Direct Effects of (−)-Epicatechin and Procyanidin B2 on the Respiration of Rat Heart Mitochondria

Abstract

Flavonol (−)-epicatechin and its derived dimer procyanidin B2, present in high amounts in cocoa products, have been shown to exert beneficial effects on the heart and cardiovascular system; however, their mechanism of action has not been fully elucidated. We studied effects of (−)-epicatechin and procyanidin B2 on the oxidative phosphorylation of isolated rat heart mitochondria. (−)-Epicatechin and procyanidin B2 had stimulating effect (up to 30% compared to control) on substrate-driven (State 2) mitochondrial respiration. Their effect was dependent on the respiratory substrates used. (−)-Epicatechin at higher concentrations (from 0.27 µg/mL) significantly decreased (up to 15%) substrate- and ADP-driven (State 3) mitochondrial respiration in case of pyruvate and malate oxidation only. Procyanidin B2 (0.7–17.9 ng/mL) inhibited State 3 respiration rate up to 19%, the most profound effect being expressed with succinate as the substrate. (−)-Epicatechin at concentrations of 0.23 µg/mL and 0.46 µg/mL prevented loss of the cytochrome c from mitochondria when substrate was succinate, supporting the evidence of membrane stabilizing properties of this flavonol. Thus, both (−)-epicatechin and procyanidin B2 directly influenced mitochondrial functions and the observed effects could help to explain cardiometabolic risk reduction ascribed to the consumption of modest amounts of cocoa products.

Proanthocyanidins Ameliorated Deficits of Lipid Metabolism in Type 2 Diabetes Mellitus Via Inhibiting Adipogenesis and Improving Mitochondrial Function

“…Early studies demonstrated that monomeric cocoa catechin promotes β-cell stability through up-regulating the expression of key genes that encode antioxidant and mitochondrial respiratory complex proteins [58]. In addition, other studies shown that epicatechin and procyanidin B2 directly influence mitochondrial functions by reducing release of cytochrome c in isolated rat heart [59]. In line with these reports, our results demonstrated that C, EC, PB7, PB6, PB3, and PB1 ameliorated Dex-induced mitochondrial deficits in 3T3-L1 adipocytes, via improving mitochondrial biogenesis, dynamics, transmembrane potential, and antioxidant defenses.…”

Annurca Apple Polyphenols Ignite Keratin Production in Hair Follicles by Inhibiting the Pentose Phosphate Pathway and Amino Acid Oxidation

“…However, in support of the second hypothesis, polyphenol have been in many contexts shown to directly affect mitochondrial activity and stimulate mitochondrial ATP production. Both epicatechin and Procyanidin B2 possess uncoupling effect on oxidative phosphorylation in cardiac mitochondria [ 63 ], suppressing activity of pyruvate and malate oxidation and stimulating fatty acid β-oxidation. Comparing our metabolic profiles with those described for murine HFs in different stages of the hair cycle [ 55 ], it seems more likely that the mitochondrial activity itself is responsible for inducing the early anagen aspect of AAE-treated HFs.…”

Flavonoids as Anticancer Agents

“…In tumor cells, mitochondria are usually hyperpolarized, and their membrane potential reaches 220 mV [186,187] making them resistant to cell death signaling. Our group evaluated direct effects of selected flavonoids on the functions of cardiac mitochondria respiring on pyruvate and malate as substrates [188][189][190][191]. The results demonstrated that (-)-epicatechin [190,191], procyanidin B2 [190,191], hyperoside [189,190], quercetin [189,190], quercitrin [189,190] and rutin [189,190] uncoupled oxidation from phosphorylation.…”