Network Pharmacology and Experimental Verification to Explore Cinnamomi Cortex against Steroid-induced Osteonecrosis of the Femoral Head.

Steroid-induced osteonecrosis of the femoral head (SONFH) causes severe pain and limited mobility, significantly impairing patients' quality of life. Cinnamomi Cortex (CC) has been shown to effectively alleviate this condition, yet its mechanism of action remains unclear. This study aims to identify the active compounds of CC and explore their mechanisms in SONFH. Active constituents were screened using the HERB 2.0, PubChem, and SwissADME databases, and their corresponding targets were predicted using the Swiss Target Prediction database. Targets for SONFH were identified by intersecting targets from GEO, DisGeNET, GeneCards, and OMIM databases with the compound-related targets. A protein-protein interaction (PPI) network was constructed using the STRING database, and GO and KEGG enrichment analyses were conducted via the DAVID database. The most promising compound-target interactions were validated through molecular docking (MD) and molecular dynamics simulations. The researchers identified 563 potential targets, including 61 SONFH-related targets, with AKT1, HIF-1α, and STAT3 serving as central nodes. KEGG enrichment analysis highlighted the HIF-1α signaling pathway as a key mechanism. Furthermore, animal experiments demonstrated that the active fraction of CC effectively mitigated femoral head structural damage in a mouse model with SONFH. The findings suggest that CC may improve SONFH by coordinating hypoxia adaptation and regulating angiogenesis and osteogenesis.