Protein Hydrolysate from Spirulina platensis Prevents Dexamethasone-Induced Muscle Atrophy via Akt/Foxo3 Signaling in C2C12 Myotubes

Loss of muscle mass is the primary symptom of sarcopenia. Protein intake is recommended to prevent muscle mass loss, and Spirulina platensis, a microalga with high protein content, is a potential protein supplement. Here, we evaluated the differentiation ability of C2C12 cells and the inhibitory effect of Spirulina hydrolysates (SPH) prepared by Collupulin on dexamethasone (DEX)-treated C2C12 cells. SPH contained 578.27 mg/g protein and 92.30 mg/g branched-chain amino acids. SPH increased C2C12 myotube length and diameter, likely owing to increased MyoD1 and Myf5 expression. Inhibition of increased Atrogin-1, MuRF-1, and FoxO3 expression by SPH in DEX-treated C2C12 cells suppressed DEX-induced muscle atrophy. Moreover, SPH inhibited the DEX-induced increase in cytosolic p-Akt protein expression and suppressed the increase in nuclear FoxO3a protein expression, thereby suppressing the increase in the protein expression of the ubiquitin-proteasome-related factors Atrogin-1 and MuRF-1, which are involved in muscle atrophy. SPH suppressed DEX-induced muscle atrophy by activating the Akt/FoxO3a pathway. SPH promoted C2C12 myoblast differentiation into myotubes and inhibited DEX-induced myotube atrophy by suppressing Atrogin-1 and MuRF-1 expression and regulating the FoxO3a transcription factor. Collectively, SPH can be used as a functional food to inhibit muscle atrophy and promote muscle regeneration.