Naringenin prevents osteoblast senescence in d-galactose-induced aging conditions via estrogen receptor-mediated pathway.

Abstract

Naringenin is a plant-derived flavonoid having anti-proliferative, anti-inflammatory, and anti-angiogenic properties against various metabolic disorders. Though there are reports demonstrating the osteogenic potential of naringenin, its effect remains largely unexplored in senile osteoporosis. The current study was planned with the objective to demonstrate the osteoprotective effect of naringenin in conditions of senile osteoporosis induced by d-galactose (D-gal). The results in the d-gal aging bone loss animal model suggest that naringenin improves bone microarchitecture, promotes ex-vivo mineralization, and alters bone serum markers. To check the mode of action of naringenin behind its protective effect, further experiments were performed at the cellular level. Naringenin facilitates osteoblast differentiation and suppresses osteoblast senescence, apoptosis, and cellular reactive oxygen species production in primary osteoblast cells after d-gal stimulation. Mechanistically, naringenin mitigates senescence through the estrogen receptor-mediated pathway, as confirmed when calvarial osteoblast cells treated with ICI182.780, an estrogen pathway inhibitor, greatly decrease its effectiveness. Taken together, these results lead us to conclude that naringenin may function as a potential therapeutic agent for senile osteoporosis.