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The Pharmaceutical Society of Korea (대한약학회)
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Suppressive Effects of Furonaphthoquinone NFD-37 on the Production of Lipopolysaccharide-Inducible Inflammatory Mediators in Macrophages RAW 264.7

  • Kim Min-Hee (College of Pharmacy & Research Center for Bioresource and Health, Chungbuk National University) ;
  • Shin Hyun-Mo (College of Pharmacy & Research Center for Bioresource and Health, Chungbuk National University) ;
  • Lee Yong Rok (School of Chemical Engineering and Technology, Yeungnam University) ;
  • Chung Eun Yong (College of Pharmacy & Research Center for Bioresource and Health, Chungbuk National University) ;
  • Chang Yoon Sook (College of Pharmacy & Research Center for Bioresource and Health, Chungbuk National University) ;
  • Min Kyung Rak (College of Pharmacy & Research Center for Bioresource and Health, Chungbuk National University) ;
  • Kim Youngsoo (College of Pharmacy & Research Center for Bioresource and Health, Chungbuk National University)
  • Published : 2005.10.01
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Abstract

2-Methyl-2-(2-methylpropenyl)-2,3-dihydronaphthoquinone[2,3-b]furan-4,9-dione (N FD-37) is a synthetic furonaphthoquinone compound. In this study, we determined that NFD-37 could inhibit the lipopolysaccharide (LPS)-induced production of inflammatory mediators in macrophages RAW 264.7. This compound inhibited LPS-induced nitric oxide (NO) or prostaglandin (PG) $E_{2}$ production in dose-dependent manners, with $IC_{50}$ values of 7.2 ${\mu}M$ and 5.3 ${\mu}m$, respectively. As the positive controls, pyrrolidine dithiocarbamate (30 ${\mu}M$) exhibited a $57{\%}$ inhibition of NO production, and NS-398 ($1{\mu}M$) manifested a $48{\%}$ inhibition of $PGE_2$ production. The inhibitory effects of NFD-37 on NO and $PGE_2$ production were determined to occur in conjunction with the suppression of inducible NO synthase or cyclooxygenase-2 expression. NFD-37 also inhibited the production of LPS-inducible tumor necrosis factor-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-6, at $IC_{50}$ values of 4.8-8.9 ${\mu}M$. We also determined the anti-inflammatory efficacy of NFD-37 using carrageenin-induced paw edema in experimental mice.

Keywords

References

  1. Arakawa, T., Higuchi, K., Fukuda, T., Fujiwara, Y., Kobayashi, K., and Kuroki, T., Prostaglandins in the stomach: an update. J. Clin. Gastroenterol., 27, S1-S11 (1998) https://doi.org/10.1097/00004836-199807000-00001
  2. Becker, J. C., Domschke, W., and Pohle, T., Current approaches to prevent NSAID-induced gastropathy: COX selectivity and beyond. Br. J. Clin. Pharmacol., 58, 587-600 (2004) https://doi.org/10.1111/j.1365-2125.2004.02198.x
  3. Bovill, J. G., Pharmacology and clinical action of COX-2 selective NSAIDs. Adv. Exp. Med. Biol., 523, 201-214 (2003)
  4. Brater, D. C., Anti-inflammatory agents and renal function. Semin. Arthritis Rheum., 32, 33-42 (2002) https://doi.org/10.1053/sarh.2002.37216
  5. Crofford, L. J., Wilder, R. L., Ristimaki, A. P., Sano, H., Remmers, E. F., Epps, H. R., and Hla, T., Cyclooxygenase-1 and -2 expression in rheumatoid synovial tissues: effects of interleukin-$1\beta$, phorbol ester, and corticosteroids. J. Clin. Invest., 93, 1095-1101 (1994) https://doi.org/10.1172/JCI117060
  6. Guha, M. and Mackman, N., LPS induction of gene expression in human monocytes. Cell Signal., 13, 85-94 (2001) https://doi.org/10.1016/S0898-6568(00)00149-2
  7. Hopkins, S. J., The pathophysiological role of cytokines. Leg. Med., 5, S45-S57 (2003) https://doi.org/10.1016/S1344-6223(02)00088-3
  8. Ignarro, L. J., Nitric oxide as a unique signaling molecule in the vascular system: a historical overview. J. Physiol. Pharmacol., 53, 503-514 (2002)
  9. Inoue, H. and Tanabe, T., Transcriptional regulation of human prostaglandin endoperoxide synthase-2 gene in vascular endothelial cells. Adv. Exp. Med. Biol., 407, 139-144 (1997)
  10. Jones, K. J., Perris, A. D., Vernallis, A. B., Worthington, T., Lambert, P. A., and Elliott, T. S., Induction of inflammatory cytokines and nitric oxide in J774.2 cells and murine macrophages by lipoteichoic acid and related cell wall antigens from Staphylococcus epidermidis. J. Med. Microbiol., 54, 315-321 (2005) https://doi.org/10.1099/jmm.0.45872-0
  11. Kamimura, D., Ishihara, K., and Hirano, T., IL-6 signal transduction and its physiological roles: the signal orchestration model. Rev. Physiol. Biochem. Pharmacol., 149, 1-38 (2003) https://doi.org/10.1007/s10254-003-0012-2
  12. Koss, K., Satsangi, J., Welsh, K. I., and Jewell, D. P., Is interleukin-6 important in inflammatory bowel disease? Genes lmmun., 1, 207-212 (2000) https://doi.org/10.1038/sj.gene.6363658
  13. Lee, Y.R., Suk, J. Y., and Kim, B. S., One-pot construction of medium- and large-sized ring substituted furans: efficient conversion to dibenzofurans, coumestans, and 4-pyrones. Org. Lett., 2, 1387-1389 (2000) https://doi.org/10.1021/ol0056933
  14. Lowenstein, C. J., Alley, E. W., Raval, P., Snowman, A.M., Snyder, S. H., Russell, S. W, and Murphy, W. J., Macrophage nitric oxide synthase gene: two upstream regions mediate induction by interferon gamma and lipopolysaccharide. Proc. Natl. Acad. Sci. U.S.A., 15, 9730-9734 (1993) https://doi.org/10.1073/pnas.90.20.9730
  15. MacMicking, J., Xie, Q. W., and Nathan, C., Nitric oxide and macrophage function. Annu. Rev. Immunol., 15, 323-350 (1997) https://doi.org/10.1146/annurev.immunol.15.1.323
  16. Masferrer, J. L., Zweifel, B. S., Colburn, S. M., Ornberg, R. L., Salvemini, D., Isakson, P. and Seibert, K., The role of cyclooxygenase-2 in inflammation. Am. J. Ther., 2, 607-610 (1995) https://doi.org/10.1097/00045391-199509000-00005
  17. Prast, H. and Philippu, A., Nitric oxide as modulator of neuronal function. Prog. Neurobiol., 64, 51-68 (2001) https://doi.org/10.1016/S0301-0082(00)00044-7
  18. Sanceau, J., Kaisho, T., Hirano, T., and Wietzerbin, J., Triggering of the human interleukin-6 gene by interferon-$\gamma$ and tumor necrosis $factor-\alpha$ in monocytic cells involves cooperation between interferon regulatory factor-1, $NF-{\kappa}B$, and Sp1 transcription factors. J. Biol. Chem., 270, 27920-27931 (1995) https://doi.org/10.1074/jbc.270.46.27920
  19. Shin, H.-M., Kim, M.-H., Kim, B. H., Jung, S.-H., Kim, Yl S., Park, H. J., Hong, J. T., Min, K. R., and Kim, Yl, Inhibitory action of novel aromatic diamine compound on lipopolysaccharide-induced nuclear translocation of $NF-\kappa B$ without affecting $l\kappa B$ degradation. FEBS Lett., 571, 50-54 (2004) https://doi.org/10.1016/j.febslet.2004.06.056
  20. Tian, B. and Brasier, A. R., Identification of a nuclear factor ${\kappa}B$-dependent gene network. Recent Prog. Harm. Res., 58, 95-130 (2003) https://doi.org/10.1210/rp.58.1.95
  21. van den Berg, W. B., Joosten, L. A., and van de Loo, F. A., $TNF\alpha$ and IL-$1\beta$ are separate targets in chronic arthritis. Clin. Exp. Rheumatol., 17, S105-S114 (1999)
  22. Watkins, L. R., Nguyen, K. T., Lee, J. E., and Maier, S. F., Dynamic regulation of pro-inflammatory cytokines. Adv. Exp. Med. Biol., 461, 153-178 (1999) https://doi.org/10.1007/b102345
  23. Wong, P. K., Campbell, I. K., Egan, P. J., Ernst, M., and Wicks, I. P., The role of the interleukin-6 family of cytokines in inflammatory arthritis and bone turnover. Arthritis Rheum., 48, 1177-1189 (2003) https://doi.org/10.1002/art.10943