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...
Main Authors: | , , , , , , , , , |
---|---|
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/ |
id |
doaj-5beb0294bb4b48cdb67133dc60d196c7 |
---|---|
record_format |
Article |
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/ |
work_keys_str_mv |
AT mantianmi chemicalstructuresof4oxoflavonoidsinrelationtoinhibitionofoxidizedlowdensitylipoproteinldlinducedvascularendothelialdysfunction AT qianyongzhang chemicalstructuresof4oxoflavonoidsinrelationtoinhibitionofoxidizedlowdensitylipoproteinldlinducedvascularendothelialdysfunction AT jundongzhu chemicalstructuresof4oxoflavonoidsinrelationtoinhibitionofoxidizedlowdensitylipoproteinldlinducedvascularendothelialdysfunction AT yongzhou chemicalstructuresof4oxoflavonoidsinrelationtoinhibitionofoxidizedlowdensitylipoproteinldlinducedvascularendothelialdysfunction AT huichang chemicalstructuresof4oxoflavonoidsinrelationtoinhibitionofoxidizedlowdensitylipoproteinldlinducedvascularendothelialdysfunction AT tingzhang chemicalstructuresof4oxoflavonoidsinrelationtoinhibitionofoxidizedlowdensitylipoproteinldlinducedvascularendothelialdysfunction AT yujiefu chemicalstructuresof4oxoflavonoidsinrelationtoinhibitionofoxidizedlowdensitylipoproteinldlinducedvascularendothelialdysfunction AT chunyechen chemicalstructuresof4oxoflavonoidsinrelationtoinhibitionofoxidizedlowdensitylipoproteinldlinducedvascularendothelialdysfunction AT xinjin chemicalstructuresof4oxoflavonoidsinrelationtoinhibitionofoxidizedlowdensitylipoproteinldlinducedvascularendothelialdysfunction AT longyi chemicalstructuresof4oxoflavonoidsinrelationtoinhibitionofoxidizedlowdensitylipoproteinldlinducedvascularendothelialdysfunction |
_version_ |
1724985662595137536 |