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1: Am J Clin Nutr. 2008 Oct;88(4):1018-25. Links
Pure dietary flavonoids quercetin and (-)-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men.Loke WM, Hodgson JM, Proudfoot JM, McKinley AJ, Puddey IB, Croft KD.
School of Medicine and Pharmacology and the School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Perth, Western Australia.

BACKGROUND: Dietary flavonoids may improve endothelial function and ultimately lead to beneficial cardiovascular effects. OBJECTIVE: The objective was to assess whether pure dietary flavonoids can modulate nitric oxide and endothelin-1 production and thereby improve endothelial function. DESIGN: A randomized, placebo-controlled, crossover trial in 12 healthy men was conducted to compare the acute effects of the oral administration of 200 mg quercetin, (-)-epicatechin, or epigallocatechin gallate on nitric oxide, endothelin-1, and oxidative stress after nitric oxide production was assessed via the measurement of plasma S-nitrosothiols and plasma and urinary nitrite and nitrate concentrations. The effects on oxidative stress were assessed by measuring plasma and urinary F(2)-isoprostanes. Plasma and urinary concentrations of quercetin, (-)-epicatechin, and epigallocatechin gallate were measured to establish the absorption of these flavonoids. RESULTS: Relative to water (control), quercetin and (-)-epicatechin resulted in a significant increase in plasma S-nitrosothiols, plasma nitrite, and urinary nitrate concentrations (P < 0.05), but not in plasma nitrate or urinary nitrite. Epigallocatechin gallate did not alter any of the measures of nitric oxide production. Quercetin and (-)-epicatechin resulted in a significant reduction in plasma endothelin-1 concentration (P < 0.05), but only quercetin significantly decreased the urinary endothelin-1 concentration. None of the 3 treatments significantly changed plasma or urinary F(2)-isoprostane concentrations. Significant increases in the circulating concentrations of the 3 flavonoids were observed (P < 0.05) after the corresponding treatment. CONCLUSIONS: Dietary flavonoids, such as quercetin and (-)-epicatechin, can augment nitric oxide status and reduce endothelin-1 concentrations and may thereby improve endothelial function.

PMID: 18842789 [PubMed - in process]

1: Peptides. 2008 Sep 16. [Epub ahead of print] Links
Regulation of glial inflammatory mediators synthesis: Possible role of endothelins.Filipovich T, Fleisher-Berkovich S.
Department of Clinical Pharmacology, Ben-Gurion University, P.O.B 653, Beer-Sheva 84105, Israel.

Endothelins are well known as modulators of inflammation in the periphery, but little is known about their possible role in brain inflammation. Stimulation of astrocyte prostaglandin, an inflammatory mediator, synthesis was shown so far only by endothelin 3 (ET-3). By contrast, several studies showed no change or slight decrease of basal nitric oxide synthesis after treatment of astrocytes with endothelin 1 (ET-1) and ET-3. However, a significant increase in astrocytic and microglial nitric oxide synthase (NOS) was observed after exposure to ET-1 and ET-3 in a model of forebrain ischaemia. Here we demonstrate that all three endothelins (ET-1, ET-2, ET-3) significantly enhanced the synthesis of prostaglandin E(2) and nitric oxide in glial cells. Each of the selective antagonists for ETA and ETB receptors (BQ123 and BQ788 respectively), significantly inhibited endothelins-induced production of both nitric oxide and prostaglandin E(2). These results suggest a regulatory mechanism of endothelins, interacting with both endothelin receptors, on glial inflammation. Therefore, inhibition of endothelin receptors may have a therapeutic potential in pathological conditions of the brain, when an uncontrolled inflammatory response is involved.

PMID: 18838093 [PubMed - as supplied by publisher]

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