Carnosic acid inhibits inflammation response and joint destruction on osteoclasts, fibroblast-like synoviocytes, and collagen-induced arthritis rats.

Abstract

The discovery of new therapeutic drugs with the ability of preventing inflammation and joint destruction with less adverse effects is urgently needed for rheumatoid arthritis (RA). Carnosic acid (CA), a major phenolic compound isolated from the leaves of Rosemary (Rosmarinus officinalis L.), has been reported to have antioxidative and antimicrobial properties. However, its effects on RA have not been elucidated. Here, we investigated the effects of CA on osteoclasts and fibroblast-like synoviocytes in vitro and on collagen-induced arthritis (CIA) in Wistar rats in vivo. Our in vitro and in vivo studies showed that CA suppressed the expression of pro-inflammatory cytokines including TNFɑ, IL-1β, IL-6, IL-8, IL-17 and MMP-3, and downregulated the production of RANKL. More importantly, we observed that CA inhibited osteoclastogenesis and bone resorption in vitro and exerted therapeutic protection against joint destruction in vivo. Further biochemical analysis demonstrated that CA suppressed RANKL-induced activations of NF-κB and MAPKs (JNK and p38) leading to the downregulation of NFATc1. Taken together, our findings provide the convincing evidence that rosemary derived CA is a promising natural compound for the treatment of RA.

• Authors: Mei Liu, Xiaotian Zhou, Lin Zhou, Zhenzhou Liu, Jinbo Yuan, Jianwen Cheng, Jinmin Zhao, Longfei Wu, Hui Li, Haiwen Qiu, Jiake Xu
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 233 Issue 8 Pg. 6291-6303 (08 2018) ISSN: 1097-4652 [Electronic] United States
• PMID: 29521424 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 Wiley Periodicals, Inc.

Chemical References

• Abietanes
• Cytokines
• Inflammation Mediators
• NF-kappa B
• NFATC Transcription Factors
• Collagen
• salvin

Topics

• Abietanes (pharmacology)
• Animals
• Arthritis, Experimental (chemically induced, drug therapy, metabolism)
• Arthritis, Rheumatoid (drug therapy, metabolism)
• Bone Resorption (drug therapy, metabolism)
• Cell Line
• Collagen (pharmacology)
• Cytokines (metabolism)
• Disease Models, Animal
• Female
• Fibroblasts (drug effects, metabolism)
• Humans
• Inflammation (drug therapy, metabolism)
• Inflammation Mediators (metabolism)
• Joints (drug effects, metabolism)
• Mice
• NF-kappa B (metabolism)
• NFATC Transcription Factors (metabolism)
• Osteoclasts (drug effects, metabolism)
• Osteogenesis (drug effects)
• RAW 264.7 Cells
• Rats
• Rats, Wistar
• Rosmarinus (chemistry)
• Synovial Membrane (drug effects, metabolism)
• Synoviocytes (drug effects, metabolism)