基于网络药理学及分子对接探究泽泻–黄芪治疗代谢综合征的作用机制

Exploring the Mechanism of Action of Alisma Orientalis and Astragalus Membranaceus in the Treatment of Metabolic Syndrome Based on Network Pharmacology and Molecular Docking

摘要: 目的：应用网络药理学及分子对接技术研究泽泻–黄芪治疗代谢综合征(Metabolic syndrome, MS)的作用机制。方法：利用TCMSP数据库筛选泽泻、黄芪的活性成分及作用靶点，Swiss Target Prediction数据库检索在TCMSP数据库未找到靶点的4个成分的靶点；借助Gene cards、OMIM、TTD数据库获得MS的相关靶点；利用DAVID数据库进行GO与KEGG富集分析，STRING数据库构建PPI网络，Cytoscape3.10.2软件构建相应网络图。选择Degree值 > 50的核心成分与Degree值 > 140的关键靶点，运用AutoDock1.5.6软件及Pymol2.1.0进行分子对接以验证上述结果。结果：泽泻–黄芪有效成分为27个、作用靶点为416个，MS共有3553个作用靶点，药对与疾病的交集靶点为228个。PPI分析可知，泽泻–黄芪治疗MS主要涉及AKT1、TNF、TP53、IL1B、ESR1等靶点。GO和KEGG富集分析显示AGE-RAGE信号通路、PI3K-Akt信号通路、MAPK信号通路、TNF信号通路等多条信号通路发挥重要作用。分子对接结果表明槲皮素、泽泻醇B、泽泻醇C与AKT1、TNF、TP53结合力良好，构象稳定，验证了上述结果。结论：泽泻–黄芪药对通过多成分、多靶点、多途径的协同作用治疗MS，其成分槲皮素、泽泻醇B、泽泻醇C等作用于AKT1、TNF、TP53等核心靶点，通过AGE-RAGE信号通路、PI3K-Akt信号通路等介导炎症、氧化应激、细胞凋亡等机制。

Abstract: Objective: To study the mechanism of action of Alisma orientalis and Astragalus membranaceus in the treatment of metabolic syndrome (MS) using network pharmacology and molecular docking technology. Methods: Using the TCMSP database to screen the active ingredients and targets of Alisma orientalis and Astragalus membranaceus, and searching the Swiss Target Prediction database for the targets of four components that were not found in the TCMSP database; Obtain MS related targets through Gene cards, OMIM, and TTD databases; Perform GO and KEGG enrichment analysis using DAVID database, construct PPI network using STRING database, and construct corresponding network diagram using Cytoscape 3.10.2 software. Select core components with a Degree value greater than 50 and key targets with a Degree value greater than 140, and use AutoDock 1.5.6 software and Pymol 2.1.0 for molecular docking to verify the above results. Results: There are a total of 27 active ingredients and 416 targets of action in Alisma orientalis and Astragalus membranaceus, and 3553 targets of action in MS, with a total of 228 intersecting targets between the two. PPI analysis shows that the treatment of MS with Alisma orientalis and Astragalus membranaceus mainly involves targets such as AKT1, TNF, TP53, IL1B, ESR1, etc. GO and KEGG enrichment analysis showed that multiple signaling pathways, including AGE-RAGE signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, and TNF signaling pathway, play important roles. The molecular docking results showed that quercetin, alisol B, and alisol C had good binding affinity with AKT1, TNF, and TP53, and their conformations were stable, confirming the above results. Conclusion: Alisma orientalis and Astragalus membranaceus medicine have a synergistic effect on treating MS through multiple components, targets, and pathways. Its components, such as quercetin, Zexie alcohol B, and Zexie alcohol C, act on core targets such as AKT1, TNF, and TP53, mediating mechanisms such as inflammation, oxidative stress, and cell apoptosis through the AGE-RAGE signaling pathway, PI3K-Akt signaling pathway.