Abstract:Objective:To explore the action mechanism of Dipsaci Radix for osteoporotic fracture (OPF) based on network pharmacology and molecular docking. Methods: The potential active components of Radix Dipsaci with high activity were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP); the related targets of OPF were screened by GeneCards and OMIM database;the potential targets of Dipsaci Radix against OPF were identified by phase mapping of the related targets of OPF by Metascape database. The "medicines- compositions- diseases- targets" network of Dipsaci Radix for OPF was constructed by Cytoscape software;the protein-protein interaction network was constructed by STRING platform; the genetic ontological (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed by the Dipsaci Radix- related targets provided by the David database. Finally, the binding ability of the core targets and the active ingredients of Dipsaci Radix was verified by molecular docking. Results: The main active ingredients of Dipsaci Radix for OPF mainly include Gentisin,β-sitosterol,Sitosterol,(E,E)-3,5-Di-O-caffeoylquinic acid and Sylvestroside Ⅲ- qt, which act on caspase 3 (CASP3), β2- adrenergic receptor gene (ADRB2), Bcl- 2 associated X protein (BAX), B lymphocytoma- 2 gene (BCL2), caspase 8 (CASP8), estrogen receptor 2 (ESR2),caspase 9 (CASP9),dipeptidyl peptidase-4 (DPP4),glycogen synthase kinase 3 (GSK3β), abnormal prothrombin (F2) and other targets. By participating in biological processes such as cysteine endopeptidase, G protein- coupled amine receptor, and peptidase activity in the executive phase of transcriptional regulation and apoptosis,Dipsaci Radix regulated cancer pathways and signaling pathways of toxoplasmosis,Kaposi sarcoma-associated herpesvirus infection,hepatitis B,colorectal cancer,lipids of small cell lung cancer, atherosclerosis, and estrogen to treat OPF. Molecular docking results showed that the active ingredients of Dipsaci Radix (E,E) -3,5-Di-O-caffeoylquinic acid,Gentianine,Cauloside A_qt, β- sitosterol had good affinity with CASP3, β2- adrenergic receptor gene (ADRB2) and CASP8. Conclusion: Dipsaci Radix can be used to treat OPF by directly acting on the pathways related to bone metabolism and participating in the regulation of multiple upstream and downstream signaling pathways. CASP3 and cancer pathways can be the key targets and pathways for the treatment of OPF.