溃疡性结肠炎
促炎细胞因子
氧化应激
化学
结肠炎
炎症
细胞凋亡
组织因子
内科学
药理学
医学
免疫学
生物化学
病理
疾病
凝结
作者
Xingqi Wang,Ya Gao,Lei Wang,Di Yang,Wei Bu,Lingshan Gou,Jinjin Huang,Xiaoyang Duan,Yue Xin Pan,Shuyan Cao,Zixuan Gao,Chen Cheng,Feng Zhao-jun,Jun Xie,Ruiqin Yao
标识
DOI:10.1021/acs.jafc.0c06755
摘要
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.
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