Ellagic acid prevents ovariectomy-induced bone loss and attenuates oxidative damage of osteoblasts by activating SIRT1.

Oxidative stress has been implicated as a causative factor for the development and progression of osteoporosis(OP). Ellagic acid (EA), a natural polyphenol, presents anti-oxidative and anti-inflammatory properties. However, EA's role and molecular mechanism in osteoblasts have not yet been elucidated. In this study, exogenous supplementation with EA restored the osteoporotic bone defects in ovariectomized (OVX)-induced osteoporotic mice. Also, EA inhibited the H₂O₂-induced apoptosis of primary osteoblasts, prevented the production of reactive oxygen species, and restored the bone-forming potential of osteoblasts. Furthermore, EA was revealed to activate Sirtuin1 (SIRT1) and its downstream Nrf2/Heme Oxygenase 1 (HO-1) signaling pathway, and EX527 (a SIRT1 inhibitor) partially counteracted the effect of EA on bone loss. The findings suggest that EA protects against osteoporotic bone loss by activating SIRT1 and its downstream Nrf2/HO-1 signaling pathway, providing novel insights into the potential of EA as a treatment agent for osteoporosis-related bone metabolism diseases.