Screening of Anti-Postmenopausal Osteoporosis Active Components With ESR2 Targeting Affinity in Dioscoreae Rhizoma...

Dioscoreae Rhizoma (DR) is a plant recognized for its dual medicinal and edible applications, exhibiting notable therapeutic efficacy, particularly in the treatment of postmenopausal osteoporosis (PMOP) associated with estrogen deficiency.

This study sought to systematically identify bioactive compounds present in DR that interact with estrogen receptor β (ESR2) and employ affinity ultrafiltration in conjunction with UPLC-QE-Orbitrap-MS to find possible therapy options for PMOP.

In this study, a C18 column was employed to fractionate the DR extract into distinct fractions, and the optimal active site in DR was identified based on its osteoprotegerin (OPG) content in MC3T3-E1 cells. To identify the DR components exhibiting high binding affinity for ESR2, affinity ultrafiltration coupled with UPLC-QE-Orbitrap-MS was utilized. These findings were further corroborated through molecular docking and molecular dynamics simulations. To further validate the osteogenic effects of the identified compounds, CCK-8 proliferation assays, along with OPG and alkaline phosphatase (ALP) activity assays, were employed.

The 30% DR fraction demonstrated significant anti-PMOP activity. Acacetin, Adenosine, and Procyanidin B2 are recognized as the principal active constituents responsible for the anti-PMOP effects of DR.

This study introduces a comprehensive approach combining affinity ultrafiltration with UPLC-QE-Orbitrap-MS and molecular docking to efficiently identify ESR2-targeted therapeutic compounds for PMOP in DR. The findings offer both theoretical and empirical foundations for the advancement of novel therapeutic strategies for PMOP.