基于网络药理学分析柿叶治疗心血管疾病的药效物质基础及作用机制

Analysis of the Pharmacodynamic Substances and Mechanisms of Persimmon Leaves in the Treatment of Cardiovascular Diseases Based on Network Pharmacology

目的基于网络药理学分析柿叶治疗心血管疾病的药效物质基础及作用机制。方法检索Si-noMed、中国知网、万方等数据库获取柿叶中的化学成分,成分录入Targetnet数据库进行潜在靶点钓取,再将靶点导入CTD数据库获得关联疾病,采用DAVID数据库对靶点进行基因功能及通路富集分析。以Cytoscape软件构建成分-靶点网络,靶点-疾病网络,提取核心成分和靶点,构建'核心成分-核心靶点-信号通路'核心网络。结果共收集到柿叶中54个成分,可作用于43个靶点。多元及核心网络分析结果显示,山奈酚(Kaempferol)、槲皮素(Quercetin)、白花蛇床子素(Droserone)等成分是治疗心血管疾病的主要物质基础,柿叶中的成分主要作用于酪氨酸蛋白磷酸酶非受体1型(PTPN1)、花生四烯酸-15-脂加氧酶(ALOX15)、雌激素受体2(ESR2)、雌激素受体1(ESR1)、前列腺素G/H合成酶1(PTGS1)等关键靶点,进一步调节催乳素信号通路(Prolactin signaling pathway)、血管内皮生长因子信号通路(VEGF signaling pathway)以及花生四烯酸代谢(Arachidonic acid metabolism)等信号通路来发挥治疗心血管疾病的作用。结论本研究揭示了柿叶多成分、多靶点、多途径的作用规律,为深入开展柿叶治疗心血管疾病的作用机制研究提供了新的依据。

Objective To explore the pharmacodynamic material basis and mechanism of persimmon leaves in the treatment of cardiovascular diseases based on network pharmacology.Methods The chemical constituents in persimmon leaves were obtained by searching the databases including Si-noMed,CNKI,Wanfang,et al.The interaction targets were predicted by Targetnet database.The corresponding diseases were obtained by importing the targets into the online CTD database.The gene function and pathway enrichment of the potential targets were studied by DAVID online analysis database.Finally,the component-target interaction network and target-disease interaction network were constructed by Cytoscape software.The core network of'core component-core target-signaling pathway'was constructed by extracting components and targets and pathways with higher degree.Results A total of 54 components from persimmon leaves were collected,and these targets could act with 43 targets.Kaempferol,quercetin,droserone and other components were found to be the main material basis for the treatment of cardiovascular diseases by multivariate and core network analysis.The components from persimmon leaves can further regulate the signal pathways of Prolactin signaling pathway,VEGF signaling pathway and Arachidonic acid metabolism by acting on key targets such as PTPN1,ALOX15,ESR1,ESR2,PTGS1 and MAOA,to treat cardiovascular diseases.Conclusion This study reflects the multi-component,multi-target and multi-pathway action of persimmon leaves,and provides a new basis for further research on the mechanism of persimmon leaves in the treatment of cardiovascular diseases.