Bioactive peptides from Morchella importuna: antioxidant and anti-fatigue activities through Nrf2/ARE and AMPK/PGC-1α pathway activation

Morchella is recognized as a valuable source of bioactive peptides due to its high protein content. In this study, bioactive peptides were produced from Morchella importuna protein through an optimized hydrolysis process. The peptides were subsequently purified using DEAE-32 ion exchange chromatography and Sephadex G-25 gel filtration, with the G3 fraction demonstrating the highest antioxidant activity. Peptide sequencing via HPLC-MS/MS identified key bioactive peptides, including RVDWEF, VDWEFT, VDWE, and DWEFT. In mouse fatigue model, administration of medium (500 mg/kg body weight/day) and high (1000 mg/kg body weight/day) doses of G3 significantly enhanced swimming and climbing endurance, alleviated liver and muscle injury, increased energy availability, reduced serum metabolites, and elevated antioxidant enzyme activities. Mechanistic investigations revealed that G3 activated the Nrf2/ARE and AMPK/PGC-1α signaling pathways, leading to a reduction in oxidative stress and inflammation while promoting mitochondrial function. Furthermore, correlation analysis showed that the abundance of G3-derived peptides was significantly associated with key biological indicators—including antioxidant enzymes, metabolic markers, and cytokines—supporting the proposed multi-target effects of the peptides. These findings suggested that Morchella importuna peptide G3 mitigates fatigue and improves exercise performance by attenuating oxidative stress and inflammation and enhancing energy metabolism in mice.