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

• Published in: BMB reports Vol. 46; no. 12; pp. 594 - 599
• Main Authors: Lee, E.J., Konkuk University, Seoul, Republic of korea, Jeong, K.W., Konkuk University, Seoul, Republic of korea, Shin, A.R., Konkuk University, Seoul, Republic of korea, Jin, B.H., Konkuk University, Seoul, Republic of korea, Jnawali, H.N., Konkuk University, Seoul, Republic of korea, Jun, B.H., Konkuk University, Seoul, Republic of korea, Lee, J.Y., Bioinformatics & Molecular Design Research Center, Seoul, Republic of Korea, Heo, Y.S., Konkuk University, Seoul, Republic of korea, Kim, Y.M., Konkuk University, Seoul, Republic of korea
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society for Biochemistry and Molecular Biology 01.12.2013; 생화학분자생물학회
• Subjects: Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - metabolism; Anti-Inflammatory Agents - pharmacology; Binding Sites; Cell Line; Cell Survival - drug effects; Chemokine CXCL2 - metabolism; Docking model,Eriodictyol,Anti-inflammatory activity,STD-NMR; Flavanones - chemistry; Flavanones - metabolism; Flavanones - pharmacology; FLAVONOIDE; FLAVONOIDES; FLAVONOIDS; Humans; Hydrogen Bonding; JNK Mitogen-Activated Protein Kinases - chemistry; JNK Mitogen-Activated Protein Kinases - metabolism; Mice; Molecular Docking Simulation; NIH 3T3 Cells; Nitrites - metabolism; Protein Binding; Protein Structure, Tertiary; Signal Transduction - drug effects; Tumor Necrosis Factor-alpha - metabolism; 화학
• ISSN: 1976-6696; 1976-670X
• DOI: 10.5483/BMBRep.2013.46.12.092

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.