Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Ginsenoside Rc from Panax ginseng exerts anti-inflammatory activity by targeting TANK-binding kinase 1/interferon regulatory factor-3 and p38/ATF-2

  • Yu, Tao (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Yang, Yanyan (Department of Genetic Engineering, Sungkyunkwan University) ;
  • Kwak, Yi-Seong (Korean Ginseng Corporation, Central Research Institute) ;
  • Song, Gwan Gyu (Division of Rheumatology, Department of Internal Medicine, Korea University Guro Hospital) ;
  • Kim, Mi-Yeon (Department of Bioinformatics and Life Science, Soongsil University) ;
  • Rhee, Man Hee (College of Veterinary Medicine, Kyungpook National University) ;
  • Cho, Jae Youl (Department of Genetic Engineering, Sungkyunkwan University)
  • Received : 2016.01.19
  • Accepted : 2016.02.02
  • Published : 2017.04.15
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Abstract

Background: Ginsenoside Rc (G-Rc) is one of the major protopanaxadiol-type saponins isolated from Panax ginseng, a well-known medicinal herb with many beneficial properties including anticancer, anti-inflammatory, antiobesity, and antidiabetic effects. In this study, we investigated the effects of G-Rc on inflammatory responses in vitro and examined the mechanisms of these effects. Methods: The in vitro inflammation system used lipopolysaccharide-treated macrophages, tumor necrosis $factor-{\alpha}/interferon-{\gamma}-treated$ synovial cells, and HEK293 cells transfected with various inducers of inflammation. Results: G-Rc significantly inhibited the expression of macrophage-derived cytokines, such as tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$. G-Rc also markedly suppressed the activation of TANK-binding kinase $1/I{\kappa}B$ kinase ${\varepsilon}/interferon$ regulatory factor-3 and p38/ATF-2 signaling in activated RAW264.7 macrophages, human synovial cells, and HEK293 cells. Conclusion: G-Rc exerts its anti-inflammatory actions by suppressing TANK-binding kinase $1/I{\kappa}B$ kinase ${\varepsilon}/interferon$ regulatory factor-3 and p38/ATF-2 signaling.

Keywords

References

  1. Lim S, Park S. Role of vascular smooth muscle cell in the inflammation of atherosclerosis. BMB Rep 2014;47:1-7. https://doi.org/10.5483/BMBRep.2014.47.1.285
  2. Ohno S, Inagawa H, Dhar DK, Fujii T, Ueda S, Tachibana M, Ohno Y, Suzuki N, Inoue M, Soma G, et al. Role of tumor-associated macrophages (TAM) in advanced gastric carcinoma: the impact on FasL-mediated counterattack. Anticancer Res 2005;25:463-70.
  3. Woo Y, Jeong D, Chung DH, Kim HY. The roles of innate lymphoid cells in the development of asthma. Immune Netw 2014;14:171-81. https://doi.org/10.4110/in.2014.14.4.171
  4. Kim KH, Kim TS, Lee JG, Park JK, Yang M, Kim JM, Jo EK, Yuk JM. Characterization of proinflammatory responses and innate signaling activation in macrophages infected with Mycobacterium scrofulaceum. Immune Netw 2014;14:307-20. https://doi.org/10.4110/in.2014.14.6.307
  5. Lee J, Kim SL, Lee S, Chung MJ, Park YI. Immunostimulating activity of maysin isolated from corn silk in murine RAW 264.7 macrophages. BMB Rep 2014;47:382-7. https://doi.org/10.5483/BMBRep.2014.47.7.191
  6. Takeuchi O, Akira S. Toll-like receptors; their physiological role and signal transduction system. Int Immunopharmacol 2001;1:625-35. https://doi.org/10.1016/S1567-5769(01)00010-8
  7. Yamamoto M, Akira S. Lipid A receptor TLR4-mediated signaling pathways. Adv Exp Med Biol 2009;667:59-68.
  8. Yu T, Li YJ, Bian AH, Zuo HB, Zhu TW, Ji SX, Kong F, Yin de Q, Wang CB, Wang ZF, et al. The regulatory role of activating transcription factor 2 in inflammation. Mediators Inflamm 2014;2014:950472.
  9. Yi YS, Son YJ, Ryou C, Sung GH, Kim JH, Cho JY. Functional roles of Syk in macrophage-mediated inflammatory responses. Mediators Inflamm 2014;2014:270302.
  10. 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. Mediators Inflamm 2014;2014:352371.
  11. Kwon DJ, Bae YS, Ju SM, Youn GS, Choi SY, Park J. Salicortin suppresses lipopolysaccharide-stimulated inflammatory responses via blockade ofNF-kappaB and JNK activation in RAW264.7 macrophages. BMB Rep 2014;47:318-23. https://doi.org/10.5483/BMBRep.2014.47.6.200
  12. Kim DH. Chemical diversity of Panax ginseng, Panax quinquifolium, and Panax notoginseng. J Ginseng Res 2012;36:1-15. https://doi.org/10.5142/jgr.2012.36.1.1
  13. Kim JH. Cardiovascular diseases and Panax ginseng: a review on molecular mechanisms and medical applications. J Ginseng Res 2012;36:16-26. https://doi.org/10.5142/jgr.2012.36.1.16
  14. Kim SK, Park JH. Trends in ginseng research in 2010. J Ginseng Res 2011;35:389-98. https://doi.org/10.5142/jgr.2011.35.4.389
  15. Choi JM, Kim SH, Shin JH, Gibson T, Yoon BS, Lee DH, Lee SK, Bothwell AL, Lim JS, Lee SK. Transduction of the cytoplasmic domain of CTLA-4 inhibits TcRspecific activation signals and prevents collagen-induced arthritis. Proc Natl Acad Sci U S A 2008;105:19875-80. https://doi.org/10.1073/pnas.0805198105
  16. Kim YO, Lee SW. Microarray analysis of gene expression by ginseng water extracts in a mouse adrenal cortex after immobilization stress. Journal of Ginseng Research 2011;35:111-23. https://doi.org/10.5142/jgr.2011.35.1.111
  17. Yang DC, Sun H, Lee OR, Kim YJ, Jeong SK, In JG, Kwon WS, Kim SY. Identification of 'Chunpoong' among Panax ginseng cultivars using real time PCR and SNP marker. J Ginseng Res 2010;34:47-50. https://doi.org/10.5142/JGR.2010.34.1.047
  18. Devitt G, Thomas M, Klibanov AM, Pfeiffer T, Bosch V. Optimized protocol for the large scale production of HIV pseudovirions by transient transfection of HEK293T cells with linear fully deacylated polyethylenimine. J Virol Methods 2007;146:298-304. https://doi.org/10.1016/j.jviromet.2007.07.011
  19. Jung KK, Lee HS, Cho JY, Shin WC, Rhee MH, Kim TG, Kang JH, Kim SH, Hong S, Kang SY. Inhibitory effect of curcumin on nitric oxide production from lipopolysaccharide-activated primary microglia. Life Sci 2006;79:2022-31. https://doi.org/10.1016/j.lfs.2006.06.048
  20. Byeon SE, Lee YG, Kim BH, Shen T, Lee SY, Park HJ, Park SC, Rhee MH, Cho JY. Surfactin blocks NO production in lipopolysaccharide-activated macrophages by inhibiting NF-kappaB activation. J Microbiol Biotechnol 2008;18:1984-9.
  21. Makino C, Sano Y, Shinagawa T, Millar JB, Ishii S. Sin1 binds to both ATF-2 and p38 and enhances ATF-2-dependent transcription in an SAPK signaling pathway. Genes Cells 2006;11:1239-51. https://doi.org/10.1111/j.1365-2443.2006.01016.x
  22. Lu LL, Puri M, Horvath CM, Sen GC. Select paramyxoviral V proteins inhibit IRF3 activation by acting as alternative substrates for inhibitor of kappaB kinase epsilon (IKKe)/TBK1. J Biol Chem 2008;283:14269-76. https://doi.org/10.1074/jbc.M710089200
  23. Migita K, Nakamura T. TBK1: a potential therapeutic target in RA. Rheumatology (Oxford) 2012;51:588-9. https://doi.org/10.1093/rheumatology/ker207
  24. Hammaker D, Boyle DL, Firestein GS. Synoviocyte innate immune responses: TANK-binding kinase-1 as a potential therapeutic target in rheumatoid arthritis. Rheumatology (Oxford) 2012;51:610-8. https://doi.org/10.1093/rheumatology/ker154
  25. Yu T, Yang Y, Yin de Q, Hong S, Son YJ, Kim JH, Cho JY. TBK1 inhibitors: a review of patent literature (2011-2014). Expert Opin Ther Pat 2015;25:1385-96. https://doi.org/10.1517/13543776.2015.1081168
  26. Yang Y, Lee GJ, Yoon DH, Yu T, Oh J, Jeong D, Lee J, Kim SH, Kim TW, Cho JY. ERK1- and TBK1-targeted anti-inflammatory activity of an ethanol extract of Dryopteris crassirhizoma. J Ethnopharmacol 2013;145:499-508. https://doi.org/10.1016/j.jep.2012.11.019
  27. Subhashini, Chauhan PS, Dash D, Paul BN, Singh R. Intranasal curcumin ameliorates airway inflammation and obstruction by regulating MAPKinase activation (p38, Erk and JNK) and prostaglandin D2 release in murine model of asthma. Int Immunopharmacol 2016;31:200-6. https://doi.org/10.1016/j.intimp.2015.12.025
  28. Liu W, Liu Y, Wang Z, Yu T, Lu Q, Chen H. Suppression of MAPK and NF-kappa B pathways by schisandrin B contributes to attenuation of DSS-induced mice model of inflammatory bowel disease. Pharmazie 2015;70:598-603.

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