title: Binding model for eriodictyol to Jun-N terminal kinase and its anti-inflammatory signaling pathway.
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-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 × 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.
authors.forename: Eunjung
authors.initials: E
authors.lastname: Lee
authors.forename: Ki-Woong
authors.initials: KW
authors.lastname: Jeong
authors.forename: Areum
authors.initials: A
authors.lastname: Shin
authors.forename: Bonghwan
authors.initials: B
authors.lastname: Jin
authors.forename: Hum Nath
authors.initials: HN
authors.lastname: Jnawali
authors.forename: Bong-Hyun
authors.initials: BH
authors.lastname: Jun
authors.forename: Jee-Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Heo
authors.affiliation: Department of Bioscience and Biotechnology, Bio-Molecular Informatics Center, Institute of KU Biotechnology, Konkuk University, Seoul 143-701, Korea ymkim@konkuk.ac.kr.
authors.forename: Yangmee
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D054426:Chemokine CXCL2 / Q000378:metabolism; D044950:Flavanones / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D006860:Hydrogen Bonding; D048031:JNK Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D062105:Molecular Docking Simulation; D041681:NIH 3T3 Cells; D009573:Nitrites / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D054426:Chemokine CXCL2; D044950:Flavanones; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases; C007619:eriodictyol