DOI QR코드

DOI QR Code

Anti-inflammatory effects of mulberry twig extracts on dextran sulfate sodium-induced colitis mouse model

상지추출물이 Dextran Sulfate Sodium으로 유도된 대장염 마우스 모델에 미치는 항염증 효능

  • Cui, Xuelei (Department of Food Science and Nutrition, Daegu Catholic University) ;
  • Kim, Eunjung (Department of Food Science and Nutrition, Daegu Catholic University)
  • 최설뢰 (대구가톨릭대학교 식품영양학과) ;
  • 김은정 (대구가톨릭대학교 식품영양학과)
  • Received : 2019.03.01
  • Accepted : 2019.03.18
  • Published : 2019.04.30

Abstract

Purpose: Ulcerative colitis is a common inflammatory bowel disease. Prolonged colitis can be a risk factor for the development of colorectal cancer. Mulberry twig (MT, Sangzhi), a dry branch of Morus alba L., which is widely distributed throughout East Asia, has been shown to have anti-inflammatory activities in the cells. However, the effects of MT extracts on colitis in in vivo are limited. Therefore, in this study, we investigated the anti-inflammatory effects of MT extracts in the dextran sulfate sodium (DSS)-induced mouse colitis model. Methods: Six week-old, male ICR mice were divided into 3 groups: Control (n = 5), DSS (n = 7), and DSS+MT (n = 7) groups. Mice in the DSS and DSS+MT groups were administrated 3% DSS in drinking water for 5 days to induce colitis. At the same time, water extracts of MT (5 g/kg body weight/day) were orally administered to mice in the DSS+MT groups for 5 days. Results: The MT extracts significantly reduced the clinical and pathological characteristics of colitis. Disease activity index, mucosal thickness, and colonocyte proliferation were significantly reduced in the DSS+MT group compared with the DSS group. Furthermore, MT administration reduced the levels of plasma $TNF-{\alpha}$, IL-6, and the colonic myeloperoxidase activity as well as mRNA expression of $TNF-{\alpha}$, IL-6, Cox-2, and iNOS. Conclusion: Taken together, these results suggest that MT water extracts have potent anti-colitis activities in the mouse colitis model.

본 연구는 DSS 유도 대장염 마우스 모델에서 MT열수 추출물의 항대장염 효능을 확인하고자 ICR 마우스에 5일 동안 3% DSS와 함께 MT추출물을 경구투여한 후 대장염의 임상적 증상 및 염증 지표들을 분석하였다. 그 결과 MT추출물의 투여는 DSS에 의해 유도된 마우스 대장염 증상의 지표들, 즉 체중 감소와 혈성 설사를 포함한 질병 활성도, 대장점막증식, 그리고 $TNF-{\alpha}$와 IL-6를 포함한 염증성 사이토카인량 증가를 개선시키는 것으로 나타났다. 또한 DSS에 의해 증가된 Cox-2, iNOS, p-Erk 등 염증 지표 단백질의 발현도 MT추출물 투여군에서 감소되었다. 이러한 결과들은 MT추출물이 항대장염 효능이 있음을 제시하며 향후 MT추출물에 포함되어 있는 생리활성물질의 효능과 관련기작이 규명된다면 상지를 물로 우려내어 섭취하는 상지차 형태의 대장염 예방 혹은 개선용 건강식품으로의 개발을 기대해 볼 수 있을 것으로 사료된다.

Keywords

References

  1. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med 2009; 361(21): 2066-2078. https://doi.org/10.1056/NEJMra0804647
  2. Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 2001; 48(4): 526-535. https://doi.org/10.1136/gut.48.4.526
  3. Gillen CD, Walmsley RS, Prior P, Andrews HA, Allan RN. Ulcerative colitis and Crohn's disease: a comparison of the colorectal cancer risk in extensive colitis. Gut 1994; 35(11): 1590-1592. https://doi.org/10.1136/gut.35.11.1590
  4. van Hogezand RA, Eichhorn RF, Choudry A, Veenendaal RA, Lamers CB. Malignancies in inflammatory bowel disease: fact or fiction? Scand J Gastroenterol Suppl 2002; 37(236): 48-53. https://doi.org/10.1080/003655202320621454
  5. Yang SK, Loftus EV Jr, Sandborn WJ. Epidemiology of inflammatory bowel disease in Asia. Inflamm Bowel Dis 2001; 7(3): 260-270. https://doi.org/10.1097/00054725-200108000-00013
  6. Ng WK, Wong SH, Ng SC. Changing epidemiological trends of inflammatory bowel disease in Asia. Intest Res 2016; 14(2): 111-119. https://doi.org/10.5217/ir.2016.14.2.111
  7. Yang DH, Yang SK. Trends in the incidence of ulcerative colitis in Korea. Korean J Med 2009; 76(6): 637-642.
  8. Medzhitov R, Janeway CA Jr. Innate immunity: impact on the adaptive immune response. Curr Opin Immunol 1997; 9(1): 4-9. https://doi.org/10.1016/S0952-7915(97)80152-5
  9. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420(6917): 860-867. https://doi.org/10.1038/nature01322
  10. Jang YJ, Leem HH, Jeon YH, Lee DH, Choi SW. Isolation and identification of ${\alpha}$-glucosidase inhibitors from morus root bark. J Korean Soc Food Sci Nutr 2015; 44(7): 1090-1099. https://doi.org/10.3746/jkfn.2015.44.7.1090
  11. Choi SW, Jang YJ, Lee YJ, Leem HH, Kim EO. Analysis of functional constituents in mulberry (Morus alba L.) twigs by different cultivars, producing areas, and heat processings. Prev Nutr Food Sci 2013; 18(4): 256-262. https://doi.org/10.3746/pnf.2013.18.4.256
  12. Zhang Z, Shi L. Anti-inflammatory and analgesic properties of cis-mulberroside A from Ramulus mori. Fitoterapia 2010; 81(3): 214-218. https://doi.org/10.1016/j.fitote.2009.09.005
  13. Chung KO, Kim BY, Lee MH, Kim YR, Chung HY, Park JH, et al. In-vitro and in-vivo anti-inflammatory effect of oxyresveratrol from Morus alba L. J Pharm Pharmacol 2003; 55(12): 1695-1700. https://doi.org/10.1211/0022357022313
  14. Cooper HS, Murthy SN, Shah RS, Sedergran DJ. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 1993; 69(2): 238-249.
  15. Hendrickson BA, Gokhale R, Cho JH. Clinical aspects and pathophysiology of inflammatory bowel disease. Clin Microbiol Rev 2002; 15(1): 79-94. https://doi.org/10.1128/CMR.15.1.79-94.2002
  16. Kornbluth A, Sachar DB; Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults: American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol 2010; 105(3): 501-523. https://doi.org/10.1038/ajg.2009.727
  17. Su C, Lichtenstein GR. Ulcerative colitis. In: Feldman M, Friedman LS, Brandt LJ, editors. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. Volume 2. 8th edition. Philadelphia (PA): Saunders; 2006. p.2499-2548.
  18. Choi CH, Moon W, Kim YS, Kim ES, Lee BI, Jung Y, et al. Second Korean guideline for the management of ulcerative colitis. Korean J Gastroenterol 2017; 69(1): 1-28. https://doi.org/10.4166/kjg.2017.69.1.1
  19. Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 1990; 98(3): 694-702. https://doi.org/10.1016/0016-5085(90)90290-H
  20. Walsh-Reitz MM, Huang EF, Musch MW, Chang EB, Martin TE, Kartha S, et al. AMP-18 protects barrier function of colonic epithelial cells: role of tight junction proteins. Am J Physiol Gastrointest Liver Physiol 2005; 289(1): G163-G171. https://doi.org/10.1152/ajpgi.00013.2005
  21. Araki Y, Sugihara H, Hattori T. In vitro effects of dextran sulfate sodium on a Caco-2 cell line and plausible mechanisms for dextran sulfate sodium-induced colitis. Oncol Rep 2006; 16(6): 1357-1362.
  22. Johansson ME, Gustafsson JK, Sjoberg KE, Petersson J, Holm L, Sjovall H, et al. Bacteria penetrate the inner mucus layer before inflammation in the dextran sulfate colitis model. PLoS One 2010; 5(8): e12238. https://doi.org/10.1371/journal.pone.0012238
  23. Morgan ME, Zheng B, Koelink PJ, van de Kant HJ, Haazen LC, van Roest M, et al. New perspective on dextran sodium sulfate colitis: antigen-specific T cell development during intestinal inflammation. PLoS One 2013; 8(7): e69936. https://doi.org/10.1371/journal.pone.0069936
  24. Forbes E, Murase T, Yang M, Matthaei KI, Lee JJ, Lee NA, et al. Immunopathogenesis of experimental ulcerative colitis is mediated by eosinophil peroxidase. J Immunol 2004; 172(9): 5664-5675. https://doi.org/10.4049/jimmunol.172.9.5664
  25. Choi IY, Lee KT, Kim MC, Kim SJ, Kim DS, Jeon YD, et al. Anti-inflammatory effects of Cheongilppong on DSS-induced ulcerative colitis in mice. Orient Pharm Exp Med 2011; 11(1): 35-39. https://doi.org/10.1007/s13596-011-0009-3
  26. Scott RJ, Hall PA, Haldane JS, van Noorden S, Price Y, Lane DP, et al. A comparison of immunohistochemical markers of cell proliferation with experimentally determined growth fraction. J Pathol 1991; 165(2): 173-178. https://doi.org/10.1002/path.1711650213
  27. Min HY, Chung HJ, Kim EH, Kim S, Park EJ, Lee SK. Inhibition of cell growth and potentiation of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-induced apoptosis by a phenanthroindolizidine alkaloid antofine in human colon cancer cells. Biochem Pharmacol 2010; 80(9): 1356-1364. https://doi.org/10.1016/j.bcp.2010.07.026
  28. Hoffmann A, Leung TH, Baltimore D. Genetic analysis of NF-${\kappa}B$/Rel transcription factors defines functional specificities. EMBO J 2003; 22(20): 5530-5539. https://doi.org/10.1093/emboj/cdg534
  29. Kinoshita T, Ito H, Miki C. Serum interleukin-6 level reflects the tumor proliferative activity in patients with colorectal carcinoma. Cancer 1999; 85(12): 2526-2531. https://doi.org/10.1002/(SICI)1097-0142(19990615)85:12<2526::AID-CNCR6>3.0.CO;2-3
  30. Janssen-Heininger YM, Poynter ME, Baeuerle PA. Recent advances towards understanding redox mechanisms in the activation of nuclear factor ${\kappa}B$. Free Radic Biol Med 2000; 28(9): 1317-1327. https://doi.org/10.1016/S0891-5849(00)00218-5
  31. Schulze-Osthoff K, Ferrari D, Riehemann K, Wesselborg S. Regulation of NF-${\kappa}B$ activation by MAP kinase cascades. Immunobiology 1997; 198(1-3): 35-49. https://doi.org/10.1016/S0171-2985(97)80025-3
  32. Costa F, Mumolo MG, Ceccarelli L, Bellini M, Romano MR, Sterpi C, et al. Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn's disease. Gut 2005; 54(3): 364-368. https://doi.org/10.1136/gut.2004.043406