Background: Durative exercise-induced fatigue influences muscle structure and exercise performance. Dietary supplements combining bioavailable proteins with essential vitamins and minerals may help reduce fatigue. Compared with proteins, whey peptides, as easily absorbed energy sources, are regarded as better promoting the utilization of vitamins and minerals. This study investigated whether the combination of whey peptides and micronutrients could synergistically improve exercise-induced fatigue and exercise performance. Methods: Four-week-old male C57BL/6J mice were forced to exercise using a treadmill for four weeks to evaluate the supplemental effects of whey peptides and/or micronutrients on exercise performance. Results: Compared with mice receiving whey peptides or micronutrients alone, mice receiving a combination of whey peptides and micronutrients displayed increased muscle mass, muscle fiber cross-sectional area, muscle strength, and exercise performance, including running exhausting time and swimming exhausting time. Consistent results were obtained in detecting fatigue-associated serum metabolites and markers reflecting muscle injury. To elucidate the anti-fatigue mechanisms of whey peptides and micronutrients, RNA transcriptome in the muscle tissues were analyzed. Enrichment analysis results suggest that micronutrients and/or whey protein alleviate exercise-induced fatigue, not only via reducing oxidative stress but also repressing excessive immune activation in muscle tissue, thereby decreasing the tissue injury caused by strenuous exercise. Conclusions: Overall, the current study indicates that the combination of whey peptides and micronutrients produces a synergistic effect on promoting exercise performance. Our findings provide scientific evidence for the development of novel and efficient anti-fatigue functional foods using whey peptides and micronutrients.

Background: Celastrol, a pentacyclic triterpenoid active component isolated from the root bark of the traditional medicinal plant Tripterygium wilfordii, displays significant anti-inflammatory, antioxidant, and immunomodulatory properties. However, its clinical application remains limited due to inadequate bioavailability. Methods: Regarding these issues, we innovatively developed a novel peanut cultivar (cel-peanut) enriched with celastrol through distant hybridization combined with metabolomics screening. Guided by the research concept of “natural anti-inflammatory diets for metabolic disease management”, we established a high-fat diet-induced ApoE^−/− atherosclerotic mouse model to systematically evaluate the anti-atherosclerosis effects and mechanisms of cel-peanut. Results: Our results revealed that cel-peanut significantly reduced serum levels of triglycerides (TGs) and increased high-density lipoprotein cholesterol (HDL-C). Concurrently, cel-peanut markedly decreased the atherosclerotic lesion area and enhanced collagen content within plaques. Mechanistic investigations demonstrated that cel-peanut reduced serum malondialdehyde (MDA) levels and suppressed the concentration of pro-inflammatory cytokine IL-6 in atherosclerotic lesions. Furthermore, cel-peanut promoted intestinal health by modulating the composition and functionality of gut microbiota, thereby attenuating atherosclerosis progression. Conclusions: Overall, these findings indicate that cel-peanut exerts therapeutic effects against atherosclerosis through its anti-inflammatory, antioxidant, and gut microbiota-modulating properties. This study proposes a novel nutritional intervention strategy for atherosclerosis and provides a promising adjuvant strategy for clinical atherosclerosis treatment.