Abstract

The research utilized network pharmacology to explore how Yixin Fumai granules mitigate sinoatrial node fibrosis caused by D-galactose in older mice by altering inflammatory reactions. Effective ingredients and targets of Yixin Fumai granules (including ginsenoside, Ophiopogonin, Schisandrin, astragaloside, Danshensu, and ligustilide) were screened from traditional Chinese medicine systems pharmacology and BATMANtraditional Chinese medicine databases. Targeted diseases were pinpointed using GeneCards, Online Mendelian Inheritance in Man, and Disgenet databases. By employing Cytoscape 3.7.2 software, a network targeting drug-effective ingredients-targets was created, accompanied by a protein-protein interaction network formed via the Search Tool for the Retrieval of Interacting Genes databases. To forecast the fundamental processes, analyses of Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were conducted utilizing the R language. The expression levels of the NOD-like receptor protein 3, caspase-1, gasdermin D, interleukin-1 beta, and interleukin-18 genes were assessed through reverse transcription polymerase chain reaction. A total of 127 components were identified, with major components including quercetin, beta-sitosterol, kaempferol, naringenin, ginsenoside Rb1, and beta-eudesmol. There were 129 therapeutic targets identified, including key targets such as tumor necrosis factor, protein kinase B serine/ threonine kinase 1, interleukin-6, tumor protein P53, interleukin-1 beta, and vascular endothelial growth factor A. The experimental findings revealed that the Yixin Fumai granules group mice, in contrast to the model group, showed enhanced mental health, a standard diet, notably better coat color, and zero fatalities. The echocardiographic results showed a rise in ejection fraction and fractional shortening, a faster heart rate, a reduction in left ventricular internal diameter end systole and left ventricular internal diameter end diastole, and an increase in left ventricular posterior wall end systole and left ventricular posterior wall end diastole in the Yixin Fumai granules group relative to the model group. This study preliminarily elucidated the active ingredients, targets, and pathways through which Yixin Fumai granules treat sick sinus syndrome using network pharmacology and further validated its mechanism through experimental verification. These findings provide new evidence and research directions for treating sick sinus syndrome induced by aging.