Troxerutin Improves Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice
Troxerutin Improves Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice
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曲克芦丁可改善 DSS 诱导的小鼠溃疡性结肠炎
DOI：
10.1021/acs.jafc.0c06755
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发表时间：
2021-02-23
影响因子：
6.1
通讯作者：
Yao, Ruiqin
中科院分区：
文献类型：
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作者：
Wang, Xingqi;Gao, Yuzhi;Yao, Ruiqin
从临床用药中筛选改善溃疡性结肠炎(UC)的潜在化合物是药物再利用的有效策略。在本研究中，我们将生物信息学和网络药理学应用到药物筛选过程中，帮助我们筛选出能改善UC的曲克芦丁。曲克芦丁属于黄酮类化合物，临床上用作抗凝剂和溶栓剂。本研究发现曲克芦丁有一种新的药理活性，即对小鼠UC有显著的改善作用。体外和体内水平的实验结果表明，曲克芦丁能有效降低导致肠上皮细胞和结肠组织损伤的氧化应激水平，维持紧密连接相关蛋白的分布和表达，保护结肠组织的屏障功能。除氧化应激外，严重的炎症反应也是UC加重的重要病理因素。但曲克芦丁可减少炎症细胞在结肠组织中的浸润，减少炎症相关蛋白和促炎细胞因子的表达。曲克芦丁由于其抗氧化和抗炎作用，抑制了结肠组织细胞的凋亡过程，减轻了结肠纤维化的程度。生物信息学分析表明曲克芦丁对UC的改善作用可能与其对信号通路的网络调控有关。综上所述，我们发现了黄酮类曲克芦丁抗UC的新药理活性，有利于黄酮类化合物在人类疾病治疗中的拓展和应用。
Screening potential compounds for improving ulcerative colitis (UC) from clinical medication is an effective strategy for drug repurposing. We applied bioinformatics and network pharmacology to the drug screening process in this study, which helped us to screen out troxerutin that could improve UC. Troxerutin belongs to flavonoids and is used clinically as an anticoagulant and thrombolytic agent. This study found a new pharmacological activity of troxerutin, that is, it had a significant improvement effect on UC in mice. Experimental results of in vitro and in vivo levels showed that troxerutin could effectively reduce the level of oxidative stress that caused damages in intestinal epithelial cells and colonic tissue, maintain the distribution and expression of tight junction-related proteins, and protect the barrier function of colon tissue. In addition to the oxidative stress, severe inflammatory response is also an important pathological factor that aggravates UC. However, troxerutin could reduce the infiltration of inflammatory cells in the colon tissue and decrease the expression of inflammation-related proteins and proinflammatory cytokines. Due to its antioxidant and anti-inflammatory effects, troxerutin inhibited the process of cell apoptosis in the colon tissue and relieved the degree of colonic fibrosis. Bioinformatics analysis showed that the ameliorating effect of troxerutin on UC was probably related to its network regulation of signaling pathways. In summary, we discovered a new pharmacological activity of the flavonoid troxerutin against UC, which is conducive to the expansion and application of flavonoids in the treatment of human diseases.