基于网络药理学预测地瓜藤抗糖尿病的作用及分子机制

Prediction of the anti-diabetes effect and molecular mechanism of Ficus tikoua based on network pharmacology

研究运用网络药理学方法筛选地瓜藤的活性成分,并构建地瓜藤活性成分—作用靶点网络和蛋白相互作用网络,对靶点涉及的生物功能和通路进行分析,探讨地瓜藤抗糖尿病的作用及机制。整理文献报道,并结合BATMAN数据库及TCMSP数据库获取地瓜藤的活性化合物,再通过TTD数据库筛选地瓜藤活性化合物的作用靶点,建立靶点数据集,OMIM数据库筛选糖尿病相关的靶标,PPI数据库构建地瓜藤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,并通过生物学信息注释数据库(DAVID)富集分析涉及的靶点基因功能及信号通路。筛选得到地瓜藤10个活性成分,网络分析表明地瓜藤活性成分涉及细胞肿瘤抗原p53、雌激素受体、Caspase-3、胰岛素受体、转录因子E2F1等靶点39个,通过调节胰岛素抵抗、TNF信号通路、2型糖尿病信号通路、胰岛素信号通路等信号通路来发挥其抗糖尿病的作用。研究结果体现了地瓜藤抗糖尿病具有多成分—多靶点—多途径的特点,为进一步研究地瓜藤抗糖尿病的作用及分子机制提供了新思路和新目标。

In this work,the active ingredients in Ficus tikoua were screened using network pharmacology,and the active ingredient-target network and the protein interaction network were established. The biological functions and pathways involved in the targets were analyzed to explore the anti-diabetes effect and the underlying mechanism of Ficus tikoua. The active compounds in Ficus tikoua were obtained by using literature,TCMSP database,and BATMAN database. Then TTD database was used to screen out the targets of the active compounds,OMIM database was used to screen out diabetes-related targets,and PPI database was used to construct the interactive targets of Ficus tikoua and diabetes. In addition,the "component-target-disease"interactive network map was constructed by Cytoscape software. The target gene function and signaling pathway were analyzed by using the biological information annotation database( DAVID). 10 active components were screened from Ficus tikoua. The network analysis indicated that the active components of Ficus tikoua affected 39 protein targets including cellular tumor antigen p53,estrogen receptor,Caspase-3,insulin receptor,transcription factor E2 F1,etc. Ficus tikoua showed anti-diabetic effect by regulating many signaling pathways such as insulin resistance,TNF signaling pathway,Type II diabetes mellitus,insulin signaling pathway,etc. This study demonstrates that Ficus tikoua has the characteristic of multi-component-multi-target-multi-pathway in treating diabetes,which provides new ideas and targets for further research on the anti-diabetic effect and underlying mechanism of Ficus tikoua.