Deciphering Matrine's Therapeutic Mechanism in Osteosarcoma: Insights from Network Pharmacology and Single-Cell RNA Sequencing

This study aimed to investigate the potential mechanisms underlying the therapeutic effect of matrine in osteosarcoma using network pharmacology and single-cell ribonucleic acid sequencing. Matrine's potential gene targets were sourced from multiple databases; comparative toxicogenomics database, SwissTargetPrediction, Binding DB, and TargetNet. We extracted gene expression data related to osteosarcoma from the GSE14359 dataset. To discern the activation pathways of genes linked to both the drug and disease, we performed differential gene analysis, Kyoto encyclopedia of genes and genomes pathway analysis, and gene ontology enrichment analysis. By employing both weighted gene co-expression network analysis and differential analysis, we pinpointed critical genes associated with osteosarcoma. Protein-protein interaction analysis was utilized to highlight hub genes. Furthermore, module analysis revealed key gene clusters that affect matrine. For a comprehensive evaluation of matrine's pharmacological targets and signaling pathways in osteosarcoma, single-cell ribonucleic acid sequencing was carried out on the GSE162454 dataset using the Seurat package in R. A total of 15 cell clusters were identified, and the analysis results suggested that the mechanism of matrine's action on osteosarcoma may involve macrophages. This study elucidated the targets and pathways through which matrine acts on osteosarcoma using network pharmacology. Moreover, single-cell sequencing identified macrophages as key cellular markers for matrine's action in osteosarcoma. These findings provide new therapeutic evidence for clinical treatment strategies.