Therapeutic Potential of Panax Ginseng-derived Nanovesicles in Osteoporosis through Enhanced Osteoblast

Osteoporosis is a skeletal disorder caused by an imbalance between bone resorption and formation, which leads to reduced bone density and increased fracture risk. Plant-derived nanovesicles have emerged as safe, biocompatible biomaterials with therapeutic potential for bone regeneration. In this work, the biological effects of Panax ginseng-derived nanovesicles (PNVs) were evaluated with a focus on osteoblast differentiation, bone formation, and mineralization. PNVs were successfully isolated, characterized, and tested for their osteogenic capacity using MC3T3-E1 cells, mouse primary osteoblasts, and osteoclasts. Treatment with PNVs (0-10 μg/mL) for 3 or 7 days markedly promoted osteoblastic maturation and matrix mineral deposition, as confirmed by Alizarin-red and Von Kossa staining. In addition, PNVs exposure upregulated key osteogenic genes, including Runx2, ALP, and OPN, while activating major signaling cascades such as BMP2/4 and phosphorylated p38, implying their involvement in osteogenic regulation. Moreover, in an ovariectomized (OVX) mouse model, oral administration of PNVs improved bone microarchitecture by stimulating osteoblast-driven bone regeneration and attenuating osteoclast-mediated bone degradation. Collectively, our findings indicate that PNVs promote osteoblast differentiation and bone matrix formation, thereby enhancing mineralization and demonstrating their potential as a natural nanotherapeutic approach for osteoporosis prevention and treatment. Graphical Abstract to describe isolation, administrations, and osteogenic functions of PNVs in vitro and in vivo .