The Journal of Internal Korean Medicine (대한한방내과학회지)

The Society of Internal Korean Medicine (대한한방내과학회)
권호 표지

The Protective Effects of Sopung-tang on Brain Damage in Photothrombotic Ischemia Mouse Model

뇌경색 마우스의 뇌손상에 대한 소풍탕(疎風湯)의 보호효과

  • Jang, Seok-O (Dept. of Third Medicine, Professional Graduate School of Oriental Medicine, Won-kwang University) ;
  • Choi, Ji-Hye (Dept. of Third Medicine, Professional Graduate School of Oriental Medicine, Won-kwang University) ;
  • Lee, John Dong-Yeop (Dept. of Third Medicine, Professional Graduate School of Oriental Medicine, Won-kwang University) ;
  • Choi, Yong-Jun (Dept. of Oriental Medicine, Graduate School of Won-kwang University) ;
  • Lee, In (Dept. of Internal Medicine, School of Oriental Medicine, Won-kwang University) ;
  • Moon, Byung-Soon (Dept. of Third Medicine, Professional Graduate School of Oriental Medicine, Won-kwang University)
  • 장석오 (원광대학교 한의학전문대학원 제3의학과) ;
  • 최지혜 (원광대학교 한의학전문대학원 제3의학과) ;
  • 이동엽 (원광대학교 한의학전문대학원 제3의학과) ;
  • 최용준 (원광대학교 대학원 한의학과) ;
  • 이인 (원광대학교 한의과대학 내과학교실) ;
  • 문병순 (원광대학교 한의학전문대학원 제3의학과)
  • Published : 2009.09.30
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Abstract

Objectives : The water extract of Sopung-tang (SPT) has been traditionally used in the treatment of acute stroke in Oriental Medicine. Pro-inflammatory cytokines play a critical role in the onset of post-ischemic inflammatory cascades. The present study was designed to investigate the effects of SPT on pro-inflammatory cytokine production in a photothrombotic ischemia mouse model. Methods : After SPT oral administration to the mice for five days, with using Rose Bengal and cold light, photothrombotic ischemia lesion was induced in stereotactically held male BALB/c mice. Also, results including, gross finding lesion size, histopathological finding changes, and inflammatory cytokine expression changes from the photothrombotic ischemia mouse model were observed. Results : The photothrombotic ischemia lesion was decreased by the oral injection of SPT. Also, SPT inhibited the expression of TNF-$\alpha$, IL-$1{\beta}$, IL-6, the active form of caspase-3 protease, and transglutaminase-2 in the photothrombotic ischemia lesion. Conclusions : These results suggest that SPT protects the ischemic death of brain cells through suppression of the production of anti-inflammatory cytokines and catalytic activation of caspase-3 protease in the photothrombotic ischemia mouse model.

Keywords

References

  1. 壟廷賢. 萬病回春. 서울: 杏林書院; 1975, p. 49.
  2. 전국한의과대학심계내과학교실. 심계내과학. 서울: 군자출판사; 2006, p. 331, 335.
  3. Clark WM. Cytokines and reperfusion injury. Neurology. 1997;49(suppl 4):10-4.
  4. Beamer NB, Coull BM, Clark WM, Hazel JS, Silberger JR. Interleukin-6 and interleukin-1 receptor antagonist in acute stroke. Ann Neurol. 1995;37:800-4. https://doi.org/10.1002/ana.410370614
  5. Tarkowski E, Rosengren L, Blomstrand C, Wikkelsoo C, Jensen C, Ekholm S, et al. Early intrathecal production of interleukin-6 predicts the size of brain lesion in stroke. Stroke. 1995;26:1393-8. https://doi.org/10.1161/01.STR.26.8.1393
  6. Vila N, Castillo J, Davalos A, Chamorro A. Proinflammatory Cytokines and Early Neurological Worsening in Ischemic Stroke. Stroke. 2000;31:2325-9. https://doi.org/10.1161/01.STR.31.10.2325
  7. Watson BD, Dietrich WD, Busto R, Wachtel MS, Ginsberg MD. Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol. 1985;17(5):497-504. https://doi.org/10.1002/ana.410170513
  8. Dietrich WD, Busto R, Watson BD, Scheinberg P, Ginsberg MD. Photochemically induced cerebral infarction. II. Edema and blood-brain barrier disruption. Acta Neuropathol (Berl). 1987;72(4):326-34. https://doi.org/10.1007/BF00687263
  9. Kim HS, Shin YI, Kim HI, Moon SK, Lee S, Moon BS, et al. Relevance of behavioral test in the photothrombotic stroke rat model. J of Korean Acad of Rehab Med. 2006;30(2):135-41.
  10. Shanina EV, Redecker C, Reinecke S, Schallert T, Witte OW. Long-term effects of sequential cortical infarcts on scar size, brain volume and cognitive function. Behav Brain Res. 2005;158:69-77. https://doi.org/10.1016/j.bbr.2004.08.007
  11. 權寧哲, 李京燮. 疎風場 및 加味疎風湯이 高脂血症에 미치는 影響. 慶熙韓醫大論文集. 1982;5:269-79.
  12. 문영희, 정명현, 주홍규, 임동윤, 유호진. 疎風湯이 흰쥐의 혈압에 미치는 영향. 생약학회지. 1990;21(2):173-8.
  13. 劉善美, 林起龍, 嚴基鎭, 文永熙. 疎風湯의 消炎.鎭痛作用에 관한 硏究. 藥學硏究誌. 1993;15:13-20.
  14. 鄭長均. 疎風湯이 實驗動物의 心血關係에 미치는 影響. 대한동의병리학회지. 1995;9(2):317-40.
  15. 鄭長均, 安日會. 疎風湯이 腦血栓症 初期 患者에 미치는 영향. 원광한의학. 1995;5(1):181-95.
  16. 田炳薰, 鄭遇悅. 實驗的 血栓症에 미치는 韓藥材의 抗血栓效果에 관한 硏究. 대한동의병리학회지. 1996;10(1):72-8.
  17. 안철우. 疎風湯이 高脂血症에 미치는 影響에 대한 寬驗的 硏究. 동의대학교 대학원. 1999.
  18. 최석진. 疎風湯이 고혈압과 동맥혈관에 미치는 영향. 동의생리병리학회지. 2005;19(6):1622-8.
  19. 鄭勝元. 疎風湯이 Glutamate에 의한 C6 Glial Cell의 Apoptosis에 미치는 影響. 원광대학교대학원. 2006.
  20. 李敏求. 疎風湯이 Glutamate에 의한 C6 glial cell 세포 손상에서 항산화 효소 발현에 미치는 영향. 원광대학교대학원. 2006.
  21. 李善佑. 疎風湯이 $H_{2}O_{2}$에 의한 혈관내피세포의 apoptosis에 미치는 앵향. 원광대학교대학원. 2007.
  22. 秋玟圭. 허혈성 뇌손상 흰쥐에셔 인지 및 운동기능회복에 미치는 疎風湯의 효과. 동신대학교대학원. 2008.
  23. 許浚. 東醫寶鑑. 서울: 南山堂; 1989, p. 361.
  24. 尹用甲. 東醫方劑와 處方解說. 서울: 醫聖堂; 1998, p. 624.
  25. Tamura A, Graham DI, McCulloch J, Teasdale GM. Focal cerebral ischemia 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
  26. Robinson MJ, Macrae IM, Todd M, Reid JL, McCulloch J. Reduction of local cerebral blood flow to pathological levels by endothelin-1 applied to the middle cerebral artery in the rat. Neurosci Lett. 1990;118:269-72. https://doi.org/10.1016/0304-3940(90)90644-O
  27. Klootzsch C, Nahser HC, Henkes H, Kuuhne D, Berlit P. Detection of microemboli distal to cerebral aneurysms before and after therapeutic embolization. Am J Neuro Radiol. 19;1315-8, 1998.
  28. Kolb B, Cote S, Ribeiro-da-Silva A, Cuello AC. Nerve growth factor treatment prevents dendritic atrophy and promotes recovery of function after cortical injury. Neuroscience. 1997;76:1139-51. https://doi.org/10.1016/S0306-4522(96)00448-4
  29. Zaremba J, Losy J. Cytokines in clinical and experimental ischemic stroke. Neurol Neurochir Pol. 2004:38(1 Suppl 1):S57-62.
  30. Yamasaki Y, Matsuura N, Shozuhara H, Onodera H, Itoyama Y, Kogure K. Interleukin-1 as a pathogenic mediator of ischemic brain damage in rats. Stroke. 1995;26:676-81. https://doi.org/10.1161/01.STR.26.4.676
  31. Barone FC, Arvin B, White RF, Miller A, Webb CL, Willette RN, et al. Tumor necrosis factor: a mediator of focal ischemic brain injury. Stroke. 1997;28:1233-44. https://doi.org/10.1161/01.STR.28.6.1233
  32. Liu T, Clark RK, McDonnel PC, Young PR, White RF, Barone FC, et al. Tumor necrosis factor-${\alpha}$ expression in ischemic neurons. Stroke. 1994;25:1481-8. https://doi.org/10.1161/01.STR.25.7.1481
  33. Rothwell NJ, Hopkins SJ. Cytokines and the nervous system II: action and mechanisms of action. Trends Neurosci. 1995;18:130-6. https://doi.org/10.1016/0166-2236(95)93890-A
  34. Mayer B, M John, B Heinzel, ER Werner, H Wachter, G Schultz, et al. Brain nitric oxide synthase is a biopterin-and flavin-containing multi-functional oxido-reductase. FEBS Lett. 1991;288:187-91. https://doi.org/10.1016/0014-5793(91)81031-3
  35. Barton BE. IL-6: Insights into novel biological activities. ClinImmunol Immunopathol. 1997;85:16-20. https://doi.org/10.1006/clin.1997.4420
  36. U Waje-Andreassen, J Krakenes, E Ulvestad, L Thomassen, K-M Myhr, J Aarseth, et al. IL-6, an early marker for outcome in acute ischemic stroke. Acta Neurologica Scandinavica. 2005;111(6):360-5. https://doi.org/10.1111/j.1600-0404.2005.00416.x
  37. Kumar S. ICE-like proteases in apoptosis. Trends Biochem Sci. 1995;20:198-202. https://doi.org/10.1016/S0968-0004(00)89007-6
  38. Salvesen GS, Dixit VM. Caspases: intracellular signaling by proteolysis. Cell. 1997;91:443-6. https://doi.org/10.1016/S0092-8674(00)80430-4
  39. Ashkenazi A, Dixit VM. Death receptors: signaling and modulation. Science. 1998;281:1305-8. https://doi.org/10.1126/science.281.5381.1305
  40. Cryns V, Yuan J. Proteases to die for. Genes Dev. 1998;12:1551-70. https://doi.org/10.1101/gad.12.11.1551
  41. Smith FB, Rumley A, Lee AJ, Leng GC, Fowkes FG, Lowe GD. Hemostatic factors and prediction of ischemic heart disease and stroke in claudicants. Br J Haematol. 1998;100(4):758-63. https://doi.org/10.1046/j.1365-2141.1998.00626.x
  42. Kim JM, Voll RE, Ko C, Kim DS, Park KS, Kim SY. A New Regulatory Mechanism of NF-kappaB Activation by I-kappaB beta in Cancer Cells. J Mol BioI. 2008;384(4):756-65. https://doi.org/10.1016/j.jmb.2008.10.010
  43. Galamb O, Gyorffy B, Sipos F, Spisak S, Nemeth AM, Miheller P, et al. Inflammation, adenoma and cancer: objective classification of colon biopsy specimens with gene expression signature. Dis Markers. 2008;25(1):1-16.
  44. Wilhelmus MM, Grunberg SC, Bol JG, van Dam AM, Hoozemans JJ, Rozemuller AJ, et al. Transglutaminases and Transglutaminase-Catalyzed Cross-Links Colocalize with the Pathological Lesions in Alzheimer's Disease Brain. Brain Pathol. 2008;19(4):612-22. https://doi.org/10.1111/j.1750-3639.2008.00197.x