Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Restorative effects of Rg3-enriched Korean Red Ginseng and Persicaria tinctoria extract on oxazolone-induced ulcerative colitis in mice

  • Ullah, H.M. Arif (Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University) ;
  • Saba, Evelyn (Department of Veterinary Biomedical Sciences, Faculty of Veterinary and Animal Sciences, Pir Mehr Ali Shah-Arid Agriculture University) ;
  • Lee, Yuan Yee (Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University) ;
  • Hong, Seung-Bok (Department of Clinical Laboratory Science, Chungbuk Health & Science University) ;
  • Hyun, Sun-Hee (R&D Headquarters, Korean Ginseng cooperation) ;
  • Kwak, Yi-Seong (R&D Headquarters, Korean Ginseng cooperation) ;
  • Park, Chae-Kyu (R&D Headquarters, Korean Ginseng cooperation) ;
  • Kim, Sung Dae (Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University) ;
  • Rhee, Man Hee (Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University)
  • Received : 2021.04.22
  • Accepted : 2022.07.07
  • Published : 2022.09.01
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Abstract

Background: Ulcerative colitis (UC) is the large intestine disease that results in chronic inflammation and ulcers in the colon. Rg3-enriched Korean Red Ginseng extract (Rg3-RGE) is known for its pharmacological activities. Persicaria tinctoria (PT) is also used in the treatment of various inflammatory diseases. The aim of this study is to investigate the attenuating effects of Rg3-RGE with PT on oxazolone (OXA)-induced UC in mice. Methods: A total of six groups of mice including control group, OXA (as model group, 1.5%) group, sulfasalazine (75 mg/kg) group, Rg3-RGE (20 mg/kg) group, PT (300 mg/kg) group, and Rg3-RGE (10 mg/kg) with PT (150 mg/kg) group. Data on the colon length, body weight, disease activity index (DAI), histological changes, nitric oxide (NO) assay, Real-time PCR of inflammatory factors, ELISA of inflammatory factors, Western blot, and flow cytometry analysis were obtained. Results: Overall, the combination treatment of Rg3-RGE and PT significantly improved the colon length and body weight and decreased the DAI in mice compared with the treatment with OXA. Additionally, the histological injury was also reduced by the combination treatment. Moreover, the NO production level and inflammatory mediators and cytokines were significantly downregulated in the Rg3-RGE with the PT group compared with the model group. Also, NLR family pyrin domain containing 3 (NLRP3) inflammasome and nuclear factor kappa B (NF-𝛋B) were suppressed in the combination treatment group compared with the OXA group. Furthermore, the number of immune cell subtypes of CD4+ T-helper cells, CD19+ B-cells, and CD4+ and CD25+ regulatory T-cells (Tregs) was improved in the Rg3-RGE with the PT group compared with the OXA group. Conclusion: Overall, the mixture of Rg3-RGE and PT is an effective therapeutic treatment for UC.

Keywords

Acknowledgement

We are grateful to Professor Man Hee Rhee for his continuous supervision and support. We are thankful to Evelyn Saba for the experiments and H M Arif Ullah for the manuscript writing and final review and editing. Also, we would like to thank Yuan Yee Lee, Sung Dae kim, Seong-Bok Hong, Sun-Hee Hyun, Yi-Seong kwak, Chae-Kyu Park for technical help.

References

  1. Feuerstein JD, Cheifetz AS. Ulcerative colitis: epidemiology, diagnosis, and management. Mayo Clinic Proceedings 2014;89(11):1553-63. https://doi.org/10.1016/j.mayocp.2014.07.002
  2. Saba E, Lee YY, Rhee MH, Kim S-D. Alleviation of ulcerative colitis potentially through th1/th2 cytokine balance by a mixture of Rg3-enriched Korean red ginseng extract and Persicaria tinctoria. Molecules 2020;25(22):5230. https://doi.org/10.3390/molecules25225230
  3. Lin WC, Chang CW, Chen MJ, Chu CH, Shih SC, Hsu TC, Wang HY. Challenges in the diagnosis of ulcerative colitis with concomitant bacterial infections and chronic infectious colitis. PloS One 2017;12(12):e0189377. https://doi.org/10.1371/journal.pone.0189377
  4. Gajendran M, Loganathan P, Jimenez G, Catinella AP, Ng N, Umapathy C, Ziade N, Hashash JG. A comprehensive review and update on ulcerative colitis. Disease-a-month 2019;65(12):100851. https://doi.org/10.1016/j.disamonth.2019.02.004
  5. Saba E, Lee YY, Kim M, Hyun SH, Park CK, Son E, Kim DS, Kim SD, Rhee MH. A novel herbal formulation consisting of red ginseng extract and Epimedium koreanum Nakai-attenuated dextran sulfate sodium-induced colitis in mice. Journal of Ginseng Research 2020;44(6):833-42. https://doi.org/10.1016/j.jgr.2020.02.003
  6. Zhang L, Cao N, Wang Y, Wang Y, Wu C, Cheng X, Wang C. Improvement of oxazolone-induced ulcerative colitis in rats using andrographolide. Molecules 2020;25(1):76.
  7. Li Z, Ji GE. Ginseng and obesity. Journal of Ginseng Research 2018;42(1):1-8. https://doi.org/10.1016/j.jgr.2016.12.005
  8. 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(1):1-9. https://doi.org/10.1186/1475-2891-11-1
  9. Park JG, Son Y-J, Aravinthan A, Kim J-H, Cho JY. Korean Red Ginseng water extract arrests growth of xenografted lymphoma cells. Journal of Ginseng Research 2016;40(4):431-6. https://doi.org/10.1016/j.jgr.2016.07.006
  10. Kim S-J, Jang TW, Kim D-W, Park JH. Study on antioxidant and antiinflammatory activities of Persicaria tinctoria. The Korea Journal of Herbology 2015;30(6):17-24. https://doi.org/10.6116/KJH.2015.30.6.17.
  11. Randhawa PK, Singh K, Singh N, Jaggi AS. A review on chemical-induced inflammatory bowel disease models in rodents. The Korean Journal of Physiology & Pharmacology: Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology 2014;18(4):279. https://doi.org/10.4196/kjpp.2014.18.4.279
  12. Gao Z, Yu C, Liang H, Wang X, Liu Y, Li X, ji K, Xu H, Yang M, Liu K. Andrographolide derivative CX-10 ameliorates dextran sulphate sodium-induced ulcerative colitis in mice: involvement of NF-kB and MAPK signalling pathways. Int Immunopharmacol 2018;57:82-90. https://doi.org/10.1016/j.intimp.2018.02.012
  13. Zhou W, Liu X, Zhang X, Tang J, Li Z, Wang Q, Hu R. Oroxylin A inhibits colitis by inactivating NLRP3 inflammasome. Oncotarget 2017;8(35):58903. https://doi.org/10.18632/oncotarget.19440
  14. Bauer C, Duewell P, Mayer C, Lehr HA, Fitzgerald KA, Dauer M, Tschopp J, Endres S, Latz E, Schnurr M. Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome. Gut 2010;59(9): 1192-9. https://doi.org/10.1136/gut.2009.197822
  15. Saba E, Irfan M, Jeong D, Ameer K, Lee YY, Park CK, Hong SB, Rhee MH. Mediation of antiinflammatory effects of Rg3-enriched red ginseng extract from Korean Red Ginseng via retinoid X receptor α-peroxisome-proliferating receptor γ nuclear receptors. Journal of Ginseng Research 2019;43(3):442-51. https://doi.org/10.1016/j.jgr.2018.06.005
  16. 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. Evidence-based complementary and alternative medicine. eCAM 2018;2018: 6874692.
  17. Ullah H, Elfadl A, Park S, Chung M-J, Son J-Y, Yun H-H, Park JM, Yim JH, Jung SJ, Park JK. Renal failure in a female muskrat. Journal of Life Science 2020;30(7): 630-3. https://doi.org/10.5352/JLS.2020.30.7.630
  18. Elfadl AK, Park S, Ullah H, Youn S-H, Chung M-J, Son J-Y, Lee JY, Lee SW, Lee AR, Baek SM. Sertoli cell tumor (SCT) in a captive black bear (Ursus americanus). Veterinary Sciences 2019;6(4):77. https://doi.org/10.3390/vetsci6040077
  19. Ullah HMA, Lee YY, Kim SD, Rhee MH. Duchesnea indica extract attenuates coal fly ash-induced inflammation in murine alveolar macrophages through the NF-kappa B pathway. Evidence-Based Complementary and Alternative Medicine 2021;2021:5546052.
  20. Ullah H, Elfadl A, Park S, Kim YD, Chung M-J, Son J-Y, Yun HH, park JM, Yim JH, Jung SJ. Nogo-A is critical for pro-inflammatory gene regulation in myocytes and macrophages. Cells 2021;10(2):282. https://doi.org/10.3390/cells10020282
  21. Lee YY, Yang WK, Han JE, Kwak D, Kim TH, Saba E, Kim KD, Lee YC, Kim JS, Kim SH. Hypericum ascyron L. extract reduces particulate matter-induced airway inflammation in mice. Phytotherapy Research : PTR 2021;35(3): 1621-33. https://doi.org/10.1002/ptr.6929
  22. 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(3):404-9. https://doi.org/10.1136/gut.47.3.404
  23. Chassaing B, Aitken JD, Malleshappa M, Vijay-Kumar M. Dextran sulfate sodium (DSS)-induced colitis in mice. Curr Protoc Immunol 2014;104(1):15-25.
  24. 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
  25. Kojima R, Kuroda S, Ohkishi T, Nakamaru K, Hatakeyama S. Oxazoloneinduced colitis in BALB/C mice: a new method to evaluate the efficacy of therapeutic agents for ulcerative colitis. Journal of Pharmacological Sciences 2004;96(3):307-13. https://doi.org/10.1254/jphs.FP0040214
  26. Gao W, Wang C, Yu L, Sheng T, Wu Z, Wang X, Zhang D, Lin Y, Gong Y. Chlorogenic acid attenuates dextran sodium sulfate-induced ulcerative colitis in mice through MAPK/ERK/JNK pathway. BioMed Research International 2019;2019:6769789.
  27. Huang Y-F, Zhou J-T, Qu C, Dou Y-X, Huang Q-H, Lin Z-X, Xian YF, Xie JH, Xie YL, Lai XP. Anti-inflammatory effects of Brucea javanica oil emulsion by suppressing NF-κB activation on dextran sulfate sodium-induced ulcerative colitis in mice. J Ethnopharmacol 2017;198:389-98. https://doi.org/10.1016/j.jep.2017.01.042
  28. Ullah HA, Zaman S, Juhara F, Akter L, Tareq SM, Masum EH, Bhattacharjee R. Evaluation of antinociceptive, in-vivo & in-vitro anti-inflammatory activity of ethanolic extract of Curcuma zedoaria rhizome. BMC Complement Altern Med 2014;14(1):346. https://doi.org/10.1186/1472-6882-14-346
  29. Heller F, Fuss IJ, Nieuwenhuis EE, Blumberg RS, Strober W. Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13- producing NK-T cells. Immunity 2002;17(5):629-38. https://doi.org/10.1016/S1074-7613(02)00453-3
  30. Wang X, Fan F, Cao Q. Modified Pulsatilla decoction attenuates oxazoloneinduced colitis in mice through suppression of inflammation and epithelial barrier disruption. Molecular Medicine Reports 2016;14(2):1173-9. https://doi.org/10.3892/mmr.2016.5358
  31. Boirivant M, Fuss IJ, Chu A, Strober W. Oxazolone colitis: a murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4. The Journal of Experimental Medicine 1998;188(10):1929-39. https://doi.org/10.1084/jem.188.10.1929
  32. Zhu G, Xin X, Liu Y, Huang Y, Li K, Wu C. Geraniin attenuates LPS-induced acute lung injury via inhibiting NF-κB and activating Nrf2 signaling pathways. Oncotarget 2017;8(14):22835. https://doi.org/10.18632/oncotarget.15227
  33. Zhang Y, Xu T, Pan Z, Ge X, Sun C, Lu C, Chen H, Xiao Z, Zhang B, Dai Y. Shikonin inhibits myeloid differentiation protein 2 to prevent LPS-induced acute lung injury. Br J Pharmacol 2018;175(5):840-54. https://doi.org/10.1111/bph.14129
  34. Lin Y, Zhang M, Lu Q, Xie J, Wu J, Chen C. A novel chalcone derivative exerts anti-inflammatory and anti-oxidant effects after acute lung injury. Aging (Albany N Y) 2019;11(18):7805.
  35. 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-κB and NLRP3 inflammasome activation. Oncotarget 2016;7(21):30536. https://doi.org/10.18632/oncotarget.8867
  36. 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-κB and NLRP3 inflammasome activation. Biochem Pharmacol 2015;94(2):142-54. https://doi.org/10.1016/j.bcp.2015.02.002
  37. Huang Z, Jiang Y, Yang Y, Shao J, Sun X, Chen J, Dong L, Zhan J. 3, 3' -Diindolylmethane alleviates oxazolone-induced colitis through Th2/Th17 suppression and Treg induction. Molecular Immunology 2013;53(4):335-44. https://doi.org/10.1016/j.molimm.2012.09.007