(–)-Epicatechin is associated with increased angiogenic and mitochondrial signalling in the hindlimb of rats selectively bred for innate low running capacity

Abstract

Alternative approaches to reduce congenital muscle dysfunction are needed in cases where the ability to exercise is limited. (−)-Epicatechin is found in cocao and may stimulate capillarity and mitochondrial proliferation in skeletal muscle. Twenty-one male rats bred for low running capacity (LCR) from generation 28 were randomized into three groups: vehicle for 30 days (control); (−)-epicatechin for 30 days; and (−)-epicatechin for 30 days followed by 15 days without (−)-epicatechin. Groups 2 and 3 received 1.0 mg/kg of body weight of (−)-epicatechin twice daily, whereas water was given to the control group. The plantaris muscle was harvested for protein and morphometric analyses. In addition, in vitro experiments were conducted to examine the role of (−)-epicatechin on mitochondrial respiratory kinetics at different incubation periods. Thirty days of (−)-epicatechin treatment increased capillarity (p < 0.001) and was associated with increases in protein expression of VEGF-A with a concomitant decrease in TSP-1 and its receptor, which remained after 15 days of (−)-epicatechin cessation. Analyses of p38 MAPK signaling pathway indicated an associated increase in phosphorylation of MKK3/6 and p38 and increased protein expression of MEF2A. In addition, we observed significant increases in protein expression of PGC-1α, PGC-1β, and Tfam, and cristae abundance. Interestingly, these increases associated with (−)-epicatechin treatment remained after 15 days of cessation. Lastly, in vitro experiments indicated that acute expose of LCR muscle to (−)-epicatechin incubation was not sufficient to increase mitochondrial respiration. The results suggest increases in skeletal muscle capillarity and mitochondrial biogenesis are associated with 30 days of (−)-epicatechin treatment and sustained 15 days following cessation of treatment. Clinically, the use of this natural compound may have potential application in populations that experience muscle fatigue and are unable to perform endurance exercise.

Pterostilbene Enhances Endurance Capacity via Promoting Skeletal Muscle Adaptations to Exercise Training in Rats

“…Therefore, exercise enhancers that can augment exercise-induced muscle adaptions, thereby partially substituting for physical exercise, have attracted much attention [15]. In recent years, some dietary polyphenols, such as (-)-epicatechin and apple polyphenols were found to promote exercise capacity through increasing skeletal muscle mitochondrial biogenesis and angiogenesis, and remodeling muscle fiber phenotype [16,17]. Resveratrol (RSV), a naturally occurring polyphenol, was found in a variety of plants, especially in the peel of grapes and peanuts [18].…”

(–)–Epicatechin combined with 8 weeks of treadmill exercise is associated with increased angiogenic and mitochondrial signaling in mice

“…The Nogueira et al (2011) study provided initial data regarding the short-term effects of (–)–epicatechin treatment on skeletal muscle structure and function. Subsequent studies on (–)–epicatechin have shown that (–)–epicatechin attenuates detraining effects on skeletal muscle ( Hüttemann et al, 2012 ) as well as increases angiogenic and mitochondrial signaling in rats with innate low running capacity (LCR; Hüttemann et al, 2013 ). These studies used either 14 ( Hüttemann et al, 2012 ) or 30 days ( Hüttemann et al, 2013 ) of (–)–epicatechin treatment in the absence of an endurance training intervention.…”

“…Subsequent studies on (–)–epicatechin have shown that (–)–epicatechin attenuates detraining effects on skeletal muscle ( Hüttemann et al, 2012 ) as well as increases angiogenic and mitochondrial signaling in rats with innate low running capacity (LCR; Hüttemann et al, 2013 ). These studies used either 14 ( Hüttemann et al, 2012 ) or 30 days ( Hüttemann et al, 2013 ) of (–)–epicatechin treatment in the absence of an endurance training intervention. These findings suggest, therefore, that (–)–epicatechin may function as a partial exercise mimetic.…”

Mechanisms of Antioxidant’s Action on the Physical Performance of Athletes

“…In addition, it was shown in the recent years that the long-term intense physical loads can induce the process of apoptosis of cells of human blood [38], which will surely affect negatively the parameters of workability, in particular, the aerobic one. A decrease in the activity of enzymatic systems including the antioxidative and detoxicative ones on the level of holistic organism, which happens under physical loads, extends the period of restoration after training exercises and complicates the formation of a required level of adaptive mechanisms in athletes [21].…”