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Food Chem Toxicol. 2018 May;115:88-97. doi: 10.1016/j.fct.2018.03.006. Epub 2018 Mar 9.

Colonic metabolites from flavanols stimulate nitric oxide production in human endothelial cells and protect against oxidative stress-induced toxicity and endothelial dysfunction.

Author information

1
Departamento de Metabolismo y Nutrición, Instituto de Ciencia y Tecnología de los Alimentos y Nutrición (ICTAN), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
2
Departamento de Metabolismo y Nutrición, Instituto de Ciencia y Tecnología de los Alimentos y Nutrición (ICTAN), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Electronic address: amartina@ictan.csic.es.

Abstract

Oxidative stress is involved in endothelial dysfunction, the key player in the development of vascular events. Flavanols, the major antioxidants in cocoa have been related to vascular protection and lower cardiovascular risk. However, the bioavailability of cocoa flavanols is very low and their bioactivity in vivo seems to be greatly mediated by the derived phenolic metabolites formed by intestinal microbiota. Hence, we investigated whether microbial-derived flavanol metabolites 3,4-dihydroxyphenylacetic acid (DHPAA), 2,3-dihydroxybenzoic acid (DHBA), 3-hydroxyphenylpropionic acid (HPPA) and a mix of them could influence endothelial function and prevent oxidative stress in human endothelial cells (Ea.hy926). Our results revealed that a mixture of flavanol colonic metabolites significantly increased phosphorylation of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production. By using specific inhibitors, we also established the participation of the adenosine monophosphate-activated protein kinase (AMPK) and protein kinase B (AKT) in eNOS activation. Likewise, flavanol metabolite mix protected against oxidative stress-induced endothelial dysfunction and cell death by preventing increased ROS generation and activation of signaling pathways related to oxidative stress. We concluded that flavanol colonic metabolites could exert beneficial effects in endothelial cells and prevent oxidative stress-induced vascular dysfunction.

KEYWORDS:

Cardiovascular diseases; Cocoa flavanols; Endothelium; Oxidative injury; Signaling pathways

PMID:
29530637
DOI:
10.1016/j.fct.2018.03.006
[Indexed for MEDLINE]

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