Resveratrol Promotes Hypertrophy in Wildtype Skeletal Muscle and Reduces Muscle Necrosis and Gene Expression of Inflammatory Markers in Mdx Mice

Molecules. 2021 Feb 6;26(4):853. doi: 10.3390/molecules26040853.

Abstract

Duchenne muscular dystrophy (DMD) is a progressive fatal neuromuscular disorder with no cure. Therapies to restore dystrophin deficiency have been approved in some jurisdictions but long-term effectiveness is yet to be established. There is a need to develop alternative strategies to treat DMD. Resveratrol is a nutraceutical with anti-inflammatory properties. Previous studies have shown high doses (100-400 mg/kg bodyweight/day) benefit mdx mice. We treated 4-week-old mdx and wildtype mice with a lower dose of resveratrol (5 mg/kg bodyweight/day) for 15 weeks. Voluntary exercise was used to test if a lower dosage than previously tested could reduce exercise-induced damage where a greater inflammatory infiltrate is present. We found resveratrol promoted skeletal muscle hypertrophy in wildtype mice. In dystrophic muscle, resveratrol reduced exercise-induced muscle necrosis. Gene expression of immune cell markers, CD86 and CD163 were reduced; however, signalling targets associated with resveratrol's mechanism of action including Sirt1 and NF-κB were unchanged. In conclusion, a lower dose of resveratrol compared to the dosage used by other studies reduced necrosis and gene expression of inflammatory cell markers in dystrophic muscle suggesting it as a therapeutic candidate for treating DMD.

Keywords: duchenne; inflammation; mdx; muscle; muscular dystrophy; nutraceuticals; resveratrol.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Gene Expression Regulation / drug effects*
  • Hypertrophy / chemically induced
  • Hypertrophy / metabolism
  • Hypertrophy / pathology
  • Inflammation / metabolism
  • Mice
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / pathology*
  • Necrosis / drug therapy
  • Resveratrol / pharmacology*
  • Resveratrol / therapeutic use

Substances

  • Biomarkers
  • Resveratrol