생약학회지 (Korean Journal of Pharmacognosy)

  • 제41권1호
  • /
  • Pages.14-20
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  • 2010
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  • 0253-3073(pISSN)
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  • 2288-9299(eISSN)
한국생약학회 (The Korean Society of Pharmacognosy)
권호 표지

Fupenjic Acid의 대식세포에서 LPS에 의해 유도되는 iNOS와 COX-2 발현 및 Cytokine들의 생성 저해 효과

Inhibition of LPS-induced iNOS, COX-2 Expression and Cytokines Production by Fupenjic Acid in Macrophage Cells

  • Yun, Chang-Hyeon (Department of pharmaceutical Biochemistry, College of Pharmacy, Kyung-Hee University) ;
  • Shin, Ji-Sun (Department of pharmaceutical Biochemistry, College of Pharmacy, Kyung-Hee University) ;
  • Park, Hee-Juhn (Division of Environmental Botany, Sangji University) ;
  • Park, Jong-Hee (College of Pharmacy, Pusan National University) ;
  • Lee, Kyung-Tae (Department of pharmaceutical Biochemistry, College of Pharmacy, Kyung-Hee University)
  • 투고 : 2010.01.06
  • 발행 : 2010.03.31
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초록

In this study, we investigated the anti-inflammatory effects of fupenjic acid (FA) isolated from the Potentilla discolor in both RAW 264.7 and mouse primary peritoneal macrophage cells. FA pretreatment significantly inhibited nitric oxide (NO) and prostaglandin $E_2(PGE_2)$ productions in the lipopolysaccharide (LPS)-induced RAW 264.7 and mouse primary peritoneal macrophage cells. Consistent with these observations, Western blot and RT-PCR analyses revealed that FA inhibited the LPS-induced expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels. In addition, FA reduced the release of tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-6 (IL-6). These results suggest that the down regulation of iNOS and COX-2 expression and TNF-$\alpha$ and IL-6 production by fupenjic acid are responsible for its anti-inflammatory effects.

키워드

참고문헌

  1. Park, H.-J., Lee, k.-T. and Park, J.-H. (2007) Isolation of Two steroids and a triterpenoid from the roots of Potentilla discolor. Kor. J. Pharmacogn. 38: 354-357
  2. Shoyakan (ed.) (1985) Encyclopedia of Chinese Medicinal Drugs, 2438-2438, Shanghai Science & Technology, Tokyo.
  3. Tomczyk M, Latte KP. (2009) Potentilla--a review of its phytochemical and pharmacological profile. J. Ethnopharmacol. 122: 184-204 https://doi.org/10.1016/j.jep.2008.12.022
  4. Syiem, D., Syngai G., Khup, P. Z., Khongwir. B. S., Kharbuli, B. and Kayang, H. (2002) Hypoglycemic effects of Potentilla fulgens L in normal and alloxan-induced diabetic mice. J. Ethnopharmacol. 83: 55-61. https://doi.org/10.1016/S0378-8741(02)00190-3
  5. Zhao, C., Qiao, W., Zhang, Y. W., Lu, B. and Duan, H. Q. (2008) Study on anti-diabetes active fraction and constituents from Potentilla chinensis. Zhongguo Zhong Yao Za Zhi. 33: 680-682.
  6. Xue, P. F., Zhao, Y. Y., Wang, B. and Liang, H. (2006) Secondary metabolites from Potentilla discolor Bunge (Rosaceae). Biochem. Syst. Ecol. 34: 825-828. https://doi.org/10.1016/j.bse.2006.07.003
  7. Jie, Y., Xiao-Qing., C., Xiao-Xiao., L., Yuan, C., Mao-Xiang, L. and Qiang, W. (2008) Structural determination of two newtriterpenoids from Potentilla discolor Bunge by NMR techniques Magn. Reson. Chem. 46: 794-797 https://doi.org/10.1002/mrc.2253
  8. Cho, W., Nam, J.-W., Kang, H.-J., Windono, T., Seo E.-K. and Lee, K.-T. (2009) Zedoarondiol isolated from the rhizoma of Curcuma heyneana is involved in the inhibition of iNOS, COX-2 and pro-inflammatory cytokines via the downregulation of NF-$\kappaB$ pathway in LPS-stimulated murine macrophages Int. Immunopharmacol. 9: 1049-1057 https://doi.org/10.1016/j.intimp.2009.04.012
  9. Iontcheva, I., Amar, S., Zawawi, K. H., Kantarci, A. and Van Dyke, T. E. (2004). Role for moesin in lipopolysaccharide-stimulated signal transduction. Infect Immun. 72: 2312-2320. https://doi.org/10.1128/IAI.72.4.2312-2320.2004
  10. Stuehr, H. H. J., Kwon, N. S., Weise, M. and Nathan, C. (1991) Purification of the cytokine-induced macrophage nitric oxide synthase: an FAD- and FMN- containing flavoprotein. Proc. Natl. Sci. USA. 88: 7773-7777. https://doi.org/10.1073/pnas.88.17.7773
  11. McCartney-Francis, N., Allen, J. B., Mizel, D. E., Albina, J. E., Xie, Q. W., Nathan, C. F. and Wahl, S. M. (1993) Suppression of arthritis by an inhibitor of nitic oxide synthase. J. Exp. Med. 178: 749-754. https://doi.org/10.1084/jem.178.2.749
  12. Weisz, A., Cicatiello, I. and Esumi, H. (1996) Regulation of the mouse inducible-type nitric oxide synthase gene promoter by interferon-gamma, bacterical lipopolysaccharide and NG-monomethyl- L-arginene. Biochem. J. 316: 209-215. https://doi.org/10.1042/bj3160209
  13. Masferrer, J., Zweifel B. S., Manning, P. T., Hauser, S. D., Leahy, K. M., Smith, W. G., Isacson, P. C. and Seibert, K. (1994) Selective inhibition of inducible cyclooxygenase 2 in vivo is anti-inflammatory and nonulcerogenic. Proc. Natl. Acad. Sci. U.S.A. 91: 3228-3232. https://doi.org/10.1073/pnas.91.8.3228
  14. Seibert, K., Zhang, Y., Leahy, K., Hauser, S., Masferrer, J., Perkins, W., Lee, L. and Ksakson, P. (1994) Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc. Natl. Acad. Sci. U.S.A. 91: 12013-12017. https://doi.org/10.1073/pnas.91.25.12013
  15. Beutler, B. and Cerami, A. (1989) The biology of cachectin/TNF-R primary mediator of the host response. Annu. ReV. Immunol. 7: 625-655. https://doi.org/10.1146/annurev.iy.07.040189.003205
  16. Dendorfer, U. (1996) Molecular biology of cytokines. Artif. Organs. 20: 437-444. https://doi.org/10.1111/j.1525-1594.1996.tb04529.x
  17. Hilliquin P, Borderie D, Hernvann A, Menkes CJ, Ekindjian OG. (1997) Nitric oxide as S-nitrosoproteins in rheumatoid arthritis. Arthritis Rheum. 40(8): 1512-1517 https://doi.org/10.1002/art.1780400820
  18. Nava, E., Palmer, R. M. and Moncada, S. (1992) The role of metric oxide in endotoxic shock: effects of NG-monomethyl-L-arginine. J. Cardiovasc. Pharmacol. 12: 132-134
  19. Hoffmann, J. A., Kafatos, F. C., Janeway, C. A. and Ezekowitz, R. A. (1999) Phylogenetic perspectives in innate immunity. Science 284: 1313-1318 https://doi.org/10.1126/science.284.5418.1313
  20. Janeway, C. A. Jr. and Medzhitov, R. (2002) Innate immune recognition. Annu. Rev. Immunol. 20: 197-216. https://doi.org/10.1146/annurev.immunol.20.083001.084359
  21. Liu, S. F. and Malik, A. B. (2005) NF-$\kappaB$ activation as a pathological mechanism of septic shock and inflammation. Am. J. Physiol. Lung Cell Mol. Physiol. 290: L622-L645.
  22. Feldmann, M., Brennan, F. M. and Maini, R. N. (1996) Role of cytokines in rheumatoid arthritis. Annu. Rev. Immunol. 14: 397-440. https://doi.org/10.1146/annurev.immunol.14.1.397
  23. Karin, M. and Ben-Neriah, Y. (2000) Phosphorylation meets ubiquitination: the control of NF-B activity. Annu. Rev. Immunol. 18: 621-663. https://doi.org/10.1146/annurev.immunol.18.1.621