首页|基于网络药理学及分子对接探讨养血清脑颗粒治疗高血压的作用机制

基于网络药理学及分子对接探讨养血清脑颗粒治疗高血压的作用机制

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目的 基于网络药理学及分子对接探讨养血清脑颗粒(四物汤加味)治疗高血压的作用机制.方法 以课题组前期对养血清脑颗粒的化学成分分析结果作为活性化合物筛选的基础,以口服生物利用度≥30%及类药性≥0.18 为筛选条件,结合文献补充入血成分.利用TCMSP平台、化学专业数据库和SWISS数据库预测养血清脑颗粒潜在活性化合物的作用靶点.通过GeneCards及DiGSeE数据库获得高血压疾病相关靶点.将高血压疾病相关靶点与养血清脑颗粒潜在活性化合物的作用靶点取交集(共同靶点),即为养血清脑颗粒治疗高血压的潜在作用靶点.将潜在作用靶点与养血清脑颗粒的潜在活性化合物进行匹配,得养血清脑颗粒的降压活性化合物.通过STRING数据库对养血清脑颗粒治疗高血压的潜在作用靶点进行PPI分析,并根据度值筛选出核心靶点.采用DAVID数据库对核心靶点进行GO功能及KEGG通路富集分析.选择度值排前 6 位的核心靶点作为对接靶蛋白,分别与降压活性化合物进行分子对接验证.结果 得到养血清脑颗粒 32 个潜在活性化合物,161 个活性化合物作用靶点,1 539 个高血压疾病相关靶点,取交集后得到 88 个养血清脑颗粒治疗高血压的潜在作用靶点(共有靶点),涉及 29 个降压活性化合物.PPI分析筛选出 14 个核心靶点:PPARG、ACHE、IL4、CCL2、JUN、NOS3、APP、IL1B、CAT、PTGS2、CASP3、TP53、TNF、IL6,涉及 158 个GO条目、13 条信号通路.通过分子对接得到绿原酸、迷迭香酸、芍药苷、儿茶酸、芦荟大黄素等 5 个关键活性成分,分别与PTGS2、CASP3、TNF、CAT、TP53、IL6 结合稳定.结论 养血清脑颗粒可能通过绿原酸、迷迭香酸等关键活性成分,作用于PTGS2、CASP3 等核心靶点,调控TNF信号通路、MAPK信号通路、Toll样受体信号通路等关键通路,通过抗炎作用发挥治疗高血压的作用.
Exploration of the Mechanism of Yangxue Qingnao Granules in the Treatment of Hypertension Based on Network Pharmacology and Molecular Docking
Objective To explore the mechanism of Yangxue Qingnao Granules(Siwu Decoction modified)in the treatment of hypertension based on network pharmacology and molecular docking.Methods The chemical composition analysis results of Yangxue Qingnao Granules in the early stage of the research group were used as the basis for the screening of active compounds.The oral bioavailability≥30%and drug-likeness≥0.18 were used as the screening conditions,and the blood components were supplemented in combination with the literature.TCMSP,chemical professional database and SWISS database were used to predict the targets of potential active compounds of Yangxue Qingnao Granules.Hypertension-related targets were obtained through GeneCards and DiGSeE databases.The intersection of the targets related to hypertension disease and the targets of the potential active compounds of Yangxue Qingnao Granules(common targets)is the potential target of Yangxue Qingnao Granules for the treatment of hypertension.The potential targets were matched with the potential active compounds of Yangxue Qingnao Granules to obtain the antihypertensive active compounds of Yangxue Qingnao Granules.PPI analysis was performed on the potential targets of serum brain granules in the treatment of hypertension through the STRING database,and the core targets were screened according to the degree value.The David database was used to analyze the GO function and KEGG pathway enrichment of the core targets.The core targets with the top six degrees were selected as the docking target proteins,and molecular docking verification was performed with the antihypertensive active compounds.Results A total of 32 potential active compounds,161 active compound targets and 1 539 hypertension-related targets were obtained.After intersection,88 potential targets(common targets)of Yangxue Qingnao Granules in the treatment of hypertension were obtained,involving 29 antihypertensive active compounds.PPI analysis screened 14 core targets:PPARG,ACHE,IL4,CCL2,JUN,NOS3,APP,IL1B,CAT,PTGS2,CASP3,TP53,TNF,IL6,involving 158 GO entries and 13 signaling pathways.Five key active ingredients,chlorogenic acid,rosmarinic acid,paeoniflorin catechinic acid and aloe emodin,were obtained by molecular docking,which were combined with PTGS2,CASP3,TNF,CAT,TP53 and IL6,respectively.Conclusion Yangxue Qingnao Granules may act on core targets such as PTGS2 and CASP3 through key active components such as chlorogenic acid and rosmarinic acid,regulate key pathways such as TNF signaling pathway,MAPK signaling pathway and Toll-like receptor signaling pathway,and play a role in the treatment of hypertension through anti-inflammatory effects.

Yangxue Qingnao GranulesSiwu Decoctionhypertensionnetwork pharmacologymolecular docking technologymechanismanti-inflammatory effect

史嘉雯、郝磊、王玉、霍志鹏、张依倩、宋兆辉、何毅

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天士力医药集团股份有限公司研究院现代中药开发中心,天津 300410

天士力医药集团股份有限公司现代中药创制全国重点实验室,天津 300410

天津大学药物科学与技术学院,天津 300072

天津中医药大学中药学院,天津 301617

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养血清脑颗粒 四物汤 高血压 网络药理学 分子对接 作用机制 抗炎作用

国家科技重大专项重大新药创制

2017ZX09301005

2024

中药新药与临床药理
广州中医药大学

中药新药与临床药理

CSTPCD北大核心
影响因子:0.908
ISSN:1003-9783
年,卷(期):2024.35(8)