Effects of (−)-epicatechin and derivatives on nitric oxide mediated induction of mitochondrial proteins

Moreno‐Ulloa, Aldo; Cid, Armando; Rubio-Gayosso, Iván; Ceballos, Guillermo; Villarreal, Francisco; Ramírez-Sánchez, Israel

doi:10.1016/j.bmcl.2013.05.079

Cited by 47 publications

(36 citation statements)

References 38 publications

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“…(−)-EPI effects on ERK 1/2 and CaMKII activation were assessed in the presence or absence of the selective GPER antagonist, G15 (30). Cells were stimulated with (−)-EPI 0.1 μM for 10 min, which evokes peak effect on endothelial cell signaling as previously reported by us (24). (−)-EPI treatment led to the activation of ERK 1/2 and CaMKII as denoted by their phosphorylation (Fig.…”

Section: Resultsmentioning

confidence: 99%

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The effects of (−)-epicatechin on endothelial cells involve the G protein-coupled estrogen receptor (GPER)

Moreno‐Ulloa

Méndez-Luna

Beltrán-Partida

et al. 2015

Pharmacological Research

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We have provided evidence that the stimulatory effects of (−)-epicatechin ((−)-EPI) on endothelial cell nitric oxide (NO) production may involve the participation of a cell-surface receptor. Thus far, such entity(ies) has not been fully elucidated. The G protein-coupled estrogen receptor (GPER) is a cell-surface receptor that has been linked to protective effects on the cardiovascular system and activation of intracellular signaling pathways (including NO production) similar to those reported with (−)-EPI. In bovine coronary artery endothelial cells (BCAEC) by the use of confocal imaging, we evidence the presence of GPER at the cell-surface and on F-actin filaments. Using in silico studies we document the favorable binding mode between (−)-EPI and GPER. Such binding is comparable to that of the GPER agonist, G1. By the use of selective blockers, we demonstrate that the activation of ERK 1/2 and CaMKII by (−)-EPI is dependent on the GPER/c-SRC/EGFR axis mimicking those effects noted with G1. We also evidence by the use of siRNA the role that GPER has on mediating ERK1/2 activation by (−)-EPI. GPER appears to be coupled to a non Gαi/o or Gαs, protein subtype. To extrapolate our findings to an ex vivo model, we employed phenylephrine pre-contracted aortic rings evidencing that (−)-EPI can mediate vasodilation through GPER activation. In conclusion, we provide evidence that suggests the GPER as a potential mediator of (−)-EPI effects and highlights the important role that GPER may have on cardiovascular system protection.

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Section: Resultsmentioning

confidence: 99%

“…Inhibitors were present during ligand stimulation. (−)-EPI was used at 0.1 μM for 10 min based on previous studies (24). As positive controls for select experiments forskolin and the GPER agonist, G1, were used at 1 μM and 0.1 μM for 10 min, respectively.…”

Section: Methodsmentioning

confidence: 99%

The effects of (−)-epicatechin on endothelial cells involve the G protein-coupled estrogen receptor (GPER)

Moreno‐Ulloa

Méndez-Luna

Beltrán-Partida

et al. 2015

Pharmacological Research

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“…Mice fed with epicatechin demonstrated improved exercise performance and fatigue resistance, and evidence for enhanced mitochondrial biogenesis including increased ETC proteins, mitofilin, porin, mitochondrial transcription factor A (Tfam), mitochondrial volume, and cristae abundance [79]. Studying cultured bovine coronary artery endothelial cells showed that epicatechin is capable of stimulating mitochondrial function as assessed by citrate synthase activity as well as induction of structural and oxidative phosphorylation protein levels [80]. An open label study evaluating the safety and efficacy of epicatechin in subjects with Friedreich ataxia is currently being conducted.…”

Section: Enhancing Mitochondrial Biogenesismentioning

confidence: 99%

Therapies for mitochondrial diseases and current clinical trials

El‐Hattab

Zarante

Almannai

et al. 2017

Molecular Genetics and Metabolism

154

113

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Mitochondrial diseases are a clinically and genetically heterogeneous group of disorders that result from dysfunction of the mitochondrial oxidative phosphorylation due to molecular defects in genes encoding mitochondrial proteins. Despite the advances in molecular and biochemical methodologies leading to better understanding of the etiology and mechanism of these diseases, there are still no satisfactory therapies available for mitochondrial disorders. Treatment for mitochondrial diseases remains largely symptomatic and does not significantly alter the course of the disease. Based on limited number of clinical trials, several agents aiming at enhancing mitochondrial function or treating the consequences of mitochondrial dysfunction have been used. Several agents are currently being evaluated for mitochondrial diseases. Therapeutic strategies for mitochondrial diseases include the use of agents enhancing electron transfer chain function (coenzyme Q10, idebenone, ribo-flavin, dichloroacetate, and thiamine), agents acting as energy buffer (creatine), antioxidants (vitamin C, vitamin E, lipoic acid, cysteine donors, and EPI-743), amino acids restoring nitric oxide production (arginine and citrulline), cardiolipin protector (elamipretide), agents enhancing mitochondrial biogenesis (bezafibrate, epicatechin, and RTA 408), nucleotide bypass therapy, liver transplantation, and gene therapy. Although, there is a lack of curative therapies for mitochondrial disorders at the current time, the increased number of clinical research evaluating agents that target different aspects of mitochondrial dysfunction is promising and is expected to generate more therapeutic options for these diseases in the future.

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“…NO is suspected to mediate the effects of cocoa on mitochondria. In support of this thesis, a recent study demonstrated, in vitro, that flavanols are capable to stimulate mitochondrial function and biogenesis; effects disappeared with the inhibition of eNOS (107,108).…”

Section: Putative Mechanismsmentioning

confidence: 55%

Cocoa, Blood Pressure, and Vascular Function

et al. 2012

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Cardiovascular disease (CVD) represents the most common cause of death worldwide. The consumption of natural polyphenol-rich foods, and cocoa in particular, has been related to a reduced risk of CVD, including coronary heart disease and stroke. Intervention studies strongly suggest that cocoa exerts a beneficial impact on cardiovascular health, through the reduction of blood pressure (BP), improvement of vascular function, modulation of lipid and glucose metabolism, and reduction of platelet aggregation. These potentially beneficial effects have been shown in healthy subjects as well as in patients with risk factors (arterial hypertension, diabetes, and smoking) or established CVD (coronary heart disease or heart failure). Several potential mechanisms are supposed to be responsible for the positive effect of cocoa; among them activation of nitric oxide (NO) synthase, increased bioavailability of NO as well as antioxidant, and anti-inflammatory properties. It is the aim of this review to summarize the findings of cocoa and chocolate on BP and vascular function.

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Effects of (−)-epicatechin and derivatives on nitric oxide mediated induction of mitochondrial proteins

Cited by 47 publications

References 38 publications

The effects of (−)-epicatechin on endothelial cells involve the G protein-coupled estrogen receptor (GPER)

The effects of (−)-epicatechin on endothelial cells involve the G protein-coupled estrogen receptor (GPER)

Therapies for mitochondrial diseases and current clinical trials

Cocoa, Blood Pressure, and Vascular Function

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