Natural Compound Resveratrol Attenuates TNF-Alpha-Induced Vascular Dysfunction in Mice and Human Endothelial Cells: The Involvement of the NF-κB Signaling Pathway
Resveratrol, a natural compound in grapes and red wine, has drawn attention due to potential cardiovascular-related health benefits. However, its effect on vascular inflammation at physiologically achievable concentrations is largely unknown. In this study, resveratrol in concentrations as low as 1...
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oai:doaj.org-article:4bbe4ec185e44b3b8d61e9e8290cb00a2021-11-25T17:57:08ZNatural Compound Resveratrol Attenuates TNF-Alpha-Induced Vascular Dysfunction in Mice and Human Endothelial Cells: The Involvement of the NF-κB Signaling Pathway10.3390/ijms2222124861422-00671661-6596https://doaj.org/article/4bbe4ec185e44b3b8d61e9e8290cb00a2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12486https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Resveratrol, a natural compound in grapes and red wine, has drawn attention due to potential cardiovascular-related health benefits. However, its effect on vascular inflammation at physiologically achievable concentrations is largely unknown. In this study, resveratrol in concentrations as low as 1 μm suppressed TNF-α-induced monocyte adhesion to human EA.hy926 endothelial cells (ECs), a key event in the initiation and development of atherosclerosis. Low concentrations of resveratrol (0.25–2 μm) also significantly attenuated TNF-α-stimulated mRNA expressions of MCP-1/CCL2 and ICAM-1, which are vital mediators of EC-monocyte adhesion molecules and cytokines for cardiovascular plaque formation. Additionally, resveratrol diminished TNF-α-induced IκB-α degradation and subsequent nuclear translocation of NF-κB p65 in ECs. In the animal study, resveratrol supplementation in diet significantly diminished TNF-α-induced increases in circulating levels of adhesion molecules and cytokines, monocyte adhesion to mouse aortic ECs, F4/80-positive macrophages and VCAM-1 expression in mice aortas and restored the disruption in aortic elastin fiber caused by TNF-α treatment. The animal study also confirmed that resveratrol blocks the activation of NF-κB In Vivo. In conclusion, resveratrol at physiologically achievable concentrations displayed protective effects against TNF-α-induced vascular endothelial inflammation in vitro and In Vivo. The ability of resveratrol in reducing inflammation may be associated with its role as a down-regulator of the NF-κB pathway.Palanisamy NallasamyZi Yae KangXiaolun SunPon Velayutham Anandh BabuDongmin LiuZhenquan JiaMDPI AGarticleresveratrolphysiological concentrationsvascular inflammationmonocyte adhesionTNF-αNF-κBBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12486, p 12486 (2021) |
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resveratrol physiological concentrations vascular inflammation monocyte adhesion TNF-α NF-κB Biology (General) QH301-705.5 Chemistry QD1-999 |
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resveratrol physiological concentrations vascular inflammation monocyte adhesion TNF-α NF-κB Biology (General) QH301-705.5 Chemistry QD1-999 Palanisamy Nallasamy Zi Yae Kang Xiaolun Sun Pon Velayutham Anandh Babu Dongmin Liu Zhenquan Jia Natural Compound Resveratrol Attenuates TNF-Alpha-Induced Vascular Dysfunction in Mice and Human Endothelial Cells: The Involvement of the NF-κB Signaling Pathway |
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Resveratrol, a natural compound in grapes and red wine, has drawn attention due to potential cardiovascular-related health benefits. However, its effect on vascular inflammation at physiologically achievable concentrations is largely unknown. In this study, resveratrol in concentrations as low as 1 μm suppressed TNF-α-induced monocyte adhesion to human EA.hy926 endothelial cells (ECs), a key event in the initiation and development of atherosclerosis. Low concentrations of resveratrol (0.25–2 μm) also significantly attenuated TNF-α-stimulated mRNA expressions of MCP-1/CCL2 and ICAM-1, which are vital mediators of EC-monocyte adhesion molecules and cytokines for cardiovascular plaque formation. Additionally, resveratrol diminished TNF-α-induced IκB-α degradation and subsequent nuclear translocation of NF-κB p65 in ECs. In the animal study, resveratrol supplementation in diet significantly diminished TNF-α-induced increases in circulating levels of adhesion molecules and cytokines, monocyte adhesion to mouse aortic ECs, F4/80-positive macrophages and VCAM-1 expression in mice aortas and restored the disruption in aortic elastin fiber caused by TNF-α treatment. The animal study also confirmed that resveratrol blocks the activation of NF-κB In Vivo. In conclusion, resveratrol at physiologically achievable concentrations displayed protective effects against TNF-α-induced vascular endothelial inflammation in vitro and In Vivo. The ability of resveratrol in reducing inflammation may be associated with its role as a down-regulator of the NF-κB pathway. |
format |
article |
author |
Palanisamy Nallasamy Zi Yae Kang Xiaolun Sun Pon Velayutham Anandh Babu Dongmin Liu Zhenquan Jia |
author_facet |
Palanisamy Nallasamy Zi Yae Kang Xiaolun Sun Pon Velayutham Anandh Babu Dongmin Liu Zhenquan Jia |
author_sort |
Palanisamy Nallasamy |
title |
Natural Compound Resveratrol Attenuates TNF-Alpha-Induced Vascular Dysfunction in Mice and Human Endothelial Cells: The Involvement of the NF-κB Signaling Pathway |
title_short |
Natural Compound Resveratrol Attenuates TNF-Alpha-Induced Vascular Dysfunction in Mice and Human Endothelial Cells: The Involvement of the NF-κB Signaling Pathway |
title_full |
Natural Compound Resveratrol Attenuates TNF-Alpha-Induced Vascular Dysfunction in Mice and Human Endothelial Cells: The Involvement of the NF-κB Signaling Pathway |
title_fullStr |
Natural Compound Resveratrol Attenuates TNF-Alpha-Induced Vascular Dysfunction in Mice and Human Endothelial Cells: The Involvement of the NF-κB Signaling Pathway |
title_full_unstemmed |
Natural Compound Resveratrol Attenuates TNF-Alpha-Induced Vascular Dysfunction in Mice and Human Endothelial Cells: The Involvement of the NF-κB Signaling Pathway |
title_sort |
natural compound resveratrol attenuates tnf-alpha-induced vascular dysfunction in mice and human endothelial cells: the involvement of the nf-κb signaling pathway |
publisher |
MDPI AG |
publishDate |
2021 |
url |
https://doaj.org/article/4bbe4ec185e44b3b8d61e9e8290cb00a |
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