DOI QR코드

DOI QR Code

황금작약탕이 DSS로 유발된 궤양성 대장염 생쥐 모델에 미치는 영향 : 장내 대사물질 변화를 포함하여

Effect of Hwanggeumjackyak-tang (HJT) on the DSS-induced ulcerative colitis mouse model : including changes in intestinal metabolites

  • 윤차경 (동신대학교 한의과대학) ;
  • 강상미 (동신대학교 한의과대학) ;
  • 손선아 (동신대학교 한의과대학) ;
  • 유양희 (동신대학교 한의과대학) ;
  • 김은주 (고려대학교 식품공학과) ;
  • 손홍석 (고려대학교 식품공학과) ;
  • 설재욱 (동신대학교 한의과대학) ;
  • 나창수 (동신대학교 한의과대학)
  • Cha-Kyung Youn (College of Korean Medicine, Dongshin University) ;
  • Sang-Mi Kang (College of Korean Medicine, Dongshin University) ;
  • Seon-Ah Son (College of Korean Medicine, Dongshin University) ;
  • Yang-Hee You (College of Korean Medicine, Dongshin University) ;
  • Eun-Ju Kim (Department of Biotechnology, Korea University) ;
  • Hong-Seok Son (Department of Biotechnology, Korea University) ;
  • Jae-Uk Sul (College of Korean Medicine, Dongshin University) ;
  • Chang-Su Na (College of Korean Medicine, Dongshin University)
  • 투고 : 2023.10.31
  • 심사 : 2023.11.17
  • 발행 : 2023.11.30

초록

Background : To investigate the effect of Hwanggeumjackyak-tang (HJT) on Dextran sulfate sodium (DSS) induced ulcerative colitis. Methods : The experimental animals were divided into three groups; group 1, normal group(Normal); group 2, DSS-induced colitis and untreated group(UT+DSS); group 3, DSS-induced colitis and HJT 200 mg-treated group(HJT200+DSS). We evaluated cytotoxicity after HJT administration and confirmed the anti-inflammatory effect by histological changes in the intestine and genetic analysis of mucosal cells after HJT administration for each group. In addition, microbiological weapons and metabolites in faeces were examined, and the correlation between gut microbiome and metabolites was also investigated. Result : HJT was not observed to be cytotoxic, even at relatively high concentrations, and was effective in protecting the barrier and preventing intestinal inflammation by suppressing the increase in mucus secretion and the expression of inflammatory factors in mucosal cells. HJT treatment affected the increase in the amount and diversity of the gut microbiome in faeces and the increase in metabolites thought to be involved in alleviating inflammation in the gut. Conclusion : This study demonstrates the therapeutic potential of HJT in ulcerative colitis. Further studies should be carried out to confirm our findings.

키워드

과제정보

This research was supported by a Korea Innovation Foundation (INNIPOLIS) grant funded by the Korean government (Ministry of Science and ICT) through a science and technology project that opens the future of the region (grant number: 2021-DD-UP-0380).

참고문헌

  1. Anand B Pithadia, Sunita Jain. Treatment of inflammatory bowel disease(IBD). Pharmacol Rep. 2011;63:629-42.  https://doi.org/10.1016/S1734-1140(11)70575-8
  2. Seo GS, Choi SC. Pathophysiology of ulcerative colitis - Realationship with genetics and immunity. Korean J Med. 2009;76(6):643-8. 
  3. Nam AY, Lee DS, Kwang-Soon Shin KS. Improvement Effects on Inflammatory Bowel Disease of Ethanol Extract Isolated from Saururus chinensis. J Convergence Cult Technol. 2019;5:317-26. 
  4. Lee YW, Ahn SH, Kim HH, Kim KB, The Anti-Inflammatory Effect of Lonicera Japonica-Glycyrrhiza Uralensis Decoction on Ulcerative Colitis Induced by DSS in Mice. J Pediatr Korean Med. 2018;32(3):16-25. 
  5. 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. J Gastroenterol Hepatol. 2019;34(6):1018-26.  https://doi.org/10.1111/jgh.14542
  6. Song YG, Ryu BH, Yoon SW. The Effects of Soyumjungjang-tang on DSS-Induced Ulcerative Colitis in Mouse. Korean J Orient Int Med. 2008;29(2):385-400. 
  7. Choi SH, Park EJ. Effects of Paeoniae Radix, Glycyrrhiza Uralensis and Jakyakgamcho-tang Treatment on Ulcerative Colitis Animal Model: Including Changes in Metabolites. J Pediatr Korean Med. 2022;36(3):19-34.  https://doi.org/10.13048/jkm.15030
  8. Park SM, Lee SH, Jeong DU, Cho SJ, Shin MR, Park HJ, Roh SS. Effect of Atractylodes macrocephala Koidzumi in DSS-induced Ulcerative Colitis Model. Kor J Herbol. 2022;37(1):19-29. 
  9. Jo HK, Kim DS, Cho SW, Shin NR, Park YM, Lee HY, Shin DS. Anti-Colitic Effects of Herbal Medicine HPL-01 on Dextran Sulfate Sodium Induced Ulcerative Colitis in Rat. J Physiol & Pathol Korean Med. 2021;35(2):64-70.  https://doi.org/10.15188/kjopp.2021.02.35.2.64
  10. Kim MJ, Shin MR, Lee JA, PARK SA, PARK HJ, Lee JH, Roh SS. Improvement Effect of Sprout of Coix lacryma-jobi var. mayuen Stapf Water Extract on DSS-Induced Ulcerative Colitis in Mice. Kor J Herbol. 2020;35(6):21-8. 
  11. Joo JH. Dang γ euijip. Seoul university publishing department. 2000:579. 
  12. Shin JY. BangYankHapPyunHaesul. Seoul:Sungbosa. 2000:249-50. 
  13. Esther Kim, Chonghwan Choi, Ilhyun Kim, Hail Lee, Yungsun Song. Antibacterial Effect of Huanggeumjakyak-tang against Methicillin-resistant Staphylococcus aureu. Journal of Korean Medicine Rehabilitation. 2013;23(3):15-26. 
  14. Oh Chun-Keun, Hwang Choong-Yeon, Lee Ki-Nam. Effects of Hwangkeumjagyag-tang Water Extract on the Plasma Cortisol Concentration in the Rabbit and on the Analgesic Effect in the Mouse. The Journal of Korean Oriental Ophthalmology & Otorhinolaryngology & Dermatology. 1990;3(1):41-57. 
  15. Ma-Ryong Kim, Ok-Hwa Kang, Sung-Bae Kim, Hee-Jung Kang, Ji-Eun Kim, Hyeong-Chil Hwang, In-Won Kim, Dong-Yeul Kwon. The Study of Anti-inflammatory Effect of Hwanggeumjakyak-tang Extract in RAW 264.7 Macrophage. The Korea Journal of Herbology. 2013;28(1):43-50.  https://doi.org/10.6116/kjh.2013.28.1.43
  16. Annalaura Mastrangelo, Alessia Ferrarini, Fernanda Rey-Stolle, Antonia Garc a, Coral Barbas. From ? sample treatment to biomarker discovery: A tutorial for untargeted metabolomics based on GC-(EI)-Q-MS. Anal Chim Acta. 2015;5:900:21-35.  https://doi.org/10.1016/j.aca.2015.10.001
  17. Korean Association for the Study of Intestinal Diseases. Inflammatory bowel disease. 1st ed. Seoul: Daehan Medical Science Book Co. 2016:2-5,41-8. 
  18. Weber CR, Nalle SC, Tretiakova M, Rubin DT, Turner JR. Claudin-1 and claudin-2 expression is elevated in inflammatory bowel disease and may contribute to early neoplastic transformation. Lab Invest. 2008;88:1110-20.  https://doi.org/10.1038/labinvest.2008.78
  19. Tanca A, Manghina V, Fraumene C, Palomba A, Abbondio M, Deligios M, Silverman M, Uzzau S. Metaproteogenomics reveals taxonomic and functional changes between cecal and fecal microbiota in mouse. Front Microbiol 2017;8:391. doi:10.3389/fmicb.2017.00391 
  20. SW Lee, S Vineet, T Unno. Differences in fecal and cecal microbiota in C57BL/6J mice fed normal and high fat diet. Journal of Applied Biological Chemistry. 2022;64(3):399-405.  https://doi.org/10.3839/jabc.2021.054
  21. Kozik AJ, Nakatsu CH, Chun H, Jones-Hall YL. Comparison of the fecal, cecal, and mucus microbiome in male and female mice after TNBS-induced colitis. PLoS One. 2019;14:e0225079. doi: 10.1371/journal. pone.0225079 
  22. Lin HM, Bernett MPG, Roy NC, Joyce NI, Zhu S, Armstrong K et al. Metabolomic analysis identified inflammatory and Noninflammatory metabolic effects of genetic modification in a mouse model of Crohns' disease. Journal of proteome. 2010;9(4):1965-75.  https://doi.org/10.1021/pr901130s
  23. Nusbaum DJ, Sun F, Ren J, Zhu Z, Ramsy N et al. Gut microbial and metabolomic profiles after fecal microbiota transplantation in pediatric ulcerative colitic patients. Microbiology ecology. 2018;94(9):133. 
  24. Wang L, Yan C, Wang L, Ai C, Wang S, Shen C et al. Ascophyllum nodosum polysaccharide regulates gut microbiota metabolites to protect against colonic inflammation in mice. Food & Function. 2023;14:810. 
  25. Papada E, Amerikanou C, Gioxari A, Kalogeropoulos N, Kaliora A. C. The association of plasma-free branched-chain amino acids with disease related parameters in ulcerative colitis. Diagnotics. 2020;10(10):798. 
  26. RC Sprong, AJ Schonewille, RV Meer. Dietary cheese whey protein protects rats against mild dextran sulfate sodium-induced colitis: role of mucin and microbiota. J Dairy Sci. 2010;93:1364-71.  https://doi.org/10.3168/jds.2009-2397
  27. Sugihara K, Morhardt TL, kamada N. The role of dietary nutrients in inflammatory bowel disease. Front mmunol. 2019;9:1-16. https://doi.org/10.3389/fimmu.2018.03183