Mechanism of action of curculigoside ameliorating osteoporosis: an analysis based on network pharmacology and experimental validation

chuan fu weiwenhuan zhangchunbiao louNianhu Li^*Hui Cao^*

• Shandong University of Traditional Chinese Medicine, Jinan, China

[Objective] To predict and verify the mechanism of curculigoside in treating osteoporosis using network pharmacology, molecular docking technology, and Micro CT technology.[Methods] Herb databases were searched to identify and screen potential targets of curculigoside. The GeneCards platform was utilized to mine osteoporosis-related targets. Cytoscape 3.6.0 software was employed to construct a compound-target-disease network. A protein-protein interaction (PPI) network for curculigoside in osteoporosis treatment was established, and core targets were screened. KEGG pathway enrichment and GO biological process analyses were performed using the Metascape database. Finally, molecular docking and Micro CT were used to validate core targets relevant to osteoporosis.[Results] A total of 166 potential curculigoside targets and 4313 osteoporosis-related targets were identified, with 91 common targets. Ten key targets, including MMP3, MMP9, IL-6, and caspase-3, were screened. KEGG pathway enrichment analysis indicated involvement in 10 pathways, such as the Rap1 signaling pathway and TNF signaling pathway. Molecular docking results demonstrated strong binding affinity between curculigoside and the core targets. Micro CT analysis revealed that curculigoside not only improved BMD, BV/TV, BS/BV, and Tb.Th but also reduced Tb.Sp in osteoporotic bone.[Conclusions] Curculigoside is likely to treat osteoporosis through targets such as MMP3, MMP9, IL-6, and caspase-3, acting on signaling pathways including Rap1 and TNF. These results indicate that curculigoside exhibits multi-target and multi-pathway characteristics in osteoporosis treatment, providing a theoretical basis for further clinical investigation.