Anti-fatigue potential of glycoprotein from Periplaneta americana: improving oxidative stress and regulating the gut microbiota

Fatigue, as a complex physiological phenomenon, has emerged as a growing global health concern. Glycoproteins from Periplaneta americana (PA), a medicinal insect resource, exhibit pharmacological activities (e.g., regulating the gut microbiota (GM), antioxidation and enhancing immunity) consistent with the core therapeutic targets for anti-fatigue. This study aimed to investigate the efficacy and mechanisms of PA glycoprotein (PAG) in anti-fatigue. The antioxidant capacity of PAG was evaluated by detecting antioxidant-related indexes in simulated gastrointestinal environment. The effectiveness of PAG in anti-fatigue was verified through swimming time measurement, histological staining and biochemical index monitoring. 16S rRNA sequencing, targeted metabolomics and Spearman correlation analysis were integrated to dissect the underlying mechanism of its anti-fatigue effect. PAG has excellent antioxidant activity. Secondly, PAG exerts anti-fatigue effects through multiple mechanisms: prolonged swimming time, improved liver injury, increased glutathione peroxidase and superoxide dismutase activities, decreased malondialdehyde level, promoted glycogen storage, simultaneously inhibited lactate dehydrogenase and creatine kinase activities, and reduced blood urea nitrogen and lactate accumulation in fatigued mice, altered the composition and structure of GM, and increased short-chain fatty acids (SCFAs) content. In conclusion, these findings suggest that PAG is promising candidates for anti-fatigue, and it warrants further systematic investigation for clinical translation.