Network pharmacology, molecular docking, and dynamics to explore the pharmacodynamic components and mechanism of epimedium in treating skeletal diseases
Periodontitis, chronic osteomyelitis of the jaw, and osteoporosis are etiologically distinct disorders but share persistent inflammation, impaired bone remodeling, and progressive bone loss. Epimedium brevicornum Maxim. has been widely used in traditional Chinese medicine for bone-related conditions; however, its shared mechanisms across these bone-destructive diseases remain insufficiently defined. This study integrated network pharmacology, molecular docking, and molecular dynamics simulations to identify potential active compounds, targets, and pathways of Epimedium. Twenty-three active compounds were screened from Epimedium, and 539 drug-related targets were obtained. A total of 966 disease-related targets were collected from public databases, yielding 160 overlapping targets. Protein-protein interaction analysis identified JUN, TNF, IL6, and TP53 as candidate hub genes. GO and KEGG analyses suggested that the common targets were mainly associated with inflammatory regulation, stress response, immune activation, and bone-homeostasis-related signaling. In the compound-target-pathway-disease network, quercetin, kaempferol, luteolin, genistein, and anhydroicaritin showed high connectivity. Molecular docking indicated favorable binding of quercetin and kaempferol with the hub proteins, with binding energies below -5.0 kcal/mol. A 50 ns molecular dynamics simulation further suggested stable TNF-quercetin and TP53-kaempferol complexes, with RMSD values remaining approximately 0.16-0.20 nm. These findings provide a computational basis for the hypothesis that Epimedium may modulate shared inflammatory and bone-remodeling networks in these diseases, which requires further experimental validation.