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柠烯通过调控 STAT3/miR-214 信号通路改善溃疡性结肠炎。

Limonin ameliorates ulcerative colitis by regulating STAT3/miR-214 signaling pathway.

机构信息

The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, China.

Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.

出版信息

Int Immunopharmacol. 2019 Oct;75:105768. doi: 10.1016/j.intimp.2019.105768. Epub 2019 Aug 2.

Abstract

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-α 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.

摘要

溃疡性结肠炎(UC)是一种主要的炎症性肠病(IBD),已成为全球公共卫生问题。柠檬苦素是从柑橘中提取的一种三萜类化合物,具有抗炎和细胞凋亡的作用。然而,柠檬苦素在治疗 UC 中的疗效和作用机制尚不清楚。在这项研究中,我们首先通过检查疾病活动指数(DAI)、结肠长度、结肠组织学和细胞/趋化因子水平,研究了柠檬苦素对葡聚糖硫酸钠(DSS)诱导的 UC 的体内治疗效果。我们发现柠檬苦素可显著降低 DAI、肠道损伤和 TNF-α和 IL-6 等促炎细胞因子的水平。在体外,柠檬苦素可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,我们证明柠檬苦素通过下调 p-STAT3/miR-214 水平来改善 UC 的预后。综上所述,我们的结果表明柠檬苦素是一种新型治疗药物,有望转化为临床应用,改善 UC 的预后。

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