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Antiinflammatory Effects of New Chemical Compounds, HS-1580 Series (HS-1580, HS-1581, HS-1582)

신화학물질 HS-1580 유도체(HS-1580 HS-1581 HS-1582)의 항염증 효과

  • Kim, Ji-Young (Department of Biology, College of Natural Sciences, Pusan National University) ;
  • Kim, Kyun-Ha (Department of Biology, College of Natural Sciences, Pusan National University) ;
  • Suh, Hong-Suk (Department of Chemistry, College of Natural Sciences, Pusan National University) ;
  • Choi, Won-Chul (Department of Biology, College of Natural Sciences, Pusan National University)
  • 김지영 (부산대학교 자연과학대학 생물학과) ;
  • 김균하 (부산대학교 자연과학대학 생물학과) ;
  • 서홍석 (부산대학교 자연과학대학 화학과) ;
  • 최원철 (부산대학교 자연과학대학 생물학과)
  • Published : 2006.12.01

Abstract

HS-1580 series (HS-1580, HS-1581, HS-1582) can produce anti-imflammatory effects were synthesized from the marine algae extraction in 2,3,6-tribromo-4,5-dihydroxy benzyl methyl ether (TDB). Raw 264.7 cells were pre-treated with $1{\mu}g/{\mu}l$ lipopolysaccharide (LPS) and later treated with HS-1580 series. These cells of inflammatory mediators were tested as well. Nitric oxide (NO) is related to autoimmune disease and is produced by inducible NOS (iNOS). When treated with HS-1580 series, the product of NO will reduce in a dose-dependent manner. HS-1580 series significantly inhibit the iNOS protein expression. Cyclooxygenase (COX) involves with the various physiologic events and catalyzes in prostaglandin. HS-1580 series also inhibit the COX-2 protein expression as well as pro-inflammatory cytokines production such as tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})\;and\;interluekin-1{\alpha]\;(IL-1{\beta})$. These upcoming results suggest that HS-1580 series have anti-inflammatory efforts in Raw 264.7 cells by inhibiting such as iNOS, COX-2, $TNF-{\alpha}\;and\;IL-1{\beta}$ as inflammatory mediators.

본 연구는 염증 형성과정에 있어서, 해조류로부터 항염증 효과를 나타내는 물질을 분리하여 그 유도체인 HS-1580 series (HS-1580, HS-1581, HS-1582)를 합성하였다. Nitiric oxide (NO) 생성에 있어 Raw 264.7 cells에서 lipopolysaccharide(LPS) 단독으로 처리하였을 때는 대조군에서보다 4배 이상 NO 생성이 증가하였지만, HS-1580 series를 처리하고 LPS를 처리한 군에서는 농도 의존적으로 NO 생성이 억제되었다. HS-1580 series가 NO 생성 자체를 억제함으로서 NO 함량이 감소되었는지, inducible NOS (iNOS) 단백질 발현을 억제에 기인한 것인지 알아보기 위해서 Western blot으로 조사하였다. iNOS protein 발현이 HS-1580 series에 의해서 억제되었고 HS-1580 series가 cyclooxygenase-2 (COX-2), tumor necrosis factor-a $TNF-{\alpha}$$interluekin-1{\beta}\;(IL-1{\beta})$ 생성을 농도 의존적으로 억제시켰다. 이상의 결과로 HS-1580 series가 iNOS 단백질 발현 억제에 기인한 NO 생성억제, COX-2 발현 억제 및 pro-inflammatory cytokines인 $TNF-{\alpha}$$IL-1{\beta}$ 생성을 억제하는 항염증 효과를 가짐을 알 수 있다.

Keywords

References

  1. Ban, H. S., Suzuki, K., Lim, S. S., Jung, S. H. and Lee, S. H. 2004. Inhibition of lipopolysaccharide-induced expression of inducible nitric oxide synthase and tumor necrosis factor-${\alpha}$ by 2-hydroxychalcone derivatives in RAW 264.7 cells. Biochem. Pharmacol. 67, 1549-1557 https://doi.org/10.1016/j.bcp.2003.12.016
  2. Bosca, L., Zeine, M. and Trares, P. G. 2005. Nitric oxide and cell viability in inflammatory cells; a role for NO in macrophage function and fate. Toxicology 208, 249-258 https://doi.org/10.1016/j.tox.2004.11.035
  3. Chou, T. Z., Fu, E. and Shen, E. C. 2003. Chitosan inhibits prostaglandin $E_2$ formation and cyclooxygenase-2 induction in lipopolysaccahride-treated RAW 264.7 macrophages. Biochem. Biophys. Res. Commun. 307, 451-458 https://doi.org/10.1016/S0006-291X(03)01210-5
  4. Chung, H. Y., Choi, H. R., Park, H. J., Choi, J. S. and Choi, W. C. 2001. Peroxinitrite scavenging and cytoprotective activity of 2,3,6-tlibromo - 4,5-dihydroxybenzyl methyl ether from the marine alga symphyocladia latiuscula. J. Arig Food Chem. 49, 3614-3621 https://doi.org/10.1021/jf0101206
  5. Cohen, R. I., Hassell, A. M., Ye, X., Marzouk, K. and Liu, S. F. 2003. Lipopolysacchalide down-regulates inducible nitric oxide synthase expression in swine heart in vivo. Biochem. Biophys. Res. Commun. 307, 451-458 https://doi.org/10.1016/S0006-291X(03)01210-5
  6. Dinarello, C. A. 2000 Proinflammatory cytokines. Chest 118, 503-508 https://doi.org/10.1378/chest.118.2.503
  7. Guastadisegni, C., Nicolini, A., Balduzzi, M., Ajmone-Cat, M. A. and Minghetti, L. 2002. Modulation of $PGE_2$ and $TNF-{\alpha}$ by nitric oxide in resting and Ips-activated raw 264.7 cells. Cytokine 19, 175-180 https://doi.org/10.1006/cyto.2002.1955
  8. Hong, C. H., Hur, S. K., Oh, O-J., Kim, S. S., Nam, K. A. and Lee, S. K. 2002. Evaluation of natural products on inhibition of inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) in cultured mouse macrophage cells. J. Ethmopharmacol. 83, 153-159 https://doi.org/10.1016/S0378-8741(02)00205-2
  9. Jacobs, A. T. and Ignarro, L. J. 2003. Cell density-enhanced expression of inducible nitric oxide synthase in murine macrophages mediated by intereron-${\beta}$. Nitric-Oxide 8, 222-230 https://doi.org/10.1016/S1089-8603(03)00027-2
  10. Jhun, B. S., Jin, Q., Oh, Y. T., Kim, S. S. and Kong, Y. 2004. 5-Aminomidazole-4-carboxamide ribiside suppresses lipopolysaccharide-induced TNF-${\alpha}$ production through inhibition of phosphatidylinositol 3-kinase/Akt activation in RAW 264.7 murine macrophages. Biochem. Biophys. Res. Commun. 318, 372-380 https://doi.org/10.1016/j.bbrc.2004.04.035
  11. Ju, H. K., Baek, S. H., An, R. B., Bae, K. H. and Son, K. H. 2003. Inhibitory effects of nardostachin on nitric oxide, prostaglandin $E_2$, and tumor necrosis factor-${\alpha}$ production in lipopolysaccharide activated macrophages. Biol. Pharm. Bull. 26, 1375-1378 https://doi.org/10.1248/bpb.26.1375
  12. Kamei, K. I., Haruyama, T., Mie, M., Yasuko, Y, Aizawa, M. and Kobatake, E. 2003. Development of immune cellular biosensing system for assessing chemicals on inducible nitric oxide synthase signaling activator. Anal. Biochem. 320, 75-81 https://doi.org/10.1016/S0003-2697(03)00360-9
  13. Kim, J. K., Noh, J. H., Lee, S. Choi, J. S. and Suh, H. 2002. The first total gynthesis of 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (TDB) and its antioxidant activity. Bull. Korean Chem. Soc. 23, 661-662 https://doi.org/10.5012/bkcs.2002.23.5.661
  14. Kim, H. J., Jang, S. I., Kim, Y. J., Chung, H. T. and Yun, Y. G. 2004. Scopoletin suppresses pro-inflammatory cytokines and $PGE_2$ from LPS-stimulated cell line, RAW 264.7 cells. Fitoterapia 75, 261-266 https://doi.org/10.1016/j.fitote.2003.12.021
  15. Kim, Y. H., Ko, W. S., Ha, M. S., Lee, C. H. and Choi, B. T. 2000. The production of nitric oxide and TNF-${\alpha}$ in peritoneal macrophages is inhibited by Dichroa feblifuga Lour. J. Ethnopharmacol. 69, 35-43 https://doi.org/10.1016/S0378-8741(99)00143-9
  16. Kim, Y. K., Kim, R. G., Park, S. J., Ha, J. H. and Choi, J. W. 2002. In vitro anti-inflammatory activity of Kaloponaxsaponin A isolated from Kalopanax pictus in murine macrophage RAW 264.7 cells. Biol. Pharm. Bull. 25, 472-476 https://doi.org/10.1248/bpb.25.472
  17. Lanza-Jacoby, S., Dicker, A. P., Miller,S., Rosato, F. E. and Flynn, J. T. 2004. Cyclooxygenase (COX)-2-dependent effects of the inhibitor SC236 when combined with ionizing radiation in mammary tumor cells derived from HER-2/neu mice. Mor. Cancer Ther. 3, 417-424 https://doi.org/10.4161/cbt.3.4.803
  18. Lee, D. U., Kang, Y. J., Park, M. K., Lee, Y. S. and Seo, H. G. 2003. Effects of 13-alkyl-substituted berberine alkaloids on the expression of COX-II TNF-${\alpha}$, iNOS, and IL-12 production in LPS-stimulated macrophages. Life Sci. 73, 1401-1402 https://doi.org/10.1016/S0024-3205(03)00435-1
  19. Lee, J. Y., Lee, M. H., Park, H. R., Choi, J. S., Seo, H. S., An, W. G. and Choi, W. C. 2003. Antioxidants of new compounds from maline Algae prevent cell death of endothelial cells. J. Fish Pathol. 16, 39-49
  20. Li, J., Simmons, D. L. and Tsang, B. K. 1996. Regulation of hen granulose cell prostaglandin production by transforming growth factors during follicular development : involvement of cyclooxygenase II. Endocrinology 137(6), 2522-2529 https://doi.org/10.1210/en.137.6.2522
  21. Liu, G., Zhai, Q., Schaffner, D., Bradburne, C. and Wu, A. 2004. IL-15 induces IFN-${\beta}$ and iNOS gene expression, and antiviral activity of murine macrophage RAW 264.7 cells. Immunol. Lett. 91, 171-178 https://doi.org/10.1016/j.imlet.2003.11.015
  22. Miller, M. J. and Grrisham, M. B. 1995. Mediators Inflamm. 4, 387-396 https://doi.org/10.1155/S0962935195000639
  23. Morikawa, A., Koide, N., Sugiyama, T., Mu, M. M. and Hassan, F. 2004. The enhancing action of D-galactosamine on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells. FEMS Immunol. Med. Microbiol. 41, 211-218 https://doi.org/10.1016/j.femsim.2004.03.008
  24. Mukhopadhyay, S., Srivastava, V. M. L., Murthy, P. K. and Hasnain, S. E. 2004. Poorer $NF-{\kappa}B$ signaling by microfilariae in macrophages from BALB/c mice affects their ability to produce cytotoxic levels of nitric oxide to kill microfilariae. FEBS Lett. 567, 275-280 https://doi.org/10.1016/j.febslet.2004.04.081
  25. Nelson, E. J., Connoly, J., and McArthur, P. 2003. Nitric oxide and S-nitrosylation: excitotoxic and cell signaling mechanism. Biol. Cell. 95, 3-8 https://doi.org/10.1016/S0248-4900(03)00004-2
  26. Opal, S. M. and Depalo, V. A. 2000 Anti-inflammatory cytokines. Chest 117, 1162-1172 https://doi.org/10.1378/chest.117.4.1162
  27. Otto, J. C. and Smith, W. L. 1996. Photolabeling prostaglandin endoperoxide H synthase-1 with 3-tirfluoro-(m-[$^{125}I$]iodophenyl) diazirine as probe of membrane association and the cyclooxygenase active site. J. Bio. Chem. 26, 9906-9910
  28. Sakata, K., Hirose, Y., Qiao, Z., Tanaka, T. and Mori, H. 2003. Inhibition of inducible isoforms of cyclooxygenases and nitric oxide synthase by flavonoid hesperidin in mouse macrophage cell line. Cancer Lett. 199, 139-145 https://doi.org/10.1016/S0304-3835(03)00386-0
  29. Schneider, C. P., Schwacha, M. G. and Chaudry, I. H. 2004. The role of interleukin-10 in the regulation of the systemic inflammatory response following trauma-hemorrhage. Biochim. Biophys. Acta 1689, 22-32 https://doi.org/10.1016/j.bbadis.2004.01.003
  30. Shin, K. M., Kim, Y. H., Park, W. S., Kang, I. S. and Ha, J. H. 2004. Inhibition of methanol extract from the fruits of Kochia scoparia on lipopolysaccharide-induced nitric oxide, prostaglandin $E_2$, and tumor necrosis factor-${\alpha}$ production from murine macrophage Raw 264.7 cells. Biol. Pharm. Bull. 27, 538-543 https://doi.org/10.1248/bpb.27.538
  31. Thomsen, L. L. and Miles, D. W. 1998. Role of nitric oxide in tumour progression: Lessons from human tumuors. Cancer Metastasis Rev. 17, 107-108 https://doi.org/10.1023/A:1005912906436
  32. Wang, C., Schuller Levis, G. B., Lee, E. B., Levis, W. R. and Lee, D. W. 2004. Platycodin D and D3 isolated from the root of Platycodon grandiflorum modulate the production of nitric oxide and secretion of TNF-${\alpha}$ in activated RAW 264.7 cells. Int. Immunopharmacol. 4, 1039-1049 https://doi.org/10.1016/j.intimp.2004.04.005
  33. Wu, D., and Meydani, S. N. 2004. Mechanism of age-associated up-regulation in macrophage $PGE_2$ synthesis. Brain Behav. Immun. 18, 487-494 https://doi.org/10.1016/j.bbi.2004.05.003

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