Mogroside V inhibits high glucose-induced inflammatory responses and promotes osteogenic differentiation in diabetic osteoporosis via the PI3K/Akt/mTOR pathway.

BACKGROUND

Osteoblast dysfunction induced by high glucose (HG) environment plays a key role in diabetic osteoporosis (DOP) pathogenesis, but effective intervention strategies are still limited. Mogroside V (Mog V), a natural compound, has anti-inflammatory and metabolic regulatory activities, but its protective effect on DOP and its molecular mechanism are still unclear.

METHODS

A HG-induced MC3T3-E1 cell injury model was established, and different concentrations of Mog V (50, 100, 200 μM) were given to the intervention. Cell viability, injury and apoptosis rate were assessed via Cell Counting Kit-8 assay, LDH kit, and flow cytometry. Osteogenic differentiation and mineralization were evaluated by alkaline phosphatase (ALP) and alizarin red staining. The DOP mouse model was induced by high-fat diet feeding and intraperitoneal injection of streptozotocin (STZ). After 8 weeks of Mog V intervention, the glucose metabolism indexes of the mice were detected, and the bone microstructure and femoral tissue damage were evaluated by Micro-CT and pathological staining. Oxidative stress markers were detected by kits, inflammatory cytokine levels were quantified using ELISA kits, and apoptosis, osteogenic differentiation, and the PI3K/Akt/mTOR axis-related protein levels were detected via Western blot.

RESULTS

HG treatment decreased MC3T3-E1 preosteoblast viability, promoted LDH release and proinflammatory cytokine secretion, and increased the apoptosis rate. Mog V treatment effectively reduced HG-induced MC3T3-E1 cell damage, inhibited inflammatory response and oxidative stress, and increased ALP activity and promoted mineralization. Mog V treatment could partially restore the activation level of PI3K/Akt/mTOR axis in HG-treated MC3T3-E1 cells. Intervention with the pathway inhibitor LY294002 attenuated the anti-apoptotic, anti-inflammatory, and pro-osteogenic impacts of Mog V. Mog V treatment improved glucose metabolism in DOP mice, while protecting bone microstructure and increasing bone morphogenetic proteins expression. Additionally, Mog V intervention effectively reduced serum proinflammatory factor levels and activated the PI3K/Akt/mTOR axis in the femoral tissue of mice.

CONCLUSION

Mog V inhibits osteoblast apoptosis and inflammatory response induced by HG, promotes osteogenic differentiation in DOP mice by activating PI3K/Akt/mTOR pathway.