Gambogenic acid inhibits LPS-simulated inflammatory response by suppressing NF-κB and MAPK in macrophages
Gambogenic acid inhibits LPS-simulated inflammatory response by suppressing NF-κB and MAPK in macrophages
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Gambogenic Acid 通过抑制巨噬细胞中的 NF-κ B 和 MAPK 来抑制 LPS 模拟的炎症反应
DOI：
10.1093/abbs/gmw021
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发表时间：
2016-05-01
影响因子：
3.7
通讯作者：
Zhang, Haibing
中科院分区：
文献类型：
--
作者：
Yu, Xianjun;Zhao, Qun;Zhang, Haibing
炎症是身体组织对损伤和感染的反应。可以抑制炎症的化合物已经显示出具有潜在的治疗临床应用。藤黄酸（GEA）具有很强的抗肿瘤和抗炎活性。本文以脂多糖（LPS）刺激的巨噬细胞为模型，探讨GEA抗炎作用的分子机制。结果表明，GEA预处理可明显抑制LPS诱导模型中白细胞介素（IL）-1 α、IL-1 β、肿瘤坏死因子-α、IFN-β、IL-12 b和IL-23 a的产生，且呈剂量依赖性。此外，该药物显着减少一氧化氮（NO）的释放，并损害诱导型NO合酶和环氧合酶2的蛋白水平。GEA的作用可能与抑制核因子-κ B（NF-κ B B）和丝裂原活化蛋白激酶（MAPK）信号通路有关。这些结果表明，GEA可以抑制LPS刺激的炎症反应，部分通过减少NO的合成和NF-κ B B和MAPK的激活，这表明它可能成为一个有效的治疗药物，用于治疗炎症性疾病。
Inflammation is a response of body tissues to injury and infection. Compounds that can inhibit inflammation have been shown to have potential therapeutic clinical application. Gambogenic acid (GEA) has potent antitumor and anti-inflammatory activities. Herein, the molecular mechanisms of GEA's anti-inflammatory effect were investigated in lipopolysaccharide (LPS)-stimulated macrophage cells. The results showed that pretreatment with GEA could markedly inhibit interleukin (IL)-1 alpha, IL-1 beta, tumor necrosis factor-alpha, IFN-beta, IL-12b, and IL-23a production in a dose-dependent manner in LPS-induced model. Furthermore, this drug significantly reduced the release of nitric oxide (NO), and impaired the protein level of inducible NO synthase and the cyclooxygenase 2. The finding also showed that the effect of GEA may be related to the suppression of the nuclear factor-kappa B (NF-kappa B) and mitogen-activated protein kinase (MAPK) signaling pathway. These results indicate that GEA could suppress LPS-simulated inflammatory response partially by attenuating NO synthesis and NF-kappa B and MAPK activation, suggesting that it may become a potent therapeutic agent for the treatment of inflammatory diseases.