Network pharmacology study of vaccarin for the prevention and treatment of postmenopausal osteoporosis

Abstract Background: As the main active ingredient of Semen Vaccariae, vaccarin is a flavonoid glycoside useful for the prevention and treatment of numerous diseases. Our previous study found that vaccarin can reduce osteolysis-induced titanium by inhibiting osteoclast formation. However, the issue of whether vaccarin can prevent and treat postmenopausal osteoporosis remains unclear.Method: In this study, we explored the mechanism of action of vaccarin for the prevention of postmenopausal osteoporosis via a network pharmacological approach. We identified the intersecting targets of osteoporosis-related genes retrieved from multiple disease target databases, as well as targets of potential action of vaccarin retrieved from drug-related databases. We then used the intersectional targets to establish a protein-protein interaction (PPI) network. Finally, we performed bioinformatics analysis to enrich Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.Results：A total of 28 cross targets of vaccarin and osteoporosis were identified. PPI network analysis identified six target proteins, namely, IL-6, TNF, VEGFA, HSP90AA1, CREB1, and IL-2, which may be the key targets of vaccarin against osteoporosis. The 28 intersectional targets were mainly involved in 23 biological processes, such as regulation of apoptosis, positive regulation of neovascularization, and angiogenesis, whereas KEGG enrichment analysis revealed that they were primarily related to 22 different signaling pathways, such as PI3K/Akt pathway, cancer pathway, hepatitis B pathway, and tuberculosis pathway.Conclusion: We used a network pharmacology approach to predict the key targets of vaccarin for the prevention of osteoporosis from a systems perspective. We determined that the signaling pathways were chiefly engaged in different pathological processes affecting differentiation and apoptosis of bone rebuilding cells, endocrine metabolic disorders, inflammatory responses, and other disease interactions. This study provides a theoretical basis and therapeutic ideas for the treatment of postmenopausal osteoporosis and offers promising directions for further research on the regulatory mechanism of vaccarin.