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Int J Cardiol. 2014 Aug 20;175(3):508-14. doi: 10.1016/j.ijcard.2014.06.045. Epub 2014 Jul 2.

Dietary ellagic acid improves oxidant-induced endothelial dysfunction and atherosclerosis: role of Nrf2 activation.

Author information

1
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, China.
2
Beijing Institute of Biotechnology, China.
3
Beijing Institute of Biotechnology, China; Department of Health Services, Fourth Military Medical University, China.
4
Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, China. Electronic address: adwen-2004@hotmail.com.

Abstract

BACKGROUND:

Oxidative stress-induced vascular endothelial cell injury is a major factor in the pathogenesis of atherosclerosis. Several evidences indicate that ellagic acid (EA), a phenolic compound, contributes to cardiovascular health. This study was to investigate the effects of EA on endothelial dysfunction and atherosclerosis via antioxidant-related mechanisms.

METHODS:

In animal studies, wild-type (WT) C57BL/6 mice and apolipoprotein E-deficient mice (ApoE(-/-)) mice were fed: a high-fat (21%) diet (HFD) or a HFD plus with EA (HFD+EA), for 14weeks. Vascular reactivity was studied in mice aortas. The effect of EA in human umbilical vein endothelial cells (HAECs) exposed to hypochlorous acid (HOCl) was also investigated.

RESULTS:

Compared with animals on HFD alone, EA attenuated atherosclerosis in WT mice. In aortic rings from two mice models, EA significantly improved endothelium-dependent relaxation and attenuated HOCl-induced endothelial dysfunction. Besides, EA significantly improved nitric oxide synthase activity, antioxidant capacity and markers of endothelial dysfunction in plasma. Western blot analysis showed that EA increased NF-E2-related factor 2 (Nrf2) and heme oxygenase-1(HO-1) expression in the aortas (P<0.05). In a separate experiment, EA did not protect against HOCl-induced endothelial dysfunction in arteries obtained from Nrf2 gene knockout mice compared with WT mice. In HAECs, EA prevented HOCl-induced cellular damage and induced HO-1 protein expression, and these effects markedly abolished by the siRNA of Nrf2.

CONCLUSIONS:

Our results provide further support for the protective effects of dietary EA particularly oxidant-induced endothelial dysfunction and atherosclerosis partly via Nrf2 activation.

KEYWORDS:

Atherosclerosis; Endothelial dysfunction; Oxidative stress

PMID:
25017906
DOI:
10.1016/j.ijcard.2014.06.045
[Indexed for MEDLINE]

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