Bioactive edestin peptides from hemp (Cannabis sativa L.) seeds improve exercise performance under hypobaric hypoxia

Hypobaric hypoxia is a major physiological challenge in high-altitude environments, impairing oxygen delivery and utilization, which adversely affects health and work efficiency. Functional foods could provide a practical solution. Here, edestin peptide (EPP) derived from hemp (Cannabis sativa L.) seed is considered a promising target. In this study, the extracted of edestin was verified by SDS-PAGE, and enzymatic digestion to prepare EPP. Freeze-dried EPP showed a homogeneous porous microstructure and was enriched in glutamic acid (19.13%), arginine (14.01%) and aspartic acid (13.28%), and nutritional indices supported high protein quality. Peptidomics defined the peptide composition, and particle size measurements indicated that hydrolysis resulted in smaller particles and a higher polydispersity index. Spectroscopic analyses consistently revealed hydrolysis-driven conformational remodeling toward a looser, random coil enriched state, accompanied by improved interfacial properties and strong in vitro radical scavenging capacity without detectable cytotoxicity. In mice, EPP supplementation significantly prolonged rotarod endurance approximately fourfold (p < 0.01) at 4000 m and increased hematological indices related to oxygen transport under hypobaric hypoxia. In a human trial, EPP markedly improved maximum oxygen uptake by 14.98%, reduced exercise-induced fluctuations in blood oxygen saturation and heart rate, and increased hypoxia tolerance and anti-fatigue capacity by 41.22% and 1.625 times at 3600 m, respectively. This study provides systematic evidence from characterization to animal and human trials, supporting EPP as a functional ingredient to improve hypoxia-related physiological indicators.