基于LC-MS/MS技术整合网络药理学研究泻肺利水合剂有效成分及其治疗心力衰竭的潜在作用机制OA
Active Ingredients of Xiefei Lishui Mixture and Its Potential Mechanisms in Treating Heart Failure Based on LC-MS/MS Technology Integrating Network Pharmacology
目的 探究泻肺利水合剂治疗心力衰竭的有效成分及潜在作用机制.方法 采用LC-MS/MS技术获取泻肺利水合剂的代谢产物及入血有效活性成分,借助Swiss Target Prediction平台进行作用靶点预测;利用DisGeNET数据库检索与心力衰竭相关的疾病靶点,并与泻肺利水合剂活性成分作用靶点映射取交集;将共同靶点导入STRING数据库,构建蛋白互作网络;应用R语言ClusterProfiler包进行基因本体(gene ontology,GO)功能及京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析.结果 通过LC-MS/MS技术,从泻肺利水合剂中共鉴别出267个活性成分,与心力衰竭交集靶点51个.靶点预测结果显示,泻肺利水合剂可能通过毛蕊异黄酮、毛蕊异黄酮-7-O-β-D-葡萄糖苷、芒柄花黄素、鸟苷、木犀草素等主要成分,调控基质金属蛋白酶2(matrix metallopeptidase 2,MMP2)、表皮生长因子受体(epidermal growth factor receptor,EGFR)、糖原合成酶激酶-3(glycogen synthase kinase-3,GSK-3β)等关键靶点,通过糖尿病并发症中的晚期糖基化终产物-糖基化终末产物受体(advanced glycosylation end products-receptor of AGEs,AGE-RAGE)信号通路、EGFR酪氨酸激酶抑制剂抗性等信号通路,发挥抗心力衰竭作用.结论 泻肺利水合剂可能主要通过改善线粒体功能,发挥抗心肌纤维化作用,从而治疗心力衰竭.
Objective To explore the active ingredients and potential mechanisms of Xiefei Lishui Mixture in treating heart failure.Methods The metabolites and blood-absorbed active ingredients of Xiefei Lishui Mixture were obtained using liquid chromatography-tandem mass spectrometry(LC-MS/MS)technology.Targets were predicted via the Swiss Target Prediction platform.Disease targets related to heart failure were searched in the DisGeNET database and were mapped and intersected with the active ingredient targets.Then,the common targets were imported into the STRING database to construct a protein-protein interaction network.Finally,Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was performed using the R language ClusterProfiler package.Results A total of 267 active ingredients were identified from Xiefei Lishui Mixture based on LC-MS/MS technology,yielding 51 targets intersecting with heart failure.According to target prediction results,Xiefei Lishui Mixture may modulate key targets such as matrix metallopeptidase 2(MMP2),epidermal growth factor receptor(EGFR),and glycogen synthase kinase-3(GSK-3β)through main components including calycosin,calycosin-7-O-β-D-glucoside,formononetin,guanosine,and luteolin.Then,the Mixture exerted an anti-heart failure effect via the advanced glycosylation end products-receptor of AGEs(AGE-RAGE)signaling pathway in diabetic complications,the epidermal growth factor receptor(EGFR)tyrosine kinase inhibitor resistance pathway,and other critical signaling pathways.Conclusion Xiefei Lishui Mixture may treat heart failure by improving mitochondrial function to exert its anti-myocardial fibrosis effects.
连妍洁;尚菊菊;刘红旭;周明学;来晓磊
首都医科大学附属北京中医医院,北京 100010首都医科大学附属北京中医医院,北京 100010首都医科大学附属北京中医医院,北京 100010北京市中医药研究所,北京 100010首都医科大学附属北京中医医院,北京 100010
医药卫生
泻肺利水心力衰竭液相色谱-质谱网络药理学作用机制
Xiefei Lishuiheart failureliquid chromatography-mass spectrometrynetwork pharmacologymechanism
《世界中西医结合杂志》 2026 (7)
1273-1282,10
北京市卫健委高层次公共卫生技术人才建设项目(学科骨干-02-25)北京市医院管理中心青年人才培养"青苗"计划(QML20231006)首都医科大学附属北京中医医院科技发展基金资助项目(LYZD202304)
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