Carnosic acid inhibits TLR4-MyD88 signaling pathway in LPS-stimulated 3T3-L1 adipocytes
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BACKGROUND/OBJECTIVES: Carnosic acid (CA), found in rosemary (Rosemarinus officinalis) leaves, is known to exhibit anti-obesityand anti-inflammatory activities. However, whether its anti-inflammatory potency can contribute to the amelioration of obesityhas not been elucidated. The aim of the current study was to investigate the effect of CA on Toll-like receptor 4 (TLR4) pathwaysin the presence of lipopolysaccharide (LPS) in 3T3-L1 adipocytes. MATERIALS/METHODS: 3T3-L1 adipocytes were treated with CA (0-20 μM) for 1 h, followed by treatment with LPS for 30 min;mRNA expression of adipokines and protein expression of TLR4-related molecules were then measured. RESULTS: LPS-stimulated 3T3-L1 adipocytes showed elevated mRNA expression of tumor necrosis factor (TNF)-α, interleukin-6,and monocyte chemoattractant protein-1, and CA significantly inhibited the expression of these adipokine genes. LPS-inducedup regulation of TLR4, myeloid differentiation factor 88, TNF receptor-associated factor 6, and nuclear factor-κB, as well asphosphorylated extracellular receptor-activated kinase were also suppressed by pre-treatment of 3T3-L1 adipocytes with CA. CONCLUSIONS: Results of this study suggest that CA directly inhibits TLR4-MyD88-dependent signaling pathways and decreasesthe inflammatory response in adipocytes.
Abstract
BACKGROUND/OBJECTIVES: Carnosic acid (CA), found in rosemary (Rosemarinus officinalis) leaves, is known to exhibit anti-obesityand anti-inflammatory activities. However, whether its anti-inflammatory potency can contribute to the amelioration of obesityhas not been elucidated. The aim of the current study was to investigate the effect of CA on Toll-like receptor 4 (TLR4) pathwaysin the presence of lipopolysaccharide (LPS) in 3T3-L1 adipocytes. MATERIALS/METHODS: 3T3-L1 adipocytes were treated with CA (0-20 μM) for 1 h, followed by treatment with LPS for 30 min;mRNA expression of adipokines and protein expression of TLR4-related molecules were then measured. RESULTS: LPS-stimulated 3T3-L1 adipocytes showed elevated mRNA expression of tumor necrosis factor (TNF)-α, interleukin-6,and monocyte chemoattractant protein-1, and CA significantly inhibited the expression of these adipokine genes. LPS-inducedup regulation of TLR4, myeloid differentiation factor 88, TNF receptor-associated factor 6, and nuclear factor-κB, as well asphosphorylated extracellular receptor-activated kinase were also suppressed by pre-treatment of 3T3-L1 adipocytes with CA. CONCLUSIONS: Results of this study suggest that CA directly inhibits TLR4-MyD88-dependent signaling pathways and decreasesthe inflammatory response in adipocytes.
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