Epimedin B protects against bone loss and inflammation in diabetic osteoporosis rats by regulating OPG/RANKL pathway

Background: Diabetes is a common disease contributing to osteoporosis. Epimedin B (EB), a major ingredient of Herba Epimedii, has been found to be effective in preventing osteoporosis in mice. However, the potential of EB to ameliorate diabetic osteoporosis (DOP) remains elusive. In this study, our goal is to investigate the functions and underlying mechanisms of EB in the progression of DOP.

Methods: A DOP rat model was established via a high-fat diet combined with intraperitoneal injection of streptozotocin (STZ). DOP rats were daily administered with EB or vehicle via intragastric administration for 8 weeks. Body weights and blood glucose levels were measured every 4 weeks during the drug administration period. Blood samples and femoral tissues were collected for further analysis. Bone parameters and bone histopathological changes were detected. Bone formation and resorption markers as well as inflammatory factors were detected using enzyme-linked immunosorbent assay kits. Reverse-transcription quantitative polymerase chain reaction and western blotting were conducted to measure the expression of Osteoprotegerin (OPG) and Rev-Erbα, receptor activator of NF-κB ligand (RANKL).

Results: EB improved weight loss and lowered blood glucose of DOP rats. EB promoted the formation of bone trabeculae and altered several bone microstructure parameters in DOP rats. EB ameliorated improved bone structure, restored histological abnormalities of femoral bone, and reduced the number of bone marrow adipocytes in DOP rats. EB inhibited excessive bone resorption and inflammation and increased bone formation in DOP rats. EB regulated the OPG/RANKL axis in DOP rats.

Conclusion: EB attenuates STZ-induced DOP in rats by maintaining the balance between bone formation and resorption and inhibiting inflammation through regulating the OPG/RANKL axis.

Bone formation; Bone resorption; Diabetes; Epimedin B; Inflammation; OPG/RANKL axis; Osteoporosis.