Muscle atrophy, which is defined as a decrease in muscle mass and strength, is caused by an imbalance between the anabolism and catabolism of
muscle proteins. Thus, modulating the homeostasis between
muscle protein synthesis and degradation represents an efficient treatment approach for this condition. In the present study, the protective effects against
muscle atrophy of
ethanol extracts of Morus alba L. (MA) and Angelica keiskei Koidz. (AK) leaves and their mixtures (MIX) were evaluated in vitro and in vivo. Our results showed that MIX increased 5-aminoimidazole-4-carboxamide
ribonucleotide-induced C2C12 myotube thinning, and enhanced soleus and gastrocnemius muscle thickness compared to each extract alone in
dexamethasone-induced
muscle atrophy Sprague Dawley rats. In addition, although MA and AK substantially improved grip strength and histological changes for
dexamethasone-induced
muscle atrophy in vivo, the efficacy was superior in the MIX-treated group. Moreover, MIX further increased the expression levels of myogenic factors (MyoD and
myogenin) and decreased the expression levels of E3
ubiquitin ligases (atrogin-1 and muscle-specific RING finger
protein-1) in vitro and in vivo compared to the MA- and AK-alone treatment groups. Furthermore, MIX increased the levels of phosphorylated
phosphoinositide 3-kinase (PI3K),
protein kinase B (Akt), and
mammalian target of rapamycin (mTOR) that were reduced by
dexamethasone, and downregulated the expression of forkhead box O3 (FoxO3a) induced by
dexamethasone. These results suggest that MIX has a protective effect against
muscle atrophy by enhancing
muscle protein anabolism through the activation of the PI3K/Akt/mTOR signaling pathway and attenuating catabolism through the inhibition of FoxO3a.