Carnosic acid disrupts toll-like receptor 2 signaling pathway in Pam3CSK4-stimulated macrophages

Abstract

Carnosic acid (CA) is a major bioactive component of rosemary (Rosmarinus officinalis) leaves and is known to exhibit anti-inflammatory activities. However, its molecular action in the inflammatory process has not been fully elucidated. In the present study, the anti-inflammatory effect of CA on Toll-like receptor 2 (TLR2) pathways in the Pam3CSK4-stimulated macrophage was investigated. Bone marrowderived macrophages (BMDM) were treated with CA (0-30 μM) for 1 h followed by Pam3CSK4 for 1 h, and then the mRNA expression levels and the production levels of cytokines were measured. Next, TLR2-related molecules were measured in Pam3CSK4-stimulated RAW264.7 macrophages. The results showed that CA significantly suppressed the secretion and mRNA expression of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in Pam3CSK4-stimulated BMDM. TLR2 mRNA expression, nuclear factorkappa B (NF-κB) activation, and mitogen-activated protein kinase (MAPK) phosphorylation were markedly diminished with CA (10 μM and 30 μM) in Pam3CSK4-stimulated macrophages. In conclusion, the anti-inflammatory activity of CA is partly due to modulation of the TLR2 and MAPK/NF-κB signaling pathway in macrophages.