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.

Carnosol Modulates Th17 Cell Differentiation and Microglial Switch in Experimental Autoimmune Encephalomyelitis

“…Rosmarinus officinalis (rosemary) and Salvia officinalis are common household plants that grow all over the world and have been used as medicinal herbs due to their powerful antioxidant and anti-inflammatory effects ( 16 , 17 ). Carnosol, a major diterpene present in R. officinalis (rosemary) and S. officinalis , has been reported to possess strong antioxidant, anti-tumor, anti-viral, and especially anti-inflammatory properties ( 18 – 20 ).…”

Carnosic acid protects against pressure overload‑induced cardiac remodelling by inhibiting the AKT/GSK3β/NOX4 signalling pathway

“…Previous studies have demonstrated that oxidative stress can activate apoptosis via different pathways and cause cardiac injury ( 14 , 26 ). CA has the ability to inhibit oxidative stress and apoptosis ( 11 ). Therefore, the present study performed TUNEL staining and detected the expression of apoptosis-associated proteins to evaluate the cardioprotective effect of CA following pressure overload in mice.…”

“…Carnosic acid (CA) is a phenolic terpenoid separated from Rosmarinus officinalis that exerts multiple pharmacological effects, including antioxidative stress (10), anti-inflammation (11) and anti-tumour effects (12). A previous study has revealed that CA inhibits arsenic-induced hepatotoxicity by inhibiting oxidative stress (10).…”

Astilbin prevents bone loss in ovariectomized mice through the inhibition of RANKL‐induced osteoclastogenesis

“…After decalcification, the femurs were embedded in paraffin and cut in the sagittal plane to produce approximately 5‐μm‐thick sections. TRAcP staining was performed by using TRAcP staining kits as described previously . The number of claret‐red granules in the vicinity of the resorbed bone was counted as TRAcP‐positive cells.…”

“…TRAcP staining was performed by using TRAcP staining kits as described previously. 25,28 The number of claret-red granules in the vicinity of the resorbed bone was counted as TRAcP-positive cells. The osteoclast number and the percentage of osteoclasts per bone surface (OcS/BS, %)…”