The Journal of Korean Medicine (대한한의학회지)

The Society of Korean Medicine (대한한의학회)
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Protective Effects of Maekmundong-tang on Elastase-induced Lung Injury

Elastase 매개성 폐조직 손상에 대한 맥문동탕(麥門冬湯)의 보호효과

  • Kim, Hyoung-Won (Division of Respiratory System, Dept. of Internal Medicine, College of Oriental Medicine, Daejeon University) ;
  • Yang, Su-Young (Division of Respiratory System, Dept. of Internal Medicine, College of Oriental Medicine, Daejeon University) ;
  • Kim, Min-Hee (Dept. of Neurophysiology, College of Oriental Medicine, Daejeon University) ;
  • NamGung, Uk (Dept. of Neurophysiology, College of Oriental Medicine, Daejeon University) ;
  • Park, Yang-Chun (Division of Respiratory System, Dept. of Internal Medicine, College of Oriental Medicine, Daejeon University)
  • 김형원 (대전대학교 한의과대학 폐계내과학교실) ;
  • 양수영 (대전대학교 한의과대학 폐계내과학교실) ;
  • 김민희 (대전대학교 한의과대학 신경생리학교실) ;
  • 남궁욱 (대전대학교 한의과대학 신경생리학교실) ;
  • 박양춘 (대전대학교 한의과대학 폐계내과학교실)
  • Received : 2011.02.07
  • Accepted : 2011.03.03
  • Published : 2011.03.30
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Abstract

Objective: This study aimed to evaluate the protective effects of Maekmundong-tang (MMDT) on an elastase-induced COPD model. Materials and Methods: The extract of MMDT was treated to A549 cells and elastase-induced COPD mice model. Then, various parameters such as cell-based cytoprotective activity and histopathological findings were analyzed. Results: MMDT showed a protective effect on elastase-induced cytotoxicity in A549 cells. This effect was correlated with analysis for caspase 3 levels, collagen and elastin contents, protein level of Cdk1, and gene expression of TNF-${\alpha}$ and IL-$1{\beta}$ in A549 cells. MMDT treatment also revealed a protective effect on the elastase-induced COPD mice model. This effect was evidenced via histopathological finding including immunofluorescence stains against elastin, collagen, and caspase 3, and protein level of Cdc2 in lung tissue. Conclusion: These data suggest that MMDT has pharmaceutical properties on COPD. This study can provide scientific evidence for the efficacy of MMDT for clinical application to patients with COPD.

Keywords

References

  1. GOLD. Global strategy for th diagnosis, management, and prevention of chronic obstructive pulmonary disease(updated 2008). 2008.
  2. Yoo CG. Pathogenesis and pathophysiology of COPD. Kor J Int Med. 2009;77:383-400.
  3. Korea National Statistical Office, Republic of Korea [Internet]. Dajeon: Korea National Statistical Office; c1996-[cited 2008 Mar]. Available from: http://www.nso.go.kr.
  4. NHLBI. NHLBI morbidity and mortality chartbook, [cited 2005 Feb] 2004. Available from: http://www.nhlbi.nih.gov/resources/docs/cht-book.htm.
  5. Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet 1997; 349:1498-504. https://doi.org/10.1016/S0140-6736(96)07492-2
  6. American Thoracic Society. Chronic bronchitis, asthma and pulmonary emphysema: a statement by the Committee on Diagnostic Standards for Nontuberculous Respiratory Diseases. Am Rev Respir Dis 1962;85:762-8.
  7. Gottlieb DJ, Stone PJ, Sparrow D, Gale ME, Weiss ST, Snider GL et al. Urinary desmosine excretion in smokers with and without rapid decline of lung function: the Normative Aging Study. Am J Respir Crit Care Med. 1996;154: 1290-5. https://doi.org/10.1164/ajrccm.154.5.8912738
  8. Harel S, Janoff A, Yu SY, Hurewitz A, Bergofsky EH. Desmosine radioimmunoassay for measuring elastin degradation in vivo. Am Rev Respir Dis. 1980;122:769-73.
  9. Cantin A, Crystal RG. Oxidants, antioxidants and the pathogenesis of emphysema. Eur J Respir Dis Suppl. 1985;139:7-17.
  10. Laurent P, Janoff A, Kagan HM. Cigarette smoke blocks cross-linking of elastin in vitro. Am Rev Respir Dis. 1983;127:189-92.
  11. Kasahara Y, Tuder RM, Cool CD, Lynch DA, Flores SC, Voelkel NF. Endothelial cell death and decreased expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema. Am J Respir Crit Care Med. 2001;163:737-44. https://doi.org/10.1164/ajrccm.163.3.2002117
  12. Tuder RM, Petrache I, Elias JA, Voelkel NF, Henson PM. Apoptosis and emphysema:the missing link. Am J Respir Cell Mol Biol. 2003;28:551-4. https://doi.org/10.1165/rcmb.F269
  13. Kasahara Y, Tuder RM, Taraseviciene-Stewart L, Le Cras TD, Abman S, Hirth PK et al. Inhibition of VEGF receptors causes lung cell apoptosis and emphysema. J Clin Invest. 2000; 106:1311-9. https://doi.org/10.1172/JCI10259
  14. 장기. 金匱要略. 북경, 인민위생출판사. 1998: 192-3.
  15. 허준. 東醫寶鑑. 서울: 남산당. 1986:477.
  16. Cheon MS, Chun JM, Yoon T, Lee A, Moon BC, Choo BK et al. Anti-carcinogenetic and Antimetastatic Effects of Extract from Maekmoondongtang in HepG2 Cells. Kor J Herbology. 2009; 24(3):161-7.
  17. Kim H, Jeong HS, Kwon J, Lee KG. Effect of Maekmoondong-tang on the immunomodulatory action. Kor J Orient Physiol & Pathol. 2003; 17(4):946-51.
  18. 정호롱, 김영신, 임윤택, 이응세. 맥문동과 맥문 동탕 투여가 심폐기능 및 피로회복효과에 미치는 영향. 대한스포츠한의학회지 2003;4(1):122-34.
  19. Kim JJ, Jung HJ, Jung SK, Rhee HK. The effects of Maekmoondong-tang and Jeongcheonhwadamgangki- tang on immune cell and serum OAspecific IgE in BALF in rat asthma model. J Kor Orient Med. 2002;23(1):37-49.
  20. 전국한의과대학 폐계내과학교실. 동의폐계내과학. 서울: 한문화사. 2002:335-46.
  21. 전국한의과대학 본초학교실. 本草學. 서울: 영림사. 1994:121-622.
  22. 高本釗. 신편중약대사전 (하). 臺北: 신문풍출판공사. 1983:4277.
  23. Nakajoh M, Fukushima T, Suzuki T, Yamaya M, Nakayama K, Sekizawa K et al. Retinoic acid inhibits elastase-induced injury in human lung epithelial cell lines. Am J Respir Cell Mol Biol. 2003;28:296-304. https://doi.org/10.1165/rcmb.4845
  24. Gottlieb DJ, Stone PJ, Sparrow D, Gale ME, Weiss ST, Snider GL et al. Urinary desmosine excretion in smokers with and without rapid decline of lung function: the Normative Aging Study. Am J Respir Crit Care Med. 1996; 154:1290-5. https://doi.org/10.1164/ajrccm.154.5.8912738
  25. Harel S, Janoff A, Yu SY, Hurewitz A, Bergofsky EH. Desmosine radioimmunoassay for measuring elastin degradation in vivo. Am Rev Respir Dis. 1980;122:769-73.
  26. Foronjy R, D'Armiento J. The role of collagenase in emphysema. Respir Res. 2001;2:348-52. https://doi.org/10.1186/rr85
  27. Yoon JM, Park YC. Protective effects of Seonpyejeongceon-tang on elastase-induced lung injury in mice. J Kor Orient Int Med. 2010; 31(1):84-101.
  28. Uhal BD. Cell cycle kinetics in the alveolar epithelium. Am J Physiol. 1997;272:L1031-45.
  29. Draetta G, Beach D. The mammalian cdc2 protein kinase: mechanisms of regulation during the cell cycle. J Cell Sci Suppl. 1989;12:21-7.
  30. Draetta G. Cell cycle control in eukaryotes: molecular mechanisms of cdc2 activation. Trends Biochem Sci. 1990;15:378-83. https://doi.org/10.1016/0968-0004(90)90235-4
  31. Moreno S, Nurse P. Substrates for p34cdc2: in vivo veritas? Cell. 1990;61:549-51. https://doi.org/10.1016/0092-8674(90)90463-O
  32. Nigg EA. The substrates of the cdc2 kinase. Semin Cell Biol. 1991;2:261-70.
  33. Nigg EA, Krek W, Peter M. Vertebrate cdc2 kinase: its regulation by phosphorylation and its mitotic targets. Cold Spring Harb Symp Quant Biol. 1991;56:539-47.
  34. Enoch T, Nurse P. Coupling M phase and S phase: controls maintaining the dependence of mitosis on chromosome replication. Cell. 1991;65:921-3. https://doi.org/10.1016/0092-8674(91)90542-7
  35. Segal RA, Greenberg ME. Intracellular signaling pathways activated by neurotrophic factors. Annu Rev Neurosci. 1996;19:463-89. https://doi.org/10.1146/annurev.ne.19.030196.002335
  36. Magnuson NS, Beck T, Vahidi H, Hahn H, Smola U, Rapp UR. The Raf-1 serine/threonine kinase. Semin Cancer Biol 1994;5:247-53.
  37. Yoon S, Seger R. The extracellular signalregulated kinase: multiple substrates regulate diverse cellular functions. Growth Factors. 2006; 24:21-44. https://doi.org/10.1080/02699050500284218
  38. Park WY, Goodman RB, Steinberg KP, Ruzinski JT, Radella F 2nd, Park DR et al. Cytokine balance in the lungs of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2001;164:1896-903. https://doi.org/10.1164/ajrccm.164.10.2104013
  39. Barnes PJ. The cytokine network in asthma and chronic obstructive pulmonary disease. J Clin Invest. 2008;118(11):3546-56. https://doi.org/10.1172/JCI36130
  40. Karadag F, Karul AB, Cildag O, Yilmaz M, Ozcan H. Biomarkers of systemic inflammation in stable and exacerbation phases of COPD. Lung. 2008;186(6):403-9. https://doi.org/10.1007/s00408-008-9106-6