Protective Effects of an Allithiamine Garlic Complex Against Forced Swimming-Induced Fatigue in Mice: Potential Roles of Oxidative Stress and Energy Metabolism

Background/Objectives: Fatigue results from prolonged physical exertion and is characterized by declining physical performance. This study assessed anti-fatigue potential of an allithiamine garlic complex (AGC) in a mouse model of forced swimming-induced fatigue. Methods: Male ICR mice were assigned to five groups (n = 8 per group)—sedentary control (normal control), forced swimming test control (FST-C), FST + AGC at 100 mg/kg (AGC100), FST + AGC at 500 mg/kg (AGC500), and FST + red ginseng at 500 mg/kg (positive control, PC). Fatigue was induced by forced swimming (15 min/day) for 1 week, after which the treatments were administered orally once daily for 7 days. On days 0 and 7, weight-loaded FSTs (5% of body weight) were conducted to measure immobility time, and mice were euthanized on day 7 for biochemical analysis (serum, liver, and gastrocnemius muscle). Results: On day 7, both AGC doses significantly reduced immobility time compared with the FST-C group, and immobility time in the AGC500 group did not differ significantly from that in the PC group. AGC significantly reduced serum lactate, free fatty acids, and ammonia levels, whereas decreases in lactate dehydrogenase, creatine kinase, and blood urea nitrogen were not statistically significant. AGC increased glycogen content in the liver and skeletal muscle. AGC upregulated the protein expression of phosphorylated adenosine monophosphate-activated protein kinase (AMPK), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in the skeletal muscle, suggesting an association with AMPK/SIRT1/PGC-1α signaling. AGC treatment reduced malondialdehyde levels and increased superoxide dismutase activity relative to the FST-C group. Conclusions: Collectively, these findings demonstrated that AGC enhances exercise endurance and alleviates fatigue by activating the AMPK/PGC-1α signaling pathway, indicating its potential as a functional ingredient for mitigating high-intensity exercise-induced fatigue.