Phytoestrogenic Potential of Resveratrol by Selective Activation of Estrogen Receptor-\u03b1 in Osteoblast Cells

Abstract

Resveratrol obtained in grape seed and skin is structurally similar to a synthetic estrogen diethylstilbestrol. The endogenous estrogen, 17β-estradiol, induces cellular responses by binding to the estrogen receptor alpha and beta. The bone fracture due to decreased bone mineral density in postmenopausal women is linked to reduced estrogen. The adverse drug reactions of hormone replacement therapy warrant identifying unique natural compounds with ER-subtype specificity to improve bone health. Resveratrol is considered a phytoestrogen; however, its isoform selectivity has not yet been established on osteoblast cell lines. Therefore, in vitro and in silico docking studies were performed to analyze the binding affinity and selectivity of resveratrol towards receptor alpha and β-isoforms. Resveratrol was evaluated for its actions on the proliferation and differentiation in the primary rat calvarial osteoblasts and bone marrow cells. Osteoblasts specifically increased receptor alpha expression in rat calvarial osteoblasts cells; however, there was no effect on receptor beta expression. In silico studies further confirmed receptor alpha isoform specificity. The observed differences in the orientation, interaction pattern, and binding affinity of resveratrol at the active site of receptor alpha and beta are supported by the western blot analysis. The estrogen mimetic action of resveratrol suggests its therapeutic potential as a bone anabolic agent for postmenopausal osteoporosis.Graphical abstract