In vitro and In vivo Protective Effect of Artemisia capillaris Extract on Osteoporosis through Regulation of Osteoclast Differentiation and Bone Resorption Activity

Abstract

Bone is dynamic tissue that is constantly destroyed or resorbed by osteoclasts and then replaced by osteoblasts in physiological process referred to as bone remodeling. In this study, the protective effect of Artemisia capillaris extract (ACE) on osteoporosis was investigated using RANKL‐induced osteoclasts and ovariectomized rats. In animal study, The total of sixty 8 week‐old female Spraque‐Dawley rats were randomly divided into sham‐operated group and four ovariectomized (OVA) groups: OVA, OVA + 17β‐estradiol (E2, 50 μg/kg/day) and OVA + ACE (125 or 250 mg/kg/day). Daily oral administration of E2 or ACE began 3 weeks after surgery and lasted for 12 weeks. ACE inhibited the decrease in total BMD and BMC of the femur induced by OVA, which was accompanied by a significant reduction in bone remodeling. The bone turnover markers such as BALP, PICP, OPG, RANKL, TRAP, and ICTP were regulated by ACE treatment. In addition, the underlying mechanism of anti‐osteoporotic effect of ACE was studied using scoparone, its major bioactive compound. The TRAP and bone resorption activity were dose‐dependently by scoparone in RANKL‐induced osteoclast differentiation. The suppressive effect of scoparone on RANKL‐induced osteoclast differentiation was executed by down‐regulating ROS production through NADPH oxidase 1 and mitochondria and by scavenging generated ROS. In conclusion, the protective of ACE on osteoporosis can be accomplished by attenuating RANKL‐induced osteoclast differentiation and bone resorption activity. These results indicate that ACE may utilized as a therapeutic agent for the prevention of bone metabolism‐related diseases.