Salvia plebeia R.Br. and Rosmarinic Acid Attenuate Dexamethasone-Induced Muscle Atrophy in C2C12 Myotubes

Abstract

Skeletal muscle atrophy occurs when protein degradation exceeds protein synthesis and is associated with increased circulating glucocorticoid levels. Salvia plebeia R.Br. (SPR) has been used as herbal remedy for a variety of inflammatory diseases and has various biological actions such as antioxidant and anti-inflammatory activities. However, there are no reports on the effects of SPR and its bioactive components on muscle atrophy. Herein, we investigated the anti-atrophic effect of SPR and rosmarinic acid (RosA), a major compound of SPR, on dexamethasone (DEX)-induced skeletal muscle atrophy in C2C12 myotubes. Myotubes were treated with 10 μM DEX in the presence or absence of SPR or RosA at different concentrations for 24 h and subjected to immunocytochemistry, western blot, and measurements of ROS and ATP levels. SPR and RosA increased viability and inhibited protein degradation in DEX-treated C2C12 myotubes. In addition, RosA promoted the Akt/p70S6K/mTOR pathway and reduced ROS production, and apoptosis. Furthermore, the treatment of RosA significantly recovered SOD activity, autophagy activity, mitochondrial contents, and APT levels in DEX-treated myotubes. These findings suggest that SPR and RosA may provide protective effects against DEX-induced muscle atrophy and have promising potential as a nutraceutical remedy for the treatment of muscle weakness and atrophy.

Effects of C-Peptide on Dexamethasone-Induced In Vitro and In Vivo Models as a Potential Therapeutic Agent for Muscle Atrophy

“…In numerous cell experiments related to muscle atrophy, DEX-treated C2C12 myotubes demonstrated significant decreases in cell viability, myotube diameter, MHC staining area, and fusion index due to muscle atrophy [15,16,34]. In this study, when DEX-induced atrophic C2C12 myotubes were treated with 1 nM C-peptide, increases in the MHC staining area, differentiation index, and fusion index were observed.…”

Potential of Lycii Radicis Cortex as an Ameliorative Agent for Skeletal Muscle Atrophy

“…Recently, there has been increasing attention on food ingredients, plant extracts, and their active compounds as substances promoting muscle health and preventing muscle wasting [ 31 ]. In addition, our previous studies demonstrated that natural products such as Justicia procumbens L., Salvia plebeia R.Br., and rosmarinic acid prevent dexamethasone (DEX)-induced muscle atrophy in C2C12 myotubes [ 28 , 32 ].…”

“…Additionally, recent research has indicated that Salvia plebeia R.Br. and rosmarinic acid significantly reverses the DEX-induced decrease in Akt/mTOR/p70S6K pathway activity [ 28 ]. LRCE was found to enhance the phosphorylation of Akt, mTOR, and p70S6K, which had been reduced by DEX treatment in C2C12 myotubes ( Figure 3 ).…”

“…To assess the cytotoxicity of LRCE, fully differentiated C2C12 cells were treated with LRCE in various concentrations (5,25,50, and 100 µg/mL) for 24 h at 37 • C. The results showed that LRCE at all concentrations tested did not exhibit any toxicity in C2C12 myotubes (Figure 1B). In addition, to determine the protective effects of LRCE against DEX-induced cytotoxicity, the myotubes were incubated with LRCE (5, 25, 50, and 100 µg/mL) and 10 µM DEX for 24 h at 37 • C [28]. DEX-treated myotubes exhibited a 36% reduction in viability compared to control, whereas co-treatment with 100 µg/mL LRCE and 10 µM DEX resulted in a recovery of cell viability (Figure 1C).…”

Isolation of Alkaloids from Sinomenium acutum by Centrifugal Partition Chromatography and Their Ameliorating Effects on Dexamethasone-Induced Atrophy in C2C12 Myotubes

“…Among medications, treatment with a high dosage of dexamethasone also decreases protein synthesis and increases protein degradation leading to muscle atrophy [3][4][5]. Consequently, dexamethasone-treated C2C12 myotubes are commonly employed as an in vitro model for skeletal muscle atrophy, aiding in the search for preventive agents such as resveratrol [5], rosmarinic acid from Salvia plebeia [6], chalcones from Ashitaba [7], and diphlorethohydroxycarmalol from Ishige okamurae [8].…”