基于网络药理学的升陷汤治疗心力衰竭的作用机制研究

Study on the Mechanism of Shengxian Decoction in Treating Heart Failure Based on Network Pharmacology

目的基于网络药理学方法探讨升陷汤治疗心力衰竭(heart failure,HF)的潜在作用机制。方法采用TCMSP、TCM-MESH、化学专业数据库、ETCM平台筛选出升陷汤的活性成分,利用TCMSP靶点预测模型预测活性成分的潜在靶点;利用Genecards、OMIM、Disgenet、DigSee数据库检索心力衰竭的相关靶点;利用Biogenet分别对药物与疾病靶点进行蛋白质相互作用网络进行构建,并提取交集网络以获得升陷汤治疗心力衰竭的关键靶点;利用Metascape对关键靶点进行GO和KEGG富集分析。结果得到药效成分60个、药物靶点156个、心力衰竭靶点1387个,最终获得关键靶点197个、KEGG通路157条。升陷汤治疗心力衰竭主要成分为槲皮素、山奈酚、黄芪多糖、黄芪甲苷等,关键靶点为TP53、ESR1、FN1、UBC、TNF-α,关键的生物学进程和通路可能包括PI3K-Akt信号通路、MAPK信号通路、TLR信号通路、HIF-1α信号通路、FoxO信号通路、细胞周期信号通路等。结论本研究初步揭示了升陷汤多成分、多靶点、多途径治疗心力衰竭的机制,为升陷汤的临床开发利用提供了依据。

Objective To explore potential mechanism of Shengxian Decoction in Treating heart failure based on a network pharmacological method. Methods Active components of Shengxian Decoction were screened out through TCMSP, TCM-MESH, Chemistry Database and ETCM. potential targets of the active components were predicted according to the target predictive model of TCMSP. Heart failure-related targets were searched through databases of Genecards, OMIM, Disgenet and DigSee. BioGenet was used for establishing protein-protein interaction(PPI) networks of medicinal substances and the disease, respectively, and an overlap network was extracted to obtain the key targets of Shengxian Decoction treating heart failure. Enrichment analyses of GO and KEGG on the key targets were performed by Metascape. Results There were 60 active components, 156 medicinal targets, 1387 targets for heart failure, 197 key targets and 157 KEGG pathways. The main components of Shengxian Decoction in treating heart failure were quercetin,kaempferol, astragalus polysaccharide, astragaloside, etc. The key targets were TP53, ESR1, FN1, UBC, TNF-α, etc.The key biological processes and pathways might include signaling pathways of PI3 K-Akt, MAPK, TLR, HIF-1α, FoxO,cell cycle, etc. Conclusion This study preliminarily reveals a This study preliminarily revealsamulti-component, multitarget and multi-pathway mechanism of Shengxian Decoction in treating heart failure. It provides a basis for clinical development and utilization of Shengxian Decoction.