Carnosol and Related Substances Modulate Chemokine and Cytokine Production in Macrophages and Chondrocytes

Abstract

Phenolic diterpenes present in Rosmarinus officinalis and Salvia officinalis have anti-inflammatory and chemoprotective effects. We investigated the in vitro effects of carnosol (CL), carnosic acid (CA), carnosic acid-12-methylether (CAME), 11,12, in murine macrophages (RAW264.7 cells) and human chondrocytes. The substances concentration-dependently reduced nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) production in LPS-stimulated macrophages (i.e., acute inflammation). They significantly blunted gene expression levels of iNOS, cytokines/interleukins (IL-1α, IL-6) and chemokines including CCL5/RANTES, CXCL10/IP-10. The substances modulated the expression of catabolic and anabolic genes in chondrosarcoma cell line SW1353 and in primary human chondrocytes that were stimulated by IL-1β (i.e., chronic inflammation In SW1353, catabolic genes like MMP-13 and ADAMTS-4 that contribute to cartilage erosion were down-regulated, while expression of anabolic genes including Col2A1 and aggrecan were shifted towards pre-pathophysiological homeostasis. CL had the strongest overall effect on inflammatory mediators, as well as on macrophage and chondrocyte gene expression. Conversely, CAME mainly affected catabolic gene expression, whereas ABTT had a more selectively altered interleukin and chemokine gene exprssion. CL inhibited the IL-1β induced nuclear translocation of NF-κBp65, suggesting that it primarily regulated via the NF-κB signalling pathway. Collectively, CL had the strongest effects on inflammatory mediators and chondrocyte gene expression. The data show that the phenolic diterpenes altered activity pattern of genes that regulate acute and chronic inflammatory processes. Since the substances affected catabolic and anabolic gene expression in cartilage cells in vitro, they may beneficially act on the aetiology of osteoarthritis.

Anti‐inflammatory effects of polyphenols in arthritis

“…Interestingly, that study showed an important inhibitory effect of carnosol on IL‐6 and PGE2 production . Similar effects have been observed in murine lipopolysaccharide (LPS)‐stimulated macrophages and human IL‐1β‐stimulated chondrocytes confirming a role for carnosol in regulating acute and chronic inflammatory processes …”

Inhibitory Effect of Carnosol on Phthalic Anhydride-Induced Atopic Dermatitis via Inhibition of STAT3

“…As one of the main active diterpene in rosemary, carnosol (CS) has been largely investigated for anti-tumoral, anti-inflammatory and anti-oxidant activities in vitro and in vivo ( Ortuno et al ., 2015 ; Sanchez et al ., 2015 ). In previously studies, carnosol significantly inhibited inflammatory responses such as IL-1β, tumor necrosis factor-α (TNF-α) and increased IL-10 in inflamed mice skin ( Yao et al ., 2014 ; Schwager et al ., 2016 ). Carnosol also inhibited NO generation and expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) in RAW 264.7 cells and mice skin ( Mengoni et al ., 2011 ).…”

Herbal Medicinal Products in the Treatment of Osteoarthritis

“…Phenolic diterpene carnosol decreased concentrations of PGE 2 and NO, and reduced gene expression of iNOS, IL-1α, IL-6, and CCL5 in LPSstimulated macrophages. In addition, it interfered with transcription factor NF-κB activation and influenced expression of anabolic and catabolic genes in chondrosarcoma cell line SW1353 and in primary human chondrocytes [86].…”