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

Hum Exp Toxicol. 2021 Dec;40(12_suppl):S125-S136. doi: 10.1177/09603271211033777. Epub 2021 Jul 21.

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.

Keywords: Chrysin; bone-remodeling markers; estradiol; estrogen receptors; ovariectomized rats.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Bone Density Conservation Agents / pharmacology
  • Bone Remodeling / drug effects*
  • Computer Simulation
  • Estrogens / pharmacology*
  • Female
  • Flavonoids / pharmacology*
  • Humans
  • Osteoporosis, Postmenopausal / metabolism
  • Osteoporosis, Postmenopausal / prevention & control
  • Ovariectomy*
  • Rats
  • Rats, Wistar

Substances

  • Biomarkers
  • Bone Density Conservation Agents
  • Estrogens
  • Flavonoids
  • chrysin