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http://dx.doi.org/10.5483/BMBRep.2013.46.12.092

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

Lee, Eunjung (Department of Bioscience and Biotechnology, Bio-Molecular Informatics Center, Institute of KU Biotechnology, Konkuk University)
Jeong, Ki-Woong (Department of Bioscience and Biotechnology, Bio-Molecular Informatics Center, Institute of KU Biotechnology, Konkuk University)
Shin, Areum (Department of Bioscience and Biotechnology, Bio-Molecular Informatics Center, Institute of KU Biotechnology, Konkuk University)
Jin, Bonghwan (Department of Bioscience and Biotechnology, Bio-Molecular Informatics Center, Institute of KU Biotechnology, Konkuk University)
Jnawali, Hum Nath (Department of Bioscience and Biotechnology, Bio-Molecular Informatics Center, Institute of KU Biotechnology, Konkuk University)
Jun, Bong-Hyun (Department of Bioscience and Biotechnology, Bio-Molecular Informatics Center, Institute of KU Biotechnology, Konkuk University)
Lee, Jee-Young (Drug Discovery Team, Bioinformatics & Molecular Design Research Center)
Heo, Yong-Seok (Department of Chemistry, Konkuk University)
Kim, Yangmee (Department of Bioscience and Biotechnology, Bio-Molecular Informatics Center, Institute of KU Biotechnology, Konkuk University)
Publication Information
BMB Reports / v.46, no.12, 2013 , pp. 594-599 More about this Journal
Abstract
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-signal-regulated 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, $8.79{\times}10^5M^{-1}$. 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.
Keywords
Anti-inflammatory activity; Docking model; Eriodictyol; Flavonoid; STD-NMR;
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