Curcumin ameliorates dextran sulfate sodium-induced experimental colitis by blocking STAT3 signaling pathway
Curcumin ameliorates dextran sulfate sodium-induced experimental colitis by blocking STAT3 signaling pathway
复制标题
姜黄素通过阻断 STAT3 信号通路改善葡聚糖硫酸钠诱导的实验性结肠炎
DOI：
10.1016/j.intimp.2013.06.020
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发表时间：
2013-10-01
影响因子：
5.6
通讯作者：
Gan, Hua Tian
中科院分区：
文献类型：
--
作者：
Liu, Liu;Liu, Yu Lan;Gan, Hua Tian
背景与目的：尽管一系列研究表明，姜黄素可通过抑制核因子-κB（NF-κB）的激活，在结肠炎中发挥抗炎作用，但截至目前，姜黄素的这些抗炎作用是否也归因于其抑制信号转导及转录激活因子3（STAT3）通路的能力，尚未在实验性结肠炎中得到验证。本研究旨在探讨姜黄素是否能通过抑制STAT3通路，在实验性结肠炎中发挥治疗作用。
材料与方法：在葡聚糖硫酸钠（DSS）诱导的实验性结肠炎模型中给予姜黄素。观察疾病活动指数（DAI）和组织学评分。通过蛋白质免疫印迹分析检测磷酸化STAT3。采用电泳迁移率变动分析（EMSA）评估STAT3二聚体的DNA结合活性。通过酶联免疫吸附试验检测肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β的表达。使用髓过氧化物酶（MPO）检测试剂盒测定MPO活性。
结果：给予姜黄素的小鼠，其DAI和组织学评分显著改善，且姜黄素处理后，DSS诱导的结肠炎小鼠中磷酸化STAT3活性、STAT3二聚体的DNA结合活性、MPO活性、IL-1β及TNF-α表达的升高均显著降低。
结论：姜黄素通过抑制STAT3通路，在实验性结肠炎中发挥有益作用，这可能有助于更好地理解姜黄素治疗结肠炎的作用机制。（C）2013爱思唯尔出版社。保留所有权利。
Background and aims: Although a series of studies have shown that curcumin can exert anti-inflammatory effects in colitis by inhibiting NF-kappa B activation, whether these anti-inflammatory effects of curcumin are also attributed to its ability to inhibiting STAT3 pathway has never been tested in experimental colitis to date. The purpose of the study was to investigate whether curcumin could exert its therapeutic effects in experimental colitis by inhibiting STAT3 pathway.Materials and methods: Curcumin was administered in experimental colitis induced by dextran sulfate sodium (DSS). The disease activity index (DAI) and histological score were observed. The phospho-STAT3 was assessed by western blot analysis. The DNA-binding activity of STAT3 dimers was evaluated by electrophoretic mobility shift assay (EMSA). The expression of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta was measured by enzyme-linked immunosorbent assay. Myeloperoxidase (MPO) activity was determined by using MPO assay kit.Results: A significant improvement was observed in DAI and histological score in mice with curcumin, and the increases in phospho-STAT3 activity, DNA-binding activity of STAT3 dimers, MPO activity, IL-1 beta, and TNF-alpha expression in mice with DSS-induced colitis were significantly reduced following treatment with curcumin.Conclusion: Curcumin exerts beneficial effects in experimental colitis by the suppression of STAT3 pathway, which may therefore provide a better understanding of the mechanism of action for curcumin in treating colitis. (C) 2013 Elsevier B.V. All rights reserved.