摘要
目的:以三藤汤的临床疗效为切入点,运用网络药理学和分子对接技术探讨三藤汤降低类风湿性关节炎(RA)并发脑卒中(CVA)发生率的机制。方法:运用TCMSP数据库检索三藤汤中黄芪、淫羊藿、青风藤、鸡血藤、络石藤的活性成分及其靶点,通过GeneCards数据库获取RA和CVA的主要靶点,并将两者靶点基因取交集,得到RA&CVA交集靶点。将药物靶点与疾病交集靶点取交集,得到三藤汤降低RA并发CVA发生率的靶点,利用STRING数据库分析蛋白质-蛋白质相互作用(PPI),构建PPI网络图,运用David数据库对交集靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析,使用Cytoscape 3.9.1软件绘制三藤汤药物成分-RA&CVA交集靶点-通路网络图。结果:三藤汤主要活性成分为槲皮素、山柰酚、木犀草素、黄芪异黄烷苷、芒柄花黄素等,主要靶点为核受体辅激活蛋白2(NCOA2)/原癌基因蛋白质c-akt(AKT1)、环氧化酶2(PTGS2)/环氧化酶1(PTGS1)/AP-1转录因子(JUN)、丝裂原活化蛋白激酶14(MAPK14)、诱导型一氧化氮合酶(NOS2)、丝氨酸蛋白酶1(PRSS1)、转录激活蛋白3(STAT3)等,主要涉及癌症的途径、脂质与动脉粥样硬化、流体剪切应力和动脉粥样硬化及糖尿病并发症中的糖基化终末产物-糖基化终末产物受体(AGE-RAGE)等信号通路。分子对接结果显示,主要靶点NCOA2/AKT1与山柰酚、PTGS2/PTGS1/AR与槲皮素、MAPK14与芒柄花黄素、NOS2与毛蕊异黄酮、PRSS1与木犀草素、STAT3与甘草查尔酮A形成稳定的对接模型。结论:三藤汤中存在槲皮素、山柰酚、木犀草素、黄芪异黄烷苷、芒柄花黄素等活性成分,可能作用于PTGS2、NCOA2、MAPK14、NOS2、PRSS1、STAT3等靶点对RA并发CVA进行干预,其主要机制可能涉及癌症的途径、脂质与动脉粥样硬化、流体剪切应力和动脉粥样硬化、AGE-RAGE等多条信号通路。
Objective:To investigate the mechanism of Santeng decoction reducing the incidence rate of rheumatoid arthritis(RA)with cerebral vascular accident(CVA)using network pharmacology and molecular doc-king,with the clinical effect of Santeng decoction as the starting point.Methods:TCMSP database was used to obtain the active components of Astragalus membranaceus,Herba Epimedii,Sinomenium acutum,Spatholobi Caulis,and Caulis Trachelospermi in Santeng decoction and their targets;GeneCards database was used to obtain the main targets of RA and CVA,and these two groups of targets were intersected to obtain the intersecting targets of RA and CVA.The targets of the drugs and the intersecting targets of RA and CVA were intersected to obtain the targets for Santeng decoction in reducing the incidence rate of RA and CVA.STRING database was used to analyze proteinprotein interaction(PPI)to construct a PPI network;David database was used to perform the gene ontology functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the intersecting targets;Cytoscape 3.9.1 was used to construct a Santeng decoction drug component-RA&CVA intersecting target-pathway network.Results:The main active components of Santeng decoction included quercetin,kaempferol,luteolin,9-O-Methylnissolin 3-O-glucoside,and formononetin,and the main targets included NCOA2/AKT1,PTGS2/PTGS1/JUN,MAPK14,NOS2,PRSS1,and STAT3.The main signaling pathways involved included the cancer pathway,lipid and atherosclerosis,fluid shear stress,and the AGE-RAGE signaling pathway.Molecular docking showed that a stable docking model was formed between NCOA2/AKT1 and kaempferol,between PTGS2/PTGS1/AR and quercetin,between MAPK14 and formononetin,between NOS2 and calycosin,between PRSS1 and luteolin,and between STAT3 and licochalcone A.Conclusion:The active components of Santeng decoction include quercetin,kaempferol,luteolin,9-O-Methylnissolin 3-O-glucoside,and formononetin,which exerts an interventional effect on RA with CVA by ac
作者
宋诚
周胜强
刘芳
SONG Cheng;ZHOU Shengqiang;LIU Fang(Hunan University of Chinese Medicine,Changsha 410208,Hunan,China;Hunan Hospital of Integrated Traditional Chinese and Western Medicine,Changsha 410006,Hunan,China)
出处
《湖南中医杂志》
2023年第9期177-185,共9页
Hunan Journal of Traditional Chinese Medicine
基金
中国中医科学院学部委员学术传承与传播专项项目。
关键词
类风湿性关节炎
脑卒中
网络药理学
分子对接
作用机制
rheumatoid arthritis
cerebral vascular accident
network pharmacology
molecular docking
mechanism of action
