Colonic metabolites from flavanols stimulate nitric oxide production in human endothelial cells and protect against oxidative stress-induced toxicity and endothelial dysfunction. (May 2018)

• Record Type: Journal Article
• Authors: Álvarez-Cilleros, David; Ramos, Sonia; Goya, Luis; Martín, María Ángeles
• Is Part Of: Food and chemical toxicology. Volume 115(2018)
• Page Start: 88
• Page End: 97
• Publication Date: 2018-05
• Subjects: Cocoa flavanols -- Endothelium -- Oxidative injury -- Signaling pathways -- Cardiovascular diseases; AKT/PKB protein kinase B -- AMPK adenosine monophosphate-activated protein kinase -- DAF-FM-DA 4-amino-5-methylamino-2, 7-difluorofluorescein diacetate -- DCFH-DA 2′, 7′-dichlorofluorescin diacetate -- DHBA 2, 3-dihydroxybenzoic acid -- DHPAA 3, 4-dihydroxyphenylacetic acid -- eNOS endothelial nitric oxide synthase -- ERK extra cellular regulated kinase -- GPx glutathione peroxidase -- GSH glutathione -- HPPA 3-hydroxyphenylpropionic acid -- JNKs Jun N-terminal kinases -- NO endothelial-derived nitric oxide -- PI3K phosphatidylinositol-3-kinase -- t-BOOH tert-butyl hydroperoxide; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2018.03.006
• Languages: English
• ISSNs: 0278-6915

Abstract

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. Highlights: Flavanol colonic metabolites stimulate NO production in human endothelial cells. Increased NO production induced by colonic metabolites is related to the activation of eNOS via AKT and AMPK signaling. Flavanol colonic metabolites prevent oxidative stress-induced endothelial dysfunction, cytotoxicity and cell death.