Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
권호 표지
DOI QR코드

DOI QR Code

Binding Model of Fisetin and Human c-Jun NH2-Terminal Kinase 1 and Its Anti-inflammatory Activity

  • Jnawali, Hum Nath (Department of Bioscience and Biotechnology, Bio-Molecular Informatics Center, Institute of SMART Biotechnology, Konkuk University) ;
  • Lee, Eunjung (Department of Bioscience and Biotechnology, Bio-Molecular Informatics Center, Institute of SMART Biotechnology, Konkuk University) ;
  • Jeong, Ki-Woong (Department of Bioscience and Biotechnology, Bio-Molecular Informatics Center, Institute of SMART Biotechnology, Konkuk University) ;
  • Heo, Yong-Seok (Department of Chemistry, Konkuk University) ;
  • Kim, Yangmee (Department of Bioscience and Biotechnology, Bio-Molecular Informatics Center, Institute of SMART Biotechnology, Konkuk University)
  • Received : 2013.06.03
  • Accepted : 2013.06.08
  • Published : 2013.09.20
Download PDF
⟨ Previous Next ⟩

Abstract

Fisetin is a naturally occurring flavonoid with some anti-cancer and anti-inflammation capabilities. In this study, we perform docking studies between human c-Jun N-terminal kinase 1 (JNK 1) and fisetin and proposed a binding model of fisetin and JNK 1, in which the hydroxyl groups of the B ring and oxygen at the 4-position of the C ring play key roles in binding interactions with JNK. Fluorescence quenching and saturation-transfer difference (STD) NMR experiments showed that fisetin exhibits good binding affinity to JNK, $1.32{\times}10^8M^{-1}$. The anti-inflammatory activity of fisetin was also investigated. Fisetin significantly suppressed tumor necrosis factor, the NO production, and macrophage inflammatory cytokine release in LPS-stimulated RAW264.7 mouse macrophages. We found that the anti-inflammatory cascade of fisetin was mediated through the JNK, and cyclooxygenase (COX)-2 pathways. Our findings suggest the potential of fisetin as an anti-inflammatory agent.

Keywords

References

  1. Shin, E. M.; Zhou, H. Y., Guo, L. Y., Kim, J. A.; Lee, S. H.; Merfort, I.; Kang, S. S., Kim, H. S.; Kim, S.; Kim, Y. S. Int. Immunopharmacol. 2008, 8, 1524. https://doi.org/10.1016/j.intimp.2008.06.008
  2. Laskin, D. L.; Pendino, K. J. Annu. Rev. Pharmacol. Toxicol. 1995, 35, 655. https://doi.org/10.1146/annurev.pa.35.040195.003255
  3. Park, Y. D.; Jin, C. H.; Choi, D. S.; Byun, M. W.; Jeong, I. Y. Arch. Pharm. Res. 2011, 34, 1277. https://doi.org/10.1007/s12272-011-0806-8
  4. Hald, A.; Rono, B.; Lund, L. R.; Egerod, K. L. Mediat. Inflamm. 2012, 2012, 157894.
  5. Nguyen, M. T.; Chen, A.; Lu, W. J.; Fan, W.; Li, P. P.; Oh, D. Y.; Patsouris, D. PLoS One 2012, 7, e34976. https://doi.org/10.1371/journal.pone.0034976
  6. Pan, C. H.; Kim, E. S.; Jung, S. H.; Nho, C. W.; Lee, J. K. Arch. Pharm. Res. 2008, 31, 1447. https://doi.org/10.1007/s12272-001-2129-7
  7. van Rooijen, N.; Sanders, A. J. Leukoc. Biol. 1997, 62, 702.
  8. Lee, Y. J.; Eun, J. R. Korean J. Physiol. Pharmacol. 2012, 16, 131. https://doi.org/10.4196/kjpp.2012.16.2.131
  9. Lee, J. W.; Bae, C. J.; Choi, Y. J.; Kim, S. I.; Kim, N. H.; Lee, H. J.; Kim, S. S.; Kwon, Y. S.; Chun, W. Korean J. Physiol. Pharmacol. 2012, 16, 107. https://doi.org/10.4196/kjpp.2012.16.2.107
  10. Nathan, C. FASEB J. 1992, 6, 3051.
  11. Laubach, V. E.; Shesely, E. G.; Smithies, O.; Sherman, P. A. Proc. Natl. Acad. Sci. U.S.A 1995, 92, 10688. https://doi.org/10.1073/pnas.92.23.10688
  12. Chen, W.; Tang, Q.; Gonzales, M. S.; Bowdwn, G. T. Oncogene. 2001, 20, 3921. https://doi.org/10.1038/sj.onc.1204530
  13. Reinhart, K.; Karzai, W. Crit. Care Med. 2001, 29, S121. https://doi.org/10.1097/00003246-200107001-00037
  14. Park, Y. D.; Jin, C. H.; Choi, D. S.; Byun, M. W.; Jeong, I. Y. Arch. Pharm. Res. 2011, 34, 1277. https://doi.org/10.1007/s12272-011-0806-8
  15. Serafini, M.; Peluso, I.; Raguzzini, A. Proc. Nutr. Soc. 2010, 69, 273. https://doi.org/10.1017/S002966511000162X
  16. Cunningham, B. D.; Threadgill, M. D.; Groundwater, P. W.; Dale, I. L.; Hickman, J. A. Anticancer Drug Des. 1992, 7, 365.
  17. Noroozi, M., Angerson, W. J.; Lean, M. E. Am. J. Clin. Nutr. 1998, 67, 1210.
  18. Higa, S.; Hirano, T.; Kotani, M.; Matsumoto, M.; Fujita, A.; Suemura, M.; Kawase, I.; Tanaka, T. J. Allergy Clin. Immunol. 2003, 111, 1299. https://doi.org/10.1067/mai.2003.1456
  19. Chen, Y. C.; Shen, S. C.; Lee, W. R.; Lin, H. Y.; Ko, C. H.; Shih, C. M.; Yang, L. L. Arch. Toxicol. 2002, 76, 351. https://doi.org/10.1007/s00204-002-0346-6
  20. Sung, B.; Pandey, M. K.; Aggarwal, B. B. Mol. Pharmacol. 2007, 71, 1703. https://doi.org/10.1124/mol.107.034512
  21. 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
  22. Lee, J. Y.; Jeong, K. W.; Lee, J. U.; Kang, D. I.; Kim, Y. Bioorg. Med. Chem. 2009, 17, 1506. https://doi.org/10.1016/j.bmc.2009.01.004
  23. 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. EMBO J. 2004, 23, 2185. https://doi.org/10.1038/sj.emboj.7600212
  24. 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.
  25. 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
  26. 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
  27. Jeon, Y. J.; Han, S. B.; Ahn, K. S.; Kim, H. M. Immunopharmacol. 1999, 43, 1. https://doi.org/10.1016/S0162-3109(99)00032-6
  28. Jung, H. W.; Mahesh, R.; Park, J. H.; Boo, Y. C.; Park, K. M.; Park, Y. K. Int. Immunopharmacol. 2010, 10, 155. https://doi.org/10.1016/j.intimp.2009.10.010
  29. Moller, M.; Denicola, A. Biochem. Mol. Biol. Educ. 2002, 30, 309. https://doi.org/10.1002/bmb.2002.494030050089
  30. Funakoshi-Tago, M.; Nakamura, K.; Tago, K.; Mashino, T.; Kasahara, T. Int. Immunopharmacol. 2011, 11, 1150. https://doi.org/10.1016/j.intimp.2011.03.012

Cited by

  1. 3,6-Dihydroxyflavone Has Antituberculosis Activity and Suppresses Lung Inflammation vol.38, pp.8, 2017, https://doi.org/10.1002/bkcs.11175