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

Bulletin of the Korean chemical society

Ki-Woong Jeong¹  Hum Nath Jnawali¹  Eunjung Lee¹  Yangmee Kim¹  Yong-Seok Heo¹ 

关键词: c-Jun N-terminal kinase 1;    Fisetin;    Anti-inflammatory activity;    Docking model;    STD-NMR;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

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.

【 授权许可】

Unknown