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Astragalin Attenuates Dextran Sulfate Sodium (DSS)-Induced Acute Experimental Colitis by Alleviating Gut Microbiota Dysbiosis and Inhibiting NF-κB Activation in Mice
Frontiers in Immunology ( IF 5.7 ) Pub Date : 2020-07-29 , DOI: 10.3389/fimmu.2020.02058
Lei Peng , Xiaoyu Gao , Long Nie , Jing Xie , Tianyi Dai , Chongying Shi , Liang Tao , Yan Wang , Yang Tian , Jun Sheng

With the ulcerative colitis (UC) incidence increasing worldwide, it is of great importance to prevent and treat UC. However, efficient treatment options for UC are relatively limited. Due to the potentially serious adverse effects of existing drugs, there is an increasing demand for alternative candidate resources derived from natural and functional foods. Astragalin (AG) is a type of anti-inflammatory flavonoid, with Moringa oleifera and Cassia alata being its main sources. In this study, we investigated the therapeutic effects of AG on mice with dextran sulfate sodium (DSS)-induced colitis. Our results suggested that AG treatment reduced weight loss and the disease activity index (DAI), prevented colon shortening and alleviated colonic tissue damage. AG treatment reduced the expression of pro-inflammatory cytokines and related mRNAs (such as TNF-α, IL-6, and IL-1β), inhibited colonic infiltration by macrophages and neutrophils, ameliorated metabolic endotoxemia, and improved intestinal mucosal barrier function (increased expression levels of mRNAs such as ZO-1, occludin, and Muc2). Western blot analysis revealed that AG downregulated the NF-κB signaling pathway. Moreover, AG treatment partially reversed the alterations in the gut microbiota in colitis mice, mainly by increasing the abundance of potentially beneficial bacteria (such as Ruminococcaceae) and decreasing the abundance of potentially harmful bacteria (such as Escherichia-Shigella). Ruminococcaceae and Enterobacteriaceae (Escherichia-Shigella) were thought to be the key groups affected by AG to improve UC. Therefore, AG might exert a good anti-UC effect through microbiota/LPS/TLR4/NF-kB-related pathways in mice. The results of this study reveal the anti-inflammatory effect and mechanism of AG and provide an important reference for studying the mechanisms of natural flavonoids involved in preventing inflammation-driven diseases.



中文翻译:

黄芪素通过减轻肠道菌群失调和抑制小鼠NF-κB活化来减轻右旋糖酐硫酸钠(DSS)诱导的急性实验性结肠炎。

随着世界范围内溃疡性结肠炎(UC)发病率的增加,预防和治疗UC非常重要。但是,UC的有效治疗选择相对有限。由于现有药物的潜在严重不利影响,对源自天然和功能食品的替代候选资源的需求日益增长。黄芪素(AG)是一种抗炎类黄酮,具有辣木决明子是其主要来源。在这项研究中,我们调查了AG对硫酸葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠的治疗作用。我们的结果表明,AG治疗可减少体重减轻和疾病活动指数(DAI),防止结肠缩短,减轻结肠组织损伤。AG治疗可降低促炎细胞因子和相关mRNA的表达(例如肿瘤坏死因子α,IL-6白介素1β),抑制巨噬细胞和嗜中性粒细胞的结肠浸润,改善代谢性内毒素血症,改善肠粘膜屏障功能(增加mRNA的表达水平,例如 ZO-1,闭合蛋白Muc2)。蛋白质印迹分析表明,AG下调了NF-κB信号通路。此外,AG治疗主要通过增加潜在有益细菌(例如Ruminococcaceae)的丰度和减少潜在有害细菌(例如Ruminococcaceae)的丰度来部分逆转结肠炎小鼠肠道微生物群的变化。大肠埃希氏菌)。球菌科和肠杆菌科(大肠埃希氏菌)被认为是受AG影响以改善UC的关键人群。因此,AG可能通过微生物/ LPS / TLR4 / NF-kB相关途径在小鼠中发挥良好的抗UC作用。这项研究的结果揭示了AG的抗炎作用及其机理,为研究天然黄酮类化合物预防炎症驱动疾病的机理提供了重要参考。

更新日期:2020-09-15
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