Kim Jun Ho, Kim Mi-Yeon, Kim Jong-Hoon, Cho Jae Youl
Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746.
School of Systems Biological Science, Soongsil University, Seoul 156-743.
Biomol Ther (Seoul). 2015 Sep;23(5):414-20. doi: 10.4062/biomolther.2015.036. Epub 2015 Sep 1.
Flavonoids, such as fisetin (3,7,3',4'-tetrahydroxyflavone), are plant secondary metabolites. It has been reported that fisetin is able to perform numerous pharmacological roles including anti-inflammatory, anti-microbial, and anti-cancer activities; however, the exact anti-inflammatory mechanism of fisetin is not understood. In this study, the pharmacological action modes of fisetin in lipopolysaccharide (LPS)-stimulated macrophage-like cells were elucidated by using immunoblotting analysis, kinase assays, and an overexpression strategy. Fisetin diminished the release of nitric oxide (NO) and reduced the mRNA levels of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-α, and cyclooxygenase (COX)-2 in LPS-stimulated RAW264.7 cells without displaying cytotoxicity. This compound also blocked the nuclear translocation of p65/nuclear factor (NF)-κB. In agreement, the upstream phosphorylation events for NF-κB activation, composed of Src, Syk, and IκBα, were also reduced by fisetin. The phospho-Src level, triggered by overexpression of wild-type Src, was also inhibited by fisetin. Therefore, these results strongly suggest that fisetin can be considered a bioactive immunomodulatory compound with anti-inflammatory properties through suppression of Src and Syk activities.
黄酮类化合物，如非瑟酮（3,7,3',4'-四羟基黄酮），是植物的次生代谢产物。据报道，非瑟酮能够发挥多种药理作用，包括抗炎、抗菌和抗癌活性；然而，非瑟酮的确切抗炎机制尚不清楚。在本研究中，通过免疫印迹分析、激酶测定和过表达策略阐明了非瑟酮在脂多糖（LPS）刺激的巨噬细胞样细胞中的药理作用模式。非瑟酮减少了一氧化氮（NO）的释放，并降低了LPS刺激的RAW264.7细胞中诱导型NO合酶（iNOS）、肿瘤坏死因子（TNF）-α和环氧化酶（COX）-2的mRNA水平，且未表现出细胞毒性。该化合物还阻断了p65/核因子（NF）-κB的核转位。同样，非瑟酮也降低了由Src、Syk和IκBα组成的NF-κB激活的上游磷酸化事件。非瑟酮还抑制了由野生型Src过表达引发的磷酸化Src水平。因此，这些结果强烈表明，非瑟酮可被认为是一种具有抗炎特性的生物活性免疫调节化合物，通过抑制Src和Syk的活性发挥作用。
