Journal
BIOCHIMIE
Volume 94, Issue 9, Pages 2035-2044Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biochi.2012.05.027
Keywords
Flavonoids; Endothelial dysfunction; Oxidized low-density lipoprotein; Atherosclerosis; Reactive oxygen species
Categories
Funding
- National Natural Science Foundation of China [81000133]
- Chongqing Key Laboratory of Nutrition and Food Safety [2006CA1003]
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Increased intracellular reactive oxygen species (ROS) is crucial for vascular endothelial dysfunction, a key step in the initiating of atherosclerosis (AS). The antioxidant activity of flavonoids has been suggested to contribute to AS prevention. However, The association of the structure characteristics to antioxidant capacities in relation to the inhibitory effects on endothelial dysfunction has not been well established. In this study, four subclasses of flavonoids with similar structures, including two anthocyanins (delphinidin and cyanidin), two flavonols (myricetin and quercetin), two flavones (luteolin and apigenin) and two isoflavones (genistein and daidzein) were examined for their inhibitory effects on intracellular ROS-mediated signaling pathway in the human umbilical vein endothelial cell EA.hy926. Cells were pre-treated with different flavonoids for 2 h and then exposed to oxLDL of 100 mu g/ml for another 24 h. It was found that treatment with different flavonoids alone had no notable effects or. cell viability. However, the oxLDL-induced decrease of cell viability, generation of O-2(center dot-) and ROS, p38MAPK activation, NF-kappa B nuclear translocation, NF-kappa B-modulated transcriptional activity as well as the rnRNA expression of genes including ICAM-1, VCAM-1, E-selectin, MMP-1, MMP-2 and MMP-9 were notably inhibited by the pretreatment of different flavonoids through blunting ROS-triggered signaling pathway, in spite of apparent differences. And the number of hydroxyl groups in total, 3',4'-ortho-dihydroxyl in B-ring and 3-hydroxyl group in C-ring of flavonoids were important structure characteristics for the inhibitory effects. Thus, anthocyanins and flavonols such as delphinidin and myricetin exert higher ROS scavenging activities and more significant endothelium-protective effects compared to the other compounds. Our results provide evidence for AS prevention and a basis for designing the potent anti-atherosclerotic agents. (C) 2012 Elsevier Masson SAS. All rights reserved.
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