Department of Gastroenterology and Geriatrics Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Int Immunopharmacol. 2012 Jan;12(1):169-74. doi: 10.1016/j.intimp.2011.11.007. Epub 2011 Dec 11.
Activation of nuclear factor-kappa B (NF-κB), which controls transcription of various pro-inflammatory cytokine genes, has been shown to play a critical role in the pathogenesis of ulcerative colitis (UC). Parthenolide, a sesquiterpene lactone compound isolated from extracts of the herb Feverfew (Tanacetum parthenium), has been demonstrated to be a potent inhibitor of NF-κB activation. This study was designed to investigate the effects of parthenolide on an experimental murine colitis model.
Experimental colitis was induced by dextran sulfate sodium (DSS), and mice were divided into 3 groups: normal control, DSS+saline, and DSS+parthenolide. The disease activity index (DAI) and histological score were observed. The tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels were measured by enzyme-linked immunosorbent assay. Phospho-IκBα, IκBα and phospho-NF-κB p65 expression were assessed by western blot analysis. Myeloperoxidase (MPO) activity was determined by using MPO assay kit.
Administration of parthenolide significantly reduced the severity of DSS-induced colitis as assessed by DAI and histological score, and resulted in downregulation of MPO activity and phospho-NF-κB p65 expression by the blockade of phosphorylation and subsequent degradation of IκB protein, strikingly reduced the production of TNF-α and IL-1β.
Parthenolide exerts beneficial effects in experimental colitis and may therefore provide a useful therapeutic approach for the treatment of UC.
核因子-κB（NF-κB）的激活控制着各种促炎细胞因子基因的转录，已被证明在溃疡性结肠炎（UC）的发病机制中起着关键作用。倍半萜内酯化合物小白菊内酯从植物 Feverfew（Tanacetum parthenium）的提取物中分离出来，已被证明是 NF-κB 激活的有效抑制剂。本研究旨在研究小白菊内酯对实验性结肠炎模型的影响。
通过葡聚糖硫酸钠（DSS）诱导实验性结肠炎，将小鼠分为 3 组：正常对照组、DSS+生理盐水组和 DSS+小白菊内酯组。观察疾病活动指数（DAI）和组织学评分。通过酶联免疫吸附试验测量肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β水平。通过 Western blot 分析评估磷酸化 IκBα、IκBα 和磷酸化 NF-κB p65 的表达。通过 MPO 测定试剂盒测定髓过氧化物酶（MPO）活性。
小白菊内酯的给药显著降低了 DAI 和组织学评分评估的 DSS 诱导的结肠炎的严重程度，并通过抑制磷酸化和随后的 IκB 蛋白降解来下调 MPO 活性和磷酸化 NF-κB p65 表达，显著减少 TNF-α 和 IL-1β 的产生。
小白菊内酯在实验性结肠炎中发挥有益作用，因此可能为 UC 的治疗提供有用的治疗方法。
