基于网络药理学和分子对接技术的灵芝改善2型糖尿病作用机制

Ganoderma lucidum Improving Type 2 Diabetes Based on Network Pharmacology and Molecular Docking Technology

目的应用网络药理学方法探讨灵芝在改善2型糖尿病(T2DM)中的作用机制。方法通过TCMSP筛选灵芝化学成分,使用SWISS Target Prediction导入主要成分的SMILE name获取单个基因名;结合DisGeNET和GeneCards获取疾病基因;利用Venn数据库筛选出交集靶点;在微生信平台构建活性成分和疾病靶点网络;利用STRING和Cytoscape数据库构建PPI网络;使用DAVID数据库进行GO和KEGG功能富集分析;使用AutoDock数据库进行分子对接。结果灵芝和2型糖尿病的共同靶点有146个;PPI网络包含灵芝和2型糖尿病共同目标有146个节点和2201条“边”;筛选出灵芝5个活性成分及与T2DM相关靶点146个;重要活性成分包括Methyl lucidenate F、环氧灵芝醇A、赤灵芝酸E、赤芝酮A、Methyl lucidenate Q,核心靶点包括PGR、PTPN1、NR3C2等;KEGG主要通路富集于卵母细胞减数分裂、NF-kappa B信号通路、长寿调节途径等;分子对接结果显示,化合物和重要靶位之间具有很强的融合作用。结论本研究进一步发现了灵芝中含有Methyl lucidenate F、环氧灵芝醇A、赤紫芝酸e、赤芝酸A、Methyl lucidenate Q等活性成分,为灵芝治疗2型糖尿病的核心组分,通过控制关键治疗靶点NR3C2和HSD11B2,影响NF-kappaB binding信息通路,从而达到改善2型糖尿病的效果。

Objective The network pharmacology was applied to delve into the mechanisms by which Ganoderma lucidum improves type 2 diabetes mellitus(T2DM).Method Ganoderma lucidum chemical components were curated from TCMSP.SMILE name of the main components were input into SWISS Target Prediction to obtain individual gene name.Disease-related genes were obtained from DisGeNET and GeneCards.Venn database was used to identify intersecting targets.A network of active components and disease targets were constructed on the bioinformatics platform.STRING and Cytoscape databases were employed to build Protein-Protein Interaction(PPI)network.GO and KEGG functional enrichment analyses were conducted by using DAVID database.Molecular docking was performed by using AutoDock database.Results Ganoderma lucidum and T2DM shared 146 common targets.The PPI network comprised 146 nodes and 2201 edges.Five active components of Ganod-erma lucidum and 146 T2DM-related targets were identified.Key active components included Methyl lucidenate F,ganoderic acid A,ganoderic acid E,ganoderic acid A,and Methyl lucidenate Q.Core targets included PGR,PTPN1,NR3C2,etc.KEGG analysis revealed enrichment in pathways such as oocyte meiosis,NF-kappa B signaling pathway,and longevity-regulating pathway.Molecular docking results indicated a strong binding affinity between compounds and important target sites.Conclusion This study identified Methyl lucidenate F,ganoderic acid A,ganoderic acid E,ganoderic acid A,and Methyl lucidenate Q,as core components of Ganoderma lucidum for treating T2DM.By controlling key therapeutic targets such as NR3C2 and HSD11B2,the NF-kappa B binding pathway was affected,thus achieving the therapeutic effects on T2DM.