title: A newly synthesized sinapic acid derivative inhibits endothelial activation in vitro and in vivo.
abstract: 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 2,2-diphenyl-1-picrylhydrazyl (DPPH(⋅)), croton oil-induced ear edema in mice, and analysis of the mRNA expression of adhesion molecules in ECs. 1-Acetyl-sinapic acyl-4-(3'-chlorine-)benzylpiperazine (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 face-to-face immunostaining showed that SA9 reduced lipopolysaccharide-induced expression of intercellular adhesion molecule-1 in mouse aortic intima. To study the molecular 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.
authors.affiliation: Cardiovascular Research Center, Shantou University Medical College, Shantou, Guangdong, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zeng
authors.forename: Jinhong
authors.initials: J
authors.lastname: Zheng
authors.forename: Chenglai
authors.initials: C
authors.lastname: Fu
authors.forename: Hang
authors.initials: H
authors.lastname: Su
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Sun
authors.forename: Xuesi
authors.initials: X
authors.lastname: Zhang
authors.forename: Yingjian
authors.initials: Y
authors.lastname: Hou
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D003373:Coumaric Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D003436:Croton Oil / Q000494:pharmacology; D004423:Ear; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010851:Picrates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001713:Biphenyl Compounds; D003373:Coumaric Acids; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010851:Picrates; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C073734:sinapinic acid; D003436:Croton Oil; C004931:1,1-diphenyl-2-picrylhydrazyl