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Bulletin of the Korean Chemical Society (BKCS)

ISSN 0253-2964(Print)
ISSN 1229-5949(Online)
Volume 34, Number 9
BKCSDE 34(9)
September 20, 2013

Title	Binding Model of Fisetin and Human c-Jun NH₂-Terminal Kinase 1 and Its Anti-inflammatory Activity
Author	Hum Nath Jnawali, Eunjung Lee, Ki-Woong Jeong, Yong-Seok Heo, Yangmee Kim*
Keywords	c-Jun N-terminal kinase 1, Fisetin, Anti-inflammatory activity, Docking model, STD-NMR
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 × 108 M−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.
Page	2629 - 2634
Full Text	PDF

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