title: Synthesis and cardiovascular protective effects of quercetin 7-O-sialic acid.
abstract: Oxidative stress and inflammation play important roles in the pathogenesis of cardiovascular disease (CVD). Oxidative stress-induced desialylation is considered to be a primary step in atherogenic modification, and therefore, the attenuation of oxidative stress and/or inflammatory reactions may ameliorate CVD. In this study, quercetin 7-O-sialic acid (QA) was synthesized aiming to put together the cardiovascular protective effect of quercetin and the recently reported anti-oxidant and anti-atherosclerosis functions of N-acetylneuraminic acid. The biological efficacy of QA was evaluated in vitro in various cellular models. The results demonstrated that 50 μM QA could effectively protect human umbilical vein endothelial cells (HUVEC, EA.hy926) against hydrogen peroxide- or oxidized low-density lipoprotein-induced oxidative damage by reducing the production of reactive oxygen species. QA attenuated hydrogen peroxide-induced desialylation of HUVEC and lipoproteins. QA decreased lipopolysaccharide-induced secretion of tumour necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), and it significantly reduced the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, TNF-α and MCP-1. Furthermore, QA effectively promoted cholesterol efflux from Raw 264.7 macrophages to apolipoprotein A-1 and high-density lipoprotein by up-regulating ATP-binding cassette transporter A1 and G1, respectively. Results indicated that the novel compound QA exhibited a better capacity than quercetin for anti-oxidation, anti-inflammation, cholesterol efflux promotion and biomolecule protection against desialylation and therefore could be a candidate compound for the prevention or treatment of CVD.
authors: Key Laboratory of Atherosclerosis in Universities of Shandong Province, Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors: Hua
authors: H
authors: Tian
authors: Department of Pharmaceutical Engineering, Northwest University, Xi'an, China.
authors: Qingchao
authors: Q
authors: Liu
authors: Key Laboratory of Atherosclerosis in Universities of Shandong Province, Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors: Shucun
authors: S
authors: Qin
authors: Key Laboratory of Atherosclerosis in Universities of Shandong Province, Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors: Chuanlong
authors: C
authors: Zong
authors: Key Laboratory of Atherosclerosis in Universities of Shandong Province, Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors: Ying
authors: Y
authors: Zhang
authors: Key Laboratory of Atherosclerosis in Universities of Shandong Province, Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors: Shutong
authors: S
authors: Yao
authors: Key Laboratory of Atherosclerosis in Universities of Shandong Province, Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors: Nana
authors: N
authors: Yang
authors: Key Laboratory of Atherosclerosis in Universities of Shandong Province, Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors: Tao
authors: T
authors: Guan
authors: Key Laboratory of Atherosclerosis in Universities of Shandong Province, Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors: Shoudong
authors: S
authors: Guo
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism; D002316:Cardiotonic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000737:chemistry* / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011794:Quercetin / Q000737:chemistry* / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D002316:Cardiotonic Agents; D018932:Chemokine CCL2; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1; D011794:Quercetin; D019158:N-Acetylneuraminic Acid
keywords: anti-inflammation; anti-oxidation; cardiovascular disease; cholesterol efflux; quercetin; sialic acid