Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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A novel herbal formulation consisting of red ginseng extract and Epimedium koreanum Nakai-attenuated dextran sulfate sodium-induced colitis in mice

  • Saba, Evelyn (Laboratory of Veterinary Physiology, College of Veterinary Medicine, Kyungpook National University) ;
  • Lee, Yuan Yee (Laboratory of Veterinary Physiology, College of Veterinary Medicine, Kyungpook National University) ;
  • Kim, Minki (Laboratory of Veterinary Physiology, College of Veterinary Medicine, Kyungpook National University) ;
  • Hyun, Sun-Hee (R&D Headquarters, Korean Ginseng Cooperation) ;
  • Park, Chae-Kyu (R&D Headquarters, Korean Ginseng Cooperation) ;
  • Son, Eunjung (KM Convergence Research Division, Korea Institute of Oriental Medicine) ;
  • Kim, Dong-Seon (KM Convergence Research Division, Korea Institute of Oriental Medicine) ;
  • Kim, Sung-Dae (Research Center, Dongnam Institute of Radiological and Medical Sciences) ;
  • Rhee, Man Hee (Laboratory of Veterinary Physiology, College of Veterinary Medicine, Kyungpook National University)
  • Received : 2020.01.04
  • Accepted : 2020.02.25
  • Published : 2020.11.15
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Abstract

Background: Ulcerative colitis (UC) is a commonly encountered large intestine disease in the contemporary world that terminates into colorectal cancer; therefore, the timely treatment of UC is of major concern. Panax ginseng Meyer is an extensively consumed herbal commodity in South East Asian countries, especially Korea. It exhibits a wide range of biologically beneficial qualities for almost head-to-toe ailments in the body. Epimedium koreanum Nakai (EKN) is also a widely used traditional Korean herbal medicine used for treating infertility, rheumatism, and cardiovascular diseases. Materials and methods: Separately the anti-inflammatory activities of both red ginseng extracts (RGEs) and EKNs had been demonstrated in the past in various inflammatory models; however, we sought to unravel the anti-inflammatory activities of the combination of these two extracts in dextran sulfate sodium (DSS)-induced ulcerative colitis in mice model because the allopathic remedies for UC involve more side effects than benefits. Results: Our results have shown that the combination of RGE + EKN synergistically alleviated the macroscopic lesions in DSS-induced colitic mice such as colon shortening, hematochezia, and weight loss. Moreover, it restored the histopathological lesions in mice and decreased the levels of proinflammatory mediators and cytokines through the repression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP-3) expression. In vitro, this combination also reduced the magnitude of nitric acid (NO), proinflammatory mediators and cytokine through NF-κB and mitogen-activated protein kinase (MAPK) pathways in RAW 264.7 mouse macrophage cells. Conclusion: In the light of these findings, we can endorse this combination extract as a functional food for the prophylactic as well as therapeutic treatment of UC in humans together with allopathic remedies.

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References

  1. Loftus Jr EV, Silverstein MD, Sandborn WJ, Tremaine WJ, Harmsen WS, Zinsmeister AR. Ulcerative colitis in Olmsted County, Minnesota, 1940-1993: incidence, prevalence, and survival. Gut 2000;46:336-43. https://doi.org/10.1136/gut.46.3.336
  2. Hanauer SB. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis 2006;12(Suppl 1):S3-9. https://doi.org/10.1097/01.MIB.0000195385.19268.68
  3. Bantel H, Berg C, Vieth M, Stolte M, Kruis W, Schulze-Osthoff K. Mesalazine inhibits activation of transcription factor NF-kappaB in inflamed mucosa of patients with ulcerative colitis. Am J Gastroenterol 2000;95:3452-7. https://doi.org/10.1016/S0002-9270(00)02153-5
  4. Kim JH. Pharmacological and medical applications of Panax ginseng and ginsenosides: a review for use in cardiovascular diseases. J Ginseng Res 2018;42:264-9. https://doi.org/10.1016/j.jgr.2017.10.004
  5. Lu JM, Yao Q, Chen C. Ginseng compounds: an update on their molecular mechanisms and medical applications. Curr Vasc Pharmacol 2009;7:293-302. https://doi.org/10.2174/157016109788340767
  6. Lee SM, Bae BS, Park HW, Ahn NG, Cho BG, Cho YL, Kwak YS. Characterization of Korean red ginseng (Panax ginseng Meyer): history, preparation method, and chemical composition. J Ginseng Res 2015;39:384-91. https://doi.org/10.1016/j.jgr.2015.04.009
  7. Park TY, Hong M, Sung H, Kim S, Suk KT. Effect of Korean Red Ginseng in chronic liver disease. J Ginseng Res 2017;41:450-5. https://doi.org/10.1016/j.jgr.2016.11.004
  8. Yoo DG, Kim MC, Park MK, Song JM, Quan FS, Park KM, Cho YK, Kang SM. Protective effect of Korean red ginseng extract on the infections by H1N1 and H3N2 influenza viruses in mice. J Med Food 2012;15:855-62. https://doi.org/10.1089/jmf.2012.0017
  9. Yun TK, Lee YS, Lee YH, Kim SI, Yun HY. Anticarcinogenic effect of Panax ginseng C.A. Meyer and identification of active compounds. J Korean Med Sci 2001;16(Suppl):S6-18. https://doi.org/10.3346/jkms.2001.16.S.S6
  10. Kim JY, Park JY, Kang HJ, Kim OY, Lee JH. Beneficial effects of Korean red ginseng on lymphocyte DNA damage, antioxidant enzyme activity, and LDL oxidation in healthy participants: a randomized, double-blind, placebocontrolled trial. Nutr J 2012;11:47. https://doi.org/10.1186/1475-2891-11-47
  11. Ma H, He X, Yang Y, Li M, Hao D, Jia Z. The genus Epimedium: an ethnopharmacological and phytochemical review. J Ethnopharmacol 2011;134:519-41. https://doi.org/10.1016/j.jep.2011.01.001
  12. Wang T, Zhang JC, Chen Y, Huang F, Yang MS, Xiao PG. Comparison of antioxidative and antitumor activities of six flavonoids from Epimedium koreanum. Zhongguo Zhong Yao Za Zhi 2007;32:715-8.
  13. Zhang W, Chen H, Wang Z, Lan G, Zhang L. Comparative studies on antioxidant activities of extracts and fractions from the leaves and stem of Epimedium koreanum Nakai. J Food Sci Technol 2013;50:1122-9. https://doi.org/10.1007/s13197-011-0447-4
  14. Jin Q, Lee C, Lee JW, Yeon ET, Lee D, Han SB, Hong JT, Kim Y, Lee MK, Hwang BY. 2-Phenoxychromones and prenylflavonoids from Epimedium koreanum and their inhibitory effects on LPS-induced nitric oxide and interleukin-1b production. J Nat Prod 2014;77:1724-8. https://doi.org/10.1021/np400831p
  15. Peng X-L, Shi J-X, Liao H-M. Effects of the extract of epimedium Korearium Nakai on immune organs and reproductive organs in female Gong Chickens. J Jishou Univ (Nat Sci Ed) 2005;3:24.
  16. Jiang J, Song J, Jia X-b. Phytochemistry and ethnopharmacology of Epimedium L. species. Chin Herb Med 2015;7:204-22. https://doi.org/10.1016/S1674-6384(15)60043-0
  17. Wang C, Feng L, Su J, Cui L, Dan L, Yan J, Ding C, Tan X, Jia X. Polysaccharides from Epimedium koreanum Nakai with immunomodulatory activity and inhibitory effect on tumor growth in LLC-bearing mice. J Ethnopharmacol 2017;207:8-18. https://doi.org/10.1016/j.jep.2017.06.014
  18. Saba E, Jeong D, Irfan M, Lee YY, Park SJ, Park CK, Rhee MH. Anti-inflammatory activity of rg3-enriched Korean red ginseng extract in murine model of sepsis. Evid Based Complement Alternat Med 2018;2018:6874692.
  19. Sann H, Erichsen J, Hessmann M, Pahl A, Hoffmeyer A. Efficacy of drugs used in the treatment of IBD and combinations thereof in acute DSS-induced colitis in mice. Life Sci 2013;92:708-18. https://doi.org/10.1016/j.lfs.2013.01.028
  20. Fischer AH, Jacobson KA, Rose J, Zeller R. Hematoxylin and eosin staining of tissue and cell sections. CSH Protoc 2008;2008. pdb prot4986.
  21. Geboes K, Riddell R, Ost A, Jensfelt B, Persson T, Lofberg R. A reproducible grading scale for histological assessment of inflammation in ulcerative colitis. Gut 2000;47:404-9. https://doi.org/10.1136/gut.47.3.404
  22. Chassaing B, Aitken JD, Malleshappa M, Vijay-Kumar M. Dextran sulfate sodium (DSS)-induced colitis in mice. Curr Protoc Immunol 2014;104. Unit 15 25.
  23. Meier J, Sturm A. Current treatment of ulcerative colitis. World J Gastroenterol 2011;17:3204-12. https://doi.org/10.3748/wjg.v17.i27.3204
  24. Fell JM, Muhammed R, Spray C, Crook K, Russell RK, group BIw. Management of ulcerative colitis. Arch Dis Child 2016;101:469-74. https://doi.org/10.1136/archdischild-2014-307218
  25. Han KH, Park JM, Jeong M, Han YM, Go EJ, Park J, Kim H, Han JG, Kwon O, Hahm KB. Heme oxygenase-1 induction and anti-inflammatory actions of atractylodes macrocephala and Taraxacum herba extracts prevented colitis and was more effective than sulfasalazine in preventing relapse. Gut Liver 2017;11:655-66. https://doi.org/10.5009/gnl16496
  26. Kim KJ, Park JM, Lee JS, Kim YS, Kangwan N, Han YM, Kang EA, An JM, Park YK, Hahm KB. Oligonol prevented the relapse of dextran sulfate sodium-ulcerative colitis through enhancing NRF2-mediated antioxidative defense mechanism. J Physiol Pharmacol 2018;69.
  27. Li YH, Zhang M, Xiao HT, Fu HB, Ho A, Lin CY, Huang Y, Lin G, Bian ZX. Addition of berberine to 5-aminosalicylic acid for treatment of dextran sulfate sodiuminduced chronic colitis in C57BL/6 mice. PLoS One 2015;10:e0144101. https://doi.org/10.1371/journal.pone.0144101
  28. Baek KS, Yi YS, Son YJ, Yoo S, Sung NY, Kim Y, Hong S, Aravinthan A, Kim JH, Cho JY. In vitro and in vivo anti-inflammatory activities of Korean Red Ginseng-derived components. J Ginseng Res 2016;40:437-44. https://doi.org/10.1016/j.jgr.2016.08.003
  29. Cho WK, Weeratunga P, Lee BH, Park JS, Kim CJ, Ma JY, Lee JS. Epimedium koreanum Nakai displays broad spectrum of antiviral activity in vitro and in vivo by inducing cellular antiviral state. Viruses 2015;7:352-77. https://doi.org/10.3390/v7010352
  30. Liu W, Guo W, Hang N, Yang Y, Wu X, Shen Y, Cao J, Sun Y, Xu Q. MALT1 inhibitors prevent the development of DSS-induced experimental colitis in mice via inhibiting NF-kappaB and NLRP3 inflammasome activation. Oncotarget 2016;7:30536-49. https://doi.org/10.18632/oncotarget.8867
  31. Yin J, Wu M, Duan J, Liu G, Cui Z, Zheng J, Chen S, Ren W, Deng J, Tan X, et al. Pyrrolidine Dithiocarbamate inhibits NF-KappaB activation and upregulates the expression of Gpx1, Gpx4, occludin, and ZO-1 in DSS-induced colitis. Appl Biochem Biotechnol 2015;177:1716-28. https://doi.org/10.1007/s12010-015-1848-z
  32. You BH, Chae HS, Song J, Ko HW, Chin YW, Choi YH. alpha-Mangostin ameliorates dextran sulfate sodium-induced colitis through inhibition of NFkappaB and MAPK pathways. Int Immunopharmacol 2017;49:212-21. https://doi.org/10.1016/j.intimp.2017.05.040
  33. Kornbluth A, Sachar DB. Practice parameters committee of the American College of G. Ulcerative colitis practice guidelines in adults: American College of gastroenterology, Practice parameters committee. Am J Gastroenterol 2010;105:501-23. quiz 524. https://doi.org/10.1038/ajg.2009.727
  34. Magro F, Langner C, Driessen A, Ensari A, Geboes K, Mantzaris GJ, Villanacci V, Becheanu G, Borralho Nunes P, Cathomas G, et al. European consensus on the histopathology of inflammatory bowel disease. J Crohns Colitis 2013;7:827-51. https://doi.org/10.1016/j.crohns.2013.06.001
  35. Abderrazak A, Syrovets T, Couchie D, El Hadri K, Friguet B, Simmet T, Rouis M. NLRP3 inflammasome: from a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases. Redox Biol 2015;4:296-307. https://doi.org/10.1016/j.redox.2015.01.008
  36. Sutterwala FS, Haasken S, Cassel SL. Mechanism of NLRP3 inflammasome activation. Ann N Y Acad Sci 2014;1319:82-95. https://doi.org/10.1111/nyas.12458
  37. Sun Y, Zhao Y, Yao J, Zhao L, Wu Z, Wang Y, Pan D, Miao H, Guo Q, Lu N. Wogonoside protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-kappaB and NLRP3 inflammasome activation. Biochem Pharmacol 2015;94:142-54. https://doi.org/10.1016/j.bcp.2015.02.002
  38. He X, Wei Z, Wang J, Kou J, Liu W, Fu Y, Yang Z. Alpinetin attenuates inflammatory responses by suppressing TLR4 and NLRP3 signaling pathways in DSS-induced acute colitis. Sci Rep 2016;6:28370. https://doi.org/10.1038/srep28370
  39. Schuler T, Qin Z, Ibe S, Noben-Trauth N, Blankenstein T. T helper cell type 1-associated and cytotoxic T lymphocyte-mediated tumor immunity is impaired in interleukin 4-deficient mice. J Exp Med 1999;189:803-10. https://doi.org/10.1084/jem.189.5.803
  40. Alex P, Zachos NC, Nguyen T, Gonzales L, Chen TE, Conklin LS, Centola M, Li X. Distinct cytokine patterns identified from multiplex profiles of murine DSS and TNBS-induced colitis. Inflamm Bowel Dis 2009;15:341-52. https://doi.org/10.1002/ibd.20753
  41. Dieleman LA, Palmen MJ, Akol H, Bloemena E, Pena AS, Meuwissen SG, Van Rees EP. Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin Exp Immunol 1998;114:385-91. https://doi.org/10.1046/j.1365-2249.1998.00728.x
  42. Ohno M, Nishida A, Sugitani Y, Nishino K, Inatomi O, Sugimoto M, Kawahara M, Andoh A. Nanoparticle curcumin ameliorates experimental colitis via modulation of gut microbiota and induction of regulatory T cells. PLoS One 2017;12:e0185999. https://doi.org/10.1371/journal.pone.0185999
  43. Zhang HL, Zheng YJ, Pan YD, Xie C, Sun H, Zhang YH, Yuan MY, Song BL, Chen JF. Regulatory T-cell depletion in the gut caused by integrin beta7 deficiency exacerbates DSS colitis by evoking aberrant innate immunity. Mucosal Immunol 2016;9:391-400. https://doi.org/10.1038/mi.2015.68
  44. Pan P, Kang S, Wang Y, Liu K, Oshima K, Huang YW, Zhang J, Yearsley M, Yu J, Wang LS. Black Raspberries enhance natural killer cell infiltration into the colon and suppress the Progression of colorectal cancer. Front Immunol 2017;8:997. https://doi.org/10.3389/fimmu.2017.00997
  45. Saubermann LJ, Beck P, De Jong YP, Pitman RS, Ryan MS, Kim HS, Exley M, Snapper S, Balk SP, Hagen SJ, et al. Activation of natural killer T cells by alphagalactosylceramide in the presence of CD1d provides protection against colitis in mice. Gastroenterology 2000;119:119-28. https://doi.org/10.1053/gast.2000.9114
  46. Sagami S, Ueno Y, Tanaka S, Fujita A, Niitsu H, Hayashi R, Hyogo H, Hinoi T, Kitadai Y, Chayama K. Choline deficiency causes colonic type II natural killer T (NKT) cell loss and alleviates murine colitis under type I NKT cell deficiency. PLoS One 2017;12:e0169681. https://doi.org/10.1371/journal.pone.0169681

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