Cedrol, a Ginger-derived sesquiterpineol, suppresses estrogen-deficient osteoporosis by intervening NFATc1 and reactive oxygen species

Osteoporosis is a prevalent bone metabolic disease in menopause, and long-term medication is accompanied by serious side effects. Ginger, a food spice and traditional medicine with ancient history, exhibits the potential to alleviate osteoporosis in preclinical experiments, whereas its complex composition leads to ambiguous pharmacological mechanisms. The purpose of this study was to investigate the effect and mechanism of Ced in estrogen-deficient osteoporosis, a sesquiterpene alcohol recently discovered from Ginger with multiple pharmacological properties. RANKL was stimulated BMM (bone marrow macrophages) differentiation into osteoclasts in vitro. And the osteoclast activity and number were assessed by TRAcP and SEM. We found that Ced mitigated RANKL-induced osteoclastogenesis by descending the ROS content and obstructing NFATc1, NF-κB, and MAPK signaling. Also, Ced-mediated anti-osteolytic property was found in ovariectomized mice by Micro-CT scanning and histological staining. Summarily, our works demonstrated the anti-osteoporotic potential of Cedrol in Ginger for the first time, which also offered more pharmacological evidence for Ginger as food or medicine used for bone metabolic disease.