基于网络药理学分析白芍药理作用机制

Analysis of Pharmacological Mechanism of Radix Paeoniae Alba Based on Network Pharmacology

目的:通过网络药理学研究白芍主要有效成分及其药理作用机制,为白芍新药研究和开发提供参考。方法:通过中药系统药理学数据库分析平台(TCMSP)收集白芍的化学成分信息,以口服生物利用度(OB)≥30%和类药性(DL)≥0.18为标准筛选活性成分,并找出活性成分对应靶点。通过UniProt数据库提取作用靶点基因,运用Cytoscape 3.6.1构建化合物-靶点网络、靶点-疾病网络图,通过蛋白相互作用(PPI)网络筛选出核心靶点,通过生物学信息注释数据库(DAVID)对靶点进行基因本体(GO)功能富集分析和基于京都基因与基因组百科全书(KEGG)通路富集分析,预测其作用机制。结果:获得山奈酚、儿茶素、芍药苷、β-谷甾醇、苯甲酰芍药苷等18个主要活性成分及与其相关的94个靶点,关键靶点有AKT1、PTGS2、TNF、JUN、VCAM1、CASP3、ICAM1、IL-6、MAPK8、MAPK1等,GO功能富集分析表明关键基因主要参与分子功能正调节、细胞凋亡调控、程序性细胞死亡调控、细胞死亡调控、细胞增殖调控等生物过程;KEGG关键通路包括癌症通路,Toll样受体信号通路,细胞凋亡、神经活性配体-受体相互作用、NOD样受体信号通路,前列腺癌、肌萎缩侧索硬化症(ALS)、小细胞肺癌、Ⅱ型糖尿病等信号通路。结论:该研究初步揭示了白芍药效物质基础及多维药理作用机制,体现了白芍多成分-多靶点-多途径的作用特点,为白芍再开发利用提供了新思路和新方法。

Objective:To study the main active components and pharmacological mechanism of Radix Paeoniae Alba based on the network pharmacology,and to provide references for research and development of new medicine.Methods:Chemical components of Radix Paeoniae Alba from the TCMSP database platform were retrieved.The active components were screened by oral bioavailability(OB)≥30%and drug-like(DL)≥0.18,and the corresponding targets of active components were identified.The target genes were extracted from UniProt database.Active components target network、target-disease network and target protein-protein interaction network were constructed by Cytoscape 3.6.1,and DAVID platform was used for target GO function enrichment and KEGG signal pathway enrichment analysis.Results:The results showed that 18 active components including Kaempferol,catechin,paeoniflorin,β-sitosterol,benzoyl paeoniflorin and 94 targets of Radix Paeoniae Alba were involved.Including 10 key targets of AKT1、PTGS2、TNF、JUN、VCAM1、CASP3、ICAM1、IL-6、MAPK8 and MAPK1.GO significant enrichment analysis showed key genes mainly involved in biological process of positive regulation of molecular function,regulation of apoptosis,regulation of programmed cell death,regulation of cell death and regulation of cell proliferation;The key pathways of KEGG included of pathways in cancer,Toll-like receptor signaling pathway,Apoptosis,Neuroactive ligand-receptor interaction,NOD-like receptor signaling pathway,Prostate cancer,Amyotrophic lateral sclerosis(ALS),Small cell lung cancer and TypeⅡdiabetes mellitus.Conclusion:This study reflects the characteristics of multi-components,multi-targets,and multi-pathways and preliminarily reveals the material basis and multi-dimensional pharmacological action of Radix Paeoniae Alba,which provides new ideas and methods for the development and utilization.