Browse > Article
http://dx.doi.org/10.1016/j.jgr.2016.10.001

Nonsaponin fractions of Korean Red Ginseng extracts prime activation of NLRP3 inflammasome  

Han, Byung-Cheol (College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University)
Ahn, Huijeong (College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University)
Lee, Jiseon (College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University)
Jeon, Eunsaem (College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University)
Seo, Sanghoon (College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University)
Jang, Kyoung Hwa (Korea Ginseng Research Institute, Korea Ginseng Corporation)
Lee, Seung-Ho (Korea Ginseng Research Institute, Korea Ginseng Corporation)
Kim, Cheon Ho (College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University)
Lee, Geun-Shik (College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University)
Publication Information
Journal of Ginseng Research / v.41, no.4, 2017 , pp. 513-523 More about this Journal
Abstract
Background: Korean Red Ginseng extracts (RGE) have been suggested as effective immune modulators, and we reported that ginsenosides possess anti-inflammasome properties. However, the properties of nonsaponin components of RGE have not been well studied. Methods: To assess the roles of nonsaponin fractions (NS) in NLRP3 inflammasome activation, we treated murine macrophages with or without first or second inflammasome activation signals with RGE, NS, or saponin fractions (SF). The first signal was nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$)-mediated transcription of pro-interleukin (IL)-$1{\beta}$ and NLRP3 while the second signal triggered assembly of inflammasome components, leading to IL-$1{\beta}$ maturation. In addition, we examined the role of NS in IL-6 production and IL-$1{\beta}$ maturation in mice. Results: NS induced IL-$1{\beta}$ and NLRP3 transcription via toll-like receptor 4 signaling, whereas SF blocked expression. During the second signal, SF attenuated NLRP3 inflammasome activation while NS did not. Further, NS-injected mice presented increased IL-$1{\beta}$ maturation and IL-6 production. Conclusion: SF and NS of RGE play differential roles in the NLRP3 inflammasome activation. Hence, RGE can be suggested as an NLRP3 inflammasome modulator.
Keywords
cytokine; inflammasome; interleukin-1beta; Korean Red Ginseng extracts; NLRP3;
Citations & Related Records
Times Cited By KSCI : 3  (Citation Analysis)
연도 인용수 순위
1 Wen H, Gris D, Lei Y, Jha S, Zhang L, Huang MT, Brickey WJ, Ting JP. Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat Immunol 2011;12:408-15.   DOI
2 Feve B, Bastard JP. The role of interleukins in insulin resistance and type 2 diabetes mellitus. Nat Rev Endocrinol 2009;5:305-11.   DOI
3 Kang S, Min H. Ginseng, the 'immunity boost': the effects of Panax ginseng on immune system. J Ginseng Res 2012;36:354-68.   DOI
4 Sohn EH, Jang SA, Lee CH, Jang KH, Kang SC, Park HJ, Pyo S. Effects of Korean Red Ginseng extract for the treatment of atopic dermatitis-like skin lesions in mice. J Ginseng Res 2011;35:479-86.   DOI
5 Henao-Mejia J, Elinav E, Thaiss CA, Flavell RA. Inflammasomes and metabolic disease. Annu Rev Physiol 2014;76:57-78.   DOI
6 Konner AC, Bruning JC. Toll-like receptors: linking inflammation to metabolism. Trends Endocrinol Metab 2011;22:16-23.   DOI
7 Larsen CM, Faulenbach M, Vaag A, Volund A, Ehses JA, Seifert B, Mandrup-Poulsen T, Donath MY. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med 2007;356:1517-26.   DOI
8 Ru W, Wang D, Xu Y, He X, Sun YE, Qian L, Zhou X, Qin Y. Chemical constituents and bioactivities of Panax ginseng (C. A. Mey.). Drug Discov Ther 2015;9:23-32.   DOI
9 Baek SH, Bae ON, Park JH. Recent methodology in ginseng analysis. J Ginseng Res 2012;36:119-34.   DOI
10 Lu JM, Yao Q, Chen C. Ginseng compounds: an update on their molecular mechanisms and medical applications. Curr Vasc Pharmacol 2009;7:293-302.   DOI
11 Kim J, Ahn H, Han BC, Lee SH, Cho YW, Kim CH, Hong EJ, An BS, Jeung EB, Lee GS. Korean Red Ginseng extracts inhibit NLRP3 and AIM2 inflammasome activation. Immunol Lett 2014;158:143-50.   DOI
12 Schroder K, Tschopp J. The inflammasomes. Cell 2010;140:821-32.   DOI
13 Lamkanfi M. Emerging inflammasome effector mechanisms. Nat Rev Immunol 2011;11:213-20.   DOI
14 Ozaki E, Campbell M, Doyle SL. Targeting the NLRP3 inflammasome in chronic inflammatory diseases: current perspectives. J Inflamm Res 2015;8:15-27.
15 Kawamoto T, Ii M, Kitazaki T, Iizawa Y, Kimura H. TAK-242 selectively suppresses Toll-like receptor 4-signaling mediated by the intracellular domain. Eur J Pharmacol 2008;584:40-8.   DOI
16 Bauernfeind FG, Horvath G, Stutz A, Alnemri ES, MacDonald K, Speert D, Fernandes-Alnemri T, Wu J, Monks BG, Fitzgerald KA, et al. Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J Immunol 2009;183:787-91.   DOI
17 Latz E, Xiao TS, Stutz A. Activation and regulation of the inflammasomes. Nat Rev Immunol 2013;13:397-411.   DOI
18 Kim J, Ahn H, Woo HM, Lee E, Lee GS. Characterization of porcine NLRP3 inflammasome activation and its upstream mechanism. Vet Res Commun 2014;38:193-200.   DOI
19 Larina L, Cho BG, Ten L, Park H. Isolation of saponin-free fraction from Ginseng (Panax ginseng C.A. Meyer) and its effects on the function of neutrophils. Korean J Chem Eng 2001;18:986-91.   DOI
20 Ahn H, Kang SG, Yoon SI, Kim PH, Kim D, Lee GS. Poly-gamma-glutamic acid from Bacillus subtilis upregulates pro-inflammatory cytokines while inhibiting NLRP3, NLRC4 and AIM2 inflammasome activation. Cell Mol Immunol Forthcoming 2016. http://dx.doi.org/10.1038/cmi.2016.13.   DOI
21 Bauernfeind F, Bartok E, Rieger A, Franchi L, Nunez G, Hornung V. Cutting edge: reactive oxygen species inhibitors block priming, but not activation, of the NLRP3 inflammasome. J Immunol 2011;187:613-7.   DOI
22 So A, De Smedt T, Revaz S, Tschopp J. A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res Ther 2007;9:R28.   DOI
23 Park J, Cho JY. Anti-inflammatory effects of ginsenosides from Panax ginseng and their structural analogs. Afr J Biotechnol 2009;8:3682-90.
24 Lim DS, Bae KG, Jung IS, Kim CH, Yun YS, Song JY. Anti-septicaemic effect of polysaccharide from Panax ginseng by macrophage activation. J Infect 2002;45:32-8.   DOI
25 Cho JY, Yoo ES, Baik KU, Park MH, Han BH. In vitro inhibitory effect of protopanaxadiol ginsenosides on tumor necrosis factor (TNF)-alpha production and its modulation by known TNF-alpha antagonists. Planta Med 2001;67:213-8.   DOI
26 Wu CF, Bi XL, Yang JY, Zhan JY, Dong YX, Wang JH, Wang JM, Zhang R, Li X. Differential effects of ginsenosides on NO and TNF-alpha production by LPS-activated N9 microglia. Int Immunopharmacol 2007;7:313-20.   DOI
27 Choo MK, Sakurai H, Kim DH, Saiki I. A ginseng saponin metabolite suppresses tumor necrosis factor-alpha-promoted metastasis by suppressing nuclear factor-kappaB signaling in murine colon cancer cells. Oncol Rep 2008;19:595-600.
28 Oh GS, Pae HO, Choi BM, Seo EA, Kim DH, Shin MK, Kim JD, Kim JB, Chung HT. 20(S)-Protopanaxatriol, one of ginsenoside metabolites, inhibits inducible nitric oxide synthase and cyclooxygenase-2 expressions through inactivation of nuclear factor-kappaB in RAW 264.7 macrophages stimulated with lipopolysaccharide. Cancer Lett 2004;205:23-9.   DOI
29 Stancheva SL, Alova LG. Ginsenoside Rg1 inhibits the brain cAMP phosphodiesterase activity in young and aged rats. Gen Pharmacol 1993;24:1459-62.   DOI
30 Shin JY, Song JY, Yun YS, Yang HO, Rhee DK, Pyo S. Immunostimulating effects of acidic polysaccharides extract of Panax ginseng on macrophage function. Immunopharmacol Immunotoxicol 2002;24:469-82.   DOI
31 Choi HS, Kim KH, Sohn E, Park JD, Kim BO, Moon EY, Rhee DK, Pyo S. Red ginseng acidic polysaccharide (RGAP) in combination with IFN-gamma results in enhanced macrophage function through activation of the NF-kappaB pathway. Biosci Biotechnol Biochem 2008;72:1817-25.   DOI
32 Byeon SE, Lee J, Kim JH, Yang WS, Kwak YS, Kim SY, Choung ES, Rhee MH, Cho JY. Molecular mechanism of macrophage activation by red ginseng acidic polysaccharide from Korean Red Ginseng. Mediators Inflamm 2012;2012:732860.
33 Nakaya TA, Kita M, Kuriyama H, Iwakura Y, Imanishi J. Panax ginseng induces production of proinflammatory cytokines via toll-like receptor. J Interferon Cytokine Res 2004;24:93-100.   DOI
34 Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, Mynatt RL, Ravussin E, Stephens JM, Dixit VD. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med 2011;17:179-88.   DOI