Hawthorn Polyphenol Nanoparticles Alleviate Exercise‐Induced Fatigue by Modulating Energy Metabolism and the Gut Microbiome in Mice

ABSTRACT Polyphenols exert a variety of physiological effects; however, their utility is hampered by their limited bioavailability owing to their unstable nature. The bioavailability can be improved by encapsulating them in nanoparticles. In this study, hawthorn polyphenol nanoparticles (HPN) were prepared using an antisolvent method and layer‐by‐layer self‐assembly, and the effects of HPN in alleviating exercise‐induced fatigue in mice were investigated. The average size of HPN was 63.37 nm. The 1,1‐diphenyl‐2‐trinitrophenylhydrazine (DPPH) radical scavenging activity and simulated intestinal fluid retention of HPN after 6 h was 65.08% and 98.91% higher, respectively, than those of the unencapsulated form. The retention time for HPN in mice extended to 19.7 h. The time to exhaustion during swimming against gravity increased from 114 s in the model group to 225 s in the HPN group ( p < 0.05). These effects were associated with reduced levels of fatigue‐related metabolites, increased antioxidant enzyme activity, reduced hormone levels, and increased energy reserves ( p < 0.05). HPN alleviated fatigue by regulating the abundance and composition of the gut microbiota and the mRNA expression levels of AMPK , PI3K , Akt , and mTOR . In summary, this study demonstrates that HPN can achieve a sustained release of polyphenols and alleviate exercise‐induced fatigue, providing a theoretical basis for its application in functional sports foods.