Natural Compounds That Enhance Motor Function in a Mouse Model of Muscle Fatigue

Musculoskeletal disease can be a serious condition associated with aging that may lead to fractures and a bedridden state due to decreased motor function. In addition to exercise training to increase muscle mass, increasing muscle function with the intake of functional foods is an effective treatment strategy for musculoskeletal disease. Muscle-specific SOD2-deficient mice (muscle-Sod2^-/-) show a severe disturbance in exercise in association with increased mitochondrial reactive oxygen species, as well as mitochondrial dysfunction and muscle damage. In the present study, to develop a therapeutic strategy for musculoskeletal disease, we searched for substances that enhanced motor function among functional compounds by in vivo screening using muscle-Sod2^-/- mice as a muscle fatigue model. We administered 96 compounds, including antioxidants, to muscle-Sod2^-/- mice and assessed their effects on treadmill performance. Among the administered compounds, gossypin, genistein, kaempferol, taxifolin, fumaric acid, β-hydroxy-β-methylbutyrate Ca, and astaxanthin, which are dietary functional food factors, increased forced running time in muscle-Sod2^-/- mice. In addition, troglitazone, tempol, trolox, and MnTE-2-PyP, which are antioxidants, also significantly increased the running ability of muscle-Sod2^-/- mice. These results suggest that the intake of functional foods with antioxidant activity can improve motor function. Muscle-Sod2^-/- mice, as a muscle fatigue model, are suitable for the in vivo screening of functional substances that promote improvements in exercise and muscle performance.