Abstract
Skeletal muscle atrophy is associated with pro-inflammatory cytokines. Salidroside is a biologically active ingredient of Rhodiola rosea, which exhibits anti-inflammatory property. However, there is little known about the effect of salidroside on denervation-induced muscle atrophy. Therefore, the present study aimed to determine whether salidroside could protect against denervation-induced muscle atrophy and to clarify potential molecular mechanisms. Denervation caused progressive accumulation of inflammatory factors in skeletal muscle, especially interleukin 6 (IL6) and its receptor, and recombinant murine IL6 (rmIL6) local infusion could induce target muscle atrophy, suggesting that denervation induced inflammation in target muscles and the inflammation may trigger muscle wasting. Salidroside alleviated denervation-induced muscle atrophy and inhibited the production of IL6. Furthermore, the inhibition of phosphorylation of signal transducer and activator of transcription 3 (STAT3), and the decreased levels of suppressor of cytokine signaling (SOCS3), muscle RING finger protein-1 (MuRF1), atrophy F-box (atrogin-1), microtubule-associated protein light chain 3 beta (LC3B) and PTEN-induced putative kinase (PINK1) were observed in denervated muscles that were treated with salidroside. Finally, all of these responses to salidroside were replicated in neutralizing antibody against IL6. Taken together, these results suggest that salidroside alleviates denervation-induced inflammation response, thereby inhibits muscle proteolysis and muscle atrophy. Therefore, it was assumed that salidroside might be a potential therapeutic candidate to prevent muscle wasting.
Highlights
Skeletal muscle is a very important organ, which maintains many important functions, such as body movement, breathing, and glucose homeostasis (Powers et al, 2016; Qiu et al, 2018), and it is a plastic organ that is maintained according to physiological and pathological conditions
Skeletal muscle homeostasis is maintained by the equilibrium of physical and functional interactions between myofibres and muscle microenvironment, which includes muscle stem cells, motoneurons, interstitial cells and a variety of secretory factors (Madaro et al, 2018)
Can we prevent muscle atrophy from protecting muscle microenvironment? To our knowledge, the current study is the first one to demonstrate that salidroside could improve muscle microenvironment to attenuate the skeletal muscle atrophy induced by denervation in adult rats
Summary
Skeletal muscle is a very important organ, which maintains many important functions, such as body movement, breathing, and glucose homeostasis (Powers et al, 2016; Qiu et al, 2018), and it is a plastic organ that is maintained according to physiological and pathological conditions. Inflammatory cytokines, important components of muscle microenvironment, such as tumor necrosis factor alpha (TNFα) and interleukin-6 (IL6) are important mediators of catabolic responses such as protein proteolysis (Le et al, 2014; Costamagna et al, 2015; Londhe and Guttridge, 2015; Ma et al, 2018). Muscle wasting, accompanied by excessive protein breakdown, can be prevented by treating tumor-bearing animals with antibodies against pro-inflammatory cytokines (Strassmann et al, 1993). The role of pro-inflammatory cytokines in denervation-induced muscle atrophy remained unclear. A variety of pro-inflammatory cytokines were observed in muscles after denervation, which might play crucial role in muscle atrophy. Given that inflammation exacerbates muscle atrophy, therapeutic drugs or countermeasures that suppress skeletal muscle inflammation and improve muscle microenvironment might be useful for preventing denervation-induced skeletal muscle atrophy
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