基于网络药理学探讨荷丹片治疗高脂血症的作用机制

Network pharmacology-based molecular mechanisms of Hedan Tablets for hyperlipidemia regression

关键词:  荷丹片  高脂血症  网络药理学  疾病-靶点网络  作用机制

Key words:  Hedan Tablets  hyperlipidemia  network pharmacology  disease-tarqet network  mechanism

摘要:

[目的] 旨在通过网络药理学方法探究荷丹片治疗高脂血症的可能作用机制。[方法] 在中药系统药理学数据库（TCMSP）和中医药百科全书（ETCM）数据库中检索得到荷丹片中5味药材类药成分与作用靶点，借助Uniprot数据库查询靶点对应基因，在DisGeNET数据库搜索得到高脂血症的疾病靶点。利用STRING数据平台构建活性组分-作用靶点和蛋白-蛋白相互作用网络（PPI）的网络图，采用Cytoscape软件构建"中药-活性成分-疾病-靶点"网络，利用DAVID生物信息学资源对相关靶点进行GO功能与KEGG通路富集分析。[结果] 从荷丹片中共筛选出61个活性化合物，对应于281个类药活性成分作用靶点，231个疾病靶点与高脂血症密切相关，其中20个疾病靶点与药物作用靶点重叠，为荷丹片治疗高脂血症具有重要意义的作用靶点。中药-活性成分-疾病-靶点可视化网络图推测发挥调节血脂作用的中药主要是丹参、山楂、补骨脂，其中关键的化合物为Ergosterol、Guercetol、Corylinal等，关键的作用靶点为PTGS1、ADRB2、F2、PPARG等。GO富集分析表明，荷丹片主要参与调节氧化还原酶活性、脂质结合、离子结合、信号转导活性、核酸结合转录因子活性、脂质代谢过程、单一有机体代谢过程、小分子代谢过程、细胞增殖等生命过程。KEGG通路富集分析结果表明，荷丹片通过调节含血清素的神经突触、PPAR信号通路、药物代谢细胞色素P450、花生四烯酸代谢、亚油酸的新陈代谢等多种途径在高脂血症中发挥药理作用。[结论] 本研究揭示了荷丹片治疗高脂血症的可能作用机制，体现了中药复方多成分、多途径、多靶点协同作用的特点，为进一步研究荷丹片治疗高脂血症的机理提供了新的思路和方法。

Abstract:

[Objective] The objective of the present study was to investigate the possible underlying cellular mechanisms responsible for Hedan Tablets' effects on hyperlipidemia based on network pharmacology.[Methods] Network pharmacology method was utilized to disclose the association between active component-target-hyperlipidemia and the molecular mechanism of Hedan Tablets on the treatment of hyperlipidemia. Chemical active components and the targets of the 5 herbs in Hedan Tablets were retrieved from TCMSP and ETCM databases. UniProt and DisGeNET databases were used to obtain the corresponding genes of the targets and the disease targets of hyperlipidemia,respectively. String data platform and Cytoscape was used to visualize and construct the network-based diagram for active component interaction target,protein-protein interaction network(PPI),and active component-disease target. Finally,DAVID bioinformatics tools were used to analyze the go-function and KEGG pathway enrichment of related targets.[Results] An active component-target-hyperlipidemia and network pathway revealed that 61 active compounds deduced from Hedan Tablets regulated 231 close targets common to Hedan Tablets and hyperlipidemia. Analysis of the common targets indicated that the anti-hyperlipidemia effects of Hedan Tablets might be related to 20 potential targets in hyperlipidemia. Visualized network diagram disclosed ergosterol,guercetol, corylinal,etc. as critical active-compounds and PTGS1,ADRB2,F2,PPARG,etc. as crucial targets. Also,the go-enrichment analysis revealed that the plausible mechanism of Hedan Tablets anti-hyperlipidemia action might be through the regulation of oxidoreductase activity,lipid and ion binding,signal transduction activity,nucleic acid binding transcription factor activity,lipid metabolism,single organism metabolism,small molecule metabolism,cell proliferation, and other life processes. KEGG pathway enrichment analysis showed that Hedan tablet played a pharmacological role in hyperlipidemia by regulating serotonin containing synapses,PPAR signaling pathway,drug metabolism cytochrome P450,arachidonic acid metabolism,linoleic acid metabolism,and other pathways.[Conclusion] Altogether,the study reveals the possible cellular processes likely to be influenced by Hedan Tablets against hyperlipidemia,and provides the platform for further pharmacological evaluation in vivo models.