摘要
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,1539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。
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 1539 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,CA
作者
史嘉雯
郝磊
王玉
霍志鹏
张依倩
宋兆辉
何毅
SHI Jiawen;HAO Lei;WANG Yu;HUO Zhipeng;ZHANG Yiqian;SONG Zhaohui;HE Yi(Development Center of Modern Chinese Medicine,Tasly Pharmaceutical Group Co.,Ltd.,Tianjin 300410,China;National Key Laboratory of Chinese Medicine Modernization,Tasly Pharmaceutical Group Co.,Ltd.,Tianjin 300410,China;School of Pharmaceutical Science and Technology,Tianjin University,Tianjin 300072,China;School of Chinese Materia Medica,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2024年第8期1206-1214,共9页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
国家科技重大专项重大新药创制——“中医药优势领域的创新中药关键技术开发研究”(2017ZX09301005)。
关键词
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
Yangxue Qingnao Granules
Siwu Decoction
hypertension
network pharmacology
molecular docking technology
mechanism
anti-inflammatory effect
