Identified the Synergistic Mechanism of Drynariae Rhizoma for Treating Fracture Based on Network Pharmacology

BACKGROUND: Drynariae Rhizoma (DR) has been widely used in the prevention and treatment of various fractures. However, the specific mechanisms of DR's active ingredients have not been elucidated. The purpose of this study was to explore the synergistic mechanisms of DR for treating fracture. METHODS: A network pharmacology approach integrating ingredient screening, target exploration, active ingredients-gene target network construction, protein-protein interaction network construction, molecular docking, gene-protein classification, gene ontology (GO) functional analysis, KEGG pathway enrichment analysis, and signaling pathway integration was used. RESULTS: This approach identified 17 active ingredients of DR, interacting with 144 common gene targets and 143 protein targets of DR and fracture. NCOA1, GSK3B, TTPA, and MAPK1 were identified as important gene targets. Five most important protein targets were also identified, including MAPK1, SRC, HRAS, RXRA, and NCOA1. Molecular docking found that DR has a good binding potential with common protein targets. GO functional analysis indicated that common genes involve multiple processes, parts and functions in biological process, cellular component, and molecular function, including positive regulation of transcription from RNA polymerase II promoter, signal transduction, cytosol, extracellular exosome, cytoplasm, and protein binding. The KEGG pathway enrichment analysis indicated that common gene targets play a role in repairing fractures in multiple signaling pathways, including MAPK, PI3K/AKT, Ras, and VEGF signaling pathways. MAPK and PI3K/AKT signaling pathways were involved in osteoblast formation, Ras signaling pathway was involved in enhancing mesenchymal stromal cell migration, and VEGF signaling pathway was involved in angiogenesis. CONCLUSION: The study revealed the correlation between DR and fracture and the potential synergistic mechanism of different targets of DR in the treatment of fractures, which provides a reference for the development of new drugs.