Methyl carnosate, a carnosic acid derivative, attenuates osteoclastogenesis via modulation of RANKL-induced NF-κB activity.

Excessive osteoclast activity underlies bone-destructive diseases including osteoporosis and rheumatoid arthritis. RANKL-induced NF-κB signaling represents a critical pathway driving osteoclastogenesis. Here, we report that methyl carnosate, a naturally occurring diterpene from rosemary, inhibits RANKL-induced osteoclastogenesis with an IC50 of 1.2 μM (95% CI: 0.9521-1.372 μM) and displays greater potency than its parent compound, carnosic acid. Promoter-reporter analysis further indicates attenuation of RANKL-induced NF-κB activity, consistent with downstream suppression of NFATc1 mRNA expression. These findings identify methyl carnosate as a promising pharmacological candidate for the development of bone-protective therapeutics.