Effect of (-)-Epicatechin on Pax-7/Myogenesis in a Murine Model of Muscular Dystrophy

Abstract

Abstract: Limb-girdle muscular dystrophies (LGMD) are genetic disorders characterized by affecting the proximal muscles of the pelvic and shoulder girdles. The chronic damage caused by this disease surpasses the muscle repair mechanisms, leading to progressive weakness, atrophy, and premature death of myofibers. Satellite cells (SCs) are a type of stem cell characterized by expressing Pax-7 on their surface, and they actively participate in skeletal muscle repair. On the other hand, it has been reported that the flavonol (-)-Epicatechin (Epi) accelerates muscle repair; however, it is unknown whether this effect is mediated through the activation of SCs and myogenic factors.

Objective: To evaluate the effect of Epi on the activation of SCs and myogenic factors in a murine model of LGMD.

Methodology: Experiments were conducted on 36 twelve-week-old male mice. The mice were divided into four groups (9 mice per group). Groups 1 and 2 were wild-type mice treated with DMSO or Epi, while groups 3 and 4 were LGMD mice treated with DMSO or Epi. At the end of the treatment, all animals were sacrificed, and the muscles of the forelimbs were extracted. For histological analysis, 8-micron sections from 3 mice per group were prepared and stained with hematoxylin-eosin (HE) and modified Gomori trichrome. The remaining animals were used for total protein extraction to detect Pax-7, β-catenin, MyoD, and Myogenin by immunoblotting.

Results: Histological analysis showed that LGMD mice treated with Epi had a reduced percentage of damage and fibrosis compared to untreated mice. Furthermore, the levels of myogenic proteins increased in Epi-treated LGMD mice compared to untreated ones.

Conclusions: Epi treatment accelerates muscle repair through the activation of myogenic proteins in a murine model of LGMD.

Keywords: Muscular dystrophy, muscle regeneration, Pax-7, (-)-Epicatechin.