S-allyl cysteine: A potential compound against skeletal muscle atrophy

Prachi Gupta; Vikas Dutt; Nirmaljeet Kaur; Priya Kalra; Sanjeev Gupta; Anita Dua; Rajesh Dabur; Vikram Saini; Ashwani Mittal

doi:10.1016/j.bbagen.2020.129676

S-allyl cysteine: A potential compound against skeletal muscle atrophy

Biochim Biophys Acta Gen Subj. 2020 Oct;1864(10):129676. doi: 10.1016/j.bbagen.2020.129676. Epub 2020 Jul 7.

Authors

Prachi Gupta¹, Vikas Dutt¹, Nirmaljeet Kaur¹, Priya Kalra², Sanjeev Gupta¹, Anita Dua¹, Rajesh Dabur³, Vikram Saini², Ashwani Mittal⁴

Affiliations

¹ Skeletal Muscle Laboratory, Institute of Integrated and Honors Studies, Kurukshetra University, Kurukshetra, Haryana 136119, India.
² Laboratory of Infection Biology and Translational Research, Department of Biotechnology, All India Institute of Medical Sciences, New Delhi 110029, India.
³ Biochemistry Department, MD University, Rohtak, Haryana 124001, India.
⁴ Skeletal Muscle Laboratory, Institute of Integrated and Honors Studies, Kurukshetra University, Kurukshetra, Haryana 136119, India. Electronic address: mittala@kuk.ac.in.

PMID: 32649980
DOI: 10.1016/j.bbagen.2020.129676

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 H₂O₂ (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 H₂O₂. Lower levels of ROS, lipid peroxidation, oxidized glutathione and altered antioxidant enzymes were observed in H₂O₂-exposed cells upon pre-treatment with SAC. SAC supplementation also suppressed the rise in cytokines levels (TWEAK/IL6/myostatin) caused by H₂O₂. SAC treatment also moderated the degradation of muscle-specific proteins (MHCf) in the H₂O₂-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 H₂O₂-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.

Keywords: Atrophy; C2C12; Denervation; Oxidative stress; SAC; Skeletal muscle.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Cysteine / analogs & derivatives*
Cysteine / pharmacology
Cysteine / therapeutic use
Disease Models, Animal
Hydrogen Peroxide / metabolism
Mice
Muscle Fibers, Skeletal / drug effects
Muscle Fibers, Skeletal / metabolism
Muscle Fibers, Skeletal / pathology
Muscular Atrophy / drug therapy*
Muscular Atrophy / metabolism
Muscular Atrophy / pathology
Oxidative Stress / drug effects
Protective Agents / pharmacology
Protective Agents / therapeutic use*

Substances

Protective Agents
S-allylcysteine
Hydrogen Peroxide
Cysteine