基于网络药理学及分子对接探讨仙鹤草改善慢性萎缩性胃炎的作用机制

Mechanism of Agrimoniae Herba in treatment of chronic atrophic gastritis based on network pharmacology and molecular docking

目的 运用网络药理学和分子对接技术探讨仙鹤草改善慢性萎缩性胃炎的物质基础及作用机制。方法 通过TCMSP数据库筛选仙鹤草的活性成分并预测其作用靶点;通过GeneCards、OMIM数据库筛选慢性萎缩性胃炎相关靶点;将活性成分靶点与慢性萎缩性胃炎靶点取交集,通过String 12.0数据库构建蛋白相互作用(PPI)网络,并运用Cytoscape 3.10.1软件构建“中药–疾病–化合物–交集靶标”网络图;通过R软件对核心靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析以预测作用机制;通过AutoDock软件进行分子对接验证。结果 从仙鹤草中筛选出5个活性成分,作用于90个靶点,其中仙鹤草改善慢性萎缩性胃炎的核心活性成分为鞣花酸、山柰酚、儿茶素、木犀草素、槲皮素;核心靶点为B淋巴细胞瘤-2(Bcl-2)、半胱氨酸天冬氨酸蛋白酶-3(CASP3)、表皮生长因子受体(EGFR)、缺氧诱导因子-1A(HIF-1A)、原癌基因(MYC)等;作用机制主要涉及抗肿瘤、调节免疫、调节脂代谢、抗病毒等多条信号通路;分子对接显示,仙鹤草核心活性成分与核心靶点具有较高亲和力。结论 仙鹤草可能通过调节细胞增殖、凋亡、炎症、代谢等相关基因及通路发挥多靶点、多通路的治疗作用。

Objective To explore the material basis and action mechanisms of Agrimoniae Herba in treatment of chronic atrophic gastritis based on network pharmacology and molecular docking techniques.Methods To screen the active ingredient of Agrimoniae Herba from the TCMSP database,and predict their target proteins.To obtain the relevant target associated with chronic atrophic gastritis from the GeneCards and OMIM databases.The intersection of target proteins between the active ingredient of Agrimoniae Herba and chronic atrophic gastritis was used to construct a PPI network via String 12.0.The network diagram of“TCM-disease-compound-intersection target”was constructed using Cytoscape 3.10.1 software.Core target proteins were subjected to GO and KEGG enrichment analysis using R software to predict the underlying mechanisms.Molecular docking was performed using AutoDock software to validate the interactions.Results Five active components were selected from Agrimoniae Herba,targeting 90 proteins.Among them,the core active components responsible for improving chronic atrophic gastritis were identified as ellagic acid,kaempferol,epicatechin,apigenin,and quercetin.Core target proteins included Bcl-2,CASP3,EGFR,HIF-1A,and MYC.The action mechanisms mainly involved multiple signaling pathways such as anti-tumor effects,immune regulation,lipid metabolism regulation,and antiviral activities.Molecular docking results demonstrated high affinity between the core active components of Agrimoniae Herba and the core target proteins.Conclusion This study unveils that Agrimoniae Herba may exert a multi-target,multi-pathway therapeutic effect through the regulation of genes and pathways associated with cell proliferation,apoptosis,inflammation,and metabolism.