Binding model for eriodictyol to Jun-N terminal kinase and its anti-inflammatory signaling pathway |
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| Authors: | Eunjung Lee Ki-Woong Jeong Areum Shin Bonghwan Jin Hum Nath Jnawali Bong-Hyun Jun Jee-Young Lee Yong-Seok Heo Yangmee Kim |
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| Institution: | 1.Department of Bioscience and Biotechnology, Bio-Molecular Informatics Center, Institute of KU Biotechnology, Konkuk University, Seoul 143-701, Korea;2.Drug Discovery Team, Bioinformatics & Molecular Design Research Center, Seoul 120-749, Korea;3.Department of Chemistry, Konkuk University, Seoul 143-701, Korea |
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| Abstract: | The anti-inflammatory activity of eriodictyol and its mode of action were investigated. Eriodictyol suppressed tumor necrosis factor (mTNF)-α, 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 × 105 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. BMB Reports 2013; 46(12): 594-599] |
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| Keywords: | Anti-inflammatory activity Docking model Eriodictyol Flavonoid STD-NMR |
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