Carnosic acid inhibits the formation of osteoclasts through attenuation of expression of RANKL

Carnosic acid is a major polyphenol of rosemary and possesses potent anti-oxidant effects. The present study was designed to evaluate in vitro and in vivo effects of carnosic acid on bone formation and maintenance. Carnosic acid attenuated H₂O₂ levels in osteoblastic MC3T3-E1 cells. This compound also inhibited the indices of osteoblast differentiation, such as alkaline phosphatase activity and calcium deposition in osteoblastic MC3T3-E1 cells at concentrations of 3-10μM. Furthermore, it decreased the formation of multinucleated osteoclasts in co-cultures of mouse spleen cells with ST2 cells. In addition, we identified a molecular pathway of osteoclast differentiation mediated by carnosic acid, which led to inhibition of the expression of receptor activator of nuclear factor-κB ligand in ST2 cells. Interestingly, intraperitoneal injection of carnosic acid at 10mg/kg body weight did not significantly affect trabecular bone loss in the femurs of ovariectomized mice. Our findings indicate that carnosic acid may be used as an effective remedy in the treatment of the symptoms of osteoporosis.