Chrysin alleviates alteration of bone-remodeling markers in ovariectomized rats and exhibits estrogen-like activity in silico

Abstract

Background Evidences are beginning to accrue that flavonoids, particularly phytoestrogens, could have beneficial effects against several age-related diseases linked to estrogen deficiency including postmenopausal osteoporosis. Methods In this study, the effect of chrysin on selected bone-remodeling markers in ovariectomized rats and its estrogen-like activity in silico were investigated. Results The data indicated that administration of chrysin at 50 mg/kg and 100 mg/kg for 6 weeks to OVX rats significantly ( p < 0.05) prevented body weight gain and partially reverse uterine weight loss. In addition, treatment of OVX rats significantly ( p < 0.01) increased femur dry weight, femur ash weight, bone ash calcium, and phosphorous levels in a dose-dependent manner. However, there was significant ( p < 0.001) decline in serum estradiol level in all OVX rats compared to the sham-operated group. Interestingly, administration of chrysin significantly ( p < 0.05) reversed the reduction of estradiol induced by ovariectomy compared to untreated OVX rats. Moreover, administration of chrysin to OVX rats significantly ( p < 0.05) suppressed excessive elevation of bone-remodeling markers expression compared to untreated OVX rats. Similarly, molecular docking analysis revealed that chrysin interacts with both α and β estrogen receptors with exothermic binding energies of −229.83 kcal/Mol and −252.72 kcal/Mol, respectively, and also fits perfectly into the active site of both α and β estrogen receptors. Conclusion This study demonstrated that chrysin exhibits potential antiosteoporotic effects against bone loss in OVX rats through enhanced bone mineral contents and preventing excessive elevation of bone-remodeling markers and bone-resorbing cytokine.