Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

Korean Red Ginseng affects ovalbumin-induced asthma by modulating IL-12, IL-4, and IL-6 levels and the NF-κB/COX-2 and PGE2 pathways

  • Lee, Soon-Young (College of Korean Medicine, Dongshin University) ;
  • Kim, Min-Hee (College of Agriculture and Life Science, Chonnam National University) ;
  • Kim, Seung-Hyun (College of Veterinary Medicine, Chonnam National University) ;
  • Ahn, Taeho (College of Veterinary Medicine, Chonnam National University) ;
  • Kim, Sung-Won (Korea Ginseng Corporation) ;
  • Kwak, Yi-Seong (Korea Ginseng Corporation) ;
  • Cho, Ik-Hyun (College of Korean Medicine, Kyung Hee University) ;
  • Nah, Seung-Yeol (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University) ;
  • Cho, Seung-Sik (Department of Biomedicine, Health & Life Convergence Sciences, BK21 Four, College of Pharmacy, Mokpo National University) ;
  • Park, Kyung Mok (College of Korean Medicine, Dongshin University) ;
  • Park, Dae-Hun (College of Korean Medicine, Dongshin University) ;
  • Bae, Chun-Sik (College of Veterinary Medicine, Chonnam National University)
  • Received : 2020.05.17
  • Accepted : 2020.10.14
  • Published : 2021.07.01
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Asthma is an incurable hyper-responsive disease of the pulmonary system that is caused by various allergens, including indoor and outdoor stimulators. According to the Global Asthma Network, 339 million people suffered from asthma in 2018, with particularly severe forms in children. Numerous treatments for asthma are available; however, they are frequently associated with adverse effects such as growth retardation, neurological disorders (e.g., catatonia, poor concentration, and insomnia), and physiological disorders (e.g., immunosuppression, hypertension, hyperglycemia, and osteoporosis). Methods: Korean Red Ginseng has long been used to treat numerous diseases in many countries, and we investigated the anti-asthmatic effects and mechanisms of action of Korean Red Ginseng. Eighty-four BALB/c mice were assigned to 6 treatment groups: control, ovalbumin-induced asthma group, dexamethasone treatment group, and 3 groups treated with Korean Red Ginseng water extract (KRGWE) at 5, 25, or 50 mg/kg/day for 5 days. Anti-asthmatic effects of KRGWE were assessed based on biological changes, such as white blood cell counts and differential counts in the bronchoalveolar lavage fluid, serum IgE levels, and histopathological changes in the lungs, and by examining anti-asthmatic mechanisms, such as the cytokines associated with Th1, Th2, and Treg cells and inflammation pathways. Results: KRGWE affected ovalbumin-induced changes, such as increased white blood cell counts, increased IgE levels, and morphological changes (mucous hypersecretion, epithelial cell hyperplasia, inflammatory cell infiltration) by downregulating cytokines such as IL-12, IL-4, and IL-6 via GATA-3 inactivation and suppression of inflammation via NF-κB/COX-2 and PGE2 pathways. Conclusion: KRGWE is a promising drug for asthma treatment.

Keywords

Acknowledgement

This work was supported by the 2016 grant from the Korean Society of Ginseng.

References

  1. The Global Asthma Network. The global asthma report 2018. Auckland: Global Asthma Network; 2018.
  2. Global Initiative for Asthma. Global strategy for asthma management and prevention. 2015.
  3. James AL, Bai TR, Mauad T, Abramson MJ, McKay KO, Maxwell PS, Elliot JG, Green FH. Airway smooth muscle thickness in asthma is related to severity but not duration of asthma. Eur Respir J 2009;34(5):1040-5. https://doi.org/10.1183/09031936.00181608
  4. Lee SY, Kang B, Bok SH, Cho SS, Park DH. Macmoondongtang modulates Th1-/Th-2-related cytokines and alleviates asthma in a murine model. PLoS One 2019;14(12):e0224517. https://doi.org/10.1371/journal.pone.0224517
  5. National Asthma Education and Prevention Program NAEaP. Expert panel report: guidelines for the diagnosis and management of asthma update on selected topicse2002. J Allergy Clin Immunol 2002;110:S141-219. https://doi.org/10.1016/S0091-6749(02)80002-1
  6. Burge HA, Rogers CA. Outdoor allergens. Environ. Health Persp 2000;108(4): 653-9.
  7. Platts-Mills TAE, Vervloet D, Thomas WR, Aalberse RC, Chapman MD. Indoor allergen and asthma: report of the third international workshop. J Allergey Clin Immunol 1997;100(6, part 1):S2-24. https://doi.org/10.1016/S0091-6749(97)70292-6
  8. Seo JH, Bang MA, Cho SS, Park DH. Erythronium japonicum significantly suppresses OVA-induced asthma via upregulation the IFN-γ expression and downregulation the expression of TNF-aαand IL-4. Int J Mol Med 2016;37(5): 1221-8. https://doi.org/10.3892/ijmm.2016.2541
  9. Zedan MM, El-Chennawi FA, Fouda AE. Interleukin-12 and peripheral blood invariant natural killer T cells as an axis in childhood asthma pathogenesis. Iran J Allergy Asthma Immunol 2010;9(1):43-8.
  10. Kalinski P, Smits HH, Schuitemaker JHN, Vieira PL, van Eijk M, de Jong EC, Wierenga EA, Kapsenberg ML. IL-4 is a mediator of IL-12p70 induction by human Th2 cells: reversal of polarized Th2 phenotype by dendritic cells. J Immunol 2000;165:1877-81. https://doi.org/10.4049/jimmunol.165.4.1877
  11. Kouro T, Takatsu K. IL-5- and eosinophil-mediated inflammation: from discovery to therapy. Int Immunol 2009;21(12):1303-6. https://doi.org/10.1093/intimm/dxp102
  12. Zhu Z, Homer RJ, Wang Z, Chen Q, Geba GP, Wang J, Zhang Y, Elias JA. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest 1999;103:779-88. https://doi.org/10.1172/JCI5909
  13. Xu HD, Cho SS, Lee SY, Oh DS, Lim SK, Park DH. Immune-stimulating Effects of Mycoleptodonoides aitchisonii water extract via TNF-α and IFN-γ. Int J Med Mushrooms 2017;19(9):809-15. https://doi.org/10.1615/IntJMedMushrooms.2017024248
  14. Lee SY, Bae CS, Seo JH, Cho SS, Oh DS, Park DH. Mycoleptodonoides aitchisoii suppresses asthma via IL-6 and IL-13 in ovalbumin-induced asthma mouse model. Mol Med Rep 2018;17(1):11-20.
  15. Ngoc LP, Gold DR, Tzianabos AO. Cytokines, allergy, and asthma. Curr Opin Allergy Clin Immunol 2005;5:161-6. https://doi.org/10.1097/01.all.0000162309.97480.45
  16. Kidd P. Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Altern Med Rev 2003;8(3):223-46.
  17. Lee SY, Bae CS, Yh Choi, Seo NS, Na CS, Yoo JC, Cho SS, Park DH. Opuntia humifusa modulates morphological changes characteristic of asthma via IL-4 and IL-13 in an asthma murine model. Food Nutr Res 2017;61(1):1393307. https://doi.org/10.1080/16546628.2017.1393307
  18. Lee SY, Bae CS, Seo NS, Na CS, Yoo HY, Oh DS, Bae MS, Kwon MS, Cho SS, Park DH. Camellia japonica oil suppressed asthma occurrence via GATA-3 & IL-4 pathway and its effective and major component is oleic acid. Phytomedicine 2019;57:84-94. https://doi.org/10.1016/j.phymed.2018.12.004
  19. Galli SJ, Tsai M, Piliponsky AM. The development of allergic inflammation. Nature 2008;454(7203):445-54. https://doi.org/10.1038/nature07204
  20. Locksley RM. Asthma and allergic inflammation. Cell 2010;140:777-83. https://doi.org/10.1016/j.cell.2010.03.004
  21. Lee SY, Cho SS, Li Y, Bae CS, Park KM, Park DH. Anti-inflammatory effect of Curcuma longa and Allium hookeri co-treatment via NF-κB and COX-2 pathways. Sci Rep-UK 2020;2020:6413491.
  22. Wise J. Corticosteroids for asthma may suppress growth in children in first year of treatment, researchers say. BMJ 2014;349. g4623. https://doi.org/10.1136/bmj.g4623
  23. Ciriaco M, Ventrice P, Russo G, Scicchitano M, Mazzitello G, Scicchitano F, Russo E. Corticosteroid-related central nervous system side effects. J Pharmacol Pharmacother 2013;4(Suppl 1):S94-8. https://doi.org/10.4103/0976-500X.120975
  24. Her J. Dongui Bogan. Seoul: Bubinmunhwasa; 2002.
  25. Kim JE, Monmai C, Rod-In W, Jang AY, You SG, Lee SM, Jung SK, Park WJ. Coimmunomodulatory activities of anionic macromolecules extracted from Codium fragile with red ginseng extract on peritoneal macrophage of immune-suppressed mice. J Microbiol Biotechnol 2020;30(3):352-8. https://doi.org/10.4014/jmb.1909.09062
  26. Yun IS, Kim YS, Roh TS, Lee WJ, Park TH, Roh H, Lew DH, Rah DK. The effect of red ginseng extract intake on ischemic flaps. J Invest Surg 2017;30(1):19-25. https://doi.org/10.1080/08941939.2016.1215577
  27. Choi JH, Jang M, Kim EJ, Lee MJ, Park KS, Kim SH, In JG, Kwak YS, Park DH, Cho SS, et al. Korean red ginseng alleviates dehydroepiandrosterone-induced polycystic ovarian syndrome in rats via its anti-inflammatory and antioxidant activities. J Gingseng Res 2020. In press.
  28. Han MJ, Kim DH. Effects of red and fermented ginseng and ginsenosides on allergic disorders. Biomolecules 2020;10(4):e634.
  29. Lee DY, Park CW, Lee SJ, Park HR, Kim SH, Son SU, Park J, Shin KS. Anti-cancer effects of Panax ginseng berry polysaccharides via activation of immune-related cells. Front Pharmacol 2019;10:1411. https://doi.org/10.3389/fphar.2019.01411
  30. Jeong E, Lim Y, Kim KJ, Ki HH, Lee D, Suh J, So SH, Kwon O, Kim JY. A systems biological approach to understanding the mechanisms underlying the therapeutic potential of red ginseng supplements against metabolic diseases. Molecules 2020;25(8):e1967.
  31. Cho I. Effects of Panax ginseng in neurodegenerative diseases. J Ginseng Res 2010;36:342-53. https://doi.org/10.5142/jgr.2012.36.4.342
  32. Jang M, Lee MJ, Kim CS, Cho IH. Korean Red ginseng extract attenuates 3-nitropropionic acid-induced Huntington's-like symptoms. Evid Based Complement Alternat Med 2013;2013:237207.
  33. Kim JE, Park KM, Lee SY, Seo JH, Yoon IS, Bae CS, Yoo JC, Bang MA, Cho SS, Park DH. Anti-inflammatory effect of Allium hookeri on carrageenan-induced air pouch mouse model. PLosOne 2017;12(12):e0190305. https://doi.org/10.1371/journal.pone.0190305
  34. Platts-Mills TAE. The role of immunoglobulin E in allergy and asthma. Am J Respir Crit Care Med 2001;164:S1-5. https://doi.org/10.1164/ajrccm.164.supplement_1.2103024
  35. Holgate ST. Pathogenesis of asthma. Clin Exp Allergy 2008;38(6):872-97. https://doi.org/10.1111/j.1365-2222.2008.02971.x
  36. Kim YG. Th1/Th2 imbalance Vs. T cell priming in asthma immuno-pathogenesis. BioWave 2005;7(4):1-15.
  37. Slejko JF, Ghushchyan VH, Sucher B, Globe DR, Lin SL, Globe G, Sullivan PW. Asthma control in the United States, 2008-2010: indicators of poor asthma control. J Allergy Clin Immunol 2014;133:1579-87. https://doi.org/10.1016/j.jaci.2013.10.028
  38. Janeway Travers. Immunobiology. The immune system in health and disease. 2nd ed. New York: Churchill Livingstone; 1996.
  39. Sigh A, Yamamoto M, Ruan J, Choi JY, Gauvreau GM, Olek S, Hoffmueller U, Carlsten C, FitzGerald JM, Boulet LP, et al. Th17/Treg ratio derived using DNA methylation analysis is associated with the late phase asthmatic response. Allergy Asthma Clin Immunol 2014;10:32. https://doi.org/10.1186/1710-1492-10-32
  40. Lukacs NW, Strieter RM, Chensue SW, Widmer M, Kunkel SI. TNF-alpha mediates recruitment of neutrophils and eosinophils during airway inflammation. J Immunol 1995;154:5411-7.
  41. Zhu J, Jankovic D, Oler AJ, Wei G, Sharma S, Hu G, Guo L, Yagi R, Yamane H, Punkosdy G, et al. The transcription factor T-bet is induced by multiple pathways and prevents and endogenous T helper-2 program during T helper-1 responses. Immunity 2012;37(4):660-73. https://doi.org/10.1016/j.immuni.2012.09.007
  42. Stirling RG, Chung KF. New immunological approaches and cytokine targets in asthma and allergy. Eur Respir J 2000;16:1158-74. https://doi.org/10.1034/j.1399-3003.2000.16f24.x
  43. Manetti R, Parronchi P, Giudizi MG, Piccinni MP, Maggi E, Trinchieri G, Romagnani S. Natural killer cell stimulatory factor (interleukin 12 (IL-12)) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells. J Exp Med 1993;177:1199-204. https://doi.org/10.1084/jem.177.4.1199
  44. Mattes J, Yang M, Mahalingam S, Kuehr J, Webb DC, Simson L, Hogan SP, Koskinen A, McKenzie AN, Dent LA, et al. Intrinsic defect in T cell production of interleukin (IL)-13 in the absence of both IL-5 and eotaxin precludes the development of eosinophilia and airways hyperreactivity in experimental asthma. J Exp Med 2002;195:1433-44. https://doi.org/10.1084/jem.20020009
  45. Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989;7:145-73. https://doi.org/10.1146/annurev.iy.07.040189.001045
  46. Barnes PJ. Immunology of asthma and chronic obstructive pulmonary disease. Nat Immunol 2008;8:183-92. https://doi.org/10.1038/nri2254
  47. Yagi R, Zhu J, Paul WE. An updated view on transcription factor GATA3-mediated regulation of Th1 and Th2 cell differentiation. Int Immunol 2011;23:415-20. https://doi.org/10.1093/intimm/dxr029
  48. Rincon M, Irvin CG. Role of IL-6 in asthma and other inflammatory pulmonary diseases. Int J Biol Sci 2012;8(9):1281-90. https://doi.org/10.7150/ijbs.4874
  49. Berry M, Brightling C, Pavord I, Wardlaw AJ. TNF-α in asthma. Curr Opin Pharmacol 2007;7:279-82. https://doi.org/10.1016/j.coph.2007.03.001