Molecular Mechanisms Underlying the Therapeutic Effects of Corydalis yanhusuo on Osteoporosis

Objective. Corydalis, a traditional Chinese medicine containing multiple active alkaloids, exhibits potential therapeutic effects on osteoporosis, though its underlying mechanisms remain unclear. This study aims to elucidate the molecular mechanisms of Corydalis in treating osteoporosis through network pharmacology research, providing theoretical support for its clinical application and drug development. Methods : Active components of Corydalis were screened using the TCMSP database (following Lipinski's rules: OB ≥ 30%, DL ≥ 0.18, etc.). Targets were standardized via UniProt and SwissTargetPrediction databases. Osteoporosis-related genes were obtained from DrugBank and GeneCards databases (screened with Score_gda ≥ 0.02 and Relevance ≥ 1.1427, respectively).Identified "drug-disease" intersection genes, constructed protein-protein interaction (PPI) networks using the STRING database and Cytoscape 3.9 to screen core targets; Performed Gene Ontology (GO) and KEGG pathway enrichment analyses using DAVID and Metascape databases; Conducted molecular docking between core targets (HIF1A, JUN, etc.) and active components (binding energy < -5.0 kcal/mol as the validity criterion). Results : 35 active components and 590 drug targets were screened from Corydalis yanhusuo, along with 1,278 osteoporosis-related genes. This yielded 112 intersecting genes, from which 21 core targets were further identified.GO analysis revealed core targets primarily involved in biological processes such as signal transduction, inflammatory response, and cell proliferation regulation. They were enriched in cellular components including plasma membrane and cytoplasm, with protein binding as the predominant molecular function.KEGG analysis indicated significant enrichment of core targets in signaling pathways including PI3K-Akt, MAPK, and AGE-RAGE. Molecular docking validation demonstrated stable hydrogen-bonded interactions between core components of Corydalis and targets such as HIF1A, AKT1, and ESR1 (all binding energies < -5.0 kcal/mol). Conclusion : Corydalis may exert anti-inflammatory effects, regulate glucose metabolism, inhibit osteoclast differentiation, and modulate parathyroid function by regulating signaling pathways such as PI3K-Akt and MAPK through core targets including HIF1A, JUN, and STAT3, thereby improving osteoporosis. This provides research directions for subsequent cellular experiments, animal validation, and clinical treatment.