Objective: To investigate the potential molecular mechanism of Epimedii Folium in the treatment of osteonecrosis of femeral head based on the network pharmacology and bioinformatics. Method: The method of network pharmacology was used to determine and screen out the potential compounds of Epimedii Folium through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform

and predict the drug-related gene/protein targets by means of such databases as TTD and DrugBank

OMIM

GAD and PharmGKB. Bioinformatic method was used to determine the specific target of Epimedii Folium in prevention and treatment of osteonecrosis of femeral head. ClueGO was applied in the signal pathway enrichment analysis to further analyze the molecular mechanism of Epimedii Folium in treatment of osteonecrosis of femeral head. Result: The 130 compounds related to Epimedii Folium were retrieved in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. According to the parameters of oral bioavailability (OB) and drug-likeness (DL)

a total of 23 blood transfusion components were screened out

and 102 targets were predicted by using the relevant target prediction technique. A total of 72 known targets closely related to the development of osteonecrosis of femeral head were retrieved in the disease-related databases. Cytoscape software was used to construct and synthesize the protein-protein interaction network of active ingredients and diseases

and 135 key genes were screened out by the network topological analysis. ClueGO analysis showed that the key signaling pathways involving the effect of Epimedii Folium on osteonecrosis of femeral head were mainly enriched in 80 signaling pathways

such as cell proliferation

apoptosis

inflammation

stress and cancer related signaling pathways. Conclusion: Epimedii Folium has the characteristics of multiple targets and multicomponents in the treatment of osteonecrosis of femeral head. Its main pathways not only directly participate in the cell proliferation

apoptosis and differentiation and the regulation of the balance of osteogenesis and osteoclasts

but also interfere and affect the bone microenvironment by regulating immunity

inflammation and stress

so as to control the occurrence and development of diseases. This is consistent with the current mechanism in treating the osteonecrosis of femeral head.