Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Anti-inflammatory Activity of 3,6,3'-Trihydroxyflavone in Mouse Macrophages, In vitro

  • Lee, Eunjung (Department of Bioscience and Biotechnology, Bio-Molecular Informatics Center, Institute of KU Biotechnology, Konkuk University) ;
  • Jeong, Ki-Woong (Department of Bioscience and Biotechnology, Bio-Molecular Informatics Center, Institute of KU Biotechnology, Konkuk University) ;
  • Shin, Areum (Department of Bioscience and Biotechnology, Bio-Molecular Informatics Center, Institute of KU Biotechnology, Konkuk University) ;
  • Kim, Yangmee (Department of Bioscience and Biotechnology, Bio-Molecular Informatics Center, Institute of KU Biotechnology, Konkuk University)
  • Received : 2014.05.03
  • Accepted : 2014.05.17
  • Published : 2014.11.20
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Abstract

Numerous studies have examined the role of flavonoids in modulating inflammatory responses in vitro. In this study, we found a novel flavonoid, 3,6,3'-trihydroxyflavone (1), with anti-inflammatory effects. Anti-inflammatory activity and mechanism of action were examined in mouse macrophages stimulated with lipopolysaccharide (LPS). Our results showed that the anti-inflammatory effects of 1 are mediated via p38 mitogen-activated protein kinase (p38 MAPK), Jun-N terminal kinase (JNK), and the extracellular-signal-regulated kinase (ERK) pathway in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Binding studies revealed that 1 had a high binding affinity to JNK1 ($1.568{\times}10^8M^{-1}$) and that the 3- and 6-hydroxyl groups of the C-ring and A-ring of 1 participated in hydrogen bonding interactions with the side chains of Asn114 and Lys55, respectively. The oxygen at the 3' position of the B-ring formed a hydrogen bond with side chain of Met111. Therefore, 1 could be a potential inhibitor of JNKs, with potent anti-inflammatory activity.

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References

  1. Balkwill, F.; Charles, K. A.; Mantovani, A. Cancer Cell 2005, 7, 211. https://doi.org/10.1016/j.ccr.2005.02.013
  2. Coussens, L. M.; Werb, Z. Nature 2002, 420, 860. https://doi.org/10.1038/nature01322
  3. Flossmann, E.; Rothwell, P. M. Lancet 2007, 369, 1603. https://doi.org/10.1016/S0140-6736(07)60747-8
  4. Wiseman, B. S.; Werb, Z. Science 2002, 296, 1046. https://doi.org/10.1126/science.1067431
  5. de Visser, K. E.; Eichten, A.; Coussens L. M. Nat. Rev. Cancer 2006, 6, 24. https://doi.org/10.1038/nrc1782
  6. Dobrovolskaia, M. A.; Vogel, S. N. Microbes Infect. 2002, 4, 903. https://doi.org/10.1016/S1286-4579(02)01613-1
  7. Stichtenoth, D. O.; Frolich, J. C. Br. J. Rheumatol. 1998, 37, 246. https://doi.org/10.1093/rheumatology/37.3.246
  8. Laubach, V. E.; Shesely, E. G.; Smithies, O.; Sherman, P. A. Proc. Natl. Acad. Sci. USA 1995, 92, 10688. https://doi.org/10.1073/pnas.92.23.10688
  9. Chen, W.; Tang, Q.; Gonzales, M. S.; Bowdwn, G. T. Oncogene 2001, 20, 3921. https://doi.org/10.1038/sj.onc.1204530
  10. Ichijo, H. Oncogene 1999, 18, 6087. https://doi.org/10.1038/sj.onc.1203129
  11. Middleton, E.; Kandaswami, C.; Theoharides, T. C. Pharmacol. Rev. 2000, 52, 673.
  12. Hari, K. N.; Kesava, V. K. R.; Ravikumar, A.; Supriya, M.; Ram, C.; Stanley, A. S. Clin. Diagn. Lab. Immunol. 2004, 11, 63.
  13. Cunningham, B. D.; Threadgill, M. D.; Groundwater, P. W.; Dale, I. L.; Hickman, J. A. Anticancer Drug Des. 1992, 7, 365.
  14. Serafini, M.; Peluso, I.; Raguzzini, A. Proc. Nutr. Soc. 2010, 69, 272. https://doi.org/10.1017/S0029665110000613
  15. Kim, O. K.; Murakami, A.; Nakamura, Y.; Ohigashi, H. Cancer Lett. 1998, 125, 199. https://doi.org/10.1016/S0304-3835(97)00513-2
  16. Lee, E.; Shin, S.; Kim, J.-K.; Woo, E.-R.; Kim, Y. Bull. Korean Chem. Soc. 2012, 33, 2878. https://doi.org/10.5012/bkcs.2012.33.9.2878
  17. Hirosumi, J.; Tuncman, G.; Chang, L.; Gorgun, C. Z.; Uysal, K. T.; Maeda, K.; Karin, M.; Hotamisligil, G. S. Nature 2002, 420, 333. https://doi.org/10.1038/nature01137
  18. Baek, S.; Kang, N. J.; Popowicz, G. M.; Arciniega, M.; Jung, S. K.; Byun, S.; Song, N. R.; Heo, Y.-S.; Kim, B. Y.; Lee, H. J.; Holak, T. A.; Augustin, M.; Bode, A. M.; Huber, R.; Dong, Z.; Lee, K. W. J. Mol. Biol. 2013, 425, 411. https://doi.org/10.1016/j.jmb.2012.10.019
  19. Lee, E.; Shin S.; Lee, J. Y.; Lee, S.; Kim, J. K.; Yoon, D. Y.; Woo, E. R.; Kim, Y. Bull. Korean Chem. Soc. 2012, 33, 2219. https://doi.org/10.5012/bkcs.2012.33.7.2219
  20. Lee, J.-Y.; Jeong, K.-W.; Shin, S.; Lee, J.-U.; Kim, Y. Bioorg. Med. Chem. 2009, 17, 5408. https://doi.org/10.1016/j.bmc.2009.06.059
  21. Jeong, K.-W.; Lee, J.-Y.; Kang, D.-I.; Lee, J.-U.; Shin, S. Y.; Kim, Y. J. Nat. Prod. 2009, 72, 719. https://doi.org/10.1021/np800698d
  22. Lee, J.-Y.; Kim, J.-K.; Cho, M.-C.; Shin, S.; Yoon, D.-Y.; Heo, Y. S.; Kim, Y. J. Nat. Prod. 2010, 73, 1261. https://doi.org/10.1021/np100148m
  23. Scudiero, D. A.; Shoemaker, R. H.; Paull, K. D.; Monks, A.; Tierney, S.; Nofziger, T. H.; Currens, M. J.; Seniff, D.; Boyd, M. R. Cancer Res. 1988, 48, 4827.
  24. Green, L. C.; Wagner, D. A.; Glogowski, J.; Skipper, P. L.; Wishnok, J. S.; Tannenbaum, S. R. Anal. Biochem. 1982, 126, 131. https://doi.org/10.1016/0003-2697(82)90118-X
  25. Kim, K. H.; Shim, J. H.; Seo, E. H.; Cho, M. C.; Kang, J. W.; Kim, S. H.; Yu, D. Y.; Song, E. Y.; Lee, H. G.; Sohn, J. H.; Kim, J. M.; Dinarello, C. A.; Yoon, D. Y. J. Immunol. Methods 2008, 333, 38. https://doi.org/10.1016/j.jim.2007.12.017
  26. Kim, J. K.; Lee, E.; Shin, S.; Jeong, K.W.; Lee, J. Y.; Bae, S. Y.; Kim, S. H.; Lee, J.; Kim, S. R.; Lee, D. G.; Hwang, J. S.; Kim, Y. J. Biol. Chem. 2011, 286, 41296. https://doi.org/10.1074/jbc.M111.269225
  27. Lee, E.; Kim, J. K.; Shin, S.; Jeong, K. W.; Shin, A.; Lee, J.; Lee, D. G.; Hwang, J. S.; Kim, Y. Biochim. Biophys. Acta 2013, 1828, 271. https://doi.org/10.1016/j.bbamem.2012.10.028
  28. Waetzig, V.; Herdegen, T. Br. J. Pharmacol. 2005, 26, 455.
  29. Heo, Y.-S.; Kim, S.-K.; Seo, C. I.; Kim, Y. K.; Sung, B.-J.; Lee, H. S.; Lee, J. I.; Park, S.-Y.; Kim, J. H.; Hwang, K. Y.; Hyun, Y.-L.; Jeon, Y. H.; Ro, S.; Cho, J. M.; Lee, T. G.; Yang, C.-H. The EMBO Journal 2004, 23, 2185. https://doi.org/10.1038/sj.emboj.7600212
  30. Tang, J.; Luan, F.; Chen, X. Bioorg. Med. Chem. 2006, 14, 3210. https://doi.org/10.1016/j.bmc.2005.12.034
  31. Vieth, M.; Hirst, J. D.; Dominy, B. N.; Daigler, H.; Brooks, C. L. J. Comput. Chem. 1998, 19, 1623. https://doi.org/10.1002/(SICI)1096-987X(19981115)19:14<1623::AID-JCC8>3.0.CO;2-L
  32. Bogoyevitch, M. A.; Kobe, B. Microbiol. Mol. Biol. Rev. 2006, 70, 1061. https://doi.org/10.1128/MMBR.00025-06

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