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However, research into the bioactive components and underlying processes of DFD in Long QT syndrome (LQTS) remains limited. All DFD compounds were gathered from the TCMSP, ETCM, and HERB databases, and the targets of active compounds were investigated using SwissTargetPrediction. The LQTS targets were obtained\/screened from the DisGeNET, OMIM, and Malacard databases. The herb-compound-target-disease (H-C-T-D) and PPI networks were built using STRING and analyzed with CytoNCA based on the data obtained earlier. Meanwhile, VarElect was used to determine the relationship between targets and illnesses. The R program is used to enrich Gene Ontology (GO) terminology as well as the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The binding ability of DFD and hub genes was examined using molecular docking, followed by experimental validation of the key findings. A total of 664 DFD and 240 LQTS targets were gathered, with 21 common targets found. The H-C-T-D network demonstrated the links between DFD, active molecules, targets, and LQTS. The PPI network revealed the major targets: KCNH2, HSP90AA1, SCN5A, and CACNA2D1. Further systematic investigation revealed DFD\u2019s potential mechanism for protecting against LQTS. Furthermore, molecular docking revealed the interactions of active drugs and targets. Finally, we discovered that DFD enhanced the levels of KCNH2, HSP90AA1, and CACNA2D1 while decreasing the level of SCN5A. DFD has the potential to cure LQTS through a complex method that involves interactions between active chemicals and targets. This study enhances our understanding of the molecular mechanisms underlying DFD\u2019s effects on LQTS.<\/jats:p>","DOI":"10.1038\/s41598-025-06515-7","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T02:28:00Z","timestamp":1751423280000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrated network pharmacology, molecular docking and experimental validation to explore the mechanism of Dingji Fumai Decoction against LQTS"],"prefix":"10.1038","volume":"15","author":[{"given":"Xiaoyan","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanghong","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangfang","family":"Lian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,2]]},"reference":[{"key":"6515_CR1","doi-asserted-by":"publisher","first-page":"2469","DOI":"10.1113\/jp270531","volume":"594","author":"B Foo","year":"2016","unstructured":"Foo, B., Williamson, B., Young, J. 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