| Summary: | Estrogen withdrawal after the menopause leads to an increased rate of bone remodeling, excessive osteoclast activity and a greater fracture risk. Hormone replacement therapy (HRT) was prescribed as a treatment for post-menopausal women to prevent bone loss; however, HRT is associated with an elevated incidence of cardiovascular disease, stroke and cancer. These side effects led to an interest in naturally occurring compounds with estrogenic action such as phytoestrogens (PEs), which are non-steroidal-plant derived compounds. The aim of this study describes investigation of the protective effect of phytoestrogen molecules (Genistein, Daidzein, Resveratrol, 6-Gingerol and Fucosterol) in the prevention of reactive oxygen species induced by H2O2 cell death in MLOY4 osteocyte like cell line. All compounds tested significantly (p < 0.05) reduced osteocyte apoptosis and decreased re-active oxygen species activity. PEs have multiple effects on different bone cells, reducing osteoblast apoptosis and inhibiting RANKL inducing osteoclast formation. The protective effect of Genistein, Daidzein and Resveratrol was not prevented by estrogen receptor inhibitor ICI 182780, suggesting a potential direct antioxidant effect. Additionally, this study offers evidence for bone protection conferred by PEs through demonstrating their potent inhibitory effect on cytokine release and activating antioxidant enzymes such as Catalase (CAT). The antioxidant effect of PEs was thought to be due to their similar phenolic structure to estrogen; therefore Genistein and Daidzein were modified by masking their hydroxyl groups and tested for their protective effects on osteocyte apoptosis. Not all modified compounds protected osteocytes from oxidative stress induced by hydrogen peroxide (H2O2). This study provides novel evidence that PEs have multiple effects on bone cell activity. Thus, PEs may not be the only treatment but possible supplementation of pharmacological or alternative to pharmacological treatment of post-menopausal osteoporosis.
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