基于网络药理学对生姜药用活性成分的发现和作用机制分析

Discovery and Mechanism Analysis of Active Components of Ginger Based on Network Pharmacology

目的:通过网络药理学研究,发现生姜重要的功能物质成分、发挥作用点、有关生物过程的信号通路和疾病信息等各方面的联系,并揭示其发挥药效的作用机制。方法:从中药系统药理数据库和分析平台(TCMSP)和Batman数据库中获得生姜的化学功能成分,并把其中活性成分的口服生物利用度(OB)≥30%和药物相似类药性(DL)≥0.18作为筛分条件,获得生姜的主要活性功能成分和疾病相关作用靶点信息。通过UniProt数据库提取作用靶点的基因名称,并用CTD网络在线分析平台得到与疾病作用点和信号路径。在此基础上用Cytoscape 3.7.2构建"发挥作用的活性成分-靶点""PPI靶点互作"和"功能靶点-疾病"网络图,采用Network Analyzer插件分析该网络图,探讨生姜的多重药理作用机制。结果:通过网络药理学研究共获得了姜8个主要活性功能成分,涉及PTGS2、TP53、HSP90AA1、ERS1、PGR等74个靶点,通过调节乙型肝炎、癌症通路、Ca+信号通路、3K-Akt信号通路等信号通路发挥治疗疾病的作用,其中肿瘤、免疫相关的占绝大部分。结论:生姜可以通过多成分、多靶点、多信号通路的协调作用发挥潜在的治疗疾病作用,其中在肿瘤疾病治疗和增强人体免疫功能方面具有比较好的优势。

Objective:To discover the main active components,target-targets,related signaling pathways and diseases of ginger by network pharmacology research,and to reveal its mechanism of action.Methods:The chemical constituents of ginger were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the batman(http://bionet.ncpsb.org/batman-tcm/)database,and the oral bioavailability(OB)≥30%and The drug-like(DL)≥0.18 was used as a screening condition to obtain the main active components of ginger and related targets.The gene name of the target was extracted by the UniProt database,and the target-related disease and signaling pathways were obtained using the CTD network online analysis platform.Finally,using Cytoscape 3.7.2 to construct the"active ingredient-target","PPI target interaction"and"target-disease"network maps,use the Network Analyzer plug-in of Cytoscape 3.7.2 to analyze the network map and explore the multiple pharmacological effects of ginger.mechanism.Results:A total of 8 major active components of ginger were obtained by pharmacological reserch and involved 74 targets including PTGS2,TP53,HSP90 AA1,ERS1,and PGR.The therapeutic pathways were modulated by regulating signaling pathways such as hepatitis B,cancer pathway,Ca+signaling pathway,and 3 K-Akt signaling pathway.The role of tumors,immune-related accounts for the vast majority.Conclusion:Ginger plays a role in the treatment of diseases through the coordinated action of multi-component,multi-target and multi-signal pathways.It has potential advantages in the treatment of tumor diseases and enhancement of human immunity.