Synergistic effects of compound plant extracts and Lactobacillus plantarum on osteogenesis: prebiotic potential and mechanistic insights from metabolomics and molecular docking

Abstract BACKGROUND Osteoporosis is a major public health challenge and innovative dietary strategies are needed to support bone health. RESULTS This study aimed to develop a functional food by promoting osteogenesis through the synergistic effects of compound plant extracts (CPE) and Lactobacillus plantarum . First, it was determined that CPE could promote the growth, metabolic activity, biofilm formation, calcium enrichment, and antioxidant properties of L. plantarum , improving the bioavailability of calcium. Cell experiments showed that the combined application of CPE and L. plantarum (CPEL) significantly promoted the proliferation, differentiation, and extracellular matrix mineralization of MC3T3‐E1 cells. Mechanistically, CPEL activated the Wnt/ β ‐catenin and BMP2/Smad signaling pathways, which are essential for bone formation. The multi‐omics integration of metabolomics and molecular docking revealed key metabolic changes, particularly in amino acid and carbohydrate metabolic pathways, contributing to enhanced osteogenic activity. Molecular docking also clarified the strong binding interactions between differential metabolites (leucine, salicylic acid, and fumaric acid) and osteogenic targets, providing new insights into plant component–microbe synergy in functional food development. CONCLUSION The combined application of CPE and L. plantarum could promote bone formation through multiple targets and pathways. These findings highlight the potential of plant extract–probiotic synergy in developing functional foods for bone health, offering a promising dietary strategy to prevent osteoporosis. © 2025 Society of Chemical Industry.