Integrated network pharmacology, molecular docking and experimental validation to explore the mechanism of Dingji Fumai Decoction against LQTS

TL;DR

This study explores how Dingji Fumai Decoction may treat Long QT syndrome by analyzing its active compounds and molecular interactions.

Contribution

The study integrates network pharmacology, molecular docking, and experimental validation to reveal DFD's mechanism against LQTS.

Findings

DFD interacts with key targets like KCNH2, HSP90AA1, SCN5A, and CACNA2D1 in LQTS.

Molecular docking confirmed interactions between DFD compounds and LQTS-related targets.

DFD increased levels of some targets while decreasing others, suggesting a regulatory role in LQTS.

Abstract

Dingji Fumai Decoction (DFD), a traditional herbal concoction, is commonly utilized in therapeutic practice to treat ventricular arrhythmia. 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’s 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’s effects on LQTS.

The online version contains supplementary material available at 10.1038/s41598-025-06515-7.

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