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

The purpose of this study was to conduct an 8 week endurance training program with and without (–)–epicatechin treatment and to determine whether there is a possible cumulative effect on protein markers of angiogenesis and mitochondrial biogenesis. Thirty-four 14-month old male mice (C57BL/6N) were randomized into four groups: control (C); (–)–epicatechin only ((–)–Epi); control with endurance training (CE); and (–)–epicatechin with endurance training ((–)–Epi-Ex). Mice in the training groups performed treadmill exercise for 8 weeks (5 × /week for 60 min/session), whereas mice in the (–)–epicatechin group received 1.0 mg/kg of body mass twice daily during the training period. At 8 weeks, distance ran on the treadmill increased by 46, 69, and 84% in the (–)–Epi, CE, and (–)–Epi-Ex groups, respectively compared to the control group (p < 0.001 for all comparisons). Furthermore, the (–)–Epi-Ex group had significantly higher exercise capacity than the (–)–Epi and CE group. For angiogenic regulators, the (–)–Epi-Ex group had significantly higher VEGF-R2 protein expression with a concomitant reduction in TSP-1 protein expression than the exercise group. Interestingly, FoxO1 protein expression was significantly reduced for all three experimental groups compared to the control group. Protein markers such as PGC-1β and TFAM were significantly higher in the (–)–Epi-Ex group compared to the three other groups. These findings suggest that (–)–epicatechin treatment combined with 8 weeks of endurance training provide a cumulative effect on a number of angiogenic and mitochondrial signaling which functionally translates to enhanced exercise tolerance.