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)
  • 투고 : 2013.06.03
  • 심사 : 2013.06.08
  • 발행 : 2013.09.20

초록

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.

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