基于网络药理学的含水蛭经方抗肿瘤机制研究

Study on antitumor mechanism of leech-contained classical prescriptions based on network pharmacology

目的利用网络药理学方法分析含水蛭抗肿瘤经方的组方规律、核心配伍中草药以及药物的起效单体、作用靶点、信号通路。方法利用TCMID数据库获取含水蛭抗肿瘤经方,采用Cytoscape软件构建中草药配伍网络图,利用Degree算法获取使用频率最高的前10味核心中草药。通过TCMSP数据库收集水蛭抗肿瘤经方的核心中草药,进行靶蛋白预测,获取交集。利用STRING数据库构建靶蛋白的蛋白-蛋白互作(PPI)网络图,利用KOBAS 3. 0数据库进行通路富集分析。利用CTD数据库预测水蛭素的靶蛋白,构建靶蛋白的PPI网络图并进行通路富集分析。结果获含水蛭抗肿瘤经方共10个,常与虻虫、大黄、桃仁、干漆、琥珀、三棱、莪术等活血化瘀药配伍。TCMSP数据库获得水蛭抗肿瘤经方中的核心中草药包括大黄、桃仁、三棱、莪术,起效单体分别有16个、23个、4个、3个。4味核心中草药协同作用的靶蛋白共16个,主要参与神经活性配体-受体相互作用。配伍中草药靶蛋白的核心子集主要参与乙型肝炎病毒、癌症通路等。水蛭素的靶蛋白主要参与补体和凝血级联、血小板活化等通路。结论水蛭或通过抗血栓形成以改善肿瘤微环境,而配伍药具有抗炎、抗肿瘤的效果。

Objective To analyze the medication rule,core compatible herbs,and active monomers,targets and signal pathways of the herbs in the leech-contained anti-tumor classical prescriptions using the network pharmacology.Methods Leech-contained anti-tumor classical prescriptions were acquired by using TCMID database,the network diagram of compatibility of herbs was constructed by Cytoscape software,and then the top 10 herbs used most frequently were acquired by Degree algorithm. Core herbs of leech-contained anti-tumor classical prescriptions were collected by TCMSP database,the target proteins were predicted,and then the intersection was conducted. The protein-protein interaction( PPI) network of the target proteins was constructed by STRING database,and the pathway enrichment analysis was conducted by KOBAS 3. 0 database. Target proteins of hirudin were predicted by CTD database,PPI network of the target proteins was constructed,and the pathway enrichment analysis was conducted. Results Ten leech-contained anti-tumor classical prescriptions were obtained,which were found compatible frequently with herbs for invigorating blood circulation and eliminating stasis including aphids,rhubarb,peach kernels,dry lacquer,amber,trigonometry,phlegm and blood stasis. The core herbs in the leech-contained anti-tumor classical prescriptions obtained from TCMSP database included rhubarb,peach kernel,trigonal and zedoary sinensis,with the number of effective monomers as 16,23,4 and 3,respectively. There existed 16 synergistic target proteins in 4 core herbs,which mainly involved in the interaction between neuroactive ligand and receptors. The core subsets of the target proteins in the compatible herbs mainly involved in hepatitis B virus and cancer pathways. The target proteins of hirudin mainly involved in pathways of complement,coagulation cascade,platelet activation,and so on. Conclusion The leech might improve the tumor microenvironment by anti-thrombosis,and the compatible herbs exert anti-inflammatory and anti-tumor effects.