Mechanism of the Salvia miltiorrhiza- Codonopsis pilosula drug pair in the treatment of premature ovarian failure based on network pharmacologymolecular docking

Objective: Premature ovarian failure (POF) is a disease characterized by irregular menstruation and results in infertility which markedly affects the reproductive health of women. TheSalvia miltiorrhiza-Codonopsis pilosula drug pair is effective at treating POF; however, knowledge of the mechanisms ofS. miltiorrhiza-C. pilosula in the treatment of POF is lacking. Thus, we carried out network pharmacology and molecular docking to clarify the mechanisms of this drug pair.Methods: The core components and targets ofS. miltiorrhiza-C. pilosula were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database and UniProt database, and the disease targets related to POF were searched using different tools to obtain the overlapping target genes ofS. miltiorrhiza andC. pilosula. A protein interaction network of the intersection target was constructed using STRING database, and the network of "traditional Chinese medicine-active ingredient-intersection target-disease" and "pathways-targets" was constructed using Cytoscape 3.8.0. The DAVID online tool was also used to determine the gene ontology functions and Kyoto Encyclopedia of Genes and Genomes pathways associated with the intersection target genes. Finally, the binding ability of the drug to the active components and potential targets were predicted using molecular docking.Results: S. miltiorrhizae-C. pilosula had 72 active components, 128 targets, 3,775 POF targets, and 106 common targets. The potential targets were mainly related to the biological processes of DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, transcription factor activity, steroid receptor activity, and hypoxia response. Further, the Kyoto Encyclopedia of Genes and Genomes enrichment pathways included PI3K-Akt signaling pathway, apoptosis, interleukin (IL)-17 signaling pathway, relaxin signaling pathway, and other biological pathways.Conclusion(s): S. miltiorrhiza-C. pilosula can inhibit ovarian granulosa cell apoptosis and improve ovarian hemodynamics through multiple targets and multiple pathways and help treat POF.