BMB Reports : 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: Eun Jung Lee, Ki Woong Jeong, Areum Shin, Bong Hwan Jin, Hum Nath Jnawali, Bong Hyun Jun, Jee Young Lee, Yong Seok Heo, Yang Mee Kim
• Format: Journal Article
• Language: Korean
• Published: 생화학분자생물학회 30.12.2013
• Subjects: Anti-inflammatory activity; Docking model; Eriodictyol; Flavonoid; STD-NMR
• ISSN: 1976-6696

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]