基于网络药理-分子对接-体外抗氧化探究沙棘防治高血压的作用机制  

Exploring the Mechanism of Seabuckthorn in Preventing and Treating Hypertension Based on Network Pharmacology,Molecular Docking and Antioxidation in Vitro

作　　者：张靖鹏 张得钧 ZHANG Jing-peng;ZHANG De-jun(College of Eco-environmental Engineering,Qinghai University,Xining810016;China Inspection and Certification Group Qinghai Co.,Ltd.,Xining810000)

机构地区：[1]青海大学生态环境工程学院,西宁810016 [2]中国检验认证集团青海有限公司,西宁810000

出　　处：《实用中西医结合临床》2024年第15期1-9,共9页Practical Clinical Journal of Integrated Traditional Chinese and Western Medicine

基　　金：地区科学基金项目(编号:82260643)。

摘　　要：目的采用网络药理学、分子对接及体外抗氧化试验方法探究沙棘防治高血压的主要药效成分、作用机制,为进一步探究沙棘防治高血压的药效物质基础提供理论参考。方法以中药沙棘、高血压为研究对象,通过中药系统药理学数据库与分析平台(TCMSP)数据库筛选药物活性成分与靶点,以Gene Cards、NCBI、OMIM及Uniprot数据库获取疾病靶点,并利用Cystoscape 3.8.0软件构建活性成分-靶点-疾病网络,使用Sting数据库绘制靶点的蛋白质互作网络(PPI网络),采用R3.6.3软件对关键靶点进行基因本体(GO)与基因功能分析(KEGG),再通过筛选度值较高的潜在靶点与沙棘活性成分进行分子对接后,对不同沙棘提取物进行体外抗氧化实验验证。结果共获得18个活性化合物;得到疾病相关关键基因为白细胞介素-6(IL-6)、白蛋白(ALB)、丝氨酸/苏氨酸激酶(AKT1)、血管内皮生长因子A(VEGFA)等,其功能多与凋亡、炎症因子、脂质代谢、细胞生长及诱导氧化应激有关;GO及KEGG分析主要涉及诱导氧化应激反应、排钠作用等;分子对接显示IL-6、ALB、AKT1和VEGFA 4个靶点均能与活性成分自发结合并形成稳定构象;体外抗氧化实验表明富含维生素C、甾醇类及黄酮类的沙棘提取物均具备较强的自由基清除能力与还原能力。结论沙棘防治高血压具有多成分、多靶点、多通路的潜在作用机制,其富含相关活性化合物的提取物均具有较高的自由基清除与还原能力,其可能通过调节IL-6、ALB、AKT1、VEGFA等相关蛋白靶点的表达,调控相关信号通路,从而发挥降低血脂、调节血压作用。Objective To explore the main pharmacological components and mechanisms of action of seabuckthorn in the preventing and treating of hypertension by using network pharmacology,molecular docking,and in vitro antioxidant tests,and to provide theoretical reference for further exploring the material basis of seabuckthorn in preventing and treating hypertension.Methods Taked traditional chinese medicine seabuckthorn and hypertension as research objects,active ingredients and targets of drugs were screened through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database,disease targets were obtained through Gene Cards,NCBI,OMIM,and Uniprot databases,and active ingredient-target-disease networks were constructed using Cystoscape 3.8.0 software.Drawed protein-protein interaction(PPI)networks for targets using String database,and key targets were analyzed for Gene ontology(GO)and gene function analysis(KEGG)using R3.6.3 software.After molecular docking with the active ingredients of seabuckthorn through screening potential targets with high degree values,in vitro antioxidant experiments were conducted on different seabuckthorn extracts to verify.Results A total of 18 active compounds were obtained.The key genes related to diseases were interleukin-6(IL-6),albumin(ALB),serine/threonine kinase(AKT1),vascular endothelial growth factor A(VEGFA),etc.Their functions were mostly related to apoptosis,inflammatory factors,lipid metabolism,cell growth,and induction of oxidative stress;GO and KEGG analysis mainly involve inducing oxidative stress reactions,sodium excretion,etc.Molecular docking showed that all four targets of IL-6,ALB,AKT1,and VEGFA could spontaneously combine with the active ingredients to form stable conformations.In vitro antioxidant experiments have shown that seabuckthorn extracts rich in vitamin C,sterols,and flavonoids have strong free radical scavenging and reducing abilities.Conclusion Seabuckthorn has a potential mechanism of action with multiple components,multipl

关 键 词：高血压 沙棘 网络药理学 分子对接 体外抗氧化 

分 类 号：R285.5[医药卫生—中药学]