The effect of Sagunja-tang on TNBS-induced Inflammatory Bowel Disease in Mouse

사군자탕(四君子湯)이 TNBS로 유발(誘發)된 생쥐의 염증성(炎症性) 장질환(腸疾患)에 미치는 영향(影響)

  • Hong, Sang-Sun (3rd Dept. of Internal Medicine, College of Oriental Medicine, Kyung-Hee University) ;
  • Ryu, Bong-Ha (3rd Dept. of Internal Medicine, College of Oriental Medicine, Kyung-Hee University) ;
  • Yoon, Seong-Woo (3rd Dept. of Internal Medicine, College of Oriental Medicine, Kyung-Hee University) ;
  • Kim, Jin-Sung (3rd Dept. of Internal Medicine, College of Oriental Medicine, Kyung-Hee University)
  • 홍상선 (경희대학교 한의과대학 비계내과학교실) ;
  • 류봉하 (경희대학교 한의과대학 비계내과학교실) ;
  • 윤성우 (경희대학교 한의과대학 비계내과학교실) ;
  • 김진성 (경희대학교 한의과대학 비계내과학교실)
  • Published : 2010.12.30

Abstract

Objectives : The present study aimed to find out the effect of Sagunja-tang on the prevention and treatment of inflammatory bowel disease using mice with TNBS-induced inflammatory bowel disease. Methods : Mice with TNBS-induced inflammatory bowel disease were medicated with Sagunja-tang, and the weight changes, colon length, lipid peroxidation, and myeloperoxidase activity were observed. Levels of the inflammatory markers interleukin (IL)-$1{\beta}$ and cyclooxygenase-2 (COX-2), its transcription factor activation, phospho-NF-${\kappa}$B (pp65), in the colon by enzyme-linked immunosorbent assay and immunoblot analysis were also measured. Finally, the activation of fecal bacterial enzyme, ${\beta}$-glucuronidase and degradation activation of fecal glycosaminoglycan (GAG) and hyaluronic acid were observed. Results : We found that oral administration of Sagunja-tang inhibited TNBS-induced colon shortening and also inhibited myeloperoxidase activity in the colon of mice as well as IL-$1{\beta}$ and COX-2 expression. Sagunja-tang also inhibited TNBSinduced lipid peroxidation and pp65 activation in the colon of mice. In addition, Sagunja-tang inhibited ${\beta}$-glucuronidase activation and fecal hyaluronic acid degradation activation. Conclusions : It is supposed that Sagunja-tang has a potential therapeutic effect on inflammatory bowel disease through the inhibition of both NF-${\kappa}$B activation and lipid peroxidation, and the improvement of intestinal conditions.

Keywords

References

  1. 김정룡. 소화기계질환. 서울: 일조각; 2000, p. 258-76.
  2. 대한소화기학회. 염증성장질환. 서울: 군자출판사; 1999, p. 1, 26-7, 49-61, 141-4, 261.
  3. 양석균. 한국인의 염증성 장질환의 현황과 임상적 특징. 대한소화기학회지. 2002;40:1-14.
  4. 대한장연구학회. 潰瘍性大腸炎. 서울: 군자출판사; 2003, p. 8.
  5. 김동현. 발효식품이 만드는 유산균이 내 몸을 살린다. 서울: 헌언; 2007, p. 95-8.
  6. 서철훈, 이형호, 최기숙, 임동석, 유형천, 이영수, 최창원, 김희철. 濕熱痢로 변증한 潰瘍性 大腸炎 환자의 芍藥湯加味方 치험 2례. 대한한방내과학회지. 2006;27(4):984-90.
  7. 차준환. 潰瘍性大腸炎과 托裏消毒飮의 協能. 대한한의학회지. 1972;12:148-57.
  8. 윤상협. 補腸健脾湯加減方으로 교원성 대장염의 15년 설사를 호전시켰던 치험 1례. 대한성인병학회지. 2001;7(1):78-81.
  9. 안중환, 최은영, 이성환, 박인식, 임성우. 黃連解毒湯이 DSS로 유발된 흰쥐의 潰瘍性 大腸炎에 미치는 영향. 대한한의학회지. 2006;27(2):182-95.
  10. 김승욱, 임성우. 導赤地楡湯이 潰瘍性 大腸炎 유발 흰쥐에 미치는 영향. 대한한의학회지. 2002;23(3):200-10.
  11. 황태현. 茵蔯五苓散이 DSS로 유발된 흰쥐의 潰瘍性 大腸炎에 미치는 영향. 東國大學校 大學院博士學位論文. 2006.
  12. 최은영. Indomethacin으로 유발된 생쥐의 大腸粘膜 손상에 대한 赤小豆當歸散의 치료효과. 東國大學校 大學院 碩士學位論文. 2004.
  13. Yoo BH, Lee BH, Kim JS, Kim NJ, Kim SH, Ryu KW. Effects of Shikunshito-Kamiho on Fecal Enzymes and Formation of Aberrant Crypt Foci Induced by 1,2-Dimethylhydrazine. Biol Pharm Bull. 2001;24(6):638-42. https://doi.org/10.1248/bpb.24.638
  14. 陳師文. 太平惠民和劑局方. 서울: 경희대학교 한의과대학; 1974, p. 115, 242.
  15. Hollenbach E, Vieth M, Rosessner A, Neumann M, Malfertheiner P, Naumann M. Inhibition of RICK/Nuclear factor-kB and p38 signalling attenuates the inflammatory response in a murine model of Crohn Disease. J Biol Chem. 2005;280:14981-8. https://doi.org/10.1074/jbc.M500966200
  16. Mullane KM, Kraemer R, Smith B. Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemic myocardium. J Pharmacol Methods. 1985;14(3):157-67. https://doi.org/10.1016/0160-5402(85)90029-4
  17. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-54. https://doi.org/10.1016/0003-2697(76)90527-3
  18. Ohkawa H, Ohishi N, Yagi K. Assay of lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biol Chem. 1978;95(2):351-8.
  19. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidases. J Lab Clin Med. 1967;70(1):158-69.
  20. Ito M, Ohishi K, Yoshida Y, Yokoi W, Sawada H. Antioxidative effects of lactic acid bacteria on the colonic mucosa of iron-overload mice. J Agric Food Chem. 2003;51(15):4456-60. https://doi.org/10.1021/jf0261957
  21. Kruis W. Antibiotics and probiotics in inflammatory bowel disease. Aliment Pharmacol Ther. 2004;20(suppl.4):75-8.
  22. Murai KJ, Hismitsu KI, Imamura L and Kobachi K. Effect of oral administration to rats of various undigestable saccharides on fecal pH, water content and enzyme activity. Bifidobacteria Microflora. 1994;13:91-8.
  23. 김태일, 정혜원, 박영수, 김원호, 최창환, 이재훈, 이현웅, 박정엽. 潰瘍性 大腸炎의 임상 경과. 대한소화기학회지. 2001;38(3):169-76.
  24. G. N. Stemmermann. Pattern of disease among Japanese living in Hawaii. Arch. Environ. Health. 1970;20:266-73. https://doi.org/10.1080/00039896.1970.10665585
  25. Yoshiyuki Morishita, Taro Tsukada. Changes in the intestinal microflora in association with colon tumorgenesis in rats treated with 1,2-dimethylhy-drazines hydrochloride. Microbiol. Immunol. 1983;27(6):485-93.
  26. 황은희. 食餌 纖維素 攝取常態와 便 膽汁酸 造成과의 관계. 韓國營養學會誌. 1996;29(1):41-9.
  27. 전정열, 이철호, 이광열, 유정준, 박세영, 임석원, 김현식, 이종균, 이중달. 염증성 장질환에서 cyclosporine의 치료효과. 대한외과학회지. 1997;53(1):62-78.
  28. Hanauer SB. Medical therapy of ulcerative colitis. Lancet. 1993;342(8868):412-7. https://doi.org/10.1016/0140-6736(93)92819-F
  29. Hanauer SB. Inflammatory bowel disease. N EngJ Med. 1996;334(13):841-8. https://doi.org/10.1056/NEJM199603283341307
  30. Sartor RB. Microbial influences in inflammatory bowel disease role in pathogenesis and clinical implications. In: Sartor RB, Sandborn WJ, ed. Kirsner's Inflammatory Bowel Disease, 6th ed. New York: Saunders; 2004, p. 138-62.
  31. Swidsinski A, Ladhoff A, Pernthaler A, Swidsinski S, Loening-Baucke V, Ortner M et al. Mucosal flora in inflammatory bowel disease. Gastroenterology. 2002;122:44-54. https://doi.org/10.1053/gast.2002.30294
  32. Startor RB. Therapeutic manipulation of the enteric microflora in inflammatory bowel disease: antibiotics, probiotics, and prebiotics. Gastroenterology. 2004;126:1620-33. https://doi.org/10.1053/j.gastro.2004.03.024
  33. 강어진, 이상선, 양차범, 신현경. 主要食餌纖維質原이 添加된 食餌가 노화 흰쥐의 腸內酵素 및 有害産物에 미치는 影響. 韓國營養學會誌. 1998;11(5):488-92.
  34. 이종훈. 病原微生物學. 서울: 壽文社; 1973, p. 133-83.
  35. 김소연, 류봉하, 박재우. 궤양성 대장염 동물모델에서 사미연견탕의 항염증 및 장내세균 효소활성 억제효과. 대한한의학회지. 2008;29(3):50-62.
  36. 김나영, 김재준, 송인성, 김정룡, 김우호. 흰쥐에서 TNBS로 유발된 염증성 대장염의 병태생리에 관한 연구. 대한내과학회지. 1994;47(1):20-35.
  37. Park IS. Histological study of experimental colitis induced by dextran sulfate sodium. The Korean J Anat. 2006;39(1):27-33.
  38. Verspaget HW, Mulder TPJ and Lamers CBHW. Reactive oxygen metabolites and colitis; a disturbed balance bet ween damage and protection. A selective review. Scand J Gastroenterol. 1991;26(suppl.188):44-51.
  39. Sartor RB. Cytokine in intestinal inflammation: Pathophysiological and clinical considerations. Gastroenterology. 1994:106;533-9.
  40. Plevy SE, Landers CJ, Prehn J, Carramanzana NM, Deem RL, Shealy D and Targan SR. A role for TNF-alpha and mucosal T helper-1 cytokines in the pathogenesis of Crohn`s disease. J Immunol. 1997;159(12):6276-6282.
  41. 서영준. 선택적 COX-2 저해약물의 화학 암 예방 효과 및 작용기전 연구. 신약개발지원사업 최종보고서. 02-PJ2-PG3-20802-0003. 2003, p. 1.
  42. Surh YJ, Chun KS, Cha HH, Han SS, Keum YS, Park KK, Lee SS. Molecular mechanisms underlying chemopreventive activities of antiinflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-$\kappa$B activation. Mutation Research. 2001;Sep 1:480-1, 243-68.
  43. Kim SJ, Choi DH, Chung YT. Gliotoxin protects against TNBS-induced colitis via down-regulation of NF-$\kappa$B activation. The Korean J Anat. 2004;37(3):309-15.
  44. Urso ML, Clarkson PM. Oxidative stress, exercise and antioxidant supplementation. Toxicol. 2003;189(1-2):41-54. https://doi.org/10.1016/S0300-483X(03)00151-3
  45. Kurutas EB, Cetimkaya A, Bulbuloglu E, Kantarceken B. Effects of antioxidant therapy on leukocyte myeloperoxidase and Cu/Zn-superoxide dismutase and plasma malondialdehyde levels in experimental colitis. Mediators inflamm. 2005;2005(6):390-4. https://doi.org/10.1155/MI.2005.390
  46. N. Nalini, K. Sabitha, P. Viswanathan, V.P. Menon. Influence of spices on the bacterial enzyme activity in experimental colon cancer. J. of Ethnopharmacology. 1998;62(1):15-24. https://doi.org/10.1016/S0378-8741(98)00007-5
  47. B. Goldin, S.L. Gorbach. Alteration in fecal microflora enzymes related to diet, age, Lactobacillus supplements, and DMH. Cancer. 1977;40:2421-6. https://doi.org/10.1002/1097-0142(197711)40:5+<2421::AID-CNCR2820400905>3.0.CO;2-I
  48. Lee HS, Han SY, Ryu KY and Kim DH. The degradation of glycosaminoglycans by intestinal microflora deteriorates colitis in mice. Inflammation. 2009;32(1):27-36. https://doi.org/10.1007/s10753-008-9099-6