Huang Xiaoyan, Jin Yanghong, Lian Jiangfang
Ningbo Institute of Innovation for Combined Medicine and Engineering, Ningbo Medical Center Lihuili Hospital, Ningbo, 315100, Zhejiang, China.
Department of Cardiology, Ningbo Medical Center Lihuili Hospital, Ningbo, 315100, Zhejiang, China.
Sci Rep. 2025 Jul 2;15(1):23037. doi: 10.1038/s41598-025-06515-7.
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.
定悸复脉汤（DFD）是一种传统草药配方，在治疗实践中常用于治疗室性心律失常。然而，关于DFD在长QT综合征（LQTS）中的生物活性成分及潜在作用机制的研究仍然有限。所有DFD化合物均从中药系统药理学数据库（TCMSP）、中药百科全书（ETCM）和草药数据库（HERB）中收集，并使用瑞士靶点预测工具（SwissTargetPrediction）研究活性化合物的靶点。LQTS靶点则从疾病基因网络（DisGeNET）、在线人类孟德尔遗传数据库（OMIM）和人类疾病综合数据库（Malacard）中获取/筛选。利用STRING构建草药-化合物-靶点-疾病（H-C-T-D）和蛋白质-蛋白质相互作用（PPI）网络，并根据前期获得的数据使用CytoNCA进行分析。同时，使用VarElect确定靶点与疾病之间的关系。利用R程序对基因本体论（GO）术语以及京都基因与基因组百科全书（KEGG）通路进行富集分析。通过分子对接检测DFD与枢纽基因的结合能力，随后对关键发现进行实验验证。共收集到664个DFD靶点和240个LQTS靶点，发现其中有21个共同靶点。H-C-T-D网络展示了DFD、活性分子、靶点和LQTS之间的联系。PPI网络揭示了主要靶点：钾通道基因（KCNH2）、热休克蛋白90α家族成员1（HSP90AA1）、钠通道蛋白5型α亚基（SCN5A）和钙通道亚基α2δ-1（CACNA2D1）。进一步的系统研究揭示了DFD预防LQTS的潜在机制。此外，分子对接揭示了活性药物与靶点之间的相互作用。最后，我们发现DFD提高了KCNH2、HSP90AA1和CACNA2D1的水平，同时降低了SCN5A的水平。DFD有可能通过一种涉及活性化学物质与靶点相互作用的复杂方式来治疗LQTS。本研究增进了我们对DFD治疗LQTS作用的分子机制的理解。
