β-细辛醚抗凝血的网络药理学作用机制研究

Study on Anticoagulation Mechanism ofβ-asarone Based on Network Pharmacology

目的利用网络药理学的方法分析β-细辛醚抗凝血的作用靶点及机制。方法通过TCMSP数据库、Swiss Target Prediction平台以及PharmMapper服务器预测出β-细辛醚可能的作用靶标。通过TTD、OMIM以及pharmgKB数据库检索凝血相关的靶点,找出两者的共有靶点即为β-细辛醚作用于凝血的直接靶点。使用Cytoscape 3.7.1下的插件BisoGenet 4.0.0,分别构建β-细辛醚和凝血相关靶点蛋白的PPI图,采用Merge功能得到两者的交集网络,随后对其进行拓扑分析,筛选出核心靶点蛋白,从中找出β-细辛醚的靶点,利用DAVID数据库对其进行GO注释和KEGG通路分析。结果β-细辛醚作用于凝血的直接靶点有3个,分别是APP、PTGS2、TBXAS1,间接靶点有TYK2、TGFBR1、HCK等26个。涉及癌症、感染性疾病、MAPK等相关生物过程和信号通路。在KEGG分析和GO富集分析中均涉及MAPK信号通路。结论β-细辛醚抗凝血的作用机制可能主要与MAPK信号通路有关。β-细辛醚可能对癌症相关凝血、感染性疾病相关弥漫性血管内凝血具有一定的作用。

Objective To analyze the anti-coagulation targets and mechanism ofβ-asarone using network pharmacology method.Methods The possible targets ofβ-asarone were predicted by the TCMSP database,the Swiss Target Prediction platform,and the PharmMapper server.Coagulation-related targets were searched by TTD,OMIM,and the pharmgKB database.The common targets,which were thought to be the direct targets ofβ-asarone on coagulation,were screened.The PPI map ofβ-asarone and coagulation-related target proteins was constructed using the plug-in BisoGenet 4.0.0 in Cytoscape 3.7.1.The merge function was used to obtain the intersection network of the two;and then the topological analysis was performed to select the core target proteins,from which the targets ofβ-asarone were obtained and analyzed by GO annotation and KEGG pathway using DAVID database.Results There are 3 direct targets ofβ-asarone on coagulation,namely APP,PTGS2 and TBXAS1;and 26 indirect targets,including TYK2,TGFBR1 and HCK,and so on.They involve cancer,infectious diseases,MAPK and other related biological processes and signaling pathways.Both KEGG analysis and GO enrichment analysis found that MAPK signaling pathways were involved.Conclusion The mechanism of anti-coagulation ofβ-asarone may mainly relate to the MAPK signaling pathway.To some extent,β-asarone may have effect on cancer-related coagulation and infectious disease-related diffuse intravascular coagulation.