S-Allyl Cysteine: A Potential Compound against Skeletal Muscle Atrophy

Abstract

Background Oxidative stress is crucial player in skeletal muscle atrophy pathogenesis. S-allyl cysteine (SAC), an organosulfur compound of Allium sativum, possesses broad-spectrum properties including immuno- and redox-modulatory impact. Considering the role of SAC in regulating redox balance, we hypothesize that SAC may have a protective role in oxidative-stress induced atrophy.Methods C2C12 myotubes were treated with H 2 O 2 (100 μM) in the presence or absence of SAC (200 μM) to study morphology, redox status, inflammatory cytokines and proteolytic systems using fluorescence microscopy, biochemical analysis, real-time PCR and immunoblotting approaches. The anti-atrophic potential of SAC was confirmed in denervation-induced atrophy model.Results SAC pre-incubation (4 h) could protect the myotube morphology (i.e. length/diameter/fusion index) from atrophic effects of H 2 O 2. Lower levels of ROS, lipid peroxidation, oxidized glutathione and altered antioxidant enzymes were observed in H 2 O 2-exposed cells upon pre-treatment with SAC. SAC supplementation also suppressed the rise in cytokines levels (TWEAK/IL6/myostatin) caused by H 2 O 2. SAC treatment also moderated the degradation of muscle-specific proteins (MHCf) in the H 2 O 2-treated myotubes supported by lower induction of diverse proteolytic systems (i.e. cathepsin, calpain, ubiquitin-proteasome E3-ligases, caspase-3, autophagy). Denervation-induced atrophy in mice illustrates that SAC administration alleviates the negative effects (i.e. mass loss, decreased cross-sectional area, up-regulation of proteolytic systems, and degradation of total/specific protein) of denervation on muscles.Conclusions SAC exerts significant anti-atrophic effects to protect myotubes from H 2 O 2-induced protein loss and myofibers from denervation-induced muscle loss, due to the prevention of elevated proteolytic systems and inflammatory/oxidative molecules.General significance The results signify the potential of SAC against muscle atrophy.