Limonin ameliorates ulcerative colitis by regulating STAT3/miR-214 signaling pathway
Limonin ameliorates ulcerative colitis by regulating STAT3/miR-214 signaling pathway
复制标题
柠檬苦素通过调节 STAT3/miR-214 信号通路改善溃疡性结肠炎
DOI：
10.1016/j.intimp.2019.105768
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发表时间：
2019-10-01
影响因子：
5.6
通讯作者：
Chen, Yugen
中科院分区：
文献类型：
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作者：
Liu, Shijia;Zhang, Shufang;Chen, Yugen
溃疡性结肠炎（UC）是一种主要的炎症性肠病（IBD），已成为一个全球性的公共卫生问题。柠檬苦素是从柑橘中提取的三萜，具有抗炎症和细胞凋亡的能力。然而，柠檬苦素治疗UC的疗效和潜在机制尚不清楚。在这项研究中，我们首先通过观察疾病活动指数（DAI）、结肠长度、结肠组织学和细胞/趋化因子水平的变化，研究柠檬苦素对葡聚糖硫酸钠（DSS）诱导的UC的治疗作用。我们发现柠檬苦素显著降低DAI、肠道损伤和促炎细胞因子水平，如tnf - α和IL-6。在体外实验中，柠檬苦素显著抑制培养的正常结肠上皮细胞中促炎细胞因子的产生。在机制上，我们证明柠檬苦素主要通过下调p-STAT3/miR-214水平改善UC的预后。综上所述，我们的研究结果表明柠檬苦素是一种新型的治疗药物，有望转化为临床改善UC的预后。
Ulcerative colitis (UC) is a major inflammatory bowel disease (IBD) which has become a global public health problem. Limonin is a triterpenoid extracted from citrus which possesses the capacities to against inflammations and cell apoptosis. However, the efficacy and the underlying mechanisms of limonin in the treatment of UC remain unclear. In this study, we first investigated the therapeutic effects of limonin on dextran sodiumsulfate (DSS)-induced UC in vivo by examining the changes of disease activity index (DAI), the colon length, the colon histology, and cyto/chemokine levels. We found that limonin markedly reduced DAI, intestinal damages, and the levels of pro-inflammatory cytokines, such as TNF-alpha and IL-6. In vitro, limonin significantly repressed the productions of pro-inflammatory cytokines in cultured normal colonic epithelial cells. Mechanistically, we demonstrated that limonin improved the prognosis of UC mainly through downregulating p-STAT3/miR-214 levels. Collectively, our results suggested that limonin was a novel therapeutic agent and it was expected to be translated into the clinic to improve the prognosis of UC.