PT  - JOURNAL ARTICLE
AU  - Xiaoyun Zeng
AU  - Jinhong Zheng
AU  - Chenglai Fu
AU  - Hang Su
AU  - Xiaoli Sun
AU  - Xuesi Zhang
AU  - Yingjian Hou
AU  - Yi Zhu
TI  - A Newly Synthesized Sinapic Acid Derivative Inhibits Endothelial Activation In Vitro and In Vivo
AID  - 10.1124/mol.112.084368
DP  - 2013 Mar 07
TA  - Molecular Pharmacology
PG  - mol.112.084368
4099  - http://molpharm.aspetjournals.org/content/early/2013/03/07/mol.112.084368.short
4100  - http://molpharm.aspetjournals.org/content/early/2013/03/07/mol.112.084368.full
AB  - Inhibition of oxidative stress and inflammation in vascular endothelial cells (ECs) may represent a new therapeutic strategy against endothelial activation. Sinapic acid (SA), a phenylpropanoid compound, is found in natural herbs and high-bran cereals and has moderate antioxidant activity. We aimed to develop new SA agents with the properties of antioxidation and blocking EC activation for possible therapy of cardiovascular disease. We designed and synthesized 10 SA derivatives according to their chemical structures. Preliminary screening of the compounds involved scavenging hydroxyl radicals and DPPH•,croton oil-induced ear edema in mice and analysis of the mRNA expression of adhesion molecules in ECs. SA9 had the strongest antioxidant and anti-inflammatory activities both in vitro and in vivo. Thus, the effect of SA9 was further studied. SA9 inhibited tumor necrosis factor α-induced upregulation of adhesion molecules in ECs at both mRNA and protein levels, as well as the consequent monocyte adhesion to ECs. In vivo, result of en face immunostaining showed that SA9 reduced lipopolysaccharide-induced expression of intercellular adhesion molecule 1in mouse aortic intima. To study the molerular mechanism, Results from luciferase assay, nuclear translocation of NF-κB and western blot indicated that the mechanism of the anti-inflammatory effects of SA9 might be suppression of intracellular generation of ROS and inhibition of NF-κB activation in ECs. SA9 is a prototype of a novel class of antioxidant with anti-inflammatory effects in ECs. It may represent a new therapeutic approach for preventing endothelial activation in cardiovascular disorders.