Binding model for eriodictyol to Jun-N terminal kinase and its anti-inflammatory signaling pathway
Lee, E; Jeong, KW; Shin, A; Jin, B; Jnawali, HN; Jun, BH; Lee, JY; Heo, YS; Kim, Y
| HERO ID | 2232934 |
|---|---|
| In Press | No |
| Year | 2013 |
| Title | Binding model for eriodictyol to Jun-N terminal kinase and its anti-inflammatory signaling pathway |
| Authors | Lee, E; Jeong, KW; Shin, A; Jin, B; Jnawali, HN; Jun, BH; Lee, JY; Heo, YS; Kim, Y |
| Journal | B M B Reports |
| Volume | 46 |
| Issue | 12 |
| Page Numbers | 594-599 |
| 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. |
| Doi | 10.5483/BMBRep.2013.46.12.092 |
| Pmid | 24195792 |
| Wosid | WOS:000328931200005 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | Anti-inflammatory activity; Docking model; Eriodictyol; Flavonoid; STD-NMR |