摘要

Objective: The present study systematically investigated the in vivo effect of ethanol extracts of eucommia ulmoides (EE-EU) on bone deteriorations in GIOP rat, which was a secondary osteoporosis experimental animal model. This animal model has typical pathologic manifestation and good replication, and could be used to study the effect of drugs. Methods: Forth 6-week-old male Sprague-Dawley rats were randomly divided into vehicle-operated group, prednisone acetate (PA) group, PA with EE-EU of graded doses (100 mg/kg/day or 500 mg/kg/day). The biomarkers in serum and urine were measured, tibias and femurs were taken for the measurement histomorphology, biomechanical parameters, genes and protein expression. Results: High concentrations of EE-EU could significantly prevent the increase in urine calcium and urine phosphorus levels in GIOP rats, meanwhile, EE-EU at a dose of 500 mg/kg/day could dramatically reverse an increase in TRAP-5b and PINP, and a decrease in ALP and FGF-23, which was induced by PA administration. Moreover, treatment with DZCE at higher doses (500 mg/kg/day) was found to be able to significantly prevent PA-induced decrease in biomechanical quality and BMD of femur. Furthermore, the decreased thickness of newly formed cartilage of the GIOP mice was effectively reversed by high concentrations EE-EU. Intriguingly, high concentrations EE-EU treatment could reverse PA-induced low mRNA, protein expression of BMP2, serum testosterone and AR protein expression. Conclusions: The present study demonstrated the anti-osteoporotic effects of EE-EU against bone deteriorations and cartilage degradations in experimentally DIOP rats, and the underlying mechanism was mediated, at least partially, through the activation of androgen receptor signaling.