Rogers SL. Perspectives in the management of Alzheimer's disease: clinical profile of donepezil. Dement Geriatr Cogn Disord. 1998;9:29-42.
  12. Roman GC, Rogers SJ. Donepezil: a clinical review of current and emerging indications. Expert Opin Pharmacother. 2004;5:161-80. https://doi.org/10.1517/14656566.5.1.161
  13. Choi SH, Cheon WH, Baek KM, Han CH, Jeon WK, Kam CW, Lee YJ. A Case Study on Drug Prescription for Vascular Dementia in Western and Oriental Medicine. Korean journal of oriental preventive medicine. 2011; 15(3):39-49.
  14. Dunn NR, Pearce GL, Shakir SA. Adverse effects associated with the use of donepezil in general practice in England. J Psychopharmacol. 2000;14: 406-8. https://doi.org/10.1177/026988110001400410
  15. Takasaki K, Uchida K, Fujikawa R, Nogami A, Nakamura K, Kawasaki C, Yamaguchi K, Morita M, Morishita K, Kubota K, Katsurabayashi S, Mishima K, Fujiwara M, Iwasaki K. Neuroprotective effects of citidine-5- diphosphocholine on impaired spatial memory in a rat model of cerebrovascular dementia. J Pharmacol Sci. 2011;116: 232-7. https://doi.org/10.1254/jphs.11013FP
  16. Hu D, Cao Y, He R, Han N, Liu Z, Miao L, Yin J. Schizandrin, an antioxidant lignan from Schisandra chinensis, ameliorates A${\beta}$1-42-induced memory impairment in mice. Oxid Med Cell Longev. 2012;721.
  17. Kim WC, Kim YS, Moon SK, Ko CN, Cho KH, Bae HS, Lee KS, Park JM. A clinical study of vascular dementia in stroke patients. Journal of korean oriental internal medicine. 1998;19:50-9.
  18. Choi SH, Ku SK, Cheon WH, Baek KM, Han CH, Jeon WK, Lee YJ. Diagnosis, Treatment and Prevention of Subcortical Vascular Dementia with a Case Report. Korean journal of oriental preventive medicine. 2010;14(3):63-75.
  19. Heart-systemic internal med. Dep. of College of Ori. med. Oriental heart-systemic internal medicine. 4th. Seoul: Seowondang. 1999:425.
  20. Sim GO. Sim Ssijonsaengseo. Taebuk:Jayu publisher. 1979:137.
  21. Heo J. Dongui bogam. Kyungnam:Dongeuibogam publisher. 2005:245.
  22. Kwak JM, Oh MS, Song TW. A Study on the Effects of Sungshimsan on the Heart Lipid Peroxide and Metabolic Enzyme System in Senescence Induced Rats. Daejeon Univ. journal of oriental medicine. 1999;8:625-41.
  23. Park YK, Cho KH, Lee WC, Kim YS, Bai HS, Lee KS, Koo BH. An Experimental Study on The Effect of Seongshimsan. Kyunghui medicine. 1989;5(4):424-31.
  24. Lee BK. Park YB, Kim TH. Oriental diagnostics. Seoul: Sungbosa. 2000:II66.
  25. De Ryck M, van Reempts J, Borgers M, Wauquier A, Janssen PAJ. Photochemical stroke model: flunarizine prevents sensorimotor deficits after neocortical infarcts in rats. Stroke. 1989;20:1383-90. https://doi.org/10.1161/01.STR.20.10.1383
  26. Borlongan CV, Sanberg PR. Elevated body swing test: a new behavioral parameter for rats with 6-hydroxydopamine-induced hemiparkinsonism. J Neurosci. 1995;15: 5372-8.
  27. Morris RGM. Development of a water maze procedure for studying spatial memory in the rat. J Neurosci Methods. 1984;11:47-60. https://doi.org/10.1016/0165-0270(84)90007-4
  28. Tamura A, Graham DI, McCulloch J, Teasdale GM. Focal cerebral ischaemia in the rat: 1.description of technique and early neuropathological consequences following middle cerebral artery occlusion. J Cereb Blood Flow Metab. 1981;1:53-60. https://doi.org/10.1038/jcbfm.1981.6
  29. Lee JY, Cho E, Ko YE, Kim I, Lee KJ, Kwon SU, Kang DW, Kim JS. Ibudilast, a phosphodiesterase inhibitor with anti-inflammatory activity, protects against ischemic brain injury in rats. Brain Res. 2012;1431:97-106. https://doi.org/10.1016/j.brainres.2011.11.007
  30. Levene A. Pathological factors influencing excision of tumours in the head and neck. Part I. Clin Otalary. 1981; 6:145-51. https://doi.org/10.1111/j.1365-2273.1981.tb01800.x
  31. Ludbrook J. Update: microcomputer statistics packages. A personal view. Clin Exp Pharmacol Physiol. 1997; 24:294-6. https://doi.org/10.1111/j.1440-1681.1997.tb01823.x
  32. Cucchiara B, Ross M. Transient ischemic attack: risk stratification and treatment. Ann Emereg Med. 2008; 52:S27-39. https://doi.org/10.1016/j.annemergmed.2008.05.019
  33. Rossini PM, Calautti C, Pauri F, Baron JC. Post-stroke plastic reorganisation in the adult brain. Lancet Neurol. 2003;2:493-502. https://doi.org/10.1016/S1474-4422(03)00485-X
  34. Lukic-Panin V, Kamiya T, Zhang H, Hayashi T, Tsuchiya A, Sehara Y, Deguchi K, Yamashita T, Abe K. Prevention of neuronal damage by calcium channel blockers with antioxidative effects after transient focal ischemia in rats. Brain Res. 2007;1176:143-50. https://doi.org/10.1016/j.brainres.2007.07.038
  35. Bisson JF, Nejdi A, Rozan P, Hidalgo S, Lalonde R, Messaoudi M. Effects of long-term administration of a cocoa polyphenolic extract (Acticoa powder) on cognitive performances in aged rats. Br J Nutr. 2008;100:94-101.
  36. Head E. Oxidative damage and cognitive dysfunction: antioxidant treatments to promote healthy brain aging. Neurochem Res. 2009;34:670-8. https://doi.org/10.1007/s11064-008-9808-4
  37. 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; 429-505.
  38. Calapai G, Crupi A, Firenzuoli F, Marciano MC, Squadrito F, Inferrera G, Parisi A, Rizzo A, Crisafulli C, Fiore A, Caputi AP. Neuroprotective effects of Ginkgo biloba extract in brain ischemia are mediated by inhibition of nitric oxide synthesis. Life Sci. 2000;67:2673-83. https://doi.org/10.1016/S0024-3205(00)00858-4
  39. Suk K, Kim SY, Leem K, Kim YO, Park SY, Hur J, Baek J, Lee KJ, Zheng HZ, Kim H. Neuroprotection by methanol extract of Uncaria rhynchophylla against global cerebral ischemia in rats. Life Sci. 2002;70:2467-80. https://doi.org/10.1016/S0024-3205(02)01534-5
  40. Koo BS, Lee WC, Chang YC, Kim CH. Protective effects of alpinae oxyphyllae fructus (Alpinia oxyphylla MIQ) water-extracts on neurons from ischemic damage and neuronal cell toxicity. Phytother Res. 2004;18:142-8. https://doi.org/10.1002/ptr.1382
  41. Zhang JB. Zhange Jingyue. Seoul:Jeongdam publisher. 1999:640.
  42. Herbal medical prof. co-editor. Herbal medicine. Seoul: Younglimsa. 1994:190, 302, 496, 523, 531, 588, 622.
  43. Jang KH, Song YK, Lim HH. Neuroprotective Effect of Ginseng radix on ICH-induced Rats. J Korean Orient Med. 2005;26:87-97.
  44. Cho IH. Effects of Panax ginseng in Neurodegenerative Diseases. J Ginseng Res. 2012;36:342-53. https://doi.org/10.5142/jgr.2012.36.4.342
  45. Kang YG, Lee TH. Liriopis Tuber improves stress-induced memorial impairments in rats. Kor. J. Herbology. 2006; 21:63-75.
  46. Moon JM, Seok GH, Cho SI. Antiproliferative effect of Schisandrae Fructus extract on PC-3 human prostate cancer cells. Korean J. Herbology. 2012;27:17-23.
  47. Son IH, Lee KS. Protective Effects of Phenolic-rich Fraction (PRF) from Fructus Schisandrae on $H_2O_2$ induced Apoptosis of SH-SY5Y Cells. Korean J Orient Int Med. 2007;28:230-41.
  48. Ban JY, Lee HJ, Lee SB, Lee YJ, Seong NS, Song KS, Bae KW, Seong YH. Methanol Extract of Polygalae Radix Protects Excitotoxicity in Cultured Neuronal Cells. Korean J Med Crop Sci. 2003;11:298-305.
  49. Kim YG, Song YK, Lim HH. Neuroprotective Effect of Aqueous Extract of Polygala tenuifolia Willdenow on Nitric Oxide-induced Apoptosis in SK-N-MC Cells. J Korean Orient Med. 2010;31:55-65.
  50. Park DJ, Jung SH, Moon IS, Lee WC, Shin GJ. Microarray Analysis of Alteration in Gene Expression by Acori graminei rhizoma (AGR) Water-Extract in a Hypoxic Model of Cultured Rat Cortical Cells. Journal of life science. 2007;17:150-61. https://doi.org/10.5352/JLS.2007.17.1.150
  51. Lee SR, Kang HW, Kim ST, Lyu YS. The Effects of anti-Alzheimer in pCT105-induced Neuroblastoma cell lines by Radix Polygalae and Rhizoma Acori Graminei mixture extract. Korean journal of oriental physiology & pathology. 2003;17(4):1037-49.
  52. Hwang YK, Lee SY, Yoon H-D, Shin OC, Park CG, Park CS. Effect of the neuroprotetion and anti-Alzheimer's disease in CT99-induced Neuro 2A cells by Ikgiansintang water extract. Herbal formula science. 2005;13:103-21.
  53. Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL, Bartkowski H. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke. 1986;17:472-6. https://doi.org/10.1161/01.STR.17.3.472
  54. Yamamoto M, Tamura A, Kirino T, Shimizu M, Sano K. Behavioral changes after focal cerebral ischemia by left middle cerebral artery occlusion in rats. Brain Res. 1988;452:323-8. https://doi.org/10.1016/0006-8993(88)90036-4
  55. 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;32:2648-57. https://doi.org/10.1161/hs1101.097397
  56. Menniti FS, Ren J, Coskran TM, Liu J, Morton D, Sietsma DK, Som A, Stephenson DT, Tate BA, Finklestein SP. Phosphodiesterase 5A inhibitors improve functional recovery after stroke in rats: optimized dosing regimen with implications for mechanism. J Pharmacol Exp Ther. 2009; 331:842-50. https://doi.org/10.1124/jpet.109.156919
  57. Hunter AJ, Mackay KB, Rogers DC. To what extent have functional studies of ischaemia in animals been useful in the assessment of potential neuroprotective agents Trends Pharmacol Sci. 1998;19:59-66. https://doi.org/10.1016/S0165-6147(97)01157-7
  58. Nishino H, Czurko A, Fukuda A, Hashitani T, Hida H, Karadi Z, Lenard L. Pathophysiological process after transient ischemia of the middle cerebral artery in the rat. Brain Res Bull. 1994;35:51-6. https://doi.org/10.1016/0361-9230(94)90215-1
  59. Witte OW, Bidmon HJ, Schiene K, Redecker C, Hagemann G. Functional differentiation of multiple perilesional zones after focal cerebral ischemia. J Cereb Blood Flow Metab. 2000;20:1149-65.
  60. Umegaki H, Itoh A, Suzuki Y, Nabeshima T. Discontinuation of donepezil for the treatment of Alzheimer's disease in geriatric practice. Int Psychogeriatr. 2008;20:800-6.
  61. Scholler K, Zausinger S, Baethmann A, Schmid-Elsaesser R. Neuroprotection in ischemic stroke-combination drug therapy and mild hypothermia in a rat model of permanent focal cerebral ischemia. Brain Res. 2004;1023: 272-8. https://doi.org/10.1016/j.brainres.2004.01.094
  62. Wang Z, Fukuda T, Azuma T, Furuhata H. Safety of low-frequency transcranial ultrasound in permanent middle cerebral artery occlusion in spontaneously hypertensive rats. Cerebrovasc Dis. 2012;33:23-9. https://doi.org/10.1159/000332034
  63. Kufemann IL. Principles of neural science. 2nd edition, New York: Elservier. 1986:806-15.
  64. Seo JH, Park YK, Kim MH, Chong YG, Chung HS, Suh JK, Lee HK, Chu JW, Lee KC. Simultaneous Stain with Neutral Red and Tetrazolium Salt for Experimental Cerebral Infarction Morphometry. Journal of Korean Neurosurgical Society. 1992;21(8):990-8.
  65. Jaspers RM, Block F, Heim C, Sontag KH. Spatial learning is affected by transient occlusion of common carotid arteries (2VO): comparison of behavioural and histopathological changes after '2VO' and 'four-vesselocclusion' in rats. Neurosci Lett. 1990;117:149-53. https://doi.org/10.1016/0304-3940(90)90135-V
  66. Yamaguchi T, Suzuki M, Yamamoto M. YM796, a novel muscarinic agonist, improves the impairment of learning behavior in a rat model of chronic focal cerebral ischemia. Brain Res. 1995;669:107-14. https://doi.org/10.1016/0006-8993(94)01268-M
  67. Colbourne F, Corbett D. Delayed and prolonged post-ischemic hypothermia is neuroprotective in the gerbil. Brain Res. 1994;654:265-72. https://doi.org/10.1016/0006-8993(94)90488-X
  68. Kawamata T, Alexis NE, Dietrich WD, Finklestein SP. Intracisternal basic fibroblast growth factor (bFGF) enhances behavioral recovery following focal cerebral infarction in the rat. J Cereb Blood Flow Metab. 1996;16: 542-7.
  69. Ritz MF, Ratajczak P, Curin Y, Cam E, Mendelowitsch A, Pinet F, Andriantsitohaina R. Chronic treatment with red wine polyphenol compounds mediates neuroprotection in a rat model of ischemic cerebral stroke. J Nutr. 2008; 138:519-25.
  70. Bednar MM. The role of sildenafil in the treatment of stroke. Curr Opin Investig Drugs. 2008;9:754-9.

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