Objective　To explore the mechanism of Sanqi⁃Epimrdii herba for the treatment of osteonecrosis of the femoral head (ONFH) by using the network pharmacology and molecular docking technique. Methods The active components and their effect targets of Sanqi⁃Epimrdii herba were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The GeneCards􀳏 and OMIM􀳏 databases were used to screen targets related to ONFH. After obtaining intersection, the potential effect targets of Sanqi⁃Epimrdii herba for the treatment of ONFH were acquired. The drugs⁃active components⁃effect targets network was established by the Cytoscape software, and the key active components were screened. The protein⁃protein interaction network was established by the STRING database and Cytoscape software for screening the core targets. The DAVID database was employed to perform functional enrichment analysis and pathway enrichment analysis on potential effect targets. Finally, the molecular docking validation was performed on the key active components and core target proteins. Results　A total of 30 active components and 214 effect targets of Sanqi⁃Epimrdii herba were eventually obtained, concerning 2112 targets related to ONFH. After obtaining intersection, there were 131 potential effect targets of Sanqi⁃Epimrdii herba for the treatment of ONFH. Quercetin, luteolin, kaempferol, anhydroicaritin were the key active components of Sanqi⁃Epimrdii herba for the treatment of ONFH, and protein kinase B1, vascular endothelial growth factor A, proto⁃oncogene c⁃Jun, tumor protein p53, and interleukin 1β were the core targets of Sanqi⁃Epimrdii herba for the treatment of ONFH. The potential effect targets of Sanqi⁃Epimrdii herba for the treatment of ONFH were mainly involved in biological processes such as response to lipopolysaccharide, response to external irritant, and response to cell hypoxia, and involved in signaling pathways in terms of interleukin 17 signaling pathway, mitogen activated protein kinase signaling pathway, advanced glycation end products⁃receptor for advanced glycation end products signaling pathway in diabetic complications, phosphoinositide 3⁃kinase/protein kinase B signaling pathway, etc. The results of molecular docking revealed that the key active components exerted favorable binding activity with the core target proteins (binding energy≤-5 kcal/mol). Conclusion The mechanism of Sanqi⁃Epimrdii herba for the treatment of ONFH may be related to response to immune⁃inflammation, regulation of apoptosis and differentiation of osteoclasts and osteoblasts, and blood supply improvement, etc.

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