Network Pharmacology Integrated with Molecular Docking Explores the Mechanisms of Naringin against Osteoporotic Fracture by Regulating Oxidative Stress

Naringin (NG), as the most abundant component of Drynariae Rhizoma (Chinese name: Gusuibu), has been proved to be an antioxidant flavonoid on promoting osteoporotic fracture (OF) healing, but relevant research is scanty on the underlying mechanisms. We adopted target prediction, protein-protein interaction (PPI) analysis, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and molecular docking to establish a system pharmacology database of NG against OF. Totally 105 targets of naringin were obtained, including 26 common targets with OF. A total of 415 entries were obtained through GO Biological Process enrichment analysis (P < 0.05), and 37 entries were obtained through KEGG pathway enrichment analysis with seven signaling pathways included (P < 0.05), which were primarily concerned with p53, IL-17, TNF, estrogen, and PPAR signaling pathways. According to the results of molecular docking, naringin is all bound in the active pockets of the core targets with 3-9 hydrogen bonds through some connections such as hydrophobic interactions, Pi-Pi stacked interactions, and salt bridge, demonstrating that naringin binds tightly to the core targets. In general, naringin may treat OF through multiple targets and multiple pathways via regulating oxidative stress, etc. Notably, it is first reported that NG may regulate osteoclast differentiation and oxidative stress through the expression of the core targets so as to treat OF.