| Objective To investigate the protective effect of puerarin against ferroptosis in high glucose-induced ferroptosis in osteoblasts and its molecular mechanism. Methods Ferroptosis in MC3T3-E1 osteoblasts was induced by high glucose medium, using different concentrations of puerarin for the intervention. The effect of puerarin on the activity of MC3T3-E1 cells were detected with CCK-8. The effect of puerarin on the osteogenic differentiation ability of MC3T3-E1 cells were detected using ALP staining, ARS staining, and qRT-PCR. The levels of ROS, GSH, SOD, and MDA in MC3T3-E1 were measured with flow cytometry, DHE staining, and kits. The expressions of SLC7A11 and GPX4 were detected with Western blotting. Results CCK-8 results showed that puerarin at concentrations below 100 μM had no significant inhibitory effect on MC3T3-E1 cell activity. Compared with that in the high glucose group, 100 μM of puerarin effectively attenuated the inhibitory effect of high glucose on proliferation of MC3T3-E1 cells (P<0.05). In addition, puerarin significantly increased the expressions of ALP, RUNX2 COL1A1, and OPN, and increased ALP activity and mineralization level in MC3T3-E1 cells compared to those in the high glucose group (P<0.05). Compared with the high glucose group, puerarin markedly decreased ROS and MDA levels and increased GSH and SOD activities in MC3T3-E1 cells (P<0.05). Western blotting results showed that high glucose intervention obviously decreased the expressions of SLC7A11 and GPX4 in MC3T3-E1 cells, whereas puerarin upregulated the expressions of SLC7A11 and GPX4 (P<0.05). Conclusion Puerarin is able to attenuate high glucose-induced ferroptosis in osteoblasts. Its mechanism may be achieved by regulating the SLC7A11/GPX4 signaling pathway. |