Journal of Ginseng Research

  • 제46권3호
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  • Pages.489-495
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  • 2022
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  • 1226-8453(pISSN)
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  • 2093-4947(eISSN)
고려인삼학회 (The Korean Society of Ginseng)
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Korean Red Ginseng saponin fraction exerts anti-inflammatory effects by targeting the NF-κB and AP-1 pathways

  • Lee, Jeong-Oog (Department of Aerospace Information Engineering, Bio-Inspired Aerospace Information Laboratory, Konkuk University) ;
  • Yang, Yanyan (Department of Immunology, Basic Medicine School, Qingdao University) ;
  • Tao, Yu (Department of Cardiac Ultrasound and Institute for Translational Medicine, The Affiliated Hospital of Qingdao University) ;
  • Yi, Young-Su (Department of Life Sciences, Kyonggi University) ;
  • Cho, Jae Youl (Department of Integrative Biotechnology, Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University)
  • 투고 : 2022.01.26
  • 심사 : 2022.02.21
  • 발행 : 2022.05.01
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초록

Background: Although ginsenosides and saponins in Korea red ginseng (KRG) shows various pharmacological roles, their roles in the inflammatory response are little known. This study investigated the anti-inflammatory role of ginsenosides identified from KRG saponin fraction (RGSF) and the potential mechanism in macrophages. Methods: The ginsenoside composition of RGSF was identified by high-performance liquid chromatography (HPLC) analysis. An anti-inflammatory effect of RGSF and its mechanisms were studied using nitric oxide (NO) and prostaglandin E2 (PGE2) production assays, mRNA expression analyses of inflammatory genes and cytokines, luciferase reporter gene assays of transcription factors, and Western blot analyses of inflammatory signaling pathways using the lipopolysaccharide (LPS)-treated RAW264.7 cells. Results: HPLC analysis identified the types and amounts of various panaxadiol ginsenosides in RGSF. RGSF reduced the generation of inflammatory molecules and mRNA levels of inflammatory enzymes and cytokines in LPS-treated RAW264.7 cells. Additionally, RGSF inhibited the signaling pathways of NF-κB and AP-1 by suppressing both transcriptional factors and signaling molecules in LPS-treated RAW264.7 cells. Conclusion: RGSF contains ginsenosides that have anti-inflammatory action via restraining the NF-κB and AP-1 signaling pathways in macrophages during inflammatory responses.

키워드

과제정보

This paper was supported by Konkuk University, Republic of Korea, in 2020.

참고문헌

  1. Janeway Jr CA, Medzhitov R. Innate immune recognition. Annu Rev Immunol 2002;20:197-216. https://doi.org/10.1146/annurev.immunol.20.083001.084359
  2. Yi YS. Folate receptor-targeted diagnostics and therapeutics for inflammatory diseases. Immune Netw 2016;16:337-43. https://doi.org/10.4110/in.2016.16.6.337
  3. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell 2010;140:805-20. https://doi.org/10.1016/j.cell.2010.01.022
  4. Straub RH, Schradin C. Chronic inflammatory systemic diseases: an evolutionary trade-off between acutely beneficial but chronically harmful programs. Evol Med Public Health 2016;2016:37-51.
  5. Liu CH, Abrams ND, Carrick DM, Chander P, Dwyer J, Hamlet MRJ, Macchiarini F, PrabhuDas M, Shen GL, Tandon P, Vedamony MM. Biomarkers of chronic inflammation in disease development and prevention: challenges and opportunities. Nat Immunol 2017;18:1175-80. https://doi.org/10.1038/ni.3828
  6. Ratan ZA, Youn SH, Kwak YS, Han CK, Haidere MF, Kim JK, Min H, Jung YJ, Hosseinzadeh H, Hyun SH, Cho JY. Adaptogenic effects of Panax ginseng on modulation of immune functions. J Ginseng Res 2021;45:32-40. https://doi.org/10.1016/j.jgr.2020.09.004
  7. Broz P, Dixit VM. Inflammasomes: mechanism of assembly, regulation and signalling. Nat Rev Immunol 2016;16:407-20. https://doi.org/10.1038/nri.2016.58
  8. Yi YS. Caspase-11 non-canonical inflammasome: a critical sensor of intracellular lipopolysaccharide in macrophage-mediated inflammatory responses. Immunology 2017;152:207-17. https://doi.org/10.1111/imm.12787
  9. Yi YS. Role of inflammasomes in inflammatory autoimmune rheumatic diseases. KOREAN J PHYSIOL PHARMACOL 2018;22:1-15. https://doi.org/10.4196/kjpp.2018.22.1.1
  10. Yi YS, Son YJ, Ryou C, Sung GH, Kim JH, Cho JY. Functional roles of Syk in macrophage-mediated inflammatory responses. Mediat Inflamm 2014;2014:270302. https://doi.org/10.1155/2014/270302
  11. Yang Y, Kim SC, Yu T, Yi YS, Rhee MH, Sung GH, Yoo BC, Cho JY. Functional roles of p38 mitogen-activated protein kinase in macrophage-mediated inflammatory responses. Mediat Inflamm 2014;2014:352371. https://doi.org/10.1155/2014/352371
  12. Yu T, Yi YS, Yang Y, Oh J, Jeong D, Cho JY. The pivotal role of TBK1 in inflammatory responses mediated by macrophages. Mediat Inflamm 2012;2012:979105.
  13. Byeon SE, Yi YS, Oh J, Yoo BC, Hong S, Cho JY. The role of Src kinase in macrophage-mediated inflammatory responses. Mediat Inflamm 2012;2012:512926. https://doi.org/10.1155/2012/512926
  14. 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
  15. Kim JH, Yi YS, Kim MY, Cho JY. Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. J Ginseng Res 2017;41:435-43. https://doi.org/10.1016/j.jgr.2016.08.004
  16. 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
  17. Ahuja A, Kim JH, Yi YS, Cho JY. Functional role of ginseng-derived compounds in cancer. J Ginseng Res 2018;42:248-54. https://doi.org/10.1016/j.jgr.2017.04.009
  18. Yi YS. Ameliorative effects of ginseng and ginsenosides on rheumatic diseases. J Ginseng Res 2019;43:335-41. https://doi.org/10.1016/j.jgr.2018.04.004
  19. 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
  20. Zhang D, Yasuda T, Yu Y, Zheng P, Kawabata T, Ma Y, Okada S. Ginseng extract scavenges hydroxyl radical and protects unsaturated fatty acids from decomposition caused by iron-mediated lipid peroxidation. Free Radic Biol Med 1996;20:145-50. https://doi.org/10.1016/0891-5849(95)02020-9
  21. Heo JH, Park MH, Lee JH. Effect of Korean Red Ginseng on cognitive function and quantitative EEG in patients with Alzheimer's disease: a preliminary study. J Alternative Compl Med 2016;22:280-5. https://doi.org/10.1089/acm.2015.0265
  22. Chung HS, Hwang I, Oh KJ, Lee MN, Park K. The Effect of Korean Red Ginseng on sexual function in premenopausal women: placebo-controlled, double-blind, crossover clinical trial. Evid Based Complement Alternat Med 2015;2015:913158.
  23. Jovanovski E, Peeva V, Sievenpiper JL, Jenkins AL, Desouza L, Rahelic D, Sung MK, Vuksan V. Modulation of endothelial function by Korean red ginseng (Panax ginseng C.A. Meyer) and its components in healthy individuals: a randomized controlled trial. Cardiovasc Ther 2014;32:163-9. https://doi.org/10.1111/1755-5922.12077
  24. Lee JW, Mo EJ, Choi JE, Jo YH, Jang H, Jeong JY, Jin Q, Chung HN, Hwang BY, Lee MK. Effect of Korean Red Ginseng extraction conditions on antioxidant activity, extraction yield, and ginsenoside Rg1 and phenolic content: optimization using response surface methodology. J Ginseng Res 2016;40: 229-36. https://doi.org/10.1016/j.jgr.2015.08.001
  25. Jin SH, Park JK, Nam KY, Park SN, Jung NP. Korean red ginseng saponins with low ratios of protopanaxadiol and protopanaxatriol saponin improve scopolamine-induced learning disability and spatial working memory in mice. J Ethnopharmacol 1999;66:123-9. https://doi.org/10.1016/S0378-8741(98)00190-1
  26. Vinh LB, Lee Y, Han YK, Kang JS, Park JU, Kim YR, Yang SY, Kim YH. Two new dammarane-type triterpene saponins from Korean red ginseng and their anti-inflammatory effects. Bioorg Med Chem Lett 2017;27:5149-53. https://doi.org/10.1016/j.bmcl.2017.10.058
  27. Lee JS, Choi HS, Kang SW, Chung JH, Park HK, Ban JY, Kwon OY, Hong HP, Ko YG. Therapeutic effect of Korean red ginseng on inflammatory cytokines in rats with focal cerebral ischemia/reperfusion injury. Am J Chin Med 2011;39:83-94. https://doi.org/10.1142/S0192415X1100866X
  28. Yu T, Rhee MH, Lee J, Kim SH, Yang Y, Kim HG, Kim Y, Kim C, Kwak YS, Kim JH, Cho JY. Ginsenoside Rc from Korean Red Ginseng (Panax ginseng C.A. Meyer) attenuates inflammatory symptoms of gastritis, hepatitis and arthritis. Am J Chin Med 2016;44:595-615. https://doi.org/10.1142/s0192415x16500336
  29. Lee HJ, Cho SH. Therapeutic Effects of Korean Red Ginseng extract in a murine model of atopic dermatitis: anti-pruritic and anti-inflammatory mechanism. J Kor Med Sci 2017;32:679-87. https://doi.org/10.3346/jkms.2017.32.4.679
  30. Yi YS. Roles of ginsenosides in inflammasome activation. J Ginseng Res 2019;43:172-8. https://doi.org/10.1016/j.jgr.2017.11.005
  31. Yi YS. New mechanisms of ginseng saponin-mediated anti-inflammatory action via targeting canonical inflammasome signaling pathways. J Ethnopharmacol 2021;278:114292. https://doi.org/10.1016/j.jep.2021.114292
  32. Jeong D, Lee J, Jeong SG, Hong YH, Yoo S, Han SY, Kim JH, Kim S, Kim JS, Chung YS, Yi YS, Cho JY. Artemisia asiatica ethanol extract exhibits anti-photoaging activity. J Ethnopharmacol 2018;220:57-66. https://doi.org/10.1016/j.jep.2018.03.037
  33. Kim HG, Choi S, Lee J, Hong YH, Jeong D, Yoon K, Yoon DH, Sung GH, Lee S, Hong S, Yi YS, Kim JH, Cho JY. Src is a prime target inhibited by Celtis choseniana methanol extract in its anti-inflammatory action. Evid Based Complement Alternat Med 2018;2018:3909038.
  34. Cho JY, Baik KU, Jung JH, Park MH. In vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappa. Eur J Pharmacol 2000;398:399-407. https://doi.org/10.1016/S0014-2999(00)00337-X
  35. Wang HP, Zhang YB, Yang XW, Zhao DQ, Wang YP. Rapid characterization of ginsenosides in the roots and rhizomes of Panax ginseng by UPLC-DAD-QTOFMS/MS and simultaneous determination of 19 ginsenosides by HPLC-ESI-MS. J Ginseng Res 2016;40:382-94. https://doi.org/10.1016/j.jgr.2015.12.001
  36. Yayeh T, Jung KH, Jeong HY, Park JH, Song YB, Kwak YS, Kang HS, Cho JY, Oh JW, Kim SK, Rhee MH. Korean Red Ginseng saponin fraction down-regulates proinflammatory mediators in LPS stimulated RAW264.7 cells and protects mice against endotoxic shock. J Ginseng Res 2012;36:263-9. https://doi.org/10.5142/jgr.2012.36.3.263
  37. Endale M, Im EJ, Lee JY, Kim SD, Yayeh T, Song YB, Kwak YS, Kim C, Kim SH, Roh SS, Cho JY, Rhee MH. Korean red ginseng saponin fraction rich in ginsenoside-Rb1, Rc and Rb2 attenuates the severity of mouse collagen-induced arthritis. Mediat Inflamm 2014;2014:748964.
  38. Yu S, Zhou X, Li F, Xu C, Zheng F, Li J, Zhao H, Dai Y, Liu S, Feng Y. Microbial transformation of ginsenoside Rb1, Re and Rg1 and its contribution to the improved anti-inflammatory activity of ginseng. Sci Rep 2017;7:138. https://doi.org/10.1038/s41598-017-00262-0
  39. Zhou P, Lu S, Luo Y, Wang S, Yang K, Zhai Y, Sun G, Sun X. Attenuation of TNF-alpha-induced inflammatory injury in endothelial cells by ginsenoside Rb1 via inhibiting NF-kappaB, JNK and p38 signaling pathways. Front Pharmacol 2017;8:464. https://doi.org/10.3389/fphar.2017.00464
  40. Yu T, Yang Y, Kwak YS, Song GG, Kim MY, Rhee MH, Cho JY. Ginsenoside Rc from Panax ginseng exerts anti-inflammatory activity by targeting TANK-binding kinase 1/interferon regulatory factor-3 and p38/ATF-2. J Ginseng Res 2017;41:127-33. https://doi.org/10.1016/j.jgr.2016.02.001
  41. Song C, Hong YH, Park JG, Kim HG, Jeong D, Oh J, Sung GH, Hossain MA, Taamalli A, Kim JH, Kim JH, Cho JY. Suppression of Src and Syk in the NF-kappaB signaling pathway by Olea europaea methanol extract is leading to its anti-inflammatory effects. J Ethnopharmacol 2019;235:38-46. https://doi.org/10.1016/j.jep.2019.01.024
  42. Han SY, Yi YS, Jeong SG, Hong YH, Choi KJ, Hossain MA, Hwang H, Rho HS, Lee J, Kim JH, Cho JY. Ethanol extract of Lilium bulbs plays an anti-inflammatory role by targeting the IKKalpha/beta-Mediated NF-kappaB pathway in macrophages. Am J Chin Med 2018;46:1281-96. https://doi.org/10.1142/S0192415X18500672
  43. Xue Q, He N, Wang Z, Fu X, Aung LHH, Liu Y, Li M, Cho JY, Yang Y, Yu T. Functional roles and mechanisms of ginsenosides from Panax ginseng in atherosclerosis. J Ginseng Res 2021;45:22-31. https://doi.org/10.1016/j.jgr.2020.07.002