An Investigation of the Mechanism of Rapid Relief of Ulcerative Colitis Induced by Five-flavor Sophora Flavescens Enteric-coated Capsules Based on Network Pharmacology
An Investigation of the Mechanism of Rapid Relief of Ulcerative Colitis Induced by Five-flavor Sophora Flavescens Enteric-coated Capsules Based on Network Pharmacology
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DOI：
10.2174/1386207323666200302121711
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发表时间：
2020-01-01
影响因子：
1.8
通讯作者：
Dou, Danbo
中科院分区：
文献类型：
--
作者：
Gu, Sizhen;Xue, Yan;Dou, Danbo
目的和目的：五味苦参肠溶胶囊（FSEC）是中国唯一批准用于治疗溃疡性结肠炎（UC）的中成药。 II、III期临床试验表明，FSEC缓解UC的疗效不逊色于美沙拉秦颗粒和肠溶片，但其药理机制尚不清楚。因此，利用网络药理学揭示FSEC治疗UC更全面的有效成分和靶点。方法：基于TCMSP数据库筛选FSEC成分，通过靶向钓鱼确定这些化合物的作用靶点，整合多个疾病基因数据库的UC疾病靶点。将两个结果进行匹配得到FSEC-UC复合目标，然后构建PPI网络分析这些目标之间的关系，并通过拓扑相关参数选择核心目标。最后利用Cluster Profiler软件包进行GO-BP和KEGG富集分析。结果：鉴定出FSEC活性成分160个，获得77个靶标。其中，30个核心靶点是FESC治疗UC的主要靶点。其中槲皮素、山奈酚、木犀草素和芒果苷被认为是FSEC的核心活性成分。 GO和KEGG富集分析筛选结果表明，FSEC主要通过IL-17、TNF、Toll样受体、NF-κB、Th17细胞分化发挥免疫识别、抗炎、抗氧化等综合治疗作用。结论：通过网络药理学预测了FSEC诱导UC缓解的分子机制。这些研究结果为进一步研究FSEC治疗UC的有效物质和机制提供了重要的理论依据。
Aim and Objective: Five-Flavor Sophora flavescens Enteric-Coated Capsules (FSEC) are the only proprietary Chinese medicine approved for the treatment of ulcerative colitis (UC) in China. Phase II and III clinical trials have shown that the curative effect of FSEC in relieving UC was not inferior to that of mesalazine granules and enteric-coated tablets, but its pharmacological mechanism is unclear. Therefore, the network pharmacology is used to reveal the more comprehensive effective components and targets of FSEC in the treatment of UC.Methods: We screened the components of FSEC based on the TCMSP database, determined the action targets of these compounds through target fishing, and integrated the UC disease targets of several disease gene databases. The FSEC-UC composite targets were obtained by matching the two results, and then a PPI network was constructed to analyze the relationship between these targets, and the core targets were selected by topological correlation parameters. Finally, GO-BP and KEGG enrichment analyses were carried out using the cluster Profiler software package.Results: One hundred and sixty active components of FSEC were identified and 77 targets were obtained. Of these, 30 core targets were the main targets of FESC in the treatment of UC. And quercetin, kaempferol, luteolin and mangiferin were regarded as the core active components of FSEC. The results screened by GO and KEGG enrichment analysis showed that FSEC played a comprehensive therapeutic role in immune recognition, anti-inflammation and antioxidation mainly through IL-17, TNF, Toll-like receptor, NF-kappa B, and Th17 cell differentiation.Conclusion: The molecular mechanism of UC remission induced by FSEC was predicted by network pharmacology. These findings provide an important theoretical basis for further study of the effective substances and mechanism of FSEC in the treatment of UC.