[关键词]
[摘要]
目的 运用网络药理学方法筛选肾气丸的活性成分及核心靶标,探讨肾气丸治疗糖尿病的作用机制。方法 经中药系统药理学分析平台(TCMSP)并结合文献查询,筛选肾气丸的活性成分;通过TTD数据库和Swiss Target Prediction数据库筛选肾气丸活性化合物的作用靶点,建立靶点数据集;通过OMIM数据库和DrugBank数据库筛选糖尿病相关的靶标;PPI数据库构建肾气丸和糖尿病的交互靶标;用Cytoscape软件构建成分-靶点-疾病交互网络图,并通过ClueGO富集分析涉及的靶点基因功能及信号通路;应用Autodock软件进行核心靶标分子对接。结果 筛选得到肾气丸100个活性成分,网络分析表明肾气丸活性成分涉及低密度脂蛋白受体相关蛋白6、胰岛素受体底物1、SHC转化蛋白1等靶点58个,靶点与调控基因的转录、细胞凋亡、细胞增殖、胰岛素受体等生物过程相关,通过调节胰岛素抵抗、TNF信号通路、2型糖尿病信号通路、胰岛素信号通路等通路来发挥其抗糖尿病作用。结论 肾气丸治疗糖尿病具有多成分-多靶点-多途径的特点,为进一步研究肾气丸治疗糖尿病的作用及分子机制提供了新思路和新方向。
[Key word]
[Abstract]
Objective The active ingredients and core targets of Shenqi Pills were screened using network pharmacology to explore the underlying mechanism of Shenqi Pills with anti-diabetic activity. Methods The active compounds and targets of Shenqi Pills were obtained by literature, TCMSP database, Swiss Target Prediction database, and TTD database. Then the target dataset was established, OMIM database and DrugBank database were used to screen the diabetes-related targets, and the interactive target of Shenqi Pills and diabetes was constructed using PPI database. In addition, the "component-target-disease" interactive network map was constructed by Cytoscape software. The target gene function and signaling pathway were analyzed by ClueGO and the molecules and core targets were docked using Autodock software. Results The results showed that 100 active constituents of Shenqi Pills were screened. Network analysis indicated that the active components of Shenqi Pills involved 58 targets, including low-density lipoprotein receptor-related protein 6, insulin receptor substrate 1, SHC-transforming protein 1, etc. Targets were involved in biological processes such as transcription, apoptosis, cell proliferation, and insulin receptors. Shenqi Pills had anti-diabetic activity by regulating many signaling pathways such as insulin resistance, TNF signaling pathway, type Ⅱ diabetes mellitus, and insulin signaling pathway. Conclusion This study demonstrates the characteristics of Shenqi Pills with multi-component-multi-target-multi-pathway to treat diabetes, and provides new ideas and targets for further research on the anti-diabetic activity and the underlying mechanism of Shenqi Pills.
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[基金项目]
贵阳中医学院博士启动基金(2017);贵州省国内一流建设学科项目(中药学)(GNYL[2017]008号)