DOI QR코드

DOI QR Code

A Study of the Effectiveness of Hwanggeum-tang and Gamchosasim-tang in the Mice Model of Inflammatory Bowel Disease

염증성 장 질환 동물 모델에서 황금탕과 감초사심탕의 효능 연구

  • Kim, Young-kwang (Dept. of Internal Medicine, College of Korean Medicine, Dong-Shin University) ;
  • Moon, Young-ho (Dept. of Internal Medicine, College of Korean Medicine, Dong-Shin University)
  • 김영광 (동신대학교 한의과대학 내과학교실) ;
  • 문영호 (동신대학교 한의과대학 내과학교실)
  • Received : 2021.05.27
  • Accepted : 2021.07.05
  • Published : 2021.06.30

Abstract

Objectives: This study investigates the mechanism of Hwanggeum-tang (HGT) and Gamchosasim-tang (GST) on inflammatory bowel disease (IBD). Methods: The mice (C57BL/6N) were treated with distilled water and 3% dextran sulfate sodium (DSS) to experimentally induce ulcerative colitis. The mice were divided into 7 groups of (6 mice: normal, negative control, positive control (with sulfasalazine), 4 experimental groups (with HGT and GST, respectively). RAW 264.7 cells were used for cell experiments. The experiment was conducted in two ways: in vitro and in vivo. Results: In the experimental group (HGT, GST) of in vitro experiments, NO production decreased, and significant changes in gene expression and protein activation were observed. The length of the colon recovered in the experimental groups (HGT, GST) of the in vivo experiment was longer than that of the negative control group, and the mucosal barrier was recovered. Sone significant changes in the amount of mRNA expression were partially observed, and significant changes in protein activation also were confirmed. Conclusions: HGT and GST are effective in treating IBD caused by DSS. In the same herbal preparation group, the higher the concentration, the better the experimental effect, and when the same concentration was tested, HGT was more effective than GST. Herbal medicine has a higher antioxidant effect than sulfasalazine, so it is also excellent for cell protection.

Keywords

References

  1. Choi EJ, Lee HJ, Kim WJ, Han KI, Iwasa M, Kobayashi K, et al. Enterococcus faecalis EF-2001 protects DNBS-induced inflammatory bowel disease in mice model. PloS one 2019;14(2):e0210854. https://doi.org/10.1371/journal.pone.0210854
  2. Korean Assosiation for the Study of Intestinal Diseases (KASID). Easy to understand ulcerative colitis. Seoul: Koonja; 2003, p. 8.
  3. Su C, Lewis JD, Goldberg B, Brensinger C, Lichtenstein GR. A meta-analysis of the placebo rates of remission and response in clinical trials of active ulcerative colitis. Gastroenterology 2007;132(2):516-26. https://doi.org/10.1053/j.gastro.2006.12.037
  4. Jeen YT, Kim J. Advances in ulcerative colitis therapy. The Korean Journal of Medicine 2009;76(6):654-60.
  5. Lin Z, Wu H, Fu Y, Dai S. Application of Herbaceous Medications for Inflammatory Bowel Disease as a Complementary and Alternative Therapy. Inflammatory bowel diseases 2019;25(12):1886-95. https://doi.org/10.1093/ibd/izz190
  6. Hwang JW, Choi HJ, Baik YS, Jeong SH, Shin GC, Lee WC. A Case of Pyungwijiyutang-gamibang Diagnosed as Constipation due to Stagnation of Eum with Ulcerative Colitis. The Journal of Internal Korean Medicine 2007;28(4):972-7.
  7. Seo CH, Lee HH, Choi KS, Lim DS, Ryu HC, Lee YS, et al. Two Cases of Ulcerative Colitis Diagnosed as Damp-Heat Dysentery Treated with Jakyaktang-gamibang. The Journal of Internal Korean Medicine 2006;27(4):984-90.
  8. Kang AM, Lim SW. Therapeutic Effects of Gaejigayonggolmoryo-tang on Dextran Sodium Sulfate-induced Ulcerative Colitis in Mice. The Journal of Internal Korean Medicine 2017;38(6):1021-34. https://doi.org/10.22246/jikm.2017.38.6.1021
  9. Choi JY, Ahn SH, Shih YH, Sa BS, Kin KB. Mitigating Effect of Jageum-jung on Dextran Sulfate Sodium-induced Ulcerative Colitis through Anti-inflammatory Regulation. The Journal of Internal Korean Medicine 2017;38(6):944-54. https://doi.org/10.22246/jikm.2017.38.6.944
  10. Kim ES, Shin MK, Kim TR, Shin MH, Lee YS. Effect of Ohmae-hwan and Mume Fructus on DSS-Induced Inflammatory Bowel Disease in a Mice Model System. The Journal of Internal Korean Medicine 2015;36(3):284-96.
  11. Kim KJ, Shin M-R, Kim SH, Kim SJ, Lee AR, Kwon OJ, et al. Anti-inflammatory and apoptosis improving effects of sulfasalazine and Cinnamomi cortex and Bupleuri radix mixture in TNBS-induced colitis mouse model. Journal of Applied Biological Chemistry 2017;60(3):227-34. https://doi.org/10.3839/jabc.2017.036
  12. Yoon SB, Han HS, Lee YJ. Effect of Scutellariae Radix Extract on the Proinflammatory Mediators in Raw 264.7 Cells Induced by LPS. The Korea Journal of Herbology 2011;26(2):75-81. https://doi.org/10.6116/KJH.2011.26.2.075
  13. Han MH, Lee MH, Hong SH, Choi YH, Moon JS, Song MK, et al. Comparison of Anti-inflammatory Activities among Ethanol Extracts of Sophora flavescens, Glycyrrhiza uralensis and Dictamnus dasycarpus, and their Mixtures in RAW 246.7 Murine Macrophages. Journal of Life Science 2014;24(3):329-35. https://doi.org/10.5352/JLS.2014.24.3.329
  14. Hu X. 胡希恕傷寒論講義. Paju: Fishwood:2019, p. 290-2, 310-1.
  15. Yang DS, Gu HJ, Yeo EJ, Yang SJ, Jo SH, Park KM. A Case of Suggested Behcet's Disease Patient Treated by Gamchosasim-tang. The Society of Korean Medicine Obstetrics and Gynecology 2009;22(4):187-93.
  16. Yang SK. Current status and clinical characteristics of inflammatory bowel disease in Korea. The Korean journal of gastroenterology 2002;40(1):1-14.
  17. Kwak MS, Cha JM, Lee HH, Choi YS, Seo SI, Ko KJ, et al. Emerging trends of inflammatory bowel disease in South Korea: a nationwide population-based study. Journal of gastroenterology and hepatology 2019;34(6):1018-26. https://doi.org/10.1111/jgh.14542
  18. "Classification of diseases (3 stage chronic disease) statistics" Healthcare Bigdata Hub. last modified Apr 1, 2020, accessed Dec 1, 2020, http://opendata.hira.or.kr/op/opc/olap3thDsInfo.do.
  19. Cha HY, Jeong AR, Cheon JH, Ahn SH, Park SY, Kim KB. The anti-oxidative and anti-inflammatory effect of Lonicera Japonica on ulcerative colitis induced by dextran sulfate sodium in mice. The Journal of Pediatrics of Korean Medicine 2015;29(3):54-64. https://doi.org/10.7778/jpkm.2015.29.3.054
  20. Department of gastrointestinal medicine Korean medicine. gastrointestinal internal medicine. Seoul: Gunja Publishing Co., Ltd.; 2008, p. 365, 374.
  21. Korean Federation of Internal Medicine compilation Harrison's Internal Medicine. Seoul: Do Seo Publising MIP; 2006, p. 1937-50.
  22. Liang HL, Ouyang Q. A clinical trial of combined use of rosiglitazone and 5-aminosalicylate for ulcerative colitis. World journal of gastroenterology: WJG 2008;14(1):114. https://doi.org/10.3748/wjg.14.114
  23. Neurath MF. Cytokines in inflammatory bowel disease. Nature Reviews Immunology 2014;14(5):329-42. https://doi.org/10.1038/nri3661
  24. Choi CH, Kim YH, Kim YS, Ye BD, Lee KM, Lee Bi, et al. Guidelines for the management of ulcerative colitis. The Korean Journal of Gastroenterology 2012;59(2):118-40. https://doi.org/10.4166/kjg.2012.59.2.118
  25. Ishiguro K, Ando T, Maeda O, Hasegawa M, Kadomatsu K, Ohmiya N, et al. Paeonol attenuates TNBS-induced colitis by inhibiting NF-κB and STAT1 transactivation. Toxicology and applied pharmacology 2006;217(1):35-42. https://doi.org/10.1016/j.taap.2006.07.002
  26. Myung NY. The inhibitory effect of Orostachys japonicus on dextran sulfate sodium-induced colitis in mice. The Korea Journal of Herbology 2014;29(4):29-34. https://doi.org/10.6116/KJH.2014.29.4.29
  27. Nathan C, Xie QW. Nitric oxide synthases: roles, tolls, and controls. Cell 1994;78(6):915-8. https://doi.org/10.1016/0092-8674(94)90266-6
  28. Stuehr DJ, Marletta MA. Mammalian nitrate biosynthesis: mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide. Proceedings of the National Academy of Sciences 1985;82(22):7738-42. https://doi.org/10.1073/pnas.82.22.7738
  29. Belvisi M, Barnes PJ, Larkin S, Yacoub M, Tadjkarimi S, Williams TJ, et al. Nitric oxide synthase activity is elevated in inflammatory lung disease in humans. European journal of pharmacology 1995;283(1-3):255-8. https://doi.org/10.1016/0014-2999(95)00421-G
  30. Kim YK, Ha HK, Lee JH, KIm CS. COX-2 inhibition and anti-inflammatory effects of traditional herbal medicine. Korean Journal of Oriental Medicine 2002;8(1):65-74.
  31. Benvenistem EN. Immunology of the Nervous System. New York: Oxford University Press; 1997, p. 419-59.
  32. Hibi M, Nakajima K, Hirano T. IL-6 cytokine family and signal transduction: a model of the cytokine system. Journal of molecular medicine 1996;74(1):1-12. https://doi.org/10.1007/BF00202068
  33. Briscoe D, Cotran R, Pober J. Effects of tumor necrosis factor, lipopolysaccharide, and IL-4 on the expression of vascular cell adhesion molecule-1 in vivo. Correlation with CD3+ T cell infiltration. The Journal of Immunology 1992;149(9):2954-60.
  34. Gamble J, Harlan J, Klebanoff S, Vadas M. Stimulation of the adherence of neutrophils to umbilical vein endothelium by human recombinant tumor necrosis factor. Proceedings of the National Academy of Sciences 1985;82(24):8667-71. https://doi.org/10.1073/pnas.82.24.8667
  35. Tracey KJ, Fong Y, Hesse DG, Manogue KR, Lee AT, Kuo GC, et al. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature 1987;330(6149):662-4. https://doi.org/10.1038/330662a0
  36. Marriott JB, Westby M, Cookson S, Guckian M, Goodbourn S, Muller G, et al. CC-3052: a water-soluble analog of thalidomide and potent inhibitor of activation-induced TNF-α production. The Journal of Immunology 1998;161(8):4236-43.
  37. Pender SL, Breese EJ, Gunther U, Howie D, Wathen NC, Schuppan D, et al. Suppression of T cell-mediated injury in human gut by interleukin 10: role of matrix metalloproteinases. Gastroenterology 1998;115(3):573-83. https://doi.org/10.1016/S0016-5085(98)70136-2
  38. Schotte H, Schluter B, Willeke P, Mickholz E, Schorat M, Domschke W, et al. Long-term treatment with etanercept significantly reduces the number of proinflammatory cytokine-secreting peripheral blood mononuclear cells in patients with rheumatoid arthritis. Rheumatology 2004; 43(8):960-4. https://doi.org/10.1093/rheumatology/keh178
  39. Diggle CP, Carr IM, Zitt E, Wusik K, Hopkin RJ, Prada CE, et al. Common and recurrent HPGD mutations in Caucasian individuals with primary hypertrophic osteoarthropathy. Rheumatology 2010;49(6):1056-62. https://doi.org/10.1093/rheumatology/keq048
  40. Park EJ, Kwon TK. NAD (P) H Quinone Oxidoreductase 1 (NQO1) as a Cancer Therapeutic Target. Journal of Life Science 2014;24(1):98-103. https://doi.org/10.5352/JLS.2014.24.1.98
  41. Li L, Grenard P, Van Nhieu JT, Julien B, Mallat A, Habib Ad, et al. Heme oxygenase-1 is an antifibrogenic protein in human hepatic myofibroblasts. Gastroenterology 2003;125(2): 460-9. https://doi.org/10.1016/S0016-5085(03)00906-5
  42. Nakao A, Otterbein LE, Overhaus M, Sarady JK, Tsung A, Kimizuka K, et al. Biliverdin protects the functional integrity of a transplanted syngeneic small bowel. Gastroenterology 2004; 127(2):595-606. https://doi.org/10.1053/j.gastro.2004.05.059
  43. Kim YR, Oh JE, Kim MS, Kang MR, Park SW, Han JY, et al. Oncogenic NFE2L2 mutations in squamous cell carcinomas of esophagus and skin. The Journal of Pathology 2010;220(4): 446-51. https://doi.org/10.1002/path.2653
  44. Mitchell TJ, John S. Signal transducer and activator of transcription (STAT) signalling and T-cell lymphomas. Immunology 2005;114(3):301-12. https://doi.org/10.1111/j.1365-2567.2005.02091.x
  45. Song HY, Lee JA, Ju SM, Yoo KY, Won MH, Kwon HJ, et al. Topical transduction of superoxide dismutase mediated by HIV-1 Tat protein transduction domain ameliorates 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice. Biochemical pharmacology 2008;75(6):1348-57. https://doi.org/10.1016/j.bcp.2007.11.015
  46. Su YW, Chiou WF, Chao SH, Lee MH, Chen CC, Tsai YC. Ligustilide prevents LPS-induced iNOS expression in RAW 264.7 macrophages by preventing ROS production and down-regulating the MAPK, NF-κB and AP-1 signaling pathways. International immunopharmacology 2011;11(9):1166-72. https://doi.org/10.1016/j.intimp.2011.03.014
  47. Thalhamer T, McGrath MA, Harnett MM. MAPKs and their relevance to arthritis and inflammation. Rheumatology 2008;47(4):409-14. https://doi.org/10.1093/rheumatology/kem297
  48. Schieven GL. The biology of p38 kinase: a central role in inflammation. Current topics in medicinal chemistry 2005;5(10):921-8. https://doi.org/10.2174/1568026054985902