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Anti-Inflammatory Effect of Ethyl Acetate Fraction Isolated from Undaria pinnatifida on Lipopolysaccharides-Stimulated RAW 264.7 Cells

LPS로 유도된 RAW 264.7 대식세포에 대한 미역(Undaria pinnatifida) Ethyl Acetate 분획물의 항염증 효과

  • Choi, Min-Woo (Department of Food Science and Nutrition, Pukyong National University) ;
  • Kim, Jae-Il (Department of Food Science and Nutrition, Pukyong National University)
  • 최민우 (부경대학교 식품영양학과) ;
  • 김재일 (부경대학교 식품영양학과)
  • Received : 2013.07.26
  • Accepted : 2013.08.02
  • Published : 2013.08.31

Abstract

An ethanolic extract of Undaria pinnatifida was fractionated using several solvents. Of the fractions, the ethyl acetate fraction had the greatest inhibitory effect on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophage cells. Using this fraction (U. pinnatifida ethyl acetate extract, UPE), we investigated the molecular mechanism underlying its inhibitory effect on LPS-stimulated RAW 264.7 cells. Pretreatment of the cells with up to $100{\mu}g/mL$ UPE significantly inhibited NO production and inducible nitric oxide synthase (iNOS) expression, in a dose-dependent manner. Similarly, UPE treatment markedly reduced the production of pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6 and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), while it strongly suppressed the nuclear translocation of nuclear factor-kappa B (NF-${\kappa}B$) by preventing proteolytic degradation of inhibitor of nuclear factor ${\kappa}B$ $(I{\kappa}B)-{\alpha}$. Moreover, UPE treatment significantly reduced the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) in LPS-stimulated cells. These results indicate that UPE contains anti-inflammatory compounds and suggest that it might be used as a functional food material that assists in prevention of inflammatory diseases.

Keywords

References

  1. Baeuerle PA and Henkel T. 1994. Function and activation of NFkB in the immune system. Annu Rev Immunol 12, 141-179. https://doi.org/10.1146/annurev.iy.12.040194.001041
  2. Beutler B and Cerami A. 1989. The biology of cachectin/TNF--a primary mediator of the host response. Annu Rev Immunol 7, 625-655. https://doi.org/10.1146/annurev.iy.07.040189.003205
  3. Chen Z, Hagler J, Palombella VJ, Melandri F, Scherer D, Ballard D and Maniatis T. 1995. Signal-induced site-specific phosphorylation targets I kappaB alpha to the ubiquitinproteasome pathway. Genes Dev 9, 1586-1597. https://doi.org/10.1101/gad.9.13.1586
  4. D'Acquisto F, Iuvone T, Rombola L, Sautebin L, Di Rosa M and Carnuccio R. 1997. Involvement of NF-${\kappa}B$ in the regulation of cyclooxygenase- 2 protein expression in LPS-stimulated J774 macrophages. FEBS Lett 418, 175-178. https://doi.org/10.1016/S0014-5793(97)01377-X
  5. Dinarello CA. 1999. Cytokines as endogenous pyrogens. J Infect Dis 179, S294-S304. https://doi.org/10.1086/513856
  6. Guha M and Mackman N. 2001. LPS induction of gene expression in human monocytes. Cell Signal 13, 85-94. https://doi.org/10.1016/S0898-6568(00)00149-2
  7. Hosokawa M, Kudo M, Maeda H, Kohno H, Tanaka T and Miyashita K. 2004. Fucoxanthin induces apoptosis and enhances the antiproliferative effect of the PPARγ ligand, troglitazone, on colon cancer cells. Biochim Biophys Acta. 1675, 113-119. https://doi.org/10.1016/j.bbagen.2004.08.012
  8. Kaplanski G, Marin V, Montero-Julian F, Mantovani A and Farnarier C. 2003. IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation. Trends Immunol 24, 25-29. https://doi.org/10.1016/S1471-4906(02)00013-3
  9. Khan MN, Lee MC, Kang JY, Park NG, Fujii H and Hong YK. 2008. Effects of the brown seaweed Undaria pinnatifida on erythematous inflammation assessed using digital photo analysis. Phytother Res 22, 634-639. http://dx.doi.org/10.1002/ptr.2349.
  10. Kim AR, Shin TS, Lee MS, Park JY, Park KE, Yoon NY, Kim JS, Choi JS, Jang BC, Byun DS, Park NK and Kim HR. 2009. Isolation and identification of phlorotannins from Ecklonia stolonifera with antioxidant and anti-inflammatory properties. J Agr Food Chem 57, 3483-3489. http://dx.doi.org/10.1021/jf900820x.
  11. Kim MJ, Jeon J and Lee JS. 2013. Fucoidan prevents high-fat diet-induced obesity in animals by suppression of fat accumulation. Phytother Res. http://dx.doi.org/10.1002/ptr.4965. [Epub ahead of print]
  12. Kim KJ, Yoon KY and Lee BY. 2012. Low molecular weight fucoidan from the sporophyll of Undaria pinnatifida suppresses inflammation by promoting the inhibition of mitogen-activated protein kinases and oxidative stress in RAW 264.7 cells. Fitoterapia 83, 1628-1635. http://dx.doi.org/10.1016/j.fitote.2012.09.014.
  13. Lawrence T, Willoughby DA and Gilroy DW. 2002. Anti-inflammatory lipid mediators and insights into resolution of inflammation. Nat Rev Immunol 2, 787-795. https://doi.org/10.1038/nri915
  14. Lebovic DI, Bentzien F, Chao VA, Garrett EN, Meng YG and Taylor RN. 2000. Induction of an angiogenic phenotype in endometriotic stromal cell cultures by interleukin-$1{\beta}$. Mol Hum Reprod 6, 269-275. https://doi.org/10.1093/molehr/6.3.269
  15. Lee MR and Dominguez C. 2005. MAP kinase p38 inhibitors: clinical results and an intimate look at their interactions with p38 alpha protein. Curr Med Chem 12, 2979-2994. https://doi.org/10.2174/092986705774462914
  16. Lee S, Lee YS, Jung SH, Kang SS and Shin KH. 2003. Anti-oxidant activities of fucosterol from the marine algae Pelvetia siliquosa. Arch Pharm Res 26, 719-722. https://doi.org/10.1007/BF02976680
  17. Lee YS, Shin KH, Kim BK and Lee S. 2004. Anti-diabetic activities of fucosterol from Pelvetia siliquosa. Arch Pharm Res 27, 1120-1122. https://doi.org/10.1007/BF02975115
  18. Maeda H, Hosokawa M, Sashima T, Takahashi N, Kawada T and Miyashita K. 2006. Fucoxanthin and its metabolite, fucoxanthinol, suppress adipocyte differentiation in 3T3-L1 cells. Int J Mol Med 18, 147-152.
  19. Libby P. 2006. Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr 83, 456S-460S.
  20. Makarov SS. 2001. NF-${\kappa}B$ in rheumatoid arthritis: a pivotal regulator of inflammation, hyperplasia, and tissue destruction. Arthritis Res 3, 200-206. https://doi.org/10.1186/ar300
  21. Marks-Konczalik J, Chu SC and Moss J. 1998. Cytokine-mediated transcriptional induction of the human inducible nitric oxide synthase gene requires both activator protein 1 and nuclear factor ${\kappa}B$-binding sites. J Biol Chem 273, 22201-22208. https://doi.org/10.1074/jbc.273.35.22201
  22. Nathan C. 1992. Nitric oxide as a secretory product of mammalian cells. FASEB J 6, 3051-3064.
  23. Packard RR and Libby P. 2008. Inflammation in atherosclerosis: from vascular biology to biomarker discovery and risk prediction. Clin Chem 54, 24-38.
  24. Pan MH, Hong HM, Lin CL, Jhang AZ, Tsai JH, Badmaev V, Nagabhushanam K, Ho CT and Chen WJ. 2011. Semethylselenocysteine inhibits lipopolysaccharide-induced NF-${\kappa}B$ activation and iNOS induction in RAW 264.7 murine macrophages. Mol Nutr Food Res 55, 723-732. http://dx.doi.org/10.1002/mnfr.201000481.
  25. Park HJ, Lee MK, Park YB, Shin YC and Choi MS. 2010. Beneficial effects of Undaria pinnatifida ethanol extract on diet-induced-insulin resistance in C57BL/6J mice. Food Chem Toxicol 49, 727-733. http://dx.doi.org/10.1016/j.fct.2010.11.032.
  26. Sachindra NM, Sato E, Maeda H, Hosokawa M, Niwano Y, Kohno M and Miyashita K. 2007. Radical scavenging and singlet oxygen quenching activity of marine carotenoid fucoxanthin and its metabolites. J Agric Food Chem 55, 8516-8522. https://doi.org/10.1021/jf071848a
  27. Schwab C and McGeer PL. 2008. Inflammatory aspects of Alzheimer disease and other neurodegenerative disorders. J Alzheimers Dis, 13: 359-369. https://doi.org/10.3233/JAD-2008-13402
  28. Sizemore N, Leung S and Stark GR. 1999. Activation of phosphatidylinositol 3-kinase in response to interleukin-1 leads to phosphorylation and activation of the NF-kappaB p65/ RelA subunit. Mol Cell Biol 19, 4798-4805. https://doi.org/10.1128/MCB.19.7.4798
  29. Solinas G, Marchesi F, Garlanda C, Mantovani A and Allavena P. 2010. Inflammation-mediated promotion of invasion and metastasis. Cancer Metastasis Rev 29, 243-248. http://dx.doi.org/10.1007/s10555-010-9227-2.
  30. Xie QW, Whisnant R and Nathan C. 1993. Promoter of the mouse gene encoding calcium-independent nitric oxide synthase confers inducibility by interferon ${\gamma}$ and bacterial lipopolysaccharide. J Exp Med 177, 1779-1784. https://doi.org/10.1084/jem.177.6.1779
  31. Yan X, Chuda Y, Suzuki M and Nagata T. 1999. Fucoxanthin as the major antioxidant in Hijikia fusiformis, a common edible seaweed. Biosci Biotechnol Biochem 63, 605-607. https://doi.org/10.1271/bbb.63.605
  32. Yoo MS, Shin JS, Choi HE, Cho YW, Bang MH, Baek NI and Lee KT. 2012. Fucosterol isolated from Undaria pinnatifida inhibits lipopolysaccharide-induced production of nitric oxide and pro-inflammatory cytokines via the inactivation of nuclear factor-${\kappa}B$ and p38 mitogen-activated protein kinase in RAW264.7 macrophages. Food Chem 135, 967-975. http://dx.doi.org/10.1016/j.foodchem.2012.05.039.
  33. Yoshimura A. 2006. Signal transduction of inflammatory cytokines and tumor development. Cancer Sci 97, 439-447. https://doi.org/10.1111/j.1349-7006.2006.00197.x
  34. Zhang G and Ghosh S. 2000. Molecular mechanisms of NF-${\kappa}B$ activation induced by bacterial lipopolysaccharide through Toll-like receptors. J Endotoxin Res 6, 453-457. https://doi.org/10.1177/09680519000060060701

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