<i>Phlomis umbrosa</i> Turcz. Water Extract Attenuates Dexamethasone-Induced Muscle Atrophy by Regulating PI3K/Akt/mTOR Pathway

Skeletal muscles, attached to bones via tendons, enable physical movement in animals. Muscle atrophy is associated with a decline in muscle mass and function and can detrimentally impact quality of life, leading to muscle weakness, altered fiber properties, and, ultimately, sarcopenia. <i>Phlomis umbrosa</i> Turcz. (Korean name: Han-Sok-Dan) has been used as a herbal medicine in Southeast Asia since ancient times. Although several studies have explored the properties of Han-Sok-Dan, further research is warranted to establish its therapeutic benefits for muscle function. This study investigated the effects of <i>Phlomis umbrosa</i> Turcz. water extract (PUW) in mice subjected to dexamethasone-induced muscle atrophy. Mice exhibiting dexamethasone-induced muscle atrophy experienced weight loss, reduced muscle mass, and functional decline. However, PUW administration effectively reversed these effects by maintaining muscle mass and strength, decreasing protein degradation-related marker expression, and enhancing signaling for protein synthesis. Notably, phosphorylations of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase beta-1, and eukaryotic translation initiation factor 4E-binding protein 1 were significantly enhanced in the PUW group, indicating the activation of anabolic signaling. Overall, PUW alleviates muscle atrophy induced by dexamethasone by modulating the balance between protein degradation and synthesis through regulation of the ubiquitin-proteasome system and phosphoinositide 3-kinase/protein kinase B/mTOR pathway. These findings reveal the potential of PUW as a natural therapeutic agent for preventing or managing muscle wasting.