Rosmarinic acid alleviates diabetic osteoporosis by suppressing the activation of NLRP3 inflammasome in rats.

Abstract

Diabetic osteoporosis is a common metabolic bone disorder characterized by bone loss in diabetic patients, which causes an enormous social burden due to the unsatisfactory outcome of current therapeutic strategy. Based on the importance of inflammasome activation in diabetic osteoporosis, we evaluated the protective effect of an antioxidant, rosmarinic acid (RA) in diabetic osteoporosis. Bone marrow-derived monocytes isolated from rats were treated with receptor activator of nuclear factor kappa-Β ligand (RANKL) and macrophage colony stimulating factor to differentiate into mature osteoclasts (OCs). Next OCs were stimulated with RA under high glucose condition to evaluate bone resorption. Next, streptozotocin (STZ)-injected rats were orally treated with 50 mg kg-1 RA to analyze its effect on diabetic osteoporosis. RA inhibited high glucose-stimulated inflammation and inflammasome activation in OCs. Bone resorption was also reduced after RA treatment as shown by the resorption pits assay. Moreover, RA significantly reduced bone resorption, alleviated bone weight loss and increased bone mineral density by inhibiting the activation of NACHT-LRR-PYD domains-containing protein 3 (NLRP3) inflammasome in STZ-induced diabetic rats, leading to the improvement of diabetic osteoporosis. RA effectively ameliorates diabetic osteoporosis in STZ-induced rats by inhibiting the activation of NLRP3 inflammasome in OCs, which suggests that RA might serve as a potential candidate drug for treating diabetic osteoporosis.