Abstract
BACKGROUND: Xianlinggubao formula (XLGB), a Chinese State Food and Drug Administration-permitted traditional Chinese herbal medicine, has been extensively used to treat osteoporosis. Although XLGB was shown to improve bone mass in ovariectomized rats and clinically alleviate osteoporosis symptoms, its pharmacological mechanisms remain unclear. METHODS: In this study, we used a network pharmacological approach to explore the potential mechanism of XLGB in treating osteoporosis. We obtained XLGB compounds from the TCMSP and TCMID databases and identified potential targets of these compounds through target fishing based on the TCMSP and Swiss Target Prediction databases. Next, we identified the osteoporosis targets by using the CTD, TTD, GeneCards, OMIM and PharmGKB databases. Then, the overlapping genes between the XLGB potential targets and the osteoporosis targets were used to establish a protein-protein interaction (PPI) network and to analyze their interactions and identify the major hub genes in this network. Subsequently, the Metascape database was utilized to conduct the enrichment of Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. RESULTS: There were 104 active compounds and 295 related targets identified overall. After the Metascape enrichment analysis, we identified the top 25 cellular biological processes and top 15 pathways based on the logP value and found that the XLGB-mediated anti-osteoporosis effect was mainly associated with reactive oxygen species, organonitrogen compound response and cell migration. Furthermore, 36 hub genes of XLGB, such as EGF, EGFR, MTOR, MAPK14 and NFKB1, were considered potential therapeutic targets, suggesting the underlying mechanisms of XLGB acting on osteoporosis. CONCLUSION: We investigated the possible therapeutic mechanisms of XLGB from a systemic perspective. These key targets and pathways provide promising directions for future research to reveal the exact regulatory mechanisms of XLGB.