Mechanism of Nuanxin Capsules in Treating Ischemic Heart Failure:A Network Pharmacology Approach with In Vivo Validation
10.13359/j.cnki.gzxbtcm.2025.09.026
- VernacularTitle:基于网络药理学及体内实验验证研究暖心胶囊治疗缺血性心力衰竭的作用机制
- Author:
Jianglin XU
1
;
Yunfeng XU
;
Chuangchang WANG
;
Shujie HAN
;
Jiangyang PENG
;
Xia WANG
Author Information
1. 广州中医药大学第二附属医院,广东 广州 510120;广东省中医院心血管科,广东 广州 510120;广州中医药大学第二临床医学院,广东 广州 510405
- Keywords:
Nuanxin Capsules;
ischemic heart failure;
lymphangiogenesis;
VEGFC;
VEGFR3;
network pharmacology;
In vivo experiment;
mice
- From:
Journal of Guangzhou University of Traditional Chinese Medicine
2025;42(9):2271-2279
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the therapeutic mechanism of Nuanxin Capsules(NXC)in ischemic heart failure(IHF)using network pharmacology and in vivo experimental validation.Methods Active components of NXC were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and SwissTargetPrediction database.Potential IHF-related targets were predicted via OMIM and GeneCards databases.Shared targets between NXC and IHF were identified to construct a"NXC-shared targets-IHF"network.Key bioactive components were screened,and protein-protein interaction(PPI)networks were built using STRING database.Core target modules were analyzed via CytoHubba plugin in Cytoscape 3.7.2.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were performed using Metascape.For in vivo validation,an IHF mouse model was established by permanent ligation of the left anterior descending coronary artery.After 4-week intervention,cardiac function/structure was assessed by echocardiography,histopathology by hematoxylin-eosin(HE)staining,lymphatic vessel density by immunofluorescence,and protein expression of vascular endothelial growth factor C(VEGFC)and vascular endothelial growth factor receptor 3(VEGFR3)by Western Blot.Results Network pharmacology identified 242 shared targets between NXC and IHF,with core components including apigenin,pongapin,naringenin,4',5,7,8-tetramethoxyflavone,and tangeretin.Four core molecular clusters were identified(e.g.,VEGFC,FLT4/VEGFR3).GO analysis revealed enrichment in cellular response to nitrogen compounds,positive regulation of cell migration/phosphorus metabolism,and inflammatory response modulation.KEGG pathways included cancer,lipid/atherosclerosis,and endocrine resistance pathways.In vivo experiments demonstrated that NXC significantly improved cardiac function,attenuated pathological changes and inflammatory infiltration,promoted lymphangiogenesis,and upregulated VEGFC/VEGFR3 protein expression in IHF mice.Conclusion NXC may ameliorate IHF by promoting cardiac lymphangiogenesis via VEGFC/VEGFR3 signaling.