Identification of Key Bioactive Compounds of Medicine–Food Homologous Substances and Their Multi-Target Intervention Effects in Osteosarcoma Treatment

Osteosarcoma (OS), a highly aggressive bone malignancy, is hard to treat due to complex molecular mechanisms. This study aimed to identify key bioactive compounds from medicine–food homologous (MFH) substances for OS intervention. We analyzed GEO transcriptomic data to get 317 differentially expressed genes (DEGs), screened bioactive compounds from 106 MFH via dual databases, predicted compound–DEG protein interactions with GraphBAN, and filtered 11 core compounds through drug-likeness/toxicity evaluations. Regulatory networks identified 5 key target genes (SOST, ACACB, TACR1, GRIN2B, MPO), 10 key compounds (e.g., ellagic acid dihydrate) and 8 MFHs (e.g., Daidaihua). Molecular docking/MD confirmed stable complexes. GSEA/GSVA revealed pathway dysregulation (e.g., upregulated WNT signaling), and immune analysis showed altered infiltration of 5 cell subsets. 143B cell experiments and qRT-PCR validated findings. MFH-derived compounds, especially ellagic acid dihydrate, have multi-target anti-OS potential, laying a foundation for novel OS therapeutics.