نبذة مختصرة : Muscle weakness and muscle loss characterize many physio-pathological conditions, including sarcopenia and many forms of muscular dystrophy, that are often also associated to mitochondrial dysfunction. Verbascoside, a phenylethanoid glycoside of plant origin, also named acteoside, has shown a high antioxidant and anti-fatigue activity in different animal models, but the molecular mechanisms underlying these effects are not completely understood. This study aims to investigate the influence of verbascoside on mitochondrial function and its protective role against H2O2-induced oxidative damage in murine C2C12 myoblasts and myotubes pre-treated with verbascoside for 24 h and exposed to H2O2. We examined the effects of verbascoside on cell viability, intracellular reactive oxygen species (ROS) production and mitochondrial function through high-resolution respirometry. Moreover, we verified if verbascoside was able to stimulate Nrf2 activity through Western blotting and confocal fluorescence microscopy and to modulate the transcription of its target genes, such as heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a), by real time-PCR. We found that verbascoside: (1) improved mitochondrial function by increasing mitochondrial spare respiratory capacity; (2) mitigated the decrease in cell viability induced by H2O2 and reduced ROS levels; (3) promoted phosphorylation of Nrf2 and its nuclear translocation; (4) increased the transcription levels of HO-1 and, in myoblasts but not in myotubes, those of PGC-1a. These findings contribute to explain verbascoside ability to relieve muscular fatigue and could have positive repercussions for the development of therapies aimed at contrasting muscle weakness and mitochondrial dysfunction.
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