基于网络药理学和分子对接研究绞股蓝皂苷L通过巨噬细胞极化治疗糖尿病肾病的机制

Investigating the Mechanism of Gypenoside L against Diabetic Nephropathy via Macrophage Polarization Using Network Pharmacology and Molecular Docking

摘要: 目的：基于网络药理学与分子对接技术，探讨绞股蓝皂苷L (Gypenoside L, GP-L)通过调控巨噬细胞极化治疗糖尿病肾病(Diabetic Nephropathy, DN)的潜在分子机制。方法：通过PubChem数据库获取GP-L的分子结构，利用SwissTargetPrediction、SEA和TTD数据库预测其作用靶点。从GeneCards和TTD数据库筛选DN及巨噬细胞极化相关靶点。取三者交集获得共同作用靶点，借助STRING数据库和Cytoscape软件构建蛋白质–蛋白质相互作用(PPI)网络并筛选核心靶点。通过DAVID数据库进行基因本体(GO)功能富集和京都基因与基因组百科全书(KEGG)通路分析。最后，采用分子对接技术验证GP-L与核心靶点之间的结合能力。结果：共筛选出31个GP-L作用于DN及巨噬细胞极化的共同靶点。PPI网络拓扑分析确定STAT3、AKT1、IL2、PTGS2、JUN等为关键核心靶点。GO与KEGG富集分析表明，这些靶点显著富集于炎症反应、细胞趋化性、PI3K-Akt信号通路、趋化因子信号通路、AGE-RAGE信号通路等生物过程与通路。分子对接结果显示，GP-L与STAT3、AKT1等大多数核心靶点具有强烈的结合活性。结论：本研究揭示了GP-L可能通过多靶点、多通路调控巨噬细胞极化，从而抑制炎症反应、改善肾脏损伤，为阐明其治疗糖尿病肾病的分子机制提供了理论依据。

Abstract: Objective: To investigate the potential molecular mechanism of Gypenoside L (GP-L) in treating diabetic nephropathy (DN) by regulating macrophage polarization based on network pharmacology and molecular docking technology. Methods: The molecular structure of GP-L was obtained from the PubChem database, and its potential targets were predicted using the SwissTargetPrediction, SEA, and TTD databases. Disease targets related to DN and macrophage polarization were screened from the GeneCards and TTD databases. The common targets among GP-L, DN, and macrophage polarization were identified and used to construct a protein-protein interaction (PPI) network via the STRING database and Cytoscape software, from which core targets were screened. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the DAVID database. Finally, molecular docking was employed to validate the binding affinity between GP-L and the core targets. Results: A total of 31 common targets of GP-L, DN, and macrophage polarization were identified. Topological analysis of the PPI network determined STAT3, AKT1, IL2, PTGS2, and JUN as key core targets. GO and KEGG enrichment analyses indicated that these targets were significantly involved in biological processes and pathways such as inflammatory response, cell chemotaxis, PI3K-Akt signaling pathway, chemokine signaling pathway, and AGE-RAGE signaling pathway. Molecular docking results demonstrated that GP-L had strong binding activity with most core targets, including STAT3 and AKT1. Conclusion: This study reveals that GP-L may regulate macrophage polarization through multiple targets and pathways, thereby inhibiting inflammatory response and improving renal injury. The findings provide a theoretical basis for elucidating the molecular mechanism of GP-L in treating DN.