摘要
目的:通过网络药理学与分子对接技术分析三叶青治疗类风湿性关节炎(RA)的作用机制。方法:检索中国知网、万方、PubMed等数据库中三叶青主要活性成分的相关文献,利用SwissTargetPrediction数据库筛选作用靶点。通过GeneCards数据库获得RA疾病基因,将活性成分对应靶点与疾病基因取交集,获得三叶青治疗RA的潜在作用靶点。将数据导入Cytoscape3.7.1软件,构建“药物-成分-靶点”网络图。使用String数据库构建蛋白质互作(PPI)网络,并筛选核心靶点。利用Metascape平台对核心靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。采用AutoDock Tools1.5.6软件,对三叶青主要活性成分与核心靶点进行分子对接验证。结果:从三叶青中筛选出30个活性成分,对应430个潜在靶点,获得主要活性成分为亚麻酸甲酯、槲皮素、山柰酚、鼠李柠檬素和白藜芦醇。RA疾病靶点1186个,通过拓扑属性值筛选后得到46个关键节点,主要包括白蛋白(ALB)、蛋白激酶B1(AKT1)、肉瘤病毒蛋白(SRC)、前列腺素G/H合酶2(PTGS2)、基质金属蛋白酶9(MMP9)、表皮生长因子受体(EGFR)、丝裂原活化蛋白激酶1(MAPK1)等基因。GO富集分析主要涉及激酶结合、转录因子结合、对肽的反应、炎症反应等。KEGG富集到209条通路,主要涉及癌症途径通路、内分泌激素耐药作用通路、癌症蛋白聚糖通路、磷脂酰肌醇3激酶(PI3K)-AKT通路等。分子对接显示鼠李柠檬素与MMP9,山奈酚与PIK3R1,白藜芦醇与MMP9,亚麻酸甲酯与MMP9,槲皮素与PIK3R1结合最稳定。结论:网络药理学分析结果显示三叶青通过亚麻酸甲酯、槲皮素、山柰酚等主要活性成分作用于MMP9、PIK3R1、AKT1等核心靶点,调控癌症途径、内分泌激素耐药作用、癌症蛋白聚糖、PI3K-AKT等通路治疗RA。
Objective:To analyze the mechanism of Tetrastigma Radix in the treatment of rheumatoid arthritis(RA)using network pharmacology and molecular docking technology.Methods:Literature on the main active ingredients of Tetrastigma Radix was retrieved from databases including China National Knowledge Infrastructure(CNKI),Wanfang Data Knowledge Service Platform(Wanfang),and PubMed,and the SwissTargetPrediction database was used to screen their potential targets.RA-related genes were obtained from the GeneCards database,and the intersection between targets of active ingredients and disease genes was identified to determine potential therapeutic targets of Tetrastigma Radix for RA.Data were imported into Cytoscape 3.7.1 to construct a“drug-ingredient-target”network.The STRING database was used to build a protein-protein interaction(PPI)network and screen core targets.The Metascape platform was employed for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the core targets.Molecular docking validation of the main active ingredients of Tetrastigma Radix and core targets was performed using AutoDock Tools 1.5.6.Results:A total of 30 active ingredients were screened out from Tetrastigma Radix,corresponding to 430 potential targets.The main active ingredients obtained are methyl linolenate,quecetin,kaempferol,rhamnocitrin and resveratrol.A total of 1186 RA-related disease targets were identified,and 46 key nodes were obtained after screening based on topological attribute values,primarily including albumin(ALB),AKT serine/threonine kinase 1(AKT1),sarcoma protooncogene(SRC),prostaglandin G/H synthase 2(PTGS2),matrix metalloproteinase 9(MMP9),epidermal growth factor receptor(EGFR),mitogen-activated protein kinase 1(MAPK1),and other genes.GO enrichment analysis mainly involved kinase binding,transcription factor binding,response to peptides,and inflammatory responses.KEGG enrichment analysis identified 209 pathways,primarily including pathways in cancer,endocrine resistance pathways,cancer proteoglycans pathways,and phosphatidylinositol 3-kinase(PI3K)-AKT signaling pathways.Molecular docking results indicated that rhamnocitrin exhibited the most stable binding with MMP9,kaempferol with PIK3R1,resveratrol with MMP9,methyl linolenate with MMP9,and quercetin with PIK3R1.Conclusion:Network pharmacology analysis revealed that Tetrastigma Radix in the treatment of RA by targeting core genes such as MMP9,PIK3R1,and AKT1 through key active ingredients like methyl linolenate,quercetin,and kaempferol,and regulating pathways in cancer,endocrine resistance pathways,cancer proteoglycans pathways,and PI3K-AKT signaling pathway.
作者
严蕊
王铁烽
赵天文
朱文瑞
YAN Rui;WANG Tiefeng;ZHAO Tianwen;ZHU Wenrui(Department of Pharmacy,Shaoxing TCM Hospital Affiliated to Zhejiang Chinese Medical University,Shaoxing Zhejiang 312000,China)
出处
《新中医》
2026年第1期175-182,共8页
New Chinese Medicine
关键词
类风湿性关节炎
三叶青
网络药理学
分子对接
作用机制
Rheumatoid arthritis
Tetrastigma Radix
Network pharmacology
Molecular docking
Mechanism
