The Role of Coicis Semen in Staphylococcus aureus -Induced Osteomyelitis: Bioinformatics Integrated with Experimental Validation

Background: Osteomyelitis, often caused by Staphylococcus aureus , presents treatment challenges owing to antibiotic resistance. This study aimed to explore the therapeutic potential of Coicis Semen against osteomyelitis through bioinformatics and experimental validation. Methods: An integrated analysis of GEO datasets (GSE16129 and GSE6269) was performed to identify osteomyelitis-related differentially expressed genes. Active compounds of Coicis Semen were screened using HERB and SwissADME, and target genes were predicted using SwissTargetPrediction. Protein-protein interaction networks, molecular docking, molecular dynamics simulations, and in vitro and in vivo experiments were conducted to validate the mechanisms. Results: Eleven bioactive compounds and three key genes, Integrin subunit beta 3 ( ITGB3), Myeloperoxidase (MPO) , and C-X-C motif chemokine ligand 8 ( CXCL8 ) were identified. Molecular docking confirmed the stable binding of 6-Methoxy-2-benzoxazolinone (MBOA)- MPO and Nonanoic acid- CXCL8 . Both compounds inhibited Staphylococcus aureus growth in vitro and reduced bone destruction in a mouse model. Conclusion: Coicis Semen may alleviate osteomyelitis through multi-target immunomodulatory and antibacterial mechanisms, offering potential adjunctive treatment options.