{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T06:03:09Z","timestamp":1774245789140,"version":"3.50.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic heart failure (CHF) represents a major global health burden characterized by complex pathologies. The Yi Qi Huo Xue compound prescription (YQHXCP) has demonstrated significant clinical efficacy in alleviating heart failure symptoms; however, its precise molecular mechanisms remain obscure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aims to elucidate the core targets and biological pathways of YQHXCP in treating CHF through an integrated approach combining network pharmacology with transcriptomic validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A rat model of heart failure was established, and transcriptomic data were acquired via RNA sequencing. Concurrently, putative targets of YQHXCP were retrieved from the TCMSP and SwissTargetPrediction databases. Key targets were identified by intersecting differentially expressed genes (DEGs) from the animal model with predicted drug targets. Subsequently, functional enrichment analysis, gene-gene interaction (GGI) network construction, and molecular docking were employed to decipher the underlying mechanisms, followed by\n                      <jats:italic>in vivo<\/jats:italic>\n                      validation using RT-qPCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Three pivotal target genes were identified: Top2a, Cdk1, and E2f2. Enrichment analysis revealed that YQHXCP primarily modulates mitochondrial protein complexes, ribosomal subunit assembly, and cell cycle checkpoints. Molecular docking demonstrated strong binding affinity between the active ingredient quercetin and both Cdk1 and E2f2 proteins. RT-qPCR confirmed that YQHXCP significantly reversed the downregulation of Cdk1 and E2f2 expression in the myocardial tissue of CHF rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>YQHXCP may exert its anti-CHF effects by targeting Cdk1 and E2f2 to regulate mitochondrial function and cell cycle homeostasis. These findings provide novel insights into the multi-target therapeutic mechanisms of traditional Chinese medicine formulations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1738535","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T05:21:26Z","timestamp":1774243286000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the mechanism of Yi Qi Huo Xue compound prescription in treating chronic heart failure based on integrated network pharmacology and transcriptomics"],"prefix":"10.3389","volume":"13","author":[{"given":"Jiadan","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Cardiology, The Third Af\ufb01liated Hospital of Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengcheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Tuberculosis, Hangzhou Red Cross Hospital","place":["Hangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuoyue","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Third Af\ufb01liated Hospital of Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Third Af\ufb01liated Hospital of Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiyun","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Longquan People\u2019s Hospital","place":["Lishui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xufeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Tongde Hospital of Zhejiang Province","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/s41586-024-08008-5","article-title":"Targeting immune-fibroblast cell communication in heart failure","volume":"635","author":"Amrute","year":"2024","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e11","DOI":"10.15420\/cfr.2023.05","article-title":"Global public health burden of heart failure: an updated review","volume":"9","author":"Shahim","year":"2023","journal-title":"Card Fail Rev"},{"key":"B3","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1161\/HHF.0b013e318291329a","article-title":"Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association","volume":"6","author":"Heidenreich","year":"2013","journal-title":"Circ Heart Fail"},{"key":"B4","doi-asserted-by":"publisher","first-page":"857","DOI":"10.2147\/ijgm.S522314","article-title":"Heterogeneity of fatigue in patients with chronic heart failure: latent categories and influencing factors","volume":"18","author":"Yang","year":"2025","journal-title":"Int J Gen Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"63","DOI":"10.2147\/rmhp.S130341","article-title":"Economic burden of hospitalizations of medicare beneficiaries with heart failure","volume":"10","author":"Kilgore","year":"2017","journal-title":"Risk Manag Healthc Policy"},{"key":"B6","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1093\/ehjqcco\/qcaa032","article-title":"The independent reduction in mortality associated with guideline-directed medical therapy in patients with coronary artery disease and heart failure with reduced ejection fraction","volume":"7","author":"Wolfe","year":"2021","journal-title":"Eur Heart J Qual Care Clin Outcomes"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1592\/phco.29.12.1492","article-title":"Dexmedetomidine-associated bradycardia progressing to pulseless electrical activity: case report and review of the literature","volume":"29","author":"Gerlach","year":"2009","journal-title":"Pharmacotherapy"},{"key":"B8","doi-asserted-by":"publisher","first-page":"155438","DOI":"10.1016\/j.phymed.2024.155438","article-title":"Yi-Qi-Huo-Xue decoction alleviates intracerebral hemorrhage injury through inhibiting neuronal autophagy of ipsilateral cortex via BDNF\/TrkB pathway","volume":"128","author":"Han","year":"2024","journal-title":"Phytomedicine"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e30082","DOI":"10.1097\/md.0000000000030082","article-title":"The efficacy of Yiqi Huoxue therapy for chronic heart failure: a meta-analysis in accordance with PRISMA guideline.","volume":"101","author":"Zhang","year":"2022","journal-title":"Medicine"},{"key":"B10","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1038\/nchembio.118","article-title":"Network pharmacology: the next paradigm in drug discovery","volume":"4","author":"Hopkins","year":"2008","journal-title":"Nat Chem Biol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"156953","DOI":"10.1016\/j.phymed.2025.156953","article-title":"Integrated metabolomics and network pharmacology reveal the PI3K\/Akt-mediated therapeutic mechanism of Abrus cantoniensis in lipid metabolism disorders","volume":"145","author":"Wang","year":"2025","journal-title":"Phytomedicine"},{"key":"B12","doi-asserted-by":"publisher","first-page":"4260","DOI":"10.1080\/21655979.2022.2031388","article-title":"Tanshinone IIA alleviates cardiac hypertrophy through m6A modification of galectin-3","volume":"13","author":"Zhang","year":"2022","journal-title":"Bioengineered"},{"key":"B13","doi-asserted-by":"publisher","first-page":"946193","DOI":"10.3389\/fphar.2022.946193","article-title":"Network pharmacology and experimental analysis to reveal the mechanism of Dan-Shen-Yin against endothelial to mesenchymal transition in atherosclerosis","volume":"13","author":"Hong","year":"2022","journal-title":"Front Pharmacol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"156187","DOI":"10.1016\/j.phymed.2024.156187","article-title":"Huangqi-Danshen decoction improves heart failure by regulating pericardial adipose tissue derived extracellular vesicular miR-27a-3p to activate AMPK\u03b12 mediated mitophagy","volume":"135","author":"Chen","year":"2024","journal-title":"Phytomedicine"},{"key":"B15","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.ymeth.2014.06.003","article-title":"Integrative analysis of independent transcriptome data for rare diseases","volume":"69","author":"Zhang","year":"2014","journal-title":"Methods"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1210\/endo-125-4-1783","article-title":"Characterization of tumor necrosis factor-alpha receptors in human and rat thyroid cells and regulation of the receptors by thyrotropin","volume":"125","author":"Pang","year":"1989","journal-title":"Endocrinology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1186\/s12864-023-09677-8","article-title":"Plotnineseqsuite: a python package for visualizing sequence data using ggplot2 style","volume":"24","author":"Cao","year":"2023","journal-title":"BMC Genomics"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1030198","DOI":"10.3389\/fimmu.2023.1030198","article-title":"Single-cell RNA and transcriptome sequencing profiles identify immune-associated key genes in the development of diabetic kidney disease","volume":"14","author":"Zhang","year":"2023","journal-title":"Front Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1332279","DOI":"10.3389\/fimmu.2024.1332279","article-title":"Identification and validation of immune and cuproptosis\u2014related genes for diabetic nephropathy by WGCNA and machine learning","volume":"15","author":"Chen","year":"2024","journal-title":"Front Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"Clusterprofiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"Omics"},{"key":"B22","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1007\/s10822-010-9352-6","article-title":"Ligand docking and binding site analysis with PyMOL and Autodock\/Vina","volume":"24","author":"Seeliger","year":"2010","journal-title":"J Comput Aided Mol Des"},{"key":"B23","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1007\/s11655-015-2085-6","article-title":"Chinese Medicine syndromes in congestive heart failure: a literature study and retrospective analysis of clinical cases","volume":"22","author":"Li","year":"2016","journal-title":"Chin J Integr Med"},{"key":"B24","first-page":"601","article-title":"Effects of \u201creinforcing Qi and activating blood\u201d on stable chronic obstructive pulmonary disease (Qi deficiency and blood stasis syndrome","volume":"45","author":"Min","year":"2014","journal-title":"Sichuan Da Xue Xue Bao Yi Xue Ban"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1038\/ncomms2599","article-title":"Topoisomerase II\u03b1 promotes activation of RNA polymerase I transcription by facilitating pre-initiation complex formation","volume":"4","author":"Ray","year":"2013","journal-title":"Nat Commun"},{"key":"B26","doi-asserted-by":"publisher","first-page":"108977","DOI":"10.1016\/j.celrep.2021.108977","article-title":"Topoisomerase II\u03b1 represses transcription by enforcing promoter-proximal pausing","volume":"35","author":"Herrero-Ruiz","year":"2021","journal-title":"Cell Rep"},{"key":"B27","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1126\/science.adh7950","article-title":"DNA Damage induces p53-independent apoptosis through ribosome stalling","volume":"384","author":"Boon","year":"2024","journal-title":"Science"},{"key":"B28","doi-asserted-by":"publisher","first-page":"426","DOI":"10.31083\/j.rcm2512426","article-title":"Comprehensive insights into mechanisms for ventricular remodeling in right heart failure","volume":"25","author":"Jiang","year":"2024","journal-title":"Rev Cardiovasc Med"},{"key":"B29","doi-asserted-by":"publisher","first-page":"4077","DOI":"10.1038\/s41598-020-61087-y","article-title":"Cryptochromes modulate E2F family transcription factors","volume":"10","author":"Chan","year":"2020","journal-title":"Sci Rep"},{"key":"B30","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1038\/nrcardio.2016.203","article-title":"Expert consensus document: mitochondrial function as a therapeutic target in heart failure","volume":"14","author":"Brown","year":"2017","journal-title":"Nat Rev Cardiol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2658","DOI":"10.3390\/cancers14112658","article-title":"An integrative human pan-cancer analysis of cyclin-dependent kinase 1 (CDK1)","volume":"14","author":"Liu","year":"2022","journal-title":"Cancers"},{"key":"B32","doi-asserted-by":"publisher","first-page":"3112","DOI":"10.1038\/s41467-025-58183-w","article-title":"Targeting CCNE1 amplified ovarian and endometrial cancers by combined inhibition of PKMYT1 and ATR","volume":"16","author":"Xu","year":"2025","journal-title":"Nat Commun"},{"key":"B33","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.devcel.2010.02.013","article-title":"Progressive activation of CyclinB1-Cdk1 coordinates entry to mitosis","volume":"18","author":"Gavet","year":"2010","journal-title":"Dev Cell"},{"key":"B34","doi-asserted-by":"publisher","first-page":"83","DOI":"10.5582\/bst.2021.01072","article-title":"The E2F transcription factor 2: what do we know?","volume":"15","author":"Li","year":"2021","journal-title":"Biosci Trends"},{"key":"B35","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.molcel.2009.06.036","article-title":"Cdk1 Participates in BRCA1-dependent S phase checkpoint control in response to DNA damage","volume":"35","author":"Johnson","year":"2009","journal-title":"Mol Cell"},{"key":"B36","doi-asserted-by":"publisher","first-page":"e2400011","DOI":"10.1002\/bies.202400011","article-title":"Activating the abscission checkpoint: top2\u03b1 senses chromatin bridges in cytokinesis: top2\u03b1 binds to DNA knots on chromatin bridges to activate the abscission checkpoint in human cells","volume":"46","author":"Petsalaki","year":"2024","journal-title":"Bioessays"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1038\/sj.onc.1209998","article-title":"E2f4 regulates a stable G2 arrest response to genotoxic stress in prostate carcinoma","volume":"26","author":"Crosby","year":"2007","journal-title":"Oncogene"},{"key":"B38","doi-asserted-by":"publisher","first-page":"17","DOI":"10.2174\/0115665232332419250213081510","article-title":"Targeting of YKL\u201340 as a protumor in personalized medicine: a new dimension in disease understanding","volume":"26","author":"Moustafa","year":"2026","journal-title":"Curr Gene Ther"},{"key":"B39","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1093\/cvr\/cvr007","article-title":"Activation of the aryl hydrocarbon receptor by doxorubicin mediates cytoprotective effects in the heart","volume":"90","author":"Volkova","year":"2011","journal-title":"Cardiovasc Res"},{"key":"B40","doi-asserted-by":"publisher","first-page":"54","DOI":"10.3967\/bes2024.006","article-title":"Quercetin alleviates lipopolysaccharide-induced cardiac inflammation via inhibiting autophagy and programmed cell death","volume":"37","author":"Yu","year":"2024","journal-title":"Biomed Environ Sci"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1738535\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T05:21:29Z","timestamp":1774243289000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1738535\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,23]]},"references-count":40,"alternative-id":["10.3389\/fcvm.2026.1738535"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2026.1738535","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,23]]},"article-number":"1738535"}}