Unveiling the therapeutic mechanisms of Eucommia ulmoides-Achyranthes bidentata in osteoporosis: A network pharmacology and molecular docking study.

Osteoporosis (OP) occurs with decreased bone mass and deterioration of the bone microarchitecture. This can lead to an increased incidence of bone fractures. In traditional Chinese medicine, the herbal pair of Eucommia ulmoides and Achyranthes bidentata is used to tonify the liver and kidney in order to strengthen bones. This study examined the network pharmacology and molecular docking of the pair to investigate the pharmacological mechanisms of the drug pair against OP. Active compounds were retrieved from the Traditional Chinese Medicine Systems Pharmacology database if they had an oral bioavailability of 30% or greater and a drug-likeness score of 0.18 or greater. OP-associated targets were identified from the GeneCards and Online Mendelian Inheritance in Man databases. The compound-target-disease network and protein-protein interaction network were built using Cytoscape and the Search Tool for the Retrieval of Interacting Genes/Proteins, respectively. Key pathways were identified using the Database for Annotation, Visualization and Integrated Discovery functional enrichment analysis. To predict the potential binding interactions between the major compounds and the hub targets, molecular docking was used. In total, 49 active compounds (28 from E ulmoides and 21 from A bidentata) and 95 overlapping therapeutic targets were found. Quercetin, kaempferol, β-sitosterol, stigmasterol and wogonin were identified as key bioactive components within the network analysis. Fourteen hub targets, including interleukin-6, vascular endothelial growth factor A, tumor necrosis factor, tumor protein p53, and mitogen-activated protein kinase 1, were identified through protein-protein interaction analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment revealed involvement in tumor necrosis factor, mitogen-activated protein kinase, hypoxia-inducible factor 1, Toll-like receptor, and NOD-like receptor signaling pathways. Molecular docking demonstrated favorable binding affinities between the key compounds and core proteins, suggesting potential interactions consistent with the network pharmacology predictions. The Eucommia-Achyranthes herbal pair may exert potential therapeutic effects on OP through multicomponent, multi-target, and multi-pathway interactions. Its main bioactive compounds may potentially interact with inflammatory and osteogenic signaling pathways via key targets such as interleukin-6, vascular endothelial growth factor A, tumor necrosis factor-alpha, tumor protein p53, and mitogen-activated protein kinase 1, which may be associated with bone metabolism and structural integrity. These findings provide a theoretical foundation for future experimental and clinical validation.