Background: Osteoporosis (OP) is determined as a chronic systemic bone disorder to increase the susceptibility to fracture. Ginsenosides have been found the anti-osteoporotic activity of in vivo and in vitro. However, its mechanism remains unknown.Methods: The potential mechanism of ginsenosides in anti-osteoporotic activity was identified by using network phamacology analysis. The active compounds of ginsenosides and their targets associated to OP were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Drug Bank, Pharmmapper, and Cytoscape. The Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis target genes were performed in String, Phenopedia, DisGeNET database, and Metascape software. The protein to protein interaction were created by String database and Cytoscape software. The molecular docking was used to investigate the interactions between active coumpounds and potential targets by utilizing SwissDock tool, UCSF Chimera, and Pymol software. Results: A total of eight important active ingredients and 17 potential targets related to OP treatment were subjected to analyze. GO analysis showed the anti-osteoporosis targets of ginsenoside mainly play a role in the response to steroid hormone. KEGG enrichment analysis indicated that ginsenoside treats OP by osteoblast differentiation signal pathway. Lastly, the molecular docking outcomes indicated that ginsenoside rh2 had a good binding ability with four target proteins IL1B, TNF, IFNG, and NFKBIA. Conclusion: IL1B, TNF, IFNG, and NFKBIA are the most important targets and osteoblast differentiation is the most valuable signaling pathways in ginsenoside for the treatment of OP, which might be beneficial to elucidate the mechanism concerned to the action of ginsenoside and might supply a better understanding of its anti-OP effects.

Objective This study aim to investigate the potential targets involving the effect of ginsenoside on osteoporosis using a network pharmacology approach. Methods Ginsenoside and its drug targets associated to osteoporosis (OP) were identified by using network analysis. First, the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), DrugBank database, Pharmmapper database and Cytoscape software were used to mine information relevant to Ginsenoside ingredients and Ginsenoside -related targets. Second, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of ginsenoside-target gene and ginsenoside-OP target gene were performed in String, Phenopedia, DisGeNET database and Metascape software. Eventually, the protein to protein interaction (PPI) of key ginsenoside-OP targets were created by String database and Cytoscape software. The validation of the binding of ginsenoside to target proteins was plotted by utilizing SwissDock tool, UCSF Chimera and Pymol software. Results A total of 8 important active ingredients of ginsenosides were obtained in the TCMSP. Eighty potential targets of ginsenoside and 1304 related targets involved in OP were subjected to network analysis, and the 17 intersection targets were indicated to be linked to ginsenoside treating OP. GO and KEGG analysis showed the top 10 items of biological processes, cellular components, molecular functions and signaling pathways in the 80 targets of ginsenoside. Then, 14 key targets were determined to be the most crucial genes by protein to protein interaction (PPI) analysis. In the 14 intersection potential targets, 10 signaling pathways were defined by Metascape software. Validation plots of four target proteins IL1B, TNF, IFNG, NFKBIA binding to ginsenoside rh2 was drew, lastly. Conclusion This study investigated the potential targets and signaling pathways of ginsenoside during the treatment of OP, which might be beneficial to elucidate the mechanism concerned to the action of ginsenoside and might supply a better understanding of its anti-OP effects.