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首页> 外文期刊>The Korean Journal of Physiology & Pharmacology >Scutellarein Reduces Inflammatory Responses by Inhibiting Src Kinase Activity
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Scutellarein Reduces Inflammatory Responses by Inhibiting Src Kinase Activity

机译：黄cut素通过抑制Src激酶活性降低炎症反应

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摘要

Flavonoids are plant pigments that have been demonstrated to exert various pharmacological effects including anti-cancer, anti-diabetic, anti-atherosclerotic, anti-bacterial, and anti-inflammatory activities. However, the molecular mechanisms in terms of exact target proteins of flavonoids are not fully elucidated yet. In this study, we aimed to evaluate the anti-inflammatory mechanism of scutellarein (SCT), a flavonoid isolated from Erigeron breviscapus , Clerodendrum phlomidis and Oroxylum indicum Vent that have been traditionally used to treat various inflammatory diseases in China and Brazil. For this purpose, a nitric oxide (NO) assay, polymerase chain reaction (PCR), nuclear fractionation, immunoblot analysis, a kinase assay, and an overexpression strategy were employed. Scutellarein significantly inhibited NO production in a dose-dependent manner and reduced the mRNA expression levels of inducible NO synthase (iNOS) and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-activated RAW264.7 cells. In addition, SCT also dampened nuclear factor (NF)-κB-driven expression of a luciferase reporter gene upon transfection of a TIR-domain-containing adapter-inducing interferon-β (TRIF) construct into Human embryonic kidney 293 (HEK 293) cells; similarly, NF-κ B nuclear translocation was inhibited by SCT. Moreover, the phosphorylation levels of various upstream signaling enzymes involved in NF-κB activation were decreased by SCT treatment in LPS-treated RAW264.7 cells. Finally, SCT strongly inhibited Src kinase activity and also inhibited the autophosphorylation of overexpressed Src. Therefore, our data suggest that SCT can block the inflammatory response by directly inhibiting Src kinase activity linked to NF-κB activation.
机译：黄酮类化合物是植物色素，已被证明具有多种药理作用，包括抗癌，抗糖尿病，抗动脉粥样硬化，抗菌和抗炎活性。然而，关于类黄酮的确切靶蛋白的分子机制尚未完全阐明。在这项研究中，我们旨在评估黄cut素（SCT）的抗炎机制，黄CT素是从灯盏花，灯盏花和印度通心草中分离出来的类黄酮，这些黄酮在中国和巴西传统上用于治疗各种炎性疾病。为此，采用了一氧化氮（NO）测定，聚合酶链反应（PCR），核分级分离，免疫印迹分析，激酶测定和过表达策略。黄cut苷以剂量依赖性方式显着抑制NO的产生，并降低脂多糖（LPS）激活的RAW264.7细胞中诱导型NO合酶（iNOS）和肿瘤坏死因子（TNF）-α的mRNA表达水平。此外，在将含有TIR域的衔接子诱导干扰素-β（TRIF）构建体转染到人胚肾293（HEK 293）细胞中后，SCT还抑制了核因子（NF）-κB驱动的荧光素酶报道基因表达。 ;同样，NF-κB核易位受到SCT的抑制。此外，在LPS处理的RAW264.7细胞中，通过SCT处理，参与NF-κB活化的各种上游信号酶的磷酸化水平降低。最后，SCT强烈抑制Src激酶活性，也抑制过表达Src的自磷酸化。因此，我们的数据表明，SCT可通过直接抑制与NF-κB激活有关的Src激酶活性来阻断炎症反应。

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