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Molecules 2016, 21(4), 465; doi:10.3390/molecules21040465

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

DSM Nutritional Products, Wurmisweg 576, P. O. Box 2676, Basel 4002, Switzerland
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Academic Editor: Maurizio Battino
Received: 4 March 2016 / Revised: 5 April 2016 / Accepted: 6 April 2016 / Published: 8 April 2016
(This article belongs to the Section Natural Products)
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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), 20-deoxocarnosol and abieta-8,11,13-triene-11,12,20-triol (ABTT) in murine macrophages (RAW264.7 cells) and human chondrocytes. The substances concentration-dependently reduced nitric oxide (NO) and prostaglandin E2 (PGE2) 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. View Full-Text
Keywords: abietanes; carnosol; chondrocyte; osteoarthritis; murine macrophages; innate immune response; acute inflammation; chronic inflammation; NF-κB signaling pathway and nuclear translocation abietanes; carnosol; chondrocyte; osteoarthritis; murine macrophages; innate immune response; acute inflammation; chronic inflammation; NF-κB signaling pathway and nuclear translocation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Schwager, J.; Richard, N.; Fowler, A.; Seifert, N.; Raederstorff, D. Carnosol and Related Substances Modulate Chemokine and Cytokine Production in Macrophages and Chondrocytes. Molecules 2016, 21, 465.

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