Abstract
Fatigue is an increasingly prominent global health issue. Periplaneta americana glycoprotein (PAG) possesses multiple pharmacological activities including antioxidation, regulation of gut microbiota (GM) and immunity, which are highly consistent with the targets of anti-fatigue treatment. This study aimed to investigate the efficacy and mechanisms of PAG in anti-fatigue. Initially, the antioxidant activity of PAG was evaluated in vitro. Subsequently, a fatigue mouse model was established to evaluate its anti-fatigue effects in vivo. Finally, Spearman correlation analysis was conducted to explore correlations between gut microbiota shifts, short-chain fatty acid (SCFA) production, and fatigue indicators. The results showed that PAG possesses significant antioxidant activity. Furthermore, PAG alleviated fatigue through multiple pathways: it prolonged swimming time, ameliorated liver injury, increased the activities of liver glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), reduced liver malondialdehyde (MDA) levels, decreased serum blood urea nitrogen (BUN) and muscle lactic acid (LA) accumulation, inhibited serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities, promoted glycogen storage in the liver and muscles of fatigued mice, altered the composition and structure of GM, and increased SCFA levels. In conclusion, these findings demonstrate that PAG alleviates fatigue by improving oxidative stress, regulating energy metabolism, and modulating the GM-SCFA axis.