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

作者：Jnawali Hum Nath; Lee Eunjung; Jeong Ki Woong; Heo Yong Seok; Kim Yangmee^*

来源：Bulletin of the Korean Chemical Society, 2013, 34(9): 2629-2634.

DOI：10.5012/bkcs.2013.34.9.2629

• c-Jun N-terminal kinase 1
• Fisetin
• Anti-inflammatory activity
• Docking model
• STD-NMR

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 INK. Fluorescence quenching and saturation-transfer difference (STD) NMR experiments showed that fisetin exhibits good binding affinity to INK, 1.32 x 10(8) 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 INK, and cyclooxygenase (COX)-2 pathways. Our findings suggest the potential of fisetin as an anti-inflammatory agent.

• 出版日期2013-9-20