Protective Effects of Socheongryong-tang on Elastase-Induced Lung Injury

Elastase로 유도된 폐손상에 대한 소청룡탕(小靑龍湯)의 보호효과

  • Lee, Ju-Guan (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)
  • 이주관 (대전대학교 한의과대학 폐계내과학교실) ;
  • 양수영 (대전대학교 한의과대학 폐계내과학교실) ;
  • 김민희 (대전대학교 한의과대학 신경생리학교실) ;
  • 남궁욱 (대전대학교 한의과대학 신경생리학교실) ;
  • 박양춘 (대전대학교 한의과대학 폐계내과학교실)
  • Received : 2011.05.19
  • Accepted : 2011.07.08
  • Published : 2011.07.30

Abstract

Objective: This study aimed to evaluate the protective effects of Socheongryong-tang (SCRT) on elastase-induced lung injury. Materials and Methods: The extract of SCRT 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: SCRT 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, and gene expression of TNF-${\alpha}$ and IL-$1{\beta}$ in A549 cells. SCRT treatment also revealed the protective effect on elastase-induced COPD mice model. This effect was evidenced via histopathological findings including immunofluoresence stains against elastin, collagen, and caspase 3, and protein level of Cdc2, cyclin B1, and phospho-Erk1/2 in lung tissue. Conclusion: These data suggest that SCRT has pharmaceutical properties on COPD. This study provides scientific evidence for the efficacy of SCRT for clinical application to patients with COPD.

Keywords

References

  1. Celli BR, MacNee W. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 2004;23(6):932-46. https://doi.org/10.1183/09031936.04.00014304
  2. Kim DS, Kim YS, Jung KS, Chang JH, Lim CM, Lee JH, et al. Prevalence of chronic obstructive pulmonary disease in Korea: a population-based spirometry survey. Am J Respir Crit Care Med. 2005;172:842-7. https://doi.org/10.1164/rccm.200502-259OC
  3. Korea National Statistical Office. Dajeon: Korea National Statistical Office; c1996-[cited 2009 Mar]. Available from: http://www.nso.go.kr
  4. World Health Report. World Health Organization, Geneva. 2000. Available from URL: http://www.who.int/whr/2000/en/ statistics.htm.
  5. Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007;176(6):532-55. https://doi.org/10.1164/rccm.200703-456SO
  6. Chang J. Pharmacologic treatment of COPD. Tuberc Respir Dis. 2005;59:231-42.
  7. Lee DJ. The effects of Lonicera japonica on the murine model of Chronic obstructive pulmonary disease. Seoul: Kyung Hee Univ.; 2009.
  8. Kim KT, Ko H. Effects of Shigyungbanha-tang on the lipopolysaccharide-induced acute lung injury in mice. Kor J Orient Physiol Pathol. 2009; 26:1349-1357.
  9. Oh JS, Park YC. Protective effects of Gamipalmihwan on elastase-induced apoptosis of A549 cells. J Kor Orient Med. 2010;31(2):137-48.
  10. Yoon JM, Park YC. Protective effects of Seonpyejeongcheon-tang on elastase-induced lung injury in mice. Kor J Orient Int Med. 2010;31(1):84-101.
  11. 장기. 중경전서. 서울: 행림출판사. 1977:460-1.
  12. 이상인. 방제학. 서울: 영림사. 1995:50.
  13. 전국한의과대학 폐계내과학교실. 동의폐계내과학. 서울: 한문화사. 2002:338-46.
  14. Jung S, Cho SJ, Moon KI, Kim HW, Kim BY, Cho SI. Effects of Socheongryong-tang on immunoglobulin production in asthmatic mice. Kor J Herbology. 2008;23(1):23-8.
  15. Kim KY, Lee JH, Kim YJ, Choi SY, Kim TH, Lyu YS, et al. Anti-allergic effects of Socheongyoung-tang on RBL-2H3 mast cell and mice-mediated allergy model. 2007;21(5):1260-70.
  16. Kim HW. Effects of Socheongryong-tang on inflammatory cells in asthmatic mice. Kor J Orient Prevent Med Soc. 2006;10(2):121-9.
  17. Jeong HJ, Hong MC, Shin MK, Bae HS. Sochungyong-tang, traditional Korean medicine, suppresses Th2 lineage development. Kor J Orient Physiol Pathol. 2005;19(2):380-8.
  18. Jung JY, Jung HJ, Jung SK, Rhee HK. The inhibitory effects of Socheongryong-tang and Socheongryong-tang plus Sasam (Adenophorae Radix) on the IL-6, IL-8 and GM-CSF mRNA levels in human epithelial cells. J Kor Orient Med. 2003;24(1):74-83.
  19. Hwang WS, Lee JS, Choi JY, Jung HJ, Rhee HK, Jung SK. Two cases of chronic sinusitis with asthma improved by Socheongryong-tang. J Kor Orient Med. 2003;24(1):207-12.
  20. Jung SK, Heo TS, Hwang WS, Ju CY, Kim YW, Jung HJ. The effects of Socheongryong-tang on serum IL-4, IL-5, and IFN-r in asthmatic patients. J Kor Orient Med. 2002;23(2):70-7.
  21. Hwang WS, Jung HJ, Ju CY, Lee JS, Lee KK, Rhee HK, et al. A study on changes in blood eosinophil, serum IgE and T lymphocyte subpopulation after Socheongryong-tang to asthmatic patients. Kor J Orient Int Med. 2002; 23(1):83-90.
  22. Heo TS, Hwang WS, Ju CY, Jung HJ, Rhee HK, Jung SK. The effects of Socheongryong-tang on pulmonary function and quality-of-life in asthmatic patients. J Kor Orient Med. 2001;22(4):131-41.
  23. Park YC. Effect of Socheongryong-tang on Punghan and Pungyeol type common cold: a double blind, placebo controlled study. Kor J Orient Physiol Pathol. 2005;19(2):524-9
  24. Na DG, Lee CJ, Park YC. Effects of Socheongryong-tang and Kamichihyo-san on mucine secretion from airway goblet cells. Kor J Orient Physiol Pathol. 2004;18(3):734-9.
  25. Kawakami M, Matsuo Y, Yoshiura K, Nagase T, Yamashita N. Sequential and quantitative analysis of a murine model of elastase-induced emphysema. Biol Pharm Bull. 2008;31:1434-8. https://doi.org/10.1248/bpb.31.1434
  26. 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
  27. Lucey EC, Goldstein RH, Stone PJ, Snider GL. Remodeling of alveolar walls after elastase treatment of hamsters. Results of elastin and collagen mRNA in situ hybridization. Am J Respir Crit Care Med. 1998;158:555-64. https://doi.org/10.1164/ajrccm.158.2.9705021
  28. Molfino NA, Jeffery PK. Chronic obstructive pulmonary disease: Histopathology, inflammation and potential therapies. Pulm Pharmacol Ther. 2007;20(5):462-72. https://doi.org/10.1016/j.pupt.2006.04.003
  29. Yoo CG. Pathogenesis and pathophysiology of COPD. Kor J Int Med. 2009;77:383-400.
  30. Abboud RT, Vimalanathan S. Pathogenesis of COPD. Part I. The role of protease-antiprotease imbalance in emphysema. Int J Tuberc Lung Dis. 2008;12(4):361-7.
  31. 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.
  32. Hogg JC, Timens W. The pathology of chronic obstructive pulmonary disease. Annu Rev Pathol. 2009;4:435-59. https://doi.org/10.1146/annurev.pathol.4.110807.092145
  33. Bowler RP, Barnes PJ, Crapo JD. The role of oxidative stress in chronic obstructive pulmonary disease. COPD. 2004;1(2):255-77. https://doi.org/10.1081/COPD-200027031
  34. Cho HY, Kleeberger SR. Genetic mechanisms of susceptibility to oxidative lung injury in mice. Free Radic Biol Med. 2007;42:433-45. https://doi.org/10.1016/j.freeradbiomed.2006.11.021
  35. Gardi C, Arezzini B, Martorana PA. Testing of compounds in models of pulmonary emphysema. Curr Med Chem. 2008;15:803-8. https://doi.org/10.2174/092986708783955536
  36. Sethi JM, Rochester CL. Smoking and chronic obstructive pulmonary disease. Clin Chest Med. 2000;21:67-86. https://doi.org/10.1016/S0272-5231(05)70008-3
  37. Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD. Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science. 1997;277:2002-4. https://doi.org/10.1126/science.277.5334.2002
  38. 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
  39. Foronjy R, D'Armiento J. The role of collagenase in emphysema. Respir Res. 2001;2:348-52. https://doi.org/10.1186/rr85
  40. Uhal BD. Cell cycle kinetics in the alveolar epithelium. Am J Physiol. 1997;272:L1031-L45.
  41. Draetta G, Beach D. The mammalian cdc2 protein kinase: mechanisms of regulation during the cell cycle. J Cell Sci Suppl. 1989;12:21-7.
  42. 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
  43. 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
  44. Norbury CJ, Nurse P. Control of the higher eukaryote cell cycle by p34cdc2 homologues. Biochim Biophys Acta. 1989;989:85-95.
  45. Nigg EA. The substrates of the cdc2 kinase. Semin Cell Biol. 1991;2:261-70.
  46. 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. https://doi.org/10.1101/SQB.1991.056.01.061
  47. 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
  48. 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
  49. Weston CR, Davis RJ. The JNK signal transduction pathway. Curr Opin Genet Dev. 2002;12:14-21. https://doi.org/10.1016/S0959-437X(01)00258-1
  50. Whitmarsh AJ, Davis RJ. Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. J Mol Med. 1996;74:589-607. https://doi.org/10.1007/s001090050063
  51. Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science. 1995;270:1326-31. https://doi.org/10.1126/science.270.5240.1326