基于网络药理学的五苓散多成分-多靶点-多通路作用机制研究

通过中药系统药理学数据库与分析平台（traditional Chinese medicine system pharmacology datebase and analysis platform,TCMSP)筛选五苓散组分白术、茯苓、猪苓、泽泻、桂枝的潜在活性成分，PharmMapper服务器预测潜在靶点，构建化合物-靶点网络、蛋白互作( protein-protein interaction，PPI) 网络，进行基因本体( gene ontology，GO) 富集分析、基于KEGG( Kyoto encyclopedia of genes and enomes) 的生物通路富集分析。结果表明，筛选得到五苓散中50种活性成分，构建化合物 靶点网络共459个节点，关键靶点包括CSDE1、PRPS1、HSD17B4、CLPP、ACBD7、AZGP1等。构建五苓散靶点的PPI互作网络包含155个节点和527条相互作用关系，关键节点包括CSDE1、CITED2、RANBP2、HSD17B4、TAF13、SOD2等。GO富集分析途径相关条目主要涉及细胞溶质、细胞对有机物质和化学刺激的反应，含氮物质代谢，有机物循环代谢进程，蛋白、小分子和离子结合及转运活性等。KEGG代谢通路分析包括膀胱癌、前列腺癌、内分泌抵抗、癌症中的蛋白聚糖、流体剪切应力和动脉粥样硬化等途径。研究结果初步验证了五苓散药理作用的分子机制，为进一步深入揭示其分子作用机制奠定了基础，预测五苓散的潜在作用靶点如PRPS1、HSD17B4等，可为五苓散的深入研究提供新思路。

Multicomponent-multitarget-multichannel mechanism of Wulingsan based on network pharmacology

The potential active components of Wulingsan were obtained using the TCMSP database, and the potential targets were predicated using PharmMapper servers. The compound target and protein-protein interaction (PPI) networks were constructed to perform enrichment analyses of gene ontology (GO) and biological pathway based on the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results show that a compound-target network comprising 50 major active components and 459 targets was obtained; the key targets included CSDE1, PRPS1, HSD17B4, CLPP, ACBD7, and AZGP1. A PPI network responsible for constructing Wulingsan targets consisted of 155 nodes and 527 interactions; key targets included CSDE1, CITED2, RANBP2, HSD17B4, TAF13, and SOD2. The items associated with the GO enrichment analysis pathway primarily involved cytosol, protein, and small molecules as well as cells’ reaction to organic substances and chemical stimulations, nitrogen metabolism, organic matter metabolism, and ion binding and transport activity. A KEGG metabolic pathway enrichment analysis included proteoglycans in cancer as well as bladder cancer, prostate cancer, endocrine resistance, fluid shear stress, and atherosclerosis. Results initially verified molecular mechanism for the pharmacological action of the main active components of Wulingsan, thereby providing evidence for further elucidation of its molecular mechanism, predicting its potential targets (such as PRPS1 and HSD17B4), and delivering a new method for studies on Wulingsan development and application.