Cordycepin exhibits anti-fatigue effect via activating TIGAR/SIRT1/PGC-1α signaling pathway

Fatigue, a most commonly sub-health condition, may cause people more susceptible to many diseases. Cordycepin, a principal active ingredient from Cordyceps militaris, exerts various pharmacological activities including anti-diabetes, anti-inflammatory, immunomodulatory and antioxidant effects. However, the anti-fatigue effect of cordycepin and specific mechanism remained unclear. This study aimed to investigate the beneficial effect of cordycepin on physical fatigue and elucidate the potential mechanism. 20 mg/kg, 40 mg/kg of cordycepin and 500 mg/kg taurine were respectively treated to mice for 28 days before weight-loaded swimming test. The results revealed that cordycepin significantly prolonged the weight-loaded swimming time of mice. Meanwhile, cordycepin decreased the levels of lactic acid, blood uric nitrogen, and malondialdehyde, and increased the contents of superoxide dismutase, glutathione, nicotinamide adenine dinucleotide phosphate, hepatic glycogen, muscle glycogen and ATP. The metabolomic study by GC-MS showed that eight biomarkers were found in livers, including L-lactic acid, L-asparagine, 3-phosphoglyceric acid, inosine, D-galactose, L-tyrosine, glyceric acid and L-threonine. There were seven biomarkers in gastrocnemius, including D-ribose-5-phosphate, acetic acid, propionic acid, butyric acid, palmitic acid, oxaloacetic acid and citric acid. The results of metabolomics indicated that cordycepin might relieve fatigue by regulating energy metabolism and pentose phosphate pathway. Furthermore, we found cordycepin significantly enhanced the protein levels of TIGAR, SIRT1, PGC-1α, NRF1 and TFAM in gastrocnemius of weight-loaded swimming mice. Taken together, the present study demonstrated that cordycepin possessed an anti-fatigue effect via activating TIGAR/SIRT1/PGC-1α signaling pathway. Our study indicated that cordycepin may be a potentially efficient candidate for fatigue.