基于网络药理学探讨茯苓-泽泻药对治疗慢性肾炎的作用机制

Discussion on the Mechanism of Poria-Alismatis Rhizoma Medicinal Pair for the Treatment of Chronic Glomerulonephritis Based on Network Pharmacology

目的 基于网络药理学方法探讨茯苓-泽泻药对治疗慢性肾炎的物质基础及作用机制。方法 通过TCMSP获取茯苓-泽泻药对的活性成分,并在PharmMapper平台预测活性成分的作用靶点;运用Cytoscape3.8.2软件构建“活性成分-靶点”网络;检索GeneCards、OMIM数据库获取慢性肾炎相关靶点;采用Venny2.1在线作图工具平台构建韦恩图,得到药物与疾病交集靶点;采用STRING数据库构建交集靶点蛋白质-蛋白质相互作用网络,利用Cytoscape3.8.2软件及CytoNCA插件筛选关键靶点;借助DAVID数据库对关键靶点进行GO功能和KEGG通路富集分析。结果 获得茯苓-泽泻药对活性成分25个,作用靶点89个,慢性肾炎相关靶点1 240个,交集靶点31个,关键靶点15个。主要活性成有茯苓新酸A、泽泻醇C、茯苓新酸B、去氢茯苓酸等,关键靶点包括ALB、EGFR、SRC、CASP3等。关键靶点GO功能富集分析得到106个相关条目,生物过程主要富集于脂质和动脉粥样硬化、内分泌抵抗、肺癌蛋白多糖等;KEGG通路富集得到81条信号通路,主要涉及血管内皮生长因子(VEGF)信号通路、肿瘤坏死因子(TNF)信号通路、白细胞介素-17(IL-17)信号通路等。结论 茯苓-泽泻药对可能通过ALB、EGFR、SRC等靶点,调控VEGF信号通路、TNF信号通路、IL-17信号通路等,发挥抗炎、抗氧化、调节细胞凋亡、抑制肾小球系膜细胞增生、延缓肾纤维化进展等药理作用治疗慢性肾炎。

Objective To explore the material basis and mechanism of Poria-Alismatis Rhizoma medicinal pair for the treatment of chronic glomerulonephritis(CGN)based on network pharmacology approach.Methods The active components of Poria-Alismatis Rhizoma medicinal pair were obtained through TCMSP database and the active component targets were predicted on PharmMapper platform;the active component-target network diagram was constructed through Cytoscape 3.8.2 software;targets related to CGN were obtained from GeneCards,OMIM database;the Venny 2.1 online drawing tool platform was used to build Wayne diagrams,to obtain the intersecting targets;the intersecting targets were imported into STRING database to construct PPI network,and the key targets were screened by Cytoscape 3.8.2 software and CytoNCA plug-in;the key targets were enriched for GO function and KEGG pathway with the help of DAVID database.Results A total of 25 active components of Poria-Alismatis Rhizoma medicinal pair,89 targets,1240 CGN-related targets,31 intersectional targets and 15 key targets were obtained.The main active components were poriaxin acid A,zeolol C,poriaxin acid B,dehydroporiaxin acid,etc.Key targets included ALB,EGFR,SRC,CASP3,etc.Key targets GO enrichment analysis yielded 106 relevant entries,biological processes were mainly enriched in lipids and atherosclerosis,endocrine resistance,lung cancer proteoglycans,etc.;the KEGG pathway obtained 81 signaling pathways,mainly involving vascular endothelial growth factor(VEGF)signaling pathway,tumor necrosis factor(TNF)signaling pathway,interleukin-17(IL-17)signaling pathway,and so on.Conclusion The Poria-Alismatis Rhizoma medicinal pair may exert pharmacological effects such as anti-inflammatory,antioxidant,regulation of apoptosis,inhibition of glomerular mesangial cell proliferation,and delaying the progression of renal fibrosis by regulating the VEGF signaling pathway,TNF signaling pathway,and IL-17 signaling pathway through the target such as ALB,EGFR,and SRC to treat CGN.