Sijunzi Decoction Regulates Adenosine Monophosphate-Activated Protein Kinase/ Forkhead Box-O-Transcription Factor 3A-Mediated Mitochondrial Dysfunction and Alleviates Dexamethasone-Induced C2C12 Myotube Muscle Atrophy

Abstract

This study aimed to investigate the regulatory functions of Sijunzi decoction on mitochondrial dysfunction in muscle atrophy progression. Cell viability was assessed using Cell Counting Kit-8 assay, and protein expressions were investigated using Western blot. The adenosine triphosphate level was measured using an adenosine triphosphate commercial kit, and the oxygen consumption rate was evaluated using the MitoXpress® Xtra oxygen consumption assay kit. Tetramethylrhodamine staining was used to quantify mitochondrial membrane potential, and C2C12 cells were treated with dexamethasone (1 μM) for 48 h to create a muscle atrophy model. We found that the decreased cell viability stimulated by dexamethasone treatment was reversed after Sijunzi treatment (50 μg/mL and 100 μg/mL). Additionally, Sijunzi treatment suppressed dexamethasone-stimulated C2C12 myotube atrophy and ameliorated dexamethasone-triggered mitochondrial dysfunction. Sijunzi treatment retarded the adenosine 5’-monophosphate-activated protein kinase/forkhead box O3 pathway. We demonstrated that Sijunzi regulates AMPK/FOXO3a-mediated mitochondrial dysfunction and alleviates DEX-induced C2C12 myotube muscle atrophy.