S-allyl Cysteine: A Potential Compound Against Skeletal Muscle Atrophy

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 HO (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 HO. Lower levels of ROS, lipid peroxidation, oxidized glutathione and altered antioxidant enzymes were observed in HO-exposed cells upon pre-treatment with SAC. SAC supplementation also suppressed the rise in cytokines levels (TWEAK/IL6/myostatin) caused by HO. SAC treatment also moderated the degradation of muscle-specific proteins (MHCf) in the HO-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 HO-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.