S-allyl cysteine inhibits TNFα-induced skeletal muscle wasting through suppressing proteolysis and expression of inflammatory molecules.

Elevated levels of inflammatory molecules are key players in muscle wasting/atrophy leading to human morbidity. TNFα is a well-known pro-inflammatory cytokine implicated in the pathogenesis of muscle wasting under diverse clinical settings. S-allyl cysteine (SAC), an active component of garlic (Allium sativum), has established anti-oxidant and anti-inflammatory effects in various cell types. However, the impact of SAC on skeletal muscle pathology remains unexplored. Owing to the known anti-inflammatory properties of SAC, we investigated whether pre-treatment with SAC has a protective role in TNFα-induced atrophy in cultured myotubes.

C2C12 myotubes were treated with TNFα (100ng/ml) in the presence or absence of SAC (0.01mM). TNFα treatment induced atrophy in myotubes by up-regulating various proteolytic systems i.e. cathepsin L, calpain, ubiquitin-proteasome E3-ligases (MuRF1/atrogin1), caspase 3 and autophagy (Beclin1/LC3B). TNFα also induced the activation of NFκB by stimulating the degradation of IκBα (inhibitor of NFκB), in myotubes. The alterations in proteolytic systems likely contribute to the degradation of muscle-specific proteins and reduce the myotube length, diameter and fusion index. The SAC supplementation significantly impedes TNFα-induced protein loss and protects myotube morphology by suppressing protein catabolic systems and endogenous level of inflammatory molecules namely TNFα, IL-6, IL-1β, TNF-like weak inducer of apoptosis (TWEAK), fibroblast growth factor-inducible 14 (Fn14) and Nox.

Our findings reveal anti-atrophic role for SAC, as it prevents alterations in protein metabolism and protects myotubes by regulating the level of inflammatory molecules and multiple proteolytic systems responsible for muscle atrophy.