基于网络药理学和分子对接的通络化浊丸治疗高脂血症作用机制研究

Mechanism of Tongluo Huazhuo Pill in the Treatment of Hyperlipidemia Based on Network Pharmacology and Molecular Docking

目的:对通络化浊丸治疗高脂血症的作用机制进行网络药理学分析。方法:通络化浊丸的活性成分和靶点从TCMSP数据库中获取。借助GeneCards、OMIM、DrugBank、TTD、PharmGkb数据库检索高脂血症的疾病靶点。利用STRING数据库、Cytoscape软件建立交集靶点的蛋白相互作用(PPI)网络和“药物-活性成分-靶点”网络,依据节点度值筛选出核心靶点。对核心靶点进行GO功能和KEGG通路富集分析,运用AutoDock Vina软件对活性成分与核心靶点进行模拟分子对接。结果:通过对100个有效组分、68个潜在靶点的筛选,确定通络化浊丸治疗高脂血症的6种活性成分(槲皮素、芦荟大黄素、人参皂苷Rh2、丹参酮、山柰酚和隐丹参酮)和10个核心靶点(VEGFA、IL1B、MMP9、EGFR、CCL2、EGF、ICAM1、IL6、SERPINE1、TNF)。分子对接结果表明,6种关键活性成分与10个核心靶点的结合活性均优于内源性配体,说明活性成分对核心靶点有良好的选择性和稳定性。结论:从分子层面阐明通络化浊丸防治高脂血症的多组分、多靶点、多途径协同作用特点,其机制主要包括抗炎症反应、抗氧化应激、调节糖脂代谢、抑制血管重塑等。

Objective:The aim of this study was to conduct a network pharmacological analysis on the mechanism of Tongluo Huazhuo Pill in the treatment of hyperlipidemia.Methods:The active ingredients and targets of Tongluo Huazhuo Pill were obtained from TCMSP database.Disease targets of hyperlipidemia were searched using GeneCards,OMIM,DrugBank,TTD,PharmGkb databases.The protein-protein interaction(PPI)network and“drug-active ingredient-target”network were established using String database and Cytoscape software,and the core targets were screened out according to node degree.GO functional analysis and KEGG pathway enrichment analysis were performed for core targets.AutoDock Vina software was used to simulate molecular docking between active components and core targets.Results:By screening 100 active components and 68 potential targets,six active ingredients(quercetin,aloe emodin,ginsenoside Rh2,tanshinone,kaempferol and cryptotanshinone)and 10 core targets(VEGFA,IL1B,MMP9,EGFR,CCL2,EGF,ICAM1,IL6,SERPINE1,TNF)of Tongluo Huazhuo Pill for hyperlipidemia were identified.Molecular docking results showed that the binding activity of 6 key active ingredients to 10 core targets was superior to that of endogenous ligands,indicating that the active ingredients had good selectivity and stability for the core targets.Conclusion:In this study,the characteristics of multi-component,multi-target and multi-pathway synergistic action of Tongluo Huazhuo Pill in the prevention and treatment of hyperlipidemia were elucidated from the molecular level,and its mechanisms of action mainly include anti-inflammatory response,anti-oxidative stress,regulation of glucose metabolism and lipid metabolism,inhibition of vascular remodeling,etc.