Chemical Structures of 4-Oxo-Flavonoids in Relation to Inhibition of Oxidized Low-Density Lipoprotein (LDL)-Induced Vascular Endothelial Dysfunction

Vascular endothelial dysfunction induced by oxidative stress has been demonstrated to be the initiation step of atherosclerosis (AS), and flavonoids may play an important role in AS prevention and therapy. Twenty-three flavonoids categorized into flavones, flavonols, isoflavones, and flavanones, all...

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Main Authors: Man-Tian Mi, Qian-Yong Zhang, Jun-Dong Zhu, Yong Zhou, Hui Chang, Ting Zhang, Yu-Jie Fu, Chun-Ye Chen, Xin Jin, Long Yi
Format: Article
Language:English
Published: MDPI AG 2011-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:http://www.mdpi.com/1422-0067/12/9/5471/
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spelling doaj-5beb0294bb4b48cdb67133dc60d196c72020-11-25T01:55:01ZengMDPI AGInternational Journal of Molecular Sciences1422-00672011-08-011295471548910.3390/ijms12095471Chemical Structures of 4-Oxo-Flavonoids in Relation to Inhibition of Oxidized Low-Density Lipoprotein (LDL)-Induced Vascular Endothelial DysfunctionMan-Tian MiQian-Yong ZhangJun-Dong ZhuYong ZhouHui ChangTing ZhangYu-Jie FuChun-Ye ChenXin JinLong YiVascular endothelial dysfunction induced by oxidative stress has been demonstrated to be the initiation step of atherosclerosis (AS), and flavonoids may play an important role in AS prevention and therapy. Twenty-three flavonoids categorized into flavones, flavonols, isoflavones, and flavanones, all with 4-oxo-pyronenucleus, were examined for what structural characteristics are required for the inhibitory effects on endothelial dysfunction induced by oxidized low-density lipoprotein (oxLDL). Human vascular endothelial cells EA.hy926 were pretreated with different 4-oxo-flavonoids for 2 hs, and then exposed to oxLDL for another 24 hs. Cell viability and the level of malondialdehyde (MDA), nitric oxide (NO) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured, respectively. Then, correlation analysis and paired comparison were used to analyze the structure–activity relationships. Significant correlations were observed between the number of –OH moieties in total or in B-ring and the inhibitory effectson endothelial dysfunction. Furthermore, 3',4'-ortho-dihydroxyl on B-ring, 3-hydroxyl on C-ring and 2,3-double bondwere correlated closely to the inhibitory effects of flavonolson cell viability decrease and lipid peroxidation. 5,7-meta-dihydroxyl group on A-ring was crucial for the anti-inflammatory effects of flavones and isoflavones in endothelial cells. Moreover, the substituted position of B-ring on C3 rather than C2 was important for NO release. Additionally, hydroxylation at C6 position significantly attenuated the inhibitory effects of 4-oxo-flavonoids on endothelial dysfunction. Our findings indicated that the effective agents in inhibiting endothelial dysfunction include myricetin, quercetin, luteolin, apigenin, genistein and daidzein. Our work might provide some evidence for AS prevention and a strategy for the design of novel AS preventive agents.http://www.mdpi.com/1422-0067/12/9/5471/flavonoidsendothelial dysfunctionoxidized low-density lipoproteinstructure-activity analysisatherosclerosisreactive oxygen species
collection DOAJ
language English
format Article
sources DOAJ
author Man-Tian Mi
Qian-Yong Zhang
Jun-Dong Zhu
Yong Zhou
Hui Chang
Ting Zhang
Yu-Jie Fu
Chun-Ye Chen
Xin Jin
Long Yi
spellingShingle Man-Tian Mi
Qian-Yong Zhang
Jun-Dong Zhu
Yong Zhou
Hui Chang
Ting Zhang
Yu-Jie Fu
Chun-Ye Chen
Xin Jin
Long Yi
Chemical Structures of 4-Oxo-Flavonoids in Relation to Inhibition of Oxidized Low-Density Lipoprotein (LDL)-Induced Vascular Endothelial Dysfunction
International Journal of Molecular Sciences
flavonoids
endothelial dysfunction
oxidized low-density lipoprotein
structure-activity analysis
atherosclerosis
reactive oxygen species
author_facet Man-Tian Mi
Qian-Yong Zhang
Jun-Dong Zhu
Yong Zhou
Hui Chang
Ting Zhang
Yu-Jie Fu
Chun-Ye Chen
Xin Jin
Long Yi
author_sort Man-Tian Mi
title Chemical Structures of 4-Oxo-Flavonoids in Relation to Inhibition of Oxidized Low-Density Lipoprotein (LDL)-Induced Vascular Endothelial Dysfunction
title_short Chemical Structures of 4-Oxo-Flavonoids in Relation to Inhibition of Oxidized Low-Density Lipoprotein (LDL)-Induced Vascular Endothelial Dysfunction
title_full Chemical Structures of 4-Oxo-Flavonoids in Relation to Inhibition of Oxidized Low-Density Lipoprotein (LDL)-Induced Vascular Endothelial Dysfunction
title_fullStr Chemical Structures of 4-Oxo-Flavonoids in Relation to Inhibition of Oxidized Low-Density Lipoprotein (LDL)-Induced Vascular Endothelial Dysfunction
title_full_unstemmed Chemical Structures of 4-Oxo-Flavonoids in Relation to Inhibition of Oxidized Low-Density Lipoprotein (LDL)-Induced Vascular Endothelial Dysfunction
title_sort chemical structures of 4-oxo-flavonoids in relation to inhibition of oxidized low-density lipoprotein (ldl)-induced vascular endothelial dysfunction
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1422-0067
publishDate 2011-08-01
description Vascular endothelial dysfunction induced by oxidative stress has been demonstrated to be the initiation step of atherosclerosis (AS), and flavonoids may play an important role in AS prevention and therapy. Twenty-three flavonoids categorized into flavones, flavonols, isoflavones, and flavanones, all with 4-oxo-pyronenucleus, were examined for what structural characteristics are required for the inhibitory effects on endothelial dysfunction induced by oxidized low-density lipoprotein (oxLDL). Human vascular endothelial cells EA.hy926 were pretreated with different 4-oxo-flavonoids for 2 hs, and then exposed to oxLDL for another 24 hs. Cell viability and the level of malondialdehyde (MDA), nitric oxide (NO) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured, respectively. Then, correlation analysis and paired comparison were used to analyze the structure–activity relationships. Significant correlations were observed between the number of –OH moieties in total or in B-ring and the inhibitory effectson endothelial dysfunction. Furthermore, 3',4'-ortho-dihydroxyl on B-ring, 3-hydroxyl on C-ring and 2,3-double bondwere correlated closely to the inhibitory effects of flavonolson cell viability decrease and lipid peroxidation. 5,7-meta-dihydroxyl group on A-ring was crucial for the anti-inflammatory effects of flavones and isoflavones in endothelial cells. Moreover, the substituted position of B-ring on C3 rather than C2 was important for NO release. Additionally, hydroxylation at C6 position significantly attenuated the inhibitory effects of 4-oxo-flavonoids on endothelial dysfunction. Our findings indicated that the effective agents in inhibiting endothelial dysfunction include myricetin, quercetin, luteolin, apigenin, genistein and daidzein. Our work might provide some evidence for AS prevention and a strategy for the design of novel AS preventive agents.
topic flavonoids
endothelial dysfunction
oxidized low-density lipoprotein
structure-activity analysis
atherosclerosis
reactive oxygen species
url http://www.mdpi.com/1422-0067/12/9/5471/
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