Abstract
Skeletal muscle atrophy is defined as wasting or loss of muscle. Although glucocorticoids (GCs) are well-known anti-inflammatory drugs, their long-term or high-dose use induces skeletal muscle atrophy. Valeriana fauriei (VF) is used to treat restlessness, anxiety, and sleep disorders; however, its effects on skeletal muscle health have not been investigated. This study investigated whether Valeriana fauriei could ameliorate muscle atrophy. We induced muscle atrophy in vitro and in vivo, by treatment with dexamethasone (DEX), a synthetic GC. In DEX-induced myotube atrophy, Valeriana fauriei treatment increased the fusion index and decreased the expression of muscle atrophic genes such as muscle atrophy F-box (MAFbx/Atrogin-1) and muscle RING-finger protein 1 (MuRF1). In DEX-treated mice with muscle atrophy, Valeriana fauriei supplementation increased the ability to exercise, muscle weight, and cross-sectional area, whereas it inhibited myosin heavy chain isoform transition and the expression of muscle atrophy biomarkers. Valeriana fauriei treatment led to via the downregulation of muscle atrophic genes via inhibition of GC receptor translocation. Valeriana fauriei was also found to act as a reactive oxygen species (ROS) scavenger. Didrovaltrate (DI), an iridoid compound from Valeriana fauriei, was found to downregulate atrophic genes and decrease ROS in the DEX-induced myotube atrophy. Consolidated, our results indicate that Valeriana fauriei prevents DEX-induced muscle atrophy by inhibiting GC receptor translocation. Further, Valeriana fauriei acts as a ROS scavenger, and its functional compound is didrovaltrate. We suggest that Valeriana fauriei and its functional compound didrovaltrate possess therapeutic potentials against muscle atrophy.
Highlights
Skeletal muscle is an important component of the body and is closely related to metabolism and locomotion
5 μM DEX treatment significantly induced reactive oxygen species (ROS) to 1.4-fold in C2C12 cells compared to that in the untreated control, whereas cotreatment with 1 μg/ mL or 2.5 μg/mL of Valeriana fauriei (VF) was found to suppress ROS (P < 0:05 or P < 0:01) (Figures 2(f) and 2(g)). These results suggest that VF possesses ROS scavenging activity and reduces DEX-induced oxidative stress in C2C12 myoblasts
VF prevented GC Receptor (GR) translocation and FOXO3a activation in C2C12 myotubes and C57BL/6 mice. These results showed that VF inhibited DEX-induced muscle atrophy by preventing DEX/GR/FOXO3a/Atrogin-1 and muscle RING-finger protein 1 (MuRF1) cascade
Summary
Skeletal muscle is an important component of the body and is closely related to metabolism and locomotion. Proteostasis, maintains the balance between protein degradation and protein synthesis. Loss of this homeostasis is associated with protein misfolding and diseases [4]. The loss of homeostasis refers to the imbalance between protein degradation and protein synthesis and causes skeletal muscle loss. Protein degradation is accelerated by the ubiquitin-proteasome system (UPS), a major intracellular proteolysis system [1]. E1 activates the ubiquitin-protein and transfers it to one of several ubiquitin-conjugating enzymes, E2s. E3 conjugates ubiquitin covalently to the substrate, which is a target for degradation. The substrate accumulates poly-ubiquitin, and the ubiquitinated protein is degraded by the 26S proteasome [5].
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