대한한방내과학회지 (The Journal of Internal Korean Medicine)

대한한방내과학회 (The Society of Internal Korean Medicine)
권호 표지

해조가 2,4,6-trinitrobenzene-sulfonic acid로 유발된 염증성 장질환 동물모델에 미치는 영향

Effects of Sargassumpallidum on 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis in Mice

  • 이상욱 (경희대학교 한의과대학 비계내과학교실) ;
  • 류봉하 (경희대학교 한의과대학 비계내과학교실) ;
  • 박재우 (경희대학교 한의과대학 비계내과학교실)
  • Lee, Sang-Wook (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) ;
  • Park, Jae-Woo (3rd Dept. of Internal Medicine, College of Oriental Medicine, Kyung-Hee University)
  • 발행 : 2010.06.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Objectives : The aim of the current study was to investigate the effects of Sargassum (Sargassum pallidum (TURN.) C. AG.; SP) on the experimental colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice. Methods : ICR mice were divided into 7 groups (NOR, CON, $SS50\times5$, $SP20\times3$, $SP50\times3$, $SP20\times5$, $SP50\times5$). TNBS processing was intrarectally applied to all experimental groups on the 3rd experiment day, except the normal group (NOR). For investigating the prophylactic effect, SP at doses of 20 mg/kg ($SP20\times5$) and 50 mg/kg ($SP50\times5$) were orally administered for 5 days. The SP at doses of 20 mg/kg ($SP20\times3$) and 50 mg/kg ($SP50\times3$) were orally administered for 3 days after the colitis induction in order to check the effect of treatment. As a positive control group, sulfasalazine 50 mg/kg ($SS50\times5$) was administrated. Macroscopic findings of epithelial tissue on mice were measured by colon length and macroscopic score. Histologic findings were also checked by crypt cell, epithelial cell, inflammatory cell and edema of submucosa. We measured the ability of SP to inhibit lipid peroxidation and myeloperoxidase activity. We also measured 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. We measured activation of fecal bacterial enzyme, $\beta$-glucuronidase and degradation activation of fecal glycosaminoglycan (GAG), and hyaluronic acid. Results : Oral administration of SP on mice inhibited TNBS-induced colon shortening and myeloperoxidase activity in the colon of mice as well as IL-$1\beta$ and COX-2 expression. SP also inhibited TNBS-induced lipid peroxidation and pp65 activation in the colon of mice. SP inhibited $\beta$-glucuronidase activation and fecal hyaluronic acid degradation activation as well. Conclusions : SP could be a possible herbal candidate and preventive prebiotic agent for treating inflammatory bowel disease (IBD). Further experiments to differentiate effects of SP on IBD, such as other solutions and extracting times, might be promising.

키워드

참고문헌

  1. 양석균. 한국인의 염증성 장질환의 현황과 임상적 특징. 대한소화기학회지. 2002;40(1):1-14.
  2. 홍은경. 염증성 장질환의 원인과 발생기전. 녹십자의보. 1997;25(1):14-24.
  3. 김영태, 안성훈, 김재효, 손일철. 천추상응부위에 구진약침 자극이 TNBS로 유도된 크론병에 미치는 영향. 경락경혈학회지. 2008;25(2):159-77.
  4. 김나영, 김재준, 송인성, 김정룡, 김우호. 흰쥐에서 TNBS로 유발된 염증성 대장염의 병태생리에 관한 연구. 대한내과학회지. 1994;47(1):20-35.
  5. 김정룡편저. 소화기계 질환. 제2판. 서울: 일조각; 2008, p. 277-8.
  6. 전정열, 이철호, 이광열, 유정준, 박세영, 임석원 등. 염증성 장질환에서 cyclosporine의 치료효과. 대한외과학회지. 1997;53(1):62-78.
  7. 송영근, 류봉하, 윤성우. 소염정장탕이 DSS로 유발된 생쥐의 궤양성 대장염에 미치는 영향. 대한한방내과학회지. 2008;29(2):385-400.
  8. 김소연, 류봉하, 박재우. 궤양성 대장염 동물모델에서 사미연견탕의 항염증 및 장내세균 효소활성 억제효과. 대한한의학회지. 2008;29(3):50-62.
  9. 劉慧榮, 馬曉梵, 趙天平, 吳煥淦. 鍼灸對克羅恩病大鼠結腸膠原合成及TGF$\beta$ mRNA表達的調節. 安徽中醫學院學報. 2005;24(4):25-9.
  10. 손덕칭, 장혜진, 선종기. 청심연자탕으로 치료하여 호전된 강직성척추염을 동반한 중증 궤양성대장염 1례. 대한한방내과학회지. 2005;26(3):685-91.
  11. 서수현, 정재욱, 이은형, 최인선, 박상은, 김원일 등. 보장건비탕으로 증상 호전 보인 크론병 의증 1례. 대한한방내과학회지. 2004;25(3):648-54.
  12. 이종수. 해조의 화학과 이용. 초판. 서울: 도서출판 효일; 2008, p. 18, 98-9, 112, 229-36, 282-7, 291-301, 321.
  13. Hong Ye, Keqi Wang, Chunhong Zhou, Jun Liu, Xiaoxiong Zeng. Purification, antitumor and antioxidant activities in vitro of polysaccharides from the brown seaweed Sargassum pallidum. Food Chem. 2008;111(2):428-32. https://doi.org/10.1016/j.foodchem.2008.04.012
  14. 배송자. 모자반 분획물의 in vitro에서의 항발암효과. 한국식품영양과학회지. 2004;33(3):480-6.
  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 Biochem. 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. 전국한의과대학 비계내과학교실. 비계내과학. 첫째판. 서울: 군자출판사; 2008, p. 366-75.
  23. 呂永慧. 炎症性腸病的中醫治療. 實用醫學雜誌. 2003;19(5):457-9.
  24. 김수현, 임상빈, 고영환, 오창경, 오명철, 박제석. 추출 용매에 따른 톳 추출물의 수율 및 항균성 검정. 한국수산학회지. 1994;27(5):462-8.
  25. 한국과학재단. 해조류로부터 수용성 항산화제의 효과적인 추출. 대전: 한국과학재단; 1995, p. 13-29.
  26. 김호철. 한약약리학. 1판. 서울: 집문당; 2008, p. 360-1.
  27. 정현채. 염증성 장질환의 실험 동물모델. 대한소화기학회지. 2001;37:69-75.
  28. 유효민, 김원호. 염증성 장질환의 실험동물모델. 녹십자의보. 1999;27(3):131-40.
  29. Lee JH, Lee BM, Lee HS, Bae EA, Lee HY, Ahn YT et al. Lactobacillus suntoryeus inhibits proinflammatory cytokine expression and TLR -4-linked NF-$\kappa$B activation in experimental colitis. Int J colorectal Dis. 2009;24:231-7. https://doi.org/10.1007/s00384-008-0618-6
  30. Lee HS, Han SY, Ryu KY, 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
  31. Daddaoua A, Martinez-Plata E, Lopez-Posadas R, Vieites JM, Gonzalez M, Requena P et al. Active hexose correlated compound acts as a prebiotic and is antiinflammatory in rats with hapten-induced colitis. J Nutr. 2007;137(5) :1222-8.
  32. Kim SJ, Choi DH, Chung YT. Gliotoxin protects against TNBS-induced colitis via down-regulation of NF-$\kappa$B activation. Kor J Anat. 2004;37(3) :309-15.
  33. Krawisz JE, Sharon P, Stenson WF. Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. Gastroenterology. 1984;87(6):1344-50.
  34. Cestari SH, Bastos JK, Di Stasi LC. Intestinal anti -inflammatory activity of baccharis dracunculifolia in the trinitrobenzenesulphonic acid model of rat colitis. Evid Based Complement Alternat Med. 2009 Jul 10. [Epub ahead of print]
  35. Urso ML, Clarkson PM. Oxidative stress, exercise and antioxidant supplementation. Toxicol. 2003 ;189:41-54. https://doi.org/10.1016/S0300-483X(03)00151-3
  36. Daniel K, Podolsky DK. Inflammatory bowel disease. N Engl J Med. 2002;347(6):417-29. https://doi.org/10.1056/NEJMra020831
  37. Jackson MJ. Free radicals in skin and muscle: damaging agents or signals for adaptation? Proc Nutr Soc. 1999;58(3):673-6.
  38. Barnes PJ, Karin M. Nuclear factor-$\kappa$B-a pivotal transcription factor in chronic inflammatory disease. N Engl J Med. 1997;336(15):1066-71. https://doi.org/10.1056/NEJM199704103361506
  39. 서영준. 선택적 COX-2 저해약물의 화학 암 예방 효과 및 작용기전 연구. 과천: 보건복지부; 2003, p. 1.
  40. 박영숙. 염증성장질환에서 COX-2 억제제의 역할; 이로운가? 해로운가? 대한소화기학회지. 2007 ;50:350-5.
  41. Lee HS, Han SY, Bae EA, Huh CS, Ahn YT, Lee JH et al. Lactic acid bacteria inhibit proinflammatory cytokine expression and bacterial glycosaminoglycan degradation activity in dextran sulfate sodium-induced colitic mice. Int Immunopharmacol. 2008;8(4):574-80. https://doi.org/10.1016/j.intimp.2008.01.009
  42. 이소영, 송유진, 김진희, 김아람, 김꽃봉우리, 박선미 등. 수산이용가공분야: 구두발표; 식품 부패 미생물에 대한 해조류 추출물의 항균활성. 2006년 수산관련학회 공동학술대회 발표 요지집. 2006;2006:93-4.