Dietary quercetin supplementation alleviates disease related muscle injury in dystrophic muscle

Duchenne muscular dystrophy is the most common, fatal, X‐linked muscle disease and is modeled by the mdx mouse. Dystrophic muscle shows signs of progressive necrosis and fibrosis leading to a loss of muscle function. Peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α) up‐regulation has been shown to alleviate some aspects of dystrophic pathology. Quercetin (QCN), a natural polyphenolic compound derived from foods such as red apples and red onions, is a potent sirtuin 1 (SIRT1) activator capable of entering muscle cells via oral delivery. SIRT1, in turn, activates PGC‐1α by deacetylation. To determine the extent to which a diet containing QCN could alter the progression of disease related muscle injury 3 mo old mdx mice were fed a diet containing 0% or 0.2% QCN for 6 mo, sacrificed, and diaphragms removed. Control and treated mice ate similar amounts of food and grew at a similar rate during the study period. Dietary QCN reduced the number of extracellular nuclei/mm 2 by 37% (p<0.05). The number of muscle cells/mm 2 was increased by 20% (p<0.05) and muscle cells with centralized nuclei were reduced by 33% (p<0.05) in diaphragms from treated animals compared to control. Fibrosis was similar between groups. These data suggest that dietary QCN is beneficial to dystrophic muscle and warrants greater exploration as a potential therapeutic agent. Partially supported by the Martin Fund.