Mechanism of Mokhyangjoki-san Extract on the Improvement in Cerebral Blood Flow in Ischemic Rats

목향조기산(木香調氣散) 추출물이 뇌허혈 흰쥐의 뇌혈류개선에 미치는 작용기전

  • Received : 2011.08.19
  • Accepted : 2011.10.05
  • Published : 2011.10.25

Abstract

This study was designed to investigate the effects of Mokhyangjoki-san extract (MJS) on the improvement in cerebral blood flow (rCBF) in cerebral ischemic rats, and further to determine cytokines production (IL-1${\beta}$, TNF-${\alpha}$, IL-10, TGF-${\beta}$) of MJS. The results in cerebral ischemic rats were as follows ; The rCBF was significantly and stably increased by MJS (10 mg/kg, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group. In cytokine production in serum from femoral arterial blood 1 hr after middle cerebral arterial occlusion, MJS significantly decreased IL-1${\beta}$ and TNF-${\alpha}$ production, and increased IL-10 production compared with control group. In cytokine production in serum from femoral arterial blood 1 hr after reperfusion, MJS significantly decreased IL-1${\beta}$ and TNF-${\alpha}$ production compared with control group. IL-10 and TGF-${\beta}$1 production in MJS group were significantly increased compared with control group. These results suggested that MJS significantly and stably increased rCBF by inhibiting the production IL-1${\beta}$ and TNF-${\alpha}$, and accelerating that of IL-10 and TGF-${\beta}$. The result in nerve cells was as follows ; MJS significantly inhibited lactate dehydrogenase activity in vitro in a dose-dependent manner. This result suggested that MJS prevented the neuronal death.

Keywords

References

  1. 의과대학 신경해부학교수 편. 증례를 통한 임상신경해부학. 한우리, 서울, p. 191, 1998.
  2. Kety, S.S., Schmidt, C.F. The nitrous oxide method for the man ; theory, procedure and normal values. J. Clin Invest. 27: 476-483, 1948. https://doi.org/10.1172/JCI101994
  3. 이경은, 김경환. 허혈, 재관류 손상에서 뇌조직 아민 변동과 Free Radical과의 관련성. 大韓神經科學會誌 8(1):2-8, 1990.
  4. 대한병리학회. 병리학. 서울, 고문사, pp 87-99, 1263-1264, 1994.
  5. 나영설, 윤상협, 민병일. 최근 뇌졸중에 대한 역학적 고찰. 경희의학, 7: 280-286, 1991.
  6. 中國中醫硏究院廣安門醫院. 實用中醫腦病學. 北京, 學苑出版社, pp 62-63, 1993.
  7. 劉完素. 素問玄機原病式. 浙江, 浙江科學技術出版社, pp 170-172, 1984.
  8. 方 廣. 丹溪心法附錄(上). 서울, 大星文化社, pp 67-69, 1982.
  9. 屈松柏, 李家庚. 實用中醫心血管病學. 北京, 科學技術文獻出版社, pp 254-266, 2000.
  10. 龔廷賢. 萬病回春. 서울, 東洋綜合通信敎育院出版部, pp 107-108, 1985.
  11. 許 浚. 東醫寶鑑. 서울, 南山堂, p 487, 983.
  12. 李仲梓. 醫宗必讀. 台南, 綜合出版社, p 223, 1984.
  13. 최정화, 정현우. 도담탕 및 그 가미방이 국소뇌혈류량 및 혈압에 미치는 영향. 동의병리학회지 14(1):99-106, 2000.
  14. 정현우, 강성용, 백승화. 석창포가 혈압 및 국소 뇌혈류량에 미치는 영향. 대한본초학회지 14(2):81-88, 1999.
  15. 최재영, 이원철, 윤상협. 흰쥐의 중대뇌동맥 폐쇄후 當歸芍藥散투여가 여성호르몬 및 뇌위축에 미치는 영향. 한방성인병학회지 4(1):70-154, 1998.
  16. 김성욱, 정현우, 위통순, 조명래, 윤여충. 홍화 약침이 국소 뇌혈류량 및 평균 혈압에 미치는 실험적 영향. 대한침구학회지 21(2):167-181, 2004.
  17. 문한주. 木香調氣散의 實驗的硏究. 方劑學會誌 4(1):99-112, 1996.
  18. 박용권. 木香調氣散과 解鬱調胃湯의 실험적 肝硬變에 대한 효과. 圓光大學校大學院, 1997.
  19. 엄현섭. 木香調氣散과 當歸活血湯의 항 Stress효과에 관한 실험적 연구. 東國大學校大學院, 1994.
  20. 심익현, 정현우. 목향조기산 추출물이 국소뇌혈류량 및 평균 혈압에 미치는 작용기전. 동의생리병리학회지 20(6):1538-1542, 2006.
  21. 全國韓醫科大學本草學敎授共編. 本草學. 서울, 永林社, pp 136-137, 289-292, 294-296, 336-337, 347-356, 409-410, 540- 541, 1999.
  22. Longa, E.Z., Weinstein, P.R., Carlson, S., Cummins, R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20(1):84-91, 1989. https://doi.org/10.1161/01.STR.20.1.84
  23. Chen, S.T., Hsu, C.Y., Hogan, E.L., Maricque, H., Balentine, J.D. A model of focal ischemic stoke in the rat ; reproducible extension cortical infarction. Stroke 17: 738-743, 1986. https://doi.org/10.1161/01.STR.17.4.738
  24. Trembaly, L.F., Valenza, S.P. and Ribelro, J.Li. Injurious ventilatory strategiea increase cytokines and c-fos mRNA expression in an isolated rat lung model. J. Clin. Invest. 99(5):944-952, 1999.
  25. Wang, C.X., Olschowka, J.A. and Wrathall, J.R. Increase of interleukin-1beta mRNA and protein in the spinal cord following experimental traumatic injury in the rat. Brain Res. 759(2):190-196, 1997. https://doi.org/10.1016/S0006-8993(97)00254-0
  26. Stepaniak, J.A., Gould, K.E, Sun, D., Swanborg, R.H. A comparative study of experimental autoimmune encephalomyelitis in Lewis and DA rats. J. Immunol. 155: 2762-2769, 1995.
  27. Rivera, D.L., Olister, S.M., Liu, X., Thompson, J.H., Zhang, X.J., Pennline, K., Azuero, R., Clark, D.A., Miller, M.J. Interleukin-10 attenuates experimental fetal growth restriction and demise. FASEB J. 12(2):189-197, 1998. https://doi.org/10.1096/fasebj.12.2.189
  28. Okura, Y., Takeda, K., Honda, S., Hanawa, H., Watanabe, H., Kodama, M., Izumi, T., Aizawa, Y., Seki, S., Abo, T. Recombinant murine interleukin-12 facilitates induction of cardiac myosin-specific type 1 helper T cells in rats. Circ Res. 82(10):1035-1042, 1998. https://doi.org/10.1161/01.RES.82.10.1035
  29. Lobell, A., Weissert, R., Storch, M.K., Svanholm, C., de Graaf, K.L., Lassmann, H., Andersson, R., Olsson, T., Wigzell, H. Vaccination with DNA encoding an immunodominant myelin basic protein peptide targeted to Fc of immunoglobulin G suppresses experimental autoimmune encephalomyelitis. J. Exp. Med. 187(9):1543-1548, 1998. https://doi.org/10.1084/jem.187.9.1543
  30. Kim, S.J., Romeo, D., Yoo, Y.D., Park, K. Transforming growth factor-beta ; expression in normal and pathological conditions. Horm. Res. 42(1-2):5-8, 1994. https://doi.org/10.1159/000184136
  31. Kloen, P., Gebhardt, M.C., Perez-Atayde, A., Rosenberg, A.E., Springfield, D.S., Gold, L.I., Mankin, H.J. Expression of transforming growth factor-beta(TGF-beta) isoforms in osteosarcomas ; TGF-beta3 is related to disease progression. Cancer 80(12):2230-2239, 1997. https://doi.org/10.1002/(SICI)1097-0142(19971215)80:12<2230::AID-CNCR3>3.0.CO;2-Y
  32. Choi, D.W. Glutamate neurotoxicity and disease of the nervous system. J. Neuron 1: 623-634, 1988. https://doi.org/10.1016/0896-6273(88)90162-6
  33. Glanz, M., Klawansky, S., Stason, W., Berkey, C. and Chalmers, T.C. Functional electrostimulation in poststroke rehabilitation ; a meta-analysis of the randomized controlled trials, Arch. Phys. Med. Rehabil. 77(6):549-553, 1996. https://doi.org/10.1016/S0003-9993(96)90293-2
  34. Dirnagl, U., Ladecola, C. and Moskowitz, M.A. Pathobiology of ischemic stroke ; An integrated view. Trends Neurosci. 22(9):391-397, 1999. https://doi.org/10.1016/S0166-2236(99)01401-0
  35. Traystman, R.J. Animal models of focal and global cerebral ischemia. ILAR J. 44(2):85-95, 2003. https://doi.org/10.1093/ilar.44.2.85
  36. Zweifler, R.M. Management of acute stroke. South Med. J. 96(4):380-385, 2003. https://doi.org/10.1097/01.SMJ.0000063467.75456.7A
  37. Adams, H., Adams, R., Del Zoppo. G., Guidelines for the early management of patients with ischemic stroke ; 2005 guidelines update a scientific statement from the Stroke Council of the American Heart Association/American Stroke Association. Stroke 36(4):916-923, 2005. https://doi.org/10.1161/01.STR.0000163257.66207.2d
  38. 서울대학교 의과대학 방사선과학교실. 신경방사선과학. 서울, 일조각, p 153, 2004.
  39. Narayanan, U., Chi, O.Z., Liu, X. and Weiss, H.R. Effect of AMPA on cerebral cortical oxygen balance of ischemic rat brain. Neurochem Res. 25(3):405-411, 2000. https://doi.org/10.1023/A:1007505507532
  40. Pieper, A.A., Verma, A., Zhang, J. Snyder, S.H. Poly(ADP-ribose) polymerase, nitric oxide and cell death. Trends Pharmacol. Sci. 20(4):171-181, 1999. https://doi.org/10.1016/S0165-6147(99)01292-4
  41. Connor, B. and Dragunow, M. The role of neuronal growth factors in neurodegenerative disorders of the human brain. Brain Res. Reviews 27(1):1-39, 1998 https://doi.org/10.1016/S0165-0173(98)00004-6
  42. Leker, R.R. and Shohami, E. Cerebral ischemia and trauma-different etiologies yet similar mechanisms ; neuroprotective opportunities. Brain Res. Rev. 39(1):55-73, 2002. https://doi.org/10.1016/S0165-0173(02)00157-1
  43. Morrison, Ⅲ B., Eberwine, J.H., Meaney, D.F. McIntosh, T.K. Traumatic injury induces differential expression of cell death gene in organotypic brain slice cultures determined by complementary DNA array hybridization. Neuroscience 96(1):131-139, 2000. https://doi.org/10.1016/S0306-4522(99)00537-0
  44. 윤상협, 류재환. Intraluminal Suture Technique에 의한 실험적 뇌허혈-재관류가 혈압, 국소뇌혈류량, 뇌경색 및 뇌부종에 미치는 영향. 경희의학 10(2):114-124, 1994.
  45. McCord, J.M. Mechanisms of disease ; oxygen-derived free radicals in postischemic tissue injury. New Eng J. Med. 312: 159-163, 1985. https://doi.org/10.1056/NEJM198501173120305
  46. Hallenbeck, J.M., Dutka, A.J., Tanishima, T., Kochanek, P.M., Kumaroo, K.K., Thompson, C.B., Obrenovich, T.P., Contreras, T.J. Polymorphonuclear leukocyteaccumulation in brain region with low blood flow during the early postischemic period. Stroke 17: 246-253, 1986. https://doi.org/10.1161/01.STR.17.2.246
  47. Garcia, J.H., Liu, K.F., Yoshida, Y., Lian, J., Chen, S., del Zoppo, G.J. Influx of leukocytes and platelets in an evolving brain infarct(Wistar rat). Am J. Pathol. 144: 188-199, 1994.
  48. Vila, N., Castillo, J., Davalos, A., Esteve, A., Planas, A.M., Chamorro, A. Levels of anti-inflammatory cytokines and neurological worsening in acute ischemic stroke. Stroke 34(3):671-675, 2003. https://doi.org/10.1161/01.STR.0000057976.53301.69
  49. 하대유 외 25인. 면역학, 서울, 고문사, pp 100-105, 1994.
  50. Hayashi, Y., Jikihara, I., Yagi, T., Fukumura, M., Ohashi, Y., Ohta, Y., Takagi, H., Maeda, M. Immunohistochemical investigation of caspase-1 and effect of caspase-1 inhibitor in delayed neuronal death after transient cerebral ischemia. Brain Res. 893(1-2):113-120, 2001. https://doi.org/10.1016/S0006-8993(00)03307-2
  51. Cain, B.S., Meldrum, D.R., Dinarello, C.A., Meng, X., Joo, K.S., Banerjee, A., Harken, A.H. Tumor necrosis factor-alpha and interleukin-1beta synergistically depress human myocardial function. Crit Care Med. 27(7):1309-1318, 1999. https://doi.org/10.1097/00003246-199907000-00018
  52. Daddi, N., Suda, T., D'Ovidio, F., Kanaan, S.A., Tagawa, T., Grapperhaus, K., Kozower, B.D., Ritter, J.H., Yew, N.S., Mohanakumar, T., Patterson, G.A. Recipient intramuscular cotransfection of naked plasmid transforming growth factor beta1 and interleukin 10 ameliorates lung graft ischemia-reperfusion injury. J. Thorac Cardiovasc Surg. 124(2):259-269, 2002. https://doi.org/10.1067/mtc.2002.122295
  53. Lei, Y., Zhen, J., Ming, X.L., Jian, H.K. Induction of higher expression of IL-beta and TNF-alpha, lower expression of IL-10 and cyclic guanosine monophosphate by pulmonary arterial hypertension following cardiopulmonary bypass. Asian J. Surg. 25(3):203-208, 2002. https://doi.org/10.1016/S1015-9584(09)60176-7
  54. Lagente, V., Naline, E., Guenon, I., Corbel, M., Boichot, E., Burgaud, J.L., Del Soldato, P., Advenier, C. A nitric oxide-releasing salbutamol, elicits potent relaxant and anti-inflammatory activities. J. Pharmacol Exp Ther. 310(1):367-375, 2004. https://doi.org/10.1124/jpet.103.061739
  55. Schubert, P., Morino, T., Miyazaki, H., Ogata, T., Nakamura, Y., Marchini, C., Ferroni, S. Cascading glia reactions ; a common pathomechanism and its differentiated control by cyclic nucleotide signaling. Ann. N. Y. Acad Sci. 903: 24-33, 2000. https://doi.org/10.1111/j.1749-6632.2000.tb06346.x
  56. Di Santo, E., Sironi, M., Pozzi, P. Interleukin-10 inhibits lipopolysaccharide-induced tumor necrosis factor and interleukin-1 beta production in the brain without affecting the activation of the hypothalamus-pituitary-adrenal axis. Neuroimmunomodulation 2(3):149-154, 1995 https://doi.org/10.1159/000096885
  57. Krupinski, J., Issa, R., Bujny, T., Slevin, M., Kumar, P., Kumar, S., Kaluza, J. A putative role for platelet-derived growth factor in angiogenesis and neuroprotection after ischemic stroke in humans. Stroke 28(3):564-573, 1997. https://doi.org/10.1161/01.STR.28.3.564
  58. Zhu, Y., Yang, G.Y., Ahlemeyer, B., Pang, L., Che, X.M., Culmsee, C., Klumpp, S., Krieglstein, J. Transforming growth factor-beta1 increases bad phosphorylation and protects neurons against damage. J Neurosci. 22(10):3898-3909, 2002. https://doi.org/10.1523/JNEUROSCI.22-10-03898.2002
  59. Cheung, J.Y., Bonventre, J.V., Malis, C.D., Leaf, A. Mechanism of disease ; calcium and ischemic injury. New Eng J. Med. 26: 1670-1676, 1986.
  60. Weisfeldt, M.L. Reperfusion and Reperfusion injury. Clin Res. 35: 13-20, 1987.
  61. 황호근. Lipopolysaccharide 세포독성에 대한 SNP 효과에 관한 연구. 원광대학교 대학원, 2000.