Caffeic acid methyl ester inhibits LPS-induced inflammatory response through Nrf2 activation and NF-κB inhibition in human umbilical vein endothelial cells

초록

Caffeic acid (CA) derivatives have been reported to exert anti-inflammatory activities in various inflammatory conditions. However, the impact of CA methyl ester (CAME) on the inflammatory response in vascular endothelial cells has not been thoroughly elucidated. In the present study, the aim was to understand how CAME can reduce inflammation in human umbilical vein endothelial cells (HUVECs), which were challenged with lipopolysaccharide (LPS), and elucidate its mechanisms. CAME significantly attenuated LPS-induced TNF-alpha and IL-1 beta release. Furthermore, CAME inhibited cyclooxygenase 2 expression and consequent secretion of prostaglandin E-2. CAME also suppressed LPS-stimulated inducible nitric oxide synthase expression. In addition, CAME significantly enhanced the expression of heme oxygenase-1 (HO-1) and nuclear factor erythroid-derived 2-related factor 2 (Nrf2) phosphorylation in the absence or presence of LPS stimulation in HUVECs. CAME also significantly suppressed LPS-induced NF-kappa B phosphorylation and inhibitor of kappa B phosphorylation and degradation. In conclusion, the present results provide clear evidence that CAME exerts its anti-inflammatory activities by increasing HO-1/Nrf2-mediated cytoprotection and inhibiting NF-kappa B-mediated pro-inflammatory pathways in HUVECs.

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