The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology (한방안이비인후피부과학회지)

The Society of Korean Medicine Ophthalmology, Otolaryngology & Dermatology (대한한방안이비인후피부과학회)
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Anti-inflammatory Effect of Stevia Rebaudiana as a Results of NF-κB and MAPK Inhibition

NF-κB와 MAPK 억제를 통한 스테비아 잎의 항염증효과

  • Kim, Seon-Young (College of Korean Medicine, Daegu Haany University) ;
  • Jo, Mi-Jeong (College of Korean Medicine, Daegu Haany University) ;
  • Hwangbo, Min (College of Korean Medicine, Daegu Haany University) ;
  • Back, Young-Doo (Dept. of Clinical Pathology, Daegu Health College) ;
  • Jeong, Tae-Young (College of Korean Medicine, Daegu Haany University) ;
  • Cho, Il-Je (College of Korean Medicine, Daegu Haany University) ;
  • Jee, Seon-Young (College of Korean Medicine, Daegu Haany University)
  • 김선영 (대구한의대학교 한의과대학) ;
  • 조미정 (대구한의대학교 한의과대학) ;
  • 황보민 (대구한의대학교 한의과대학) ;
  • 백영두 (대구보건대학교 임상병리과) ;
  • 정태영 (대구한의대학교 한의과대학) ;
  • 조일제 (대구한의대학교 한의과대학) ;
  • 지선영 (대구한의대학교 한의과대학)
  • Received : 2013.07.26
  • Accepted : 2013.08.15
  • Published : 2013.08.25
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Abstract

Objectives : Stevia rebaudiana is a well-known herbal sweetener in the Korea, Japan and China, and its medical uses were originated from countries in South America. Although it has been shown the various medical effects of S. rebaudiana including contraception and treatment of human diseases such as hyperglycemia, it has almost not been studied about the efficacy of S. rebaudiana methanolic extract (SRE) on the acute inflammation and its action mechanism. Methods : To investigate the anti-inflammatory effects of SRE, we treated SRE and examined the level of inflammatory mediators in LPS-stimulated Raw264.7 cells. Results : Treatment of macrophage with LPS markedly induced the production of NO, $PGE_2$ and pro-inflammatory cytokines. Pretreatment of SRE blocked the induction of inflammatory mediators and the expression of iNOS protein. More importantly, LPS-induced phosphorylation of $I{\kappa}B-{\alpha}$ was suppressed by the treatment of SRE, suggesting SRE inhibition of NF-${\kappa}B$ activation. Furthermore, SRE blocked LPS-induced phosphorylation of MAPKs. Conclusions : SRE inhibited the induction of NO, PGE2 and pro-inflammatory cytokines in Raw264.7 cells. SRE's effect may be mediated with its inhibition of NF-${\kappa}B$ activation and MAPK phosphorylation, which suggests its uses as an anti-inflammatory agents.

Keywords

References

  1. Kindt TJ, Goldsby RA, Osborne BA, Kuby J. Kuby Immunology. 6th Edit. New York:W.H. Freeman and Company. 2007:52-75.
  2. Park SM, Byun SH, Kim YW, Cho IJ, Kim SC. Inhibitory Effect of Mori Folium ethanol extract on pro-inflammatory mediator in lipopolysaccharide-activated Raw264.7 cells. Kor J Herbology. 2012;27:31-8.
  3. Park DC, Lee YH. Production, transglycosylation and application of stevioside. J Korean Soc Food Sci Nutr. 1997;2:31-41.
  4. Komisseranko NF, Derkuch AI, Kovalyou IP, Bublik NP. Diterpene glycoside and phenylpropanoid of Stevia rebaudiana bertoni (astercae). Rast Res. 1994;1:53-64.
  5. Dyrskog SE, Jeppensen PB, Colombo M, Abudula R, Hermansen K. Preventive effects of soy based diet supplemented with stevioside on development of type 2 diabetes. Metabolism. 2005;54:1181-8. https://doi.org/10.1016/j.metabol.2005.03.026
  6. Chan P, Xu DY, Liu JC, Chen YJ, Tomlinson B, Huang WP, et al. The effect of stevioside on blood pressure and plasma catecholamines in pontaneously hypertension rats. Life Sci. 1998;19:1679-84.
  7. Srijani G, Anindita B, Avijit P, Sharmila C. Oxidative DNA damage preventive activity and antioxidant potential of Stevia rebaudiana (bertoni) bertoni, a natural sweetener. J Agric Food Chem. 2007;55:10962-7. https://doi.org/10.1021/jf071892q
  8. Yasukawa K, Kitanaka S, Shujiro S. Inhibitory effect of stevioside on tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin. Biol Pharm Bull. 2002;25:1488-90. https://doi.org/10.1248/bpb.25.1488
  9. Wang MT, Honn KV, Nie D. Cycloxygenases, prostanoids and tumor progression. Cancer Metastasis Rev. 2007;26:525-34. https://doi.org/10.1007/s10555-007-9096-5
  10. Qiao-Wen X, Richard W, Carl N. Promoter of the mouse gene encoding calciumindependent nitric oxide synthase confers inducibility by interferon-${\gamma}$ and bacterial lipopolysaccharide. J Exp Med. 1993;177: 1779-84. https://doi.org/10.1084/jem.177.6.1779
  11. Rhodes KL, Golub SH, Economou JS. The regulation of the human tumor necrosis factor alpha promoter region in macrophage, T cell, and B cell lines. J Biol Chem. 1992;267: 22102-7.
  12. Libermann TA, Baltimore D. Activation of interleukin-6 gene expression through the NF-kB transcription factor. Mol Cell Biol. 1990;10:2327-34. https://doi.org/10.1128/MCB.10.5.2327
  13. Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science. 2002;298:1911-2. https://doi.org/10.1126/science.1072682
  14. Oshima Y, Saito JI, Hikino H. Sterebins A, B, C and D, bisnorditerpenoids of Stevia rebaudiana leaves. Tetrahedron. 1986;42: 6443-6. https://doi.org/10.1016/S0040-4020(01)88106-0
  15. Oshima Y, Saito JI, Hikino H. Sterebins E, F, G and H, diterpenoids of Stevia rebaudiana leaves. Phyochemistry. 1988;27:624-6. https://doi.org/10.1016/0031-9422(88)83157-1
  16. Dacome AS, da Silva CC, da Costa CEM, Fontana JD, Adelmann J, da Costa SC. Sweet diterpenic glycoside balance of a new cultivar of Stevia rebaudiana (Bert.) Bertoni: isolation and quantitative distribution by chromatography, spectroscopic, and electrophoretic methods. Process Biochem. 2005;40:3587-94. https://doi.org/10.1016/j.procbio.2005.03.035
  17. Park JE, Kee HJ, Cha YS. Effect of Stevia rebaudiana Bertoni Leaf Extract on Antiobesity in C57BL/6J Mice. Korean J Food Sci Technol. 2010;42:586-92.
  18. Byun MW. Anti-Inflammatory Activity of Austroinulin from Stevia rebaudiana in LPS-induced Raw264.7 cells. J Korean Soc Food Sci Nutr. 2012;41:456-61. https://doi.org/10.3746/jkfn.2012.41.4.456
  19. Liew FY, Xu D, Brint EK, O’Neill LA. Negative regulation of Toll-like receptorediated immune responses. Nat Rev Immunol. 2005;5:446-58. https://doi.org/10.1038/nri1630
  20. O'Neill LA. How Toll-like receptors signal: what we know and what we don't know. Curr Opin Immunol. 2006;18:3-9. https://doi.org/10.1016/j.coi.2005.11.012
  21. Wadleigh DJ, Redddy ST, Kopp E, Ghosh S, Herschman HR. Transcriptional activation of the cyclooxygenase-2 gene in endotoxinreated Raw264.7 macrophages. J Biol Chem. 2000;275:6259-66. https://doi.org/10.1074/jbc.275.9.6259
  22. Byun SH, Yang CH, Kim SC. Inhibitory effect of Sctophulariae Radix extract on TNF-${\alpha}$, IL-1${\beta}$, IL-6 and Nitric Oxide production in lipoposaccharide-activated Raw264.7 cells. Kor J Herbology. 2005;20:7-16.
  23. Dong C, Davis RJ, Flavell RA. MAP kinases in the immune response. Annu Rev Immuno. 2002;20:55-72. https://doi.org/10.1146/annurev.immunol.20.091301.131133
  24. Palombella VJ, Rando OJ, Goldberg AL, Maniatis T. The ubiquitin-proteasome pathway is required for processing the NF-${\kappa}$B1 precursor protein and the activation of NF-${\kappa}$ B. Cell. 1996;78:773-85.
  25. Ki SH, Choi MJ, Lee CH, Kim SG. Galpha12 specifically regulates COX-2 induction by sphingosine 1-phosphate. Role for JNKdependent ubiquitination and degradation of I kappa B alpha. J Biol Chem. 2007;282: 1938-47. https://doi.org/10.1074/jbc.M606080200

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