Effects of (−)-epicatechin on molecular modulators of skeletal muscle growth and differentiation

Abstract

Sarcopenia is a notable and debilitating age-associated condition. Flavonoids are known for their healthy effects and limited toxicity. The flavanol (−)-epicatechin (Epi) enhances exercise capacity in mice and Epi-rich cocoa improves skeletal muscle structure in heart failure patients. (−)-Epicatechin may thus, hold promise as treatment for sarcopenia. We examined changes in protein levels of molecular modulators of growth and differentiation in young vs. old, human and mouse skeletal muscle. We report the effects of Epi in mice and the results of an initial proof-of-concept trial in humans, where muscle strength and levels of modulators of muscle growth were measured. In mice, myostatin and senescence-associated β-galactosidase levels increase with aging, while those of follistatin and Myf5 decrease. (−)-Epicatechin decreases myostatin and β-galactosidase and increases levels of markers of muscle growth. In humans, myostatin and β-galactosidase increase with aging while follistatin, MyoD and myogenin decrease. Treatment for 7 days with (−)-epicatechin increases hand grip strength and the ratio of plasma follistatin/myostatin. In conclusion, aging has deleterious effects on modulators of muscle growth/differentiation, the consumption of modest amounts of the flavanol (−)-epicatechin can partially reverse these changes. This flavanol warrants its comprehensive evaluation for the treatment of sarcopenia

(‐)‐Epicatechin regulates blood lipids and attenuates hepatic steatosis in rats fed high‐fat diet

“…As being mentioned early, EC significantly reduced TG at a very low dose (1 mg/kg BW) , but not at a much higher dose (0.01 mol/kg BW). Incredibly wide range doses of EC, from 1 mg/kg BW to 3 g/kg BW , were found in the studies to investigate the cardiovascular benefits of EC. Nevertheless, most studies selected the physiological or near physiological doses, which fell in the range of 10–50 mg/kg BW.…”

“…The molecular mechanisms are largely unknown. In one study to evaluate the effects of EC on a high‐fat diet induced rat model of cardiometabolic risk factors, EC was found to significantly reduce TG at a very lower dose (1 mg/kg BW) . Another study conducted by the same group confirmed that, when consuming two capsules of 25 mg EC twice a day orally, human subject with hypertriglyceridemia displayed a significantly drop of TG by 75 mg/dL.…”

Effects of tannase-converted green tea extract on skeletal muscle development

“…Lee et al reported a dose-dependent effect of EC on the protein levels of MHC, MyoD and myogenin, and stimulation of promyogenic signaling pathways, p38 MAPK and Akt, in EC-treated C2C12 myoblasts [24]. In addition, Gutierrz-Salmean et al proved that EC treatment resulted in a significant increase in the levels of MEF2, Myf5, MyoD, and myogenin in the skeletal muscles of old EC-treated mice (25 months) and the muscle strength in human hands [25]. Experimental evidence found using HepG2 cells and C2C12 skeletal muscle myotubes demonstrated that FOXO transcription factors are sufficient for activating and increasing the levels of a MuRF1 promotor fragment, atrogin-1, and/or MuRF1 mRNA expression [26].…”

Epicatechin elicits MyoD-dependent myoblast differentiation and myogenic conversion of fibroblasts

“…In this study, we have tried to investigate the effect and molecular mechanism of EC as a compound for improving muscle differentiation. The positive role of EC in the regulation of muscle growth and differentiation has been previously referred by Ramirez-Sanchez group [13]. However, the molecular mechanism by which EC modulates myogenic differentiation was unclear.…”

“…EC significantly promotes osteogenic proliferation, differentiation and mineralization [12]. Furthermore, the treatment of EC enhances the level of myogenic genes, such as MEF2, Myf5 and MyoD in skeletal muscles of old mice, and one week treatment with EC in humans increased muscle strength in hands [13]. However, the detailed mechanism of the positive effect of EC on muscle growth has not been examined.…”