A comprehensive study on <i>Herba Epimedium</i>-derived extracellular nanovesicles as a prospective therapy for alveolar bone regeneration in postmenopausal osteoporosis

Natural products rich in phytoestrogens, particularly those derived from traditional Chinese medicine (TCM) herbs, have garnered increased attention. Plant-derived extracellular vesicles are emerging as a promising strategy in cell communication and disease defense. Here, a comprehensive study on <i>Herba Epimedium</i>-derived extracellular nanovesicles (EELNs) for postmenopausal osteoporosis treatment was conducted. The results showed that EELNs exhibit a typical exosome morphology with an average diameter of 130 nm and are rich in specific small-molecule metabolites and miRNAs. Network pharmacology and KEGG analysis highlighted the therapeutic potential of EELNs in osteoporosis through multiple classical osteogenic pathways. <i>In vitro</i> experiments proved that EELNs potentiated the osteogenic differentiation of BMSCs by targeting the Pi3k/Akt/mTOR pathway. <i>In vivo</i>, EELN-loaded hydroxyapatite nano-whisker (E-GW) composites were used to repair mandibular defects in an OVX-induced osteoporosis rat model. The results indicate that EELNs are promising therapeutic agents for the regeneration and bone mass maintenance of alveolar defects in postmenopausal osteoporosis patients and offer potential perspectives for natural products in postmenopausal osteoporosis treatment.