Binding model for eriodictyol to Jun-N terminal kinase and its anti-inflammatory signaling pathway

作者：Lee Eunjung; Jeong Ki Woong; Shin Areum; Jin Bonghwan; Jnawali Hum Nath; Jun Bong Hyun; Lee Jee Young; Heo Yong Seok; Kim Yangmee^*

来源：BMB Reports, 2013, 46(12): 594-599.

DOI：10.5483/BMBRep.2013.46.12.092

• Anti-inflammatory activity
• Docking model
• Eriodictyol
• Flavonoid
• STD-NMR

The anti-inflammatory activity of eriodictyol and its mode of action were investigated. Eriodictyol suppressed tumor necrosis factor (mTNF)-alpha, inducible nitric oxide synthase (miNOS), interleukin (mIL)-6, macrophage inflammatory protein (mMIP)-1, and mMIP-2 cytokine release in LPS-stimulated macrophages. We found that the anti-inflammatory cascade of eriodictyol is mediated through the Toll-like Receptor (TLR)4/CD14, p38 mitogen-activated protein kinases (MAPK), extracellular-signalregulated kinase (ERK), Jun-N terminal kinase (JNK), and cyclooxygenase (COX)-2 pathway. Fluorescence quenching and saturation-transfer difference (STD) NMR experiments showed that eriodictyol exhibits good binding affinity to JNK, 8.79 x 10(5) M-1. Based on a docking study, we propose a model of eriodictyol and JNK binding, in which eriodictyol forms 3 hydrogen bonds with the side chains of Lys55, Met111, and Asp169 in JNK, and in which the hydroxyl groups of the B ring play key roles in binding interactions with JNK. Therefore, eriodictyol may be a potent anti-inflammatory inhibitor of JNK.

• 出版日期2013-12-31