Abstract
Skeletal muscle atrophy is a common and debilitating condition that lacks an effective therapy. Oxidative stress and inflammation are two main molecular mechanisms involved in muscle atrophy. In the current study, we want to explore whether and how salidroside, with antioxidant and anti-inflammatory properties, protects against skeletal muscle atrophy induced by denervation. First, oxidative stress and inflammatory response were examined during myotube atrophy induced by nutrition deprivation. The results demonstrated that oxidative stress and inflammatory response were induced in cultured myotubes suffered from nutrition deprivation, and salidroside not only inhibited oxidative stress and inflammatory response but also attenuated nutrition deprivation-induced myotube atrophy, as evidenced by an increased myotube diameter. The antioxidant, anti-inflammatory, and antiatrophic properties of salidroside in cultured myotubes were confirmed in denervated mouse models. The mice treated with salidroside showed less oxidative stress and less inflammatory cytokines, as well as higher skeletal muscle wet weight ratio and larger average cross sectional areas of myofibers compared with those treated with saline only during denervation-induced skeletal muscle atrophy. Moreover, salidroside treatment of denervated mice resulted in an inhibition of the activation of mitophagy in skeletal muscle. Furthermore, salidroside reduced the expression of atrophic genes, including MuRF1 and MAFbx, autophagy genes, including PINK1, BNIP3, LC3B, ATG7, and Beclin1, and transcription factor forkhead box O3 A (Foxo3A), and improved the expression of myosin heavy chain and transcriptional factor phosphorylated Foxo3A. Taken together, these results suggested that salidroside alleviated denervation-induced muscle atrophy by suppressing oxidative stress and inflammation.
Highlights
Skeletal muscle is the largest tissue in the body, and loss of its function results in debilitating musculoskeletal disorders, impairing quality of life, increasing morbidity and mortality, and bringing the economic and social burden for families and communities (Chal and Pourquie, 2017; Qiu et al, 2018)
Oxidative stress and inflammation are two main molecular mechanisms involved in muscle atrophy
To evaluate whether salidroside could protect against myotube atrophy induced by nutrition deprivation, C2C12 myotubes were incubated in Hank’s balanced salt solution (HBSS) for 12 h with or without the presence of salidroside (Sal L: 40 μM, Sal M: 80 μM, Sal H: 160 μM) or NAC (5 mM), after which the C2C12 myotubes were stained with myosin heavy chain (MHC)
Summary
Skeletal muscle is the largest tissue in the body, and loss of its function results in debilitating musculoskeletal disorders, impairing quality of life, increasing morbidity and mortality, and bringing the economic and social burden for families and communities (Chal and Pourquie, 2017; Qiu et al, 2018). Growing evidences suggested that increased reactive oxygen species (ROS) production in skeletal muscles significantly induced mitochondrial dysfunction, activated forkhead box class O (FoxO) transcription factors, and contributed to inactivityinduced muscle atrophy (McClung et al, 2007; Powers et al, 2012; Matsui, 2017). Inflammation is an important pathogenic factor, which contributes to the dysfunction of skeletal muscle. It impairs muscle homeostasis and myogenesis, activates the family of FoxO transcription factors, and contributes to skeletal muscle atrophy (Costamagna et al, 2015; Milan et al, 2015). Oxidative stress and inflammation might be a potential therapeutic target against denervation-induced skeletal muscle atrophy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
