The flavonoid glabridin attenuates 2-deoxy-D-ribose-induced oxidative damage and cellular dysfunction in MC3T3-E1 osteoblastic cells

Reducing sugar 2-deoxy-D-ribose (dRib) produces reactive oxygen species (ROS) through autoxidation and protein glycosylation and causes dysfunction of osteoblasts. In the present study, glabridin, a natural flavonoid, was investigated to determine whether it could influence dRib-induced oxidative damage and cellular dysfunction in the MC3T3-E1 mouse osteoblastic cell line. Osteoblastic cells were treated with dRib in the presence or absence of glabridin. Cell viability, apoptosis, ROS production and mitochondrial membrane potential (ΔΨ_m) were subsequently examined. It was observed that dRib reduced cell survival and ΔΨ_m, while it markedly increased intracellular levels of ROS and apoptosis. However, pretreatment of cells with glabridin attenuated all the dRib-induced effects. The antioxidant N-acetyl-L-cysteine (NAC) also prevented dRib-induced oxidative cell damage. In addition, treatment with glabridin resulted in a significant elevation of alkaline phosphatase (ALP) activity, collagen contents and osteoblast differentiation genes [ALP, collagen, osteopontin (OPN), osteoprotegerin (OPG) and osteocalcin (OC)] and bone morphogenetic protein (BMP) genes (BMP2, BMP4 and BMP7). In mechanistic studies of the antioxidative potential of glabridin, we found that glabridin activated dRib-induced decreased expression of phosphatidylinositol 3'-kinase (PI3K) and protein kinase B 2 (AKT2) genes, which are master regulators of survival-related signaling pathways. Glabridin also upregulated the gene expression of antioxidant enzymes, superoxide dismutase 1 (SOD1) and glutathione peroxidase 4 (GPX4), which were inhibited by dRib. Taken together, these results suggest that glabridin attenuates dRib-induced cell damage in osteoblastic cells and may be useful for the treatment of diabetes-related bone disease.