基于网络药理学探讨逍生散治疗干眼的作用机制OA
Exploring the Mechanism of Action of Xiaosheng Powder in Treating Dry Eye Based on Network Pharmacology
目的 基于网络药理学及分子对接技术探讨逍生散治疗干眼的作用机制.方法 使用中药系统药理学数据库和分析平台(TCMSP)和Herb数据库检索逍生散药味的活性成分及相关靶点,Swiss Target Prediction平台预测有效化合物靶点.检索GeneCards、OMIM、TTD、PharmGkb、DrugBank数据库获得干眼相关靶点,制作Venn图得到药物-疾病对应数据.将交集基因上传至STRING平台,构建蛋白互作关系(PPI)网络,将交集靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析.将所得核心靶点与调控网络中度值靠前的活性成分进行分子对接验证.结果(1)活性成分及靶点:筛选得到逍生散的活性成分共718个,活性成分作用靶点817个,与干眼相关疾病靶点基因4,498个取交集,获得445个"药物活性成分-疾病"共同靶点基因.(2)药物-成分-靶点-疾病网络构建:药物-成分-靶点-疾病网络图共包括550个节点和2,042条边.(3)PPI网络:共同作用靶点的PPI网络包含376个节点及3,010个边.其中,Degree值排名前3位的依次是肿瘤蛋白p53(TP53)、信号转导与转录激活因子3(STAT3)、原癌基因酪氨酸蛋白激酶Src(SRC).(4)GO和KEGG通路富集分析:生物过程主要集中在丝裂原活化蛋白激酶(MAPK)级联的正向调节、对外源性刺激的反应和激酶活性的正向调节等;细胞组分主要集中在膜筏、膜微区和神经元细胞体等;分子功能主要集中在丝氨酸/苏氨酸激酶活性等.关键通路主要包括磷脂酰肌醇3-激酶(PI3K)/蛋白激酶(AKT)、MAPK等信号通路.(5)分子对接:核心靶点与主要活性成分之间均具有较强的结合能力.结论 逍生散治疗干眼的核心靶点为PI3K/AKT、MAPK等信号通路,其活性成分与核心靶点之间具有良好的结合活性.本研究在分子层面阐释了该方治疗干眼的作用机制.
OBJECTIVE To investigate the mechanism of action of Xiaosheng Powder in treating dry eye based on network pharmacology and molecular docking technology.METHODS The active components and related targets of the medicine components of Xiaosheng Powder were retrieved using the TCMSP and medicine databases.The Swiss Target Prediction platform was used to predict targets of the effective compounds.Dry eye-related targets were obtained by searching the GeneCards,OMIM,TTD,PharmGkb,and DrugBank databases.A Venn diagram was constructed to obtain the medicine-disease intersection data.The intersecting genes were uploaded to the STRING platform to construct a protein-protein interaction(PPI)network.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed on the intersecting targets.Molecular docking verification was conducted between the obtained core targets and the active components with high degree values in the regulatory network.RESULTS(1)Active components and targets:A total of 718 active components of Xiaosheng Powder were screened,with 817 corresponding targets.Intersection with 4,498 dry eye-related disease target genes yielded 445 common"medicine active component-disease"target genes.(2)Construction of the medicine-component-target-disease network:The medicine-component-target-disease network diagram included 550 nodes and 2,042 edges.(3)PPI network:The PPI network of the common targets contained 376 nodes and 3,010 edges.The top three targets by Degree value were tumor protein p53(TP53),signal transducer and activator of transcription 3(STAT3),and proto-oncogene tyrosine-protein kinase Src(SRC).(4)GO and KEGG pathway enrichment analyses:Biological processes were mainly concentrated in the positive regulation of the mitogen-activated protein kinase(MAPK)cascade,response to external stimuli,and positive regulation of kinase activity,etc.Cellular components were mainly concentrated in membrane rafts,membrane microdomains,and neuronal cell bodies,etc.Molecular functions were mainly concentrated on serine/threonine kinase activity,etc.Key pathways mainly included the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)and MAPK signaling pathways.(5)Molecular docking:The core targets and the main active components all exhibited strong binding affinities.CONCLUSIONS The core targets of Xiaosheng Powder in treating dry eye involve signaling pathways such as PI3K/AKT and MAPK,and its active components show good binding activity with these core targets.This study elucidates the molecular-level mechanism of action of this formula in treating dry eye.
李晓宇;谢立科;郝晓凤;秦睿;刘亮;鞠品
中国中医科学院眼科医院,北京 100040||全国中医药老年眼病防治中心,北京 100040中国中医科学院眼科医院,北京 100040中国中医科学院眼科医院,北京 100040中国中医科学院眼科医院,北京 100040中国中医科学院眼科医院,北京 100040中国中医科学院眼科医院,北京 100040
医药卫生
逍生散作用机制网络药理学PI3K/AKT
Xiaosheng Powdermechanism of actionnetwork pharmacologyPI3K/AKT
《中国中医眼科杂志》 2026 (5)
426-433,8
1 国家自然科学基金项目(82174445、82405491)2 中国中医科学院眼科医院高水平中医院揭榜挂帅项目(GSP4-02)3 中国中医科学院眼科医院新入职青年科研人员培养专项(XJ2023001302)
评论