Studies in humans have found consumption of certain flavanoid‐containing foods to be associated with improvement in endothelial function and with reduction of blood pressure (BP). (–)‐Epicatechin is a compound representative of the flavanols (a subfamily of flavonoids), abundant in cocoa seeds, which is preserved during the industrialization process to chocolate. The antihypertensive effect of dietary (–)‐epicatechin was investigated on spontaneously hypertensive rats (SHRs). Consumption of (–)‐epicatechin‐supplemented diet (3 g (–)‐epicatechin/kg diet) decreased BP in SHR by 27 and 23 mm Hg on days 2 and 6, respectively. On day 6, a 173% increase of nitric oxide synthase (NOS) activity was observed in the aorta of EPI‐SHR as compared to nonsupplemented SHR (P < 0.05). Responses to acetylcholine (ACh) were then examined in femoral arteries in the absence and the presence of L‐NAME, a nonselective NOS inhibitor, to assess the ACh‐mediated relaxation ascribed to NO‐dependent and ‐independent mechanisms. Acetylcholine‐induced endothelium‐dependent relaxation in the femoral artery was significantly higher in EPI‐SHR than in SHR, with a predominance of the NO‐dependent component of this relaxation. The endothelium‐independent relaxation, assayed by using the NO donor sodium nitroprusside, resulted in nonsignificant difference in the three experimental groups, demonstrating an unaffected function of vascular smooth muscle cells. These results give further support to the concept that (–)‐epicatechin can modulate BP in hypertension by increasing NO levels in the vasculature. © 2013 IUBMB Life, 65(8):710–715, 2013

High fructose consumption has been associated to deleterious metabolic conditions. In the kidney, high fructose causes renal alterations that contribute to the development of chronic kidney disease. Evidence suggests that dietary flavonoids have the ability to prevent/attenuate risk factors of chronic diseases. This work investigated the capacity of (-)-epicatechin to prevent the renal damage induced by high fructose consumption in rats. Male Sprague Dawley rats received 10% (w/v) fructose in the drinking water for 8 weeks, with or without supplementation with (-)-epicatechin (20mg/kg body weight/d) in the rat chow diet. Results showed that, in the presence of mild proteinuria, the renal cortex from fructose-fed rats exhibited fibrosis and decreases in nephrin, synaptopodin, and WT1, all indicators of podocyte function in association with: (i) increased markers of oxidative stress; (ii) modifications in the determinants of NO bioavailability, i.e., NO synthase (NOS) activity and expression; and (iii) development of a pro-inflammatory condition, manifested as NF-κB activation, and associated with high expression of TNFα, iNOS, and IL-6. Dietary supplementation with (-)-epicatechin prevented or ameliorated the adverse effects of high fructose consumption. These results suggest that (-)-epicatechin ingestion would benefit when renal alterations occur associated with inflammation or metabolic diseases.

This work investigated the capacity of (-)-epicatechin to prevent the renal damage induced by LPS administration in rats. Male Sprague Dawley rats were fed for 4 days a diet without or with supplementation with (-)-epicatechin (80mg/kg BW/d), and subsequently i.p. injected with lipopolysaccharide (LPS). Six hours after injection, LPS-treated rats exhibited increased plasma creatinine and urea levels as indicators of impaired renal function. The renal cortex of the LPS-treated rats showed: i) increased expression of inflammatory molecules (TNF-α, iNOS and IL-6); ii) activation of several steps of NF-κB pathway; iii) overexpression of TLR4, and iv) higher superoxide anion production and lipid peroxidation index in association with increased levels of gp91phox and p47phox (NOX2) and NOX4. Pretreatment with dietary (-)-epicatechin prevented the adverse effects of LPS challenge essentially by inhibiting TLR4 upregulation and NOX activation and the consequent downstream events, e.g. NF-kB activation.

Identification of the links among flavonoid consumption, mitigation of oxidative stress and improvement of disease in humans has significantly advanced in the last decades. This review used (-)-epicatechin (EC) as an example of dietary flavonoids, and inflammation, endothelial dysfunction/hypertension and insulin resistance/diabetes as paradigms of human disease. In these pathologies, oxidative stress is part of their development and/or their perpetuation. Evidence from both, rodent studies and characterization of mechanisms in cell cultures are encouraging and mostly support indirect antioxidant actions of EC and EC metabolites in endothelial dysfunction and insulin resistance. Human studies also show beneficial effects of EC on these pathologies based on biomarkers of disease. However, there is limited available information on oxidative stress biomarkers and flavonoid consumption to allow establishing conclusive associations. The evolving discovery of metabolites that could serve as reliable markers of intake of specific flavonoids constitutes a powerful tool to link flavonoid consumption to disease and prevention of oxidative stress in human populations.