DOI QR코드

DOI QR Code

허혈성뇌졸중 흰쥐모델에서 가미보양환오탕(加味補陽還五湯)와 주요 구성약재인 황기(黃芪), 단삼(丹蔘)의 뇌신경보호효과에 대한 연구

Neuroprotective effect of modified Boyanghwano-Tang and the major medicinal plants, Astragali Radix and Salviae Miltiorrhizae Radix on ischemic stroke in rats

  • 손혜영 (동국대학교 한방신약개발센터) ;
  • 박용기 (동국대학교 한방신약개발센터)
  • 투고 : 2010.04.22
  • 심사 : 2010.06.22
  • 발행 : 2010.06.30

초록

Objectives : In this study, the neuroprotective effects of modified Boyanghwano-Tang (mBHT) and the major medicinal plants, Astragali Radix(AR) and Salviae Miltiorrhizae Radix(SMR) were investigated in transient middle cerebral artery occlusion (tMCAO)-induced ischemic stroke of rats. Methods : mBHT(400 mg/kg) and AR(154 mg/kg) or SMR(62 mg/kg) water extract orally injected in rats after 90 min occlusion of MCA and then allow reperfusion to 24 h. Brain infarction was measured by TTC staining and the expressions of NOS isoforms and apoptotic molecules were determined in ischemic brain by Western blot. Results : The results showed that mBHT has stronger neuropreotective property through inhibitions of the PARP cleaved and caspase-3 activation in ischemic rats, and could reduced infarction volumes comparison of those of AR or SMR, respectively. While, AR extract has an angiogenic property through increasing the expressions of eNOS and VEGF, and SMR extract has a strong anti-inflammatory effects through inhibition of iNOS expression in ischemic brains. Conclusions : These results suggest that mBHT has multifactorial therapeutic advantages through anti-apoptosis, anti-inflammation and angiogenesis for ischemic stroke based on a synergistic combination of ingradients rather than monotherapy.

키워드

참고문헌

  1. 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
  2. Lee JC, Kim WK. Aging and Stroke. Kor J Gerontol 2006;16:11-16.
  3. Wang Q, Tang XN, Yenari MA. The inflammatory response in stroke. 2007;184: 53-68. https://doi.org/10.1016/j.jneuroim.2006.11.014
  4. Kim JH, Park CO, Hyun DK, Ha YS. Correlation between Activity of Nitric Oxide Synthases and Apoptotic Change in the Closed Head Injury Animal Model. J Korean Neurosurg Soc 2002;32:142-148.
  5. Bredt DS, Ferris CD, Snyder SH. Nitric oxide synthase regu-latory sites; Phosphorylation by cyclic AMP-dependent proteinkinase, protein kinase, calcium /calmodulin protein kinase;id-entification of flavin and calmodulin binding sites. J Biol Chem 1992;16:10976-10982.
  6. Ignarro L, Murad F. Nitric Oxide: Biochemistry, Molecular Biology, and Therapeutic Implications. Advances in Pharmacology, 1995;34:511-516.
  7. Knowles RG, Salter M, Brooks SL, Moncada S. Anti-inflammatory glucocorticoids inhibit the induction by endotoxin of nitric oxide synthase in the lung, liver and aorta of the rat. 1990;172:1042-1048. https://doi.org/10.1016/0006-291X(90)91551-3
  8. Beckman JS, Koppenol W. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol. 1996;271: C1424-1437.
  9. Toda N, Ayajiki K, Okamura T. Cerebral blood flow regulation by nitric oxide: recent advances. Pharmacol Rev. 2009;61:62-97. https://doi.org/10.1124/pr.108.000547
  10. Sawada N, Liao JK., Moskowitz MA. Targeting eNOS and beyond: emerging heterogeneity of the role of endothelial Rho proteins in stroke protection. Expert Rev Neurother. 2009;9:1171-1186. https://doi.org/10.1586/ern.09.70
  11. Chung HY, Park JN, Kim YJ, Kye IS, Lee JY, Kim KW. Molecular Mechanism of Vascular Development and Aging. Kor J Gerontol. 2002;12:15-30.
  12. Won, S. J., Kim, D. Y., Gwang, B.J. 2002. Cellular and molecular pathways of ischemic neuronal death. J Biochem and Molecular bio. 35(1):67-86. https://doi.org/10.5483/BMBRep.2002.35.1.067
  13. Lafuente JV, Argandona EG, Mitre B. VEGFR-2 expression in brain injury: its distribution related to brain-blood barrier markers. 2006;113:487-496. https://doi.org/10.1007/s00702-005-0407-0
  14. Cheon YS, Kim SH. The effect of Boyangwhanotang and Kami-Boyang whanohtang on intravascular coagulation induced by endotoxin in rats. J of oriental medical pathology 2003;8:157-176.
  15. Choi EJ. The effects of Boyanghwno-tang extraction on reversible forebrain ischemia in Mongolian gerbil. Ph. D. Thesis, Dongguk University, Kyeonju, Korea, 1999.
  16. Jang HN. Study on the selective priming of Th1 and suppression of Th2-type immune response flowing oral administration of Korean traditional medicine. MD. Thesis, Chonbuk National University, Jenonju, South Korea, 2003.
  17. Kim NY. Effect of Boyanghwanohtang extract on the blood pressure and regional cerebral blood flow in rats. Ph. D. Thesis, Wonkwang University, Iksan, South Korea, 1985.
  18. Kim YH. Regulation of immune response by Bo-yang-hwan-oh-tang used for improvement of blood stasis. MD. Thesis, Jeonju University, Jenonju, South Korea, 2002.
  19. Soul IC, Kim BT. Effects of Kamiboyanghwanotang(KBHT) on hyperlipidemia, thrombosis, thrombosis, hyperviscosity, hypertension and brain damage. J of Korean Oriental Chronic Disease 1998;4: 133-162.
  20. Tak ES. Effects of Bo Yang Hwan Oh Tang on experimental thrombosis. MD. Thesis, Dongguk University, Kyeonju, South Korea, 1990.
  21. 김영석. 임상중풍학. 서울, 서원당, 1997:303-308.
  22. 왕청임. 의림개착. 대북, 대련국풍출판사, 1975:40-44.
  23. 남경중의학원, 중의방제대사전, 북경, 인민위생출판사, 1995:891.
  24. 신민교, 임상본초학, 서울, 영림사, 1986:169-171, 221-223, 249-250, 300-301, 464-468, 662-663.
  25. 신길구, 신씨본초학, 서울, 수문사, 1988:9-12, 80-84, 448-450, 521-522, 554-556, 562-564, 600-603.
  26. 김창민, 중약대사전, 서울, 정담, 1998:592-599, 1159-1168, 1353-1358, 4839-4845, 5258-5265, 6357-6362, 6460-6471.
  27. Bendek A, Moricz K, Juranyi Z, Gigler G, Levay G, Harsing LG Jr, Matyus P, Szenasi P, Albert M. Use of TTC staining for the evaluation of tissue injury in the early phases of reperfusion after focal cerebral ischemia in rats Brain Research 2006;111:159-165.
  28. Naka M, Nanbu T, Kobayashi K. Kamanaka Y, Komeno M, Yanase R, Fukutomi T, Fujimura S, Seo HG, Fujiwara N, Ohuchida S, Suzuki K, Kondo K, A potent inhibitor of inducible nitric oxide synthase, ONO-1714, a cyclic amidine derivative. 2000; 270:663-667. https://doi.org/10.1006/bbrc.2000.2474
  29. Bae MK, Kwon YW, Kim MS, Bae SK, Bae MH, Lee YM, Kim YJ, Kim KW. Identification of genes differentially expressed by hypoxia in hepatocellular carcinoma cells. 1998;243:158-162. https://doi.org/10.1006/bbrc.1998.8074
  30. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Science 1989;246: 1306-1309. https://doi.org/10.1126/science.2479986
  31. Yao X, Miao W, Li M, Wang M, Ma J, Wang Y, Miao L, Feng H. Protective effect of albumin on VEGF and brain edema in acute ischemia in rats. Neurosci Lett. 2010;472:179-183. https://doi.org/10.1016/j.neulet.2010.02.002
  32. Krupinski J, Ferrer I, Barrachina M, Secades JJ, Mercadal J, Lozano R. CDP-choline reduces pro-caspase and cleaved caspase-3 expression, nuclear DNA fragmentation, and specific PARP-cleaved products of caspase activation following middle cerebral artery occlusion in the rat. Neuropharmacology. 2002;42:846-854. https://doi.org/10.1016/S0028-3908(02)00032-1

피인용 문헌

  1. Bilateral Medial Medullary Infarction (Dejerene Syndrome) Patient Suffering from Quadriplegia Treated by Korean Traditional Medicine: a Case Report vol.41, pp.5, 2010, https://doi.org/10.22246/jikm.2020.41.5.902
  2. 단삼(丹參)을 뇌졸중 동물모델에 적용하기 위한 기초적인 네트워크 약리학 분석 vol.29, pp.1, 2010, https://doi.org/10.14374/hfs.2021.29.1.19