Methyl Carnosate, a Carnosic Acid Derivative, Attenuates Osteoclastogenesis via Modulation of RANKL-Induced NF-κB Activity

ABSTRACT 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 IC 50 of 1.2 μM and displays greater potency than its parent compound, carnosic acid. Promoter–reporter analysis further indicates attenuation of RANKL-induced NF-κB activity. These findings identify methyl carnosate as a potential lead compound for the development of bone-protective therapeutics.