Exercise Performance In Mice Research Articles

Improved skeletal muscle mass and strength through Protamex-mediated hydrolysis of perilla seed cake: Elevated rosmarinic acid levels as a contributing factor

Perilla seed cake (PSC) is a byproduct of oil extraction from perilla seeds. It is rich in proteins and bioactive compounds. PSC was enzymatically hydrolyzed to form PSC hydrolysate (PSCH) to enhance the absorption of PSC, and their effects on muscle health in mice were compared. High performance liquid chromatography-tandem mass spectrometry analysis revealed that PSC contains several polyphenols, including rosmarinic acid (RA), caffeic acid, apigenin, and luteolin. The hydrolysate showed 1.44- and 7.04-fold increases in RA and caffeic acid contents, respectively, compared to those of PSC. The intake of PSC, PSCH, and RA significantly improved muscle mass and exercise performance in mice by upregulating protein synthesis, myogenic differentiation, oxidative muscle fiber formation, fatty acid oxidation, and mitochondrial biogenesis; however, PSCH had better promoting effects than PSC. In conclusion, PSCH improves muscle health through its bioactive compounds (particularly RA), indicating the potential of PSCH and RA in functional foods.

Gut microbiota‐directed dietary factors enhance exercise performance in mice

AbstractThis study investigated the effect of dietary interventions targeting gut microbiota on exercise performance in mice. Analysis of the gut microbiota of individuals with varying levels of physical activity revealed enrichment of Eubacterium rectale and Faecalibacterium prausnitzii in the active population. Through in vitro fecal fermentation experiments, dietary factor combinations that promote the abundance of these bacteria were identified. Dietary interventions, including E. rectale supplementation, FAG combination (gavage of Fructus Arctii extract, Agaricus blazei Murrill polysaccharides, and galactooligosaccharides mixture), and CFG combination (gavage of curcumin, Fructus Arctii extract, and galactooligosaccharides mixture), significantly improved mouse exercise performance, increased glycogen accumulation, regulated serum biochemical parameters, and increased short‐chain fatty acid and fatty acid amide levels in feces. Metagenomic sequencing revealed alterations in the composition of the gut microbiota. Fecal metabolome analysis highlighted changes in metabolites related to lipids, organic acids, nucleic acids, and carbohydrates. These findings suggest that E. rectale and dietary interventions positively affect exercise performance by modulating the gut microbiota and associated metabolites.

Effects of Trimethylamine N-Oxide in Improving Exercise Performance in Mice: A 1H-NMR-Based Metabolomic Analysis Approach.

To improve exercise performance, the supplement of nutrients has become a common practice before prolonged exercise. Trimethylamine N-oxide (TMAO) has been shown to ameliorate oxidative stress damage, which may be beneficial in improving exercise capacity. Here, we assessed the effects of TMAO on mice with exhaustive swimming, analyzed the metabolic changes, and identified significantly altered metabolic pathways of skeletal muscle using a nuclear magnetic resonance-based (NMR-based) metabolomics approach to uncover the effects of TMAO improving exercise performance of mice. We found that TMAO pre-administration markedly prolonged the exhaustive time in mice. Further investigation showed that TMAO pre-administration increased levels of 3-hydroxybutyrate, isocitrate, anserine, TMA, taurine, glycine, and glutathione and disturbed the three metabolic pathways related to oxidative stress and protein synthesis in skeletal muscle. Our results provide a metabolic mechanistic understanding of the effects of TMAO supplements on the exercise performance of skeletal muscle in mice. This work may be beneficial in exploring the potential of TMAO to be applied in nutritional supplementation to improve exercise performance. This work will lay a scientific foundation and be beneficial to exploring the potential of TMAO to apply in nutritional supplementation.

MicroRNA-1 Regulates Metabolic Flexibility in Skeletal Muscle via Pyruvate Metabolism.

MicroRNA-1 (miR-1) is the most abundant miRNA in adult skeletal muscle. To determine the function of miR-1 in adult skeletal muscle, we generated an inducible, skeletal muscle-specific miR-1 knockout (KO) mouse. Integration of RNA-sequencing (RNA-seq) data from miR-1 KO muscle with Argonaute 2 enhanced crosslinking and immunoprecipitation sequencing (AGO2 eCLIP-seq) from human skeletal muscle identified miR-1 target genes involved with glycolysis and pyruvate metabolism. The loss of miR-1 in skeletal muscle induced cancer-like metabolic reprogramming, as shown by higher pyruvate kinase muscle isozyme M2 (PKM2) protein levels, which promoted glycolysis. Comprehensive bioenergetic and metabolic phenotyping combined with skeletal muscle proteomics and metabolomics further demonstrated that miR-1 KO induced metabolic inflexibility as a result of pyruvate oxidation resistance. While the genetic loss of miR-1 reduced endurance exercise performance in mice and in C. elegans, the physiological down-regulation of miR-1 expression in response to a hypertrophic stimulus in both humans and mice causes a similar metabolic reprogramming that supports muscle cell growth. Taken together, these data identify a novel post-translational mechanism of adult skeletal muscle metabolism regulation mediated by miR-1.

Endothelin-1 impairs skeletal muscle myogenesis and development via ETB receptors and p38 MAPK signaling pathway.

Myopenia is a condition marked by progressive decline of muscle mass and strength and is associated with aging or obesity. It poses the risk of falling, with potential bone fractures, thereby also increasing the burden on family and society. Skeletal muscle wasting is characterized by a reduced number of myoblasts, impaired muscle regeneration and increased muscle atrophy markers (Atrogin-1, MuRF-1). Endotheline-1 (ET-1) is a potent vasoconstrictor peptide. Increased circulating levels of ET-1 is noted with aging and is associated with muscular fibrosis and decline of strength. However, the regulatory mechanism controlling its effect on myogenesis and atrophy remains unknown. In the present study, the effects of ET-1 on myoblast proliferation, differentiation and development were investigated in C2C12 cells and in ET-1-infused mice. The results show that ET-1, acting via ETB receptors, reduced insulin-stimulated cell proliferation, and also reduced MyoD, MyoG and MyHC expression in the differentiation processes of C2C12 myoblasts. ET-1 inhibited myoblast differentiation through ETB receptors and the p38 mitogen-activated protein kinase (MAPK)-dependent pathway. Additionally, ET-1 decreased MyHC expression in differentiated myotubes. Inhibition of proteasome activity by MG132 ameliorated the ET-1-stimulated protein degradation in differentiated C2C12 myotubes. Furthermore, chronic ET-1 infusion caused skeletal muscle atrophy and impaired exercise performance in mice. In conclusion, ET-1 inhibits insulin-induced cell proliferation, impairs myogenesis and induces muscle atrophy via ETB receptors and the p38 MAPK-dependent pathway.

Effects of exercise training with intermittent hyperoxic intervention on endurance performance and muscle metabolic properties in male mice.

This study aimed to investigate how intermittent hyperoxic exposure (three cycles of 21% O2 [10 min] and 30% O2 [15 min]) affects exercise performance in mice. Three hours after the acute exposure, there was an observed increase in mRNA levels of phosphofructokinase (Bayes factor [BF] ≥ 10), mitochondrial transcription factor-A (BF ≥10), PPAR-α (BF ≥3), and PPAR-γ (BF ≥3) in the red gastrocnemius muscle (Gr). Four weeks of exercise training under intermittent (INT), but not continuous (HYP), hyperoxia significantly (BF ≥30) increased maximal exercise capacity compared to normoxic exercise-trained (ET) group. INT group exhibited significantly higher activity levels of 3-hydroxyacyl-CoA-dehydrogenase (HAD) in Gr (BF = 7.9) compared to ET group. Pyruvate dehydrogenase complex activity levels were significantly higher in INT group compared to ET group in white gastrocnemius, diaphragm, and left ventricle (BF ≥3). NT-PGC1α protein levels in Gr (BF = 7.7) and HAD activity levels in Gr (BF = 6.9) and soleus muscles (BF = 3.3) showed a significant positive correlation with maximal work values. These findings suggest that exercise training under intermittent hyperoxia is a beneficial strategy for enhancing endurance performance by improving fatty acid and pyruvic acid utilization.

The role of brown adipose tissue in mediating healthful longevity.

There are two major subtypes of adipose tissue, i.e., white adipose tissue (WAT) and brown adipose tissue (BAT). It has been known for a long time that WAT mediates obesity and impairs healthful longevity. More recently, interest has focused on BAT, which, unlike WAT, actually augments healthful aging. The goal of this review is to examine the role of BAT in mediating healthful longevity. A major role for BAT and its related beige adipose tissue is thermogenesis, as a mechanism to maintain body temperature by producing heat through uncoupling protein 1 (UCP1) or through UCP1-independent thermogenic pathways. Our hypothesis is that healthful longevity is, in part, mediated by BAT. BAT protects against the major causes of impaired healthful longevity, i.e., obesity, diabetes, cardiovascular disorders, cancer, Alzheimer's disease, reduced exercise tolerance, and impaired blood flow. Several genetically engineered mouse models have shown that BAT enhances healthful aging and that their BAT is more potent than wild-type (WT) BAT. For example, when BAT, which increases longevity and exercise performance in mice with disruption of the regulator of G protein signaling 14 (RGS14), is transplanted to WT mice, their exercise capacity is enhanced at 3 days after BAT transplantation, whereas BAT transplantation from WT to WT mice also resulted in increased exercise performance, but only at 8 weeks after transplantation. In view of the ability of BAT to mediate healthful longevity, it is likely that a pharmaceutical analog of BAT will become a novel therapeutic modality.

Comparison of Ginseng Leaf Extract and Its Acid-Treated Form, UG0712 Between Their Effects on Exercise Performance in Mice

Comparison of Ginseng Leaf Extract and Its Acid-Treated Form, UG0712 Between Their Effects on Exercise Performance in Mice

Exercise performance is not improved in mice with skeletal muscle deletion of natriuretic peptide clearance receptor.

Natriuretic peptides (NP), including atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP), play essential roles in regulating blood pressure, cardiovascular homeostasis, and systemic metabolism. One of the major metabolic effects of NP is manifested by their capacity to stimulate lipolysis and the thermogenesis gene program in adipocytes, however, in skeletal muscle their effects on metabolism and muscle function are not as well understood. There are three NP receptors (NPR): NPRA, NPRB, and NPRC, and all three NPR genes are expressed in skeletal muscle and C2C12 myocytes. In C2C12 myocytes treatment with either ANP, BNP, or CNP evokes the cGMP signaling pathway. Since NPRC functions as a clearance receptor and the amount of NPRC in a cell type determines the signaling strength of NPs, we generated a genetic model with Nprc gene deletion in skeletal muscle and tested whether enhancing NP signaling by preventing its clearance in skeletal muscle would improve exercise performance in mice. Under sedentary conditions, Nprc skeletal muscle knockout (MKO) mice showed comparable exercise performance to their floxed littermates in terms of maximal running velocity and total endurance running time. Eight weeks of voluntary running-wheel training in a young cohort significantly increased exercise performance, but no significant differences were observed in MKO compared with floxed control mice. Furthermore, 6-weeks of treadmill training in a relatively aged cohort also increased exercise performance compared with their baseline values, but again there were no differences between genotypes. In summary, our study suggests that NP signaling is potentially important in skeletal myocytes but its function in skeletal muscle in vivo needs to be further studied in additional physiological conditions or with new genetic mouse models.

Novel herbal beverage ameliorates exercise-induced fatigue in mice by modulating oxidative stress and reshaping the gut microbiota

With the demands of enhancing exercise performance, dietary supplements are widely used in the health management of athletes and who engaged in strenuous exercise. Based on the list of edible and medicinal materials approved by China's National Health Commission, we composed an herbal beverage formula named SRB, initially identified its chemical composition, and clarified its preventive effect on exercise-induced fatigue (EIF). SRB supplementation for four weeks significantly enhanced exercise performance in mice, as reflected by exhaustive swimming test and treadmill exercise test. In mice that underwent one single exhaustive exercise, SRB supplementation markedly reduced metabolite accumulation, increased glycogen contents in the liver and muscle, promoted anti-oxidative enzyme activities, decreased hepatic malondialdehyde (MDA) level, and protected quadriceps femoris morphology, respectively. Anti-oxidative stress effect of SRB may be relevant with increased gene expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2) and antioxidant response element (ARE)-dependent gene. Moreover, SRB treatment altered gut bacterial community structure, e.g., increased the relative abundance of short-chain fatty acids (SCFAs)-producing bacteria and decreased the relative abundance of sulfate-reducing bacteria. Altogether, we identified SRB as an effective anti-EIF dietary supplement with prebiotic effects in C57BL/6 mice.

Cysteine-cysteine Chemokine Receptor Type 5 Plays a Critical Role in Exercise Performance by Regulating Mitochondrial Content in Skeletal Muscle.

Cysteine-cysteine chemokine receptor type 5 (CCR5) is thought to play an important role in the trafficking of lymphoid cells but has recently also been associated with AMPK signaling pathways that are implicated in energy metabolism in skeletal muscle. We hypothesized that genetic deletions of CCR5 would alter mitochondria content and exercise performance in mice. CCR5-/- and wild-type mice with the same genetic background were subjected to endurance exercise and grip strength tests. The soleus muscle was stained with immunofluorescence for myosin heavy chain 7 (MYH7) and succinate dehydrogenase (SDH) analysis as well as the expression of genes associated with muscle atrophy and mitochondrial oxidative phosphorylation were measured using qPCR. Although there were no differences in the weight of the soleus muscle between the CCR5-/- group and the wild-type mice, the CCR5-/- mice showed the following muscular dysfunctions: (i) decreased MYH7 percentage and cross-section area, (ii) higher myostatin and atrogin-1 mRNA levels, (iii) dropped expression of mitochondrial DNA-encoded electron respiratory chain genes (cytochrome B, cytochrome c oxidase subunit III, and ATP synthase subunit 6) as well as mitochondrial generation genes (PPARγandPGC-1α), and (iv) lower SDH activity and exercise performance when compared with wild-type mice. In addition, genes associated with mitochondrial biogenesis (PGC-1α, PPARγ, and MFN2) and mitochondrial complex (ND4 and Cytb) were upregulated when the skeletal muscle cell line C2C12 was exposed to cysteine-cysteine chemokine ligand 4 (a ligand of CCR5) in vitro. These findings suggested that attenuation of endurance exercise performance is related to the loss of mitochondrial content and lower SDH activity of soleus muscle in CCR5 knockout mice. The present study provides evidence indicating that the chemokine receptor CCR5 might modulate the skeletal muscle metabolic energy system during exercise.

Arctigenin derivatives improve exercise performance in mice: synthesis and biological evaluation.

Arctigenin (ARG) has potent antifatigue activity, but its clinical application has been restricted for its poor water solubility. In this study, seven ARG derivatives containing different amino acids coupled via an ethoxy linker were synthesized, and tested for their solubility, as well as activities to improve exercise performance in mice. All of the derivatives showed improved solubility compared to that of ARG. Derivative Z-A-6 exhibited the highest activity, showing that the mice ran a 4.88-fold greater distance in the running wheel test and swam a 2.86-fold greater time in the swimming test than those in the blank control group. Z-A-6 treatment increased the plasma superoxide dismutase and catalase concentrations as well as reduced lactic acid and blood urea nitrogen accumulation during exercise. Z-A-6 treatment enhanced the phosphorylation of adenosine monophosphate-activated protein kinase, and no acute toxicity was observed. The results will contribute to the development of potential antifatigue agents.

Bacteroides uniformis and its preferred substrate, α-cyclodextrin, enhance endurance exercise performance in mice and human males.

Although gut microbiota has been linked to exercise, whether alterations in the abundance of specific bacteria improve exercise performance remains ambiguous. In a cross-sectional study involving 25 male long-distance runners, we found a correlation between Bacteroides uniformis abundance in feces and the 3000-m race time. In addition, we administered flaxseed lignan or α-cyclodextrin as a test tablet to healthy, active males who regularly exercised in a randomized, double-blind, placebo-controlled study to increase B. uniformis in the gut (UMIN000033748). The results indicated that α-cyclodextrin supplementation improved human endurance exercise performance. Moreover, B. uniformis administration in mice increased swimming time to exhaustion, cecal short-chain fatty acid concentrations, and the gene expression of enzymes associated with gluconeogenesis in the liver while decreasing hepatic glycogen content. These findings indicate that B. uniformis enhances endurance exercise performance, which may be mediated by facilitating hepatic endogenous glucose production.

A FRET-based respirasome assembly screen identifies spleen tyrosine kinase as a target to improve muscle mitochondrial respiration and exercise performance in mice

Aerobic muscle activities predominantly depend on fuel energy supply by mitochondrial respiration, thus, mitochondrial activity enhancement may become a therapeutic intervention for muscle disturbances. The assembly of mitochondrial respiratory complexes into higher-order “supercomplex” structures has been proposed to be an efficient biological process for energy synthesis, although there is controversy in its physiological relevance. We here established Förster resonance energy transfer (FRET) phenomenon-based live imaging of mitochondrial respiratory complexes I and IV interactions using murine myoblastic cells, whose signals represent in vivo supercomplex assembly of complexes I, III, and IV, or respirasomes. The live FRET signals were well correlated with supercomplex assembly observed by blue native polyacrylamide gel electrophoresis (BN-PAGE) and oxygen consumption rates. FRET-based live cell screen defined that the inhibition of spleen tyrosine kinase (SYK), a non-receptor protein tyrosine kinase that belongs to the SYK/ zeta-chain-associated protein kinase 70 (ZAP-70) family, leads to an increase in supercomplex assembly in murine myoblastic cells. In parallel, SYK inhibition enhanced mitochondrial respiration in the cells. Notably, SYK inhibitor administration enhances exercise performance in mice. Overall, this study proves the feasibility of FRET-based respirasome assembly assay, which recapitulates in vivo mitochondrial respiration activities.

The effect of fermented wheat protein hydrolysate on the exercise performance in mice

Backgrouds. Fermented wheat protein hydrolysate (FWPH) is obtained by lightly hydrolysing wheat protein and then fermented using lactic acid bacteria (LAB). Protein supplementation could stimulate muscle protein synthesis and alleviate fatigue. The objectives of this study were to assess the effects of fermented wheat protein hydrolysate (FWPH) on the capacity of exercise and intestinal flora composition in mice. The results showed that FWPH can improve the ability of anti-fatigue by decresing creatine kinase activity, blood urea nitrogen, and lactic acid levels and increasing liver and muscle glycogen. The consequence of by prolonged exhausted swimming time, enhanced the histology of muscle tissue and increased the MyoG (50.01%) and MYOD1 (32.12%) expression indicated that the administration of FWPH were conducive to exercise performance. And the FWPH could cause significant changes on the phylum Actinobacteria and Proteobacteria and genus Faecalibaculum and Turicibacter in the intestinal flora, compared with casein (NC), whey potein (WP). Our research indicated that the supplementation of FWPH could aid in overcoming physical fatigue, improving the capacity of exercise and alter the intestinal flora composition.

Lactobacillus plantarum PL-02 Supplementation Combined With Resistance Training Improved Muscle Mass, Force, and Exercise Performance in Mice.

Increasing numbers of researchers are investigating the benefits of probiotics in enhancing exercise performance and verifying the role of the gut–muscle axis. In our previous study, Lactobacillus plantarum PL-02 improved exercise performance and muscle mass. Therefore, the purpose of this study was to investigate whether supplementation with PL-02 combined with resistance training has a synergistic effect on exercise performance and muscle mass. All the animals were assigned into four groups (n = 8/group): a sedentary control with normal distilled water group (vehicle, n = 8); PL-02 supplementation group (PL-02, 2.05 × 109 CFU, n = 8); resistance training group (RT, n = 8); PL-02 supplementation combined with resistance training group (PL-02 + RT, 2.05 × 109 CFU, n = 8). Supplementation with PL-02 for four consecutive weeks combined with resistance exercise training significantly improved the grip strength and the maximum number of crawls; increased the time of exhaustive exercise; significantly reduced the time required for a single climb; and reduced the lactate, blood ammonia, creatine kinase, and blood urea nitrogen produced after exercise (p < 0.05). In addition, it produced substantial benefits for increasing muscle mass without causing any physical damage. In summary, our findings confirmed that PL-02 or RT supplementation alone is effective in improving muscle mass and exercise performance and in reducing exercise fatigue, but the combination of the two can achieve increased benefits.

Sirt6 reprograms myofibers to oxidative type through CREB-dependent Sox6 suppression

Expanding the exercise capacity of skeletal muscle is an emerging strategy to combat obesity-related metabolic diseases and this can be achieved by shifting skeletal muscle fibers toward slow-twitch oxidative type. Here, we report that Sirt6, an anti-aging histone deacetylase, is critical in regulating myofiber configuration toward oxidative type and that Sirt6 activator can be an exercise mimetic. Genetic inactivation of Sirt6 in skeletal muscle reduced while its transgenic overexpression increased mitochondrial oxidative capacity and exercise performance in mice. Mechanistically, we show that Sirt6 downregulated Sox6, a key repressor of slow fiber specific gene, by increasing the transcription of CREB. Sirt6 expression is elevated in chronically exercised humans, and mice treated with an activator of Sirt6 showed an increase in exercise endurance as compared to exercise-trained controls. Thus, the current study identifies Sirt6 as a molecular target for reprogramming myofiber composition toward the oxidative type and for improving muscle performance.

Anti-fatigue activity of Brassica rapa L. extract and correlation among biochemical changes in forced swimming mice

Brassica rapa L. is an edible and medical plant in China used for treating various diseases, especially in the Tibet region. In this study, the chemical constituents of Brassica rapa L. extract (BE) was clarified by UHPLC-MS and anti-fatigue ability of BE was assessed through the behavior test and weight-loaded forced swimming test in mice. Then we determined several biochemical parameters related to fatigue to explore possible reasons. Results indicate that BE could significantly enhance exercise performance in mice, and there was a significant improvement in both grip-strength and the time on rota-rods. Meanwhile, BE showed significant anti-fatigue effects by decreasing the blood lactic acid (BLA), blood urea nitrogen (BUN), and creatine kinase (CK) levels and increasing the lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels. Increases in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were observed and reactive oxygen species (ROS) levels was regulated. Liver and muscle glycogen levels and adenosine triphosphate (ATP) levels were also significantly increased. Pearson correlation analysis indicates that fatigue-related indexes including metabolites and energy-related indexes were significantly correlated with antioxidant levels. In conclusion, BE possesses remarkable anti-fatigue activity, thereby shows great potential for improving exercise performance and alleviating physical fatigue and can be considered as a functional food supplement for further development.

The Effect of Hot Water Extract of Tilapia on Exercise Capacity in Mice

Tilapia (Oreochromis mossambicus) has become one of the main aquatic products of Taiwan. The aim of this study was to evaluate the efficacy of a hot water extract of tilapia (HWET) in relieving fatigue and enhancing exercise performance in mice in a swimming endurance test. Male ICR mice were randomly divided into four groups (n = 10 per group) and treated with either a vehicle (control group) or different doses of HWET, which were designated as HWET-L (800 mg/kg/day), HWET-M (1600 mg/kg/day), and HWET-H (4000 mg/kg/day). The results of the swimming endurance test showed that HWET treatment significantly improved exercise-induced fatigue as the swimming time of the mice increased (p &lt; 0.05). One hour after the test, blood samples were collected from each mouse and serum biochemical parameters were measured. The serum levels of lactate, creatine kinase (CK), and blood urea nitrogen (BUN) were lower in mice treated with HWET compared to the control group. Moreover, HWET treatment increased serum glucose levels and glycogen content in the liver. Enhanced glutathione (GSH) content in the liver and muscle was also found in the HWET-M and HWET-H groups. Western blot results showed that the expression of tumor necrosis factor-α (TNF-α) in the liver tissue was downregulated by HWET treatment. Taken together, our results demonstrate that HWET supplementation could enhance exercise performance and alleviate fatigue via biochemical profile improvements. This suggests that HWET has the potential for future development into functional foods or nutritional supplements to relieve fatigue.

The anti-fatigue activity of corn peptides and their effect on gut bacteria.

Corn peptides (CPs) are rich in branched-chain amino acids such as leucine and have a variety of biological activities such as antioxidant and improved lipid distribution. In this article, we prepared CPs by enzymatic digestion of corn proteins and evaluated their anti-fatigue activity. We evaluated the anti-fatigue effect of CPs through an exhaustive swimming experiment. The results showed that CPs were able to significantly reduce the rate of body weight gain and prolong the duration of exhaustive swimming. Besides, CPs reduced blood urea nitrogen (BUN) levels after exercise, while they significantly increased muscle glycogen and liver glycogen stores. They reduced muscle cell damage from exercise. In addition, CPs were effective in increasing AMPK, PGC-1α and PI3K protein expression levels and promoting Akt phosphorylation. Correlation analysis showed that CPs increased the abundance of probiotics such as Lactobacillus and Akkermansia in the gut microflora. CPs, which enhanced exercise performance in mice and could modulate gut microbial composition, had significant anti-fatigue activity. © 2021 Society of Chemical Industry.