Ku Kuei-Ting, Huang Yu-Ling, Huang Yu-Jou, Chiou Wen-Fei
Institute of Life Science, College of Science and Engineering, National Taitung University, Taitung.
J Agric Food Chem. 2008 Oct 8;56(19):8911-8. doi: 10.1021/jf8019369. Epub 2008 Sep 11.
The anti-inflammatory effect of miyabenol A, a stilbene isolated from Vitis thunbergii, on lipopolysaccaride (LPS)-induced nitric oxide (NO) production in RAW264.7 macrophages was studied. Miyabenol A inhibited NO production (EC 50: 2.7 muM) and iNOS protein and mRNA expression in a parallel concentration-dependent manner. LPS-evoked NF-kappaB nuclear translocation and associated IkappaB degradation were abrogated by miyabenol A treatment. Phosphorylations of IKKalpha/beta, ERK1/2, JNK p38 MAPK, and Akt were observed in LPS-stimulated cells; nevertheless, miyabenol A selectively blocked IKKalpha/beta, p38, and Akt phosphorylation. Furthermore, LPS-stimulated IKKalpha/beta and Akt phosphorylation was abolished by p38 inhibitor SB203580. Wortmannin (a PI3K inhibitor) also attenuated LPS-induced IKKalpha/beta phosphorylation, although to a less extent than SB203580, but failed to affect p38 phosphorylation. These observations suggested that PI3K/Akt might lie downstream of p38 MAPK to coregulate LPS-induced IKKalpha/beta phosphorylation. Taken together, miyabenol A acted via interfering with p38 MAPK-related signal pathways to down-regulate IKK/IkappaB activation and NO production.
研究了从野生葡萄中分离得到的芪类化合物宫部醇A对脂多糖（LPS）诱导的RAW264.7巨噬细胞中一氧化氮（NO）生成的抗炎作用。宫部醇A以平行的浓度依赖性方式抑制NO生成（半数有效浓度：2.7 μM）以及诱导型一氧化氮合酶（iNOS）蛋白和mRNA表达。宫部醇A处理可消除LPS诱导的核因子κB（NF-κB）核转位及相关的IκB降解。在LPS刺激的细胞中观察到IκB激酶α/β（IKKα/β）、细胞外信号调节激酶1/2（ERK1/2）、c-Jun氨基末端激酶（JNK）、p38丝裂原活化蛋白激酶（MAPK）和蛋白激酶B（Akt）的磷酸化；然而，宫部醇A选择性地阻断IKKα/β、p38和Akt的磷酸化。此外，p38抑制剂SB203580可消除LPS刺激的IKKα/β和Akt磷酸化。渥曼青霉素（一种磷脂酰肌醇-3激酶（PI3K）抑制剂）也可减弱LPS诱导的IKKα/β磷酸化，尽管程度小于SB203580，但未能影响p38磷酸化。这些观察结果表明，PI3K/Akt可能位于p38 MAPK的下游，共同调节LPS诱导的IKKα/β磷酸化。综上所述，宫部醇A通过干扰p38 MAPK相关信号通路来下调IKK/IκB激活和NO生成。
