Exploring the mechanism of saffron in treating viral myocarditis using network pharmacology and molecular docking

Viral myocarditis (VM) is a cardiovascular disorder that can lead to heart failure and cardiogenic shock. Saffron, a traditional Chinese medicinal herb, has shown therapeutic potential against VM in numerous studies. However, the mechanisms through which saffron exerts its effects on VM remain poorly understood. Thus, this study aimed to elucidate the active compounds, molecular targets, and signaling pathways involved in saffron's therapeutic action against VM by employing network pharmacology and molecular docking approaches. The active compounds and corresponding targets of saffron were retrieved from the Traditional Chinese Medicine Systems Pharmacology database. VM-associated targets were sourced from the GeneCards database. Overlapping targets between saffron and VM were then identified. Protein-protein interaction networks were established and analyzed utilizing the STRING platform and Cytoscape software to determine core targets. Furthermore, gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were carried out utilizing Bioconductor in R to explore the potential biological activities and signaling pathways through which saffron may act against VM. Finally, molecular docking and model visualization were carried out using AutoDock Tools and PyMOL open-source software. From the database, we identified 4 active compounds in saffron with potential effects against VM: crocetin, isorhamnetin, kaempferol, and quercetin. A total of 60 corresponding targets were observed, with TNF, IL-6, IL-1β, CXCL8, and JUN emerging as core targets. Kyoto encyclopedia of genes and genomes enrichment analysis revealed 155 regulatory signaling pathways, among which the TNF, AGE-RAGE, and IL-17 signaling pathways, lipid metabolism, and atherosclerosis were the most prominent. Molecular docking results indicated that quercetin showed the strongest binding affinity toward IL-1β and CXCL8. The therapeutic effect of saffron against VM is not driven by a single factor, but rather involves multiple active compounds, targets, and signaling pathways.