Transcranial magnetic stimulation in the assessment of acupuncture effect on exercise-induced fatigue.

BACKGROUND: Acupuncture as a traditional Chinese medicine therapy relies on unique theories to alleviate fatigue. The aim of this study is to evaluate the effect of acupuncture on exercise-induced fatigue utilizing transcranial magnetic stimulation (TMS). METHODS: A total of 20 participants with regular exercise habits were recruited for this study. All participants were randomly assigned to receive either acupuncture or sham acupuncture intervention for exercise-induced fatigue. TMS and a heart rate monitor were used to measure the amplitude and latency of motor evoked potential (MEP) as well as heart rate every 5 min over a 30-min period. The blood lactic acid (BLA) levels were measured using Lactate Scout+ at baseline, 0 min, and 30 min after fatigue. Two-way repeated measures analysis of variance was utilized to compare the differences between the effects of acupuncture method and time. Bonferroni post hoc tests were conducted to compare specific differences. Statistical significance was set at p < .05. RESULTS: Interaction effect was observed between acupuncture method and time effect in terms of amplitude (F(1, 38) = 5.40, p < .001, η2 = 0.12) and latency (F(1, 38) = 3.78, p = .008, η2 = .09) of MEP. The application of acupuncture can promote the recovery of heart rate especially at 30 min (p < .05), but which seem insufficient to generate significant difference in BLA (F(1, 38) = 0.067, p = .797, η2 = 0.002). CONCLUSIONS: Acupuncture can promote the increase of MEP amplitude, shorten MEP latency, and restore heart rate. Preliminary findings provide novel insights for individuals with exercise habits to alleviate fatigue and enhance sports performance.

Novel peptides from sea cucumber intestines hydrolyzed by neutral protease alleviate exercise-induced fatigue via upregulating the glutaminemediated Ca2+ /Calcineurin signaling pathway in mice.

Sea cucumber intestines are considered a valuable resource in the sea cucumber processing industry due to their balanced amino acid composition. Studies have reported that peptides rich in glutamate and branched-chain amino acids have anti-fatigue properties. However, the function of the sea cucumber intestine in reducing exercise-induced fatigue remains unclear. In this study, we enzymatically hydrolyzed low molecular weight peptides from sea cucumber intestines (SCIP) and administered SCIP orally to mice to examine its effects on exercise-induced fatigue using swimming and pole-climbing exhaustion experiments. The results revealed that supplementation with SCIP significantly prolonged the exhaustion time of swimming in mice, decreased blood lactate and urea nitrogen levels, and increased liver and muscle glycogen levels following a weight-loaded swimming test. Immunofluorescence analysis indicated a notable increase the proportion of slow-twitch muscle fiber and a significant decrease the proportion of fast-twitch muscle fiber following SCIP supplementation. Furthermore, SCIP upregulated mRNA expression levels of Ca2+ /Calcineurin upstream and downstream regulators, thereby contributing to the promotion of skeletal muscle fiber type conversion. This study presents the initial evidence establishing SCIP as a potential enhancer of skeletal muscle fatigue resistance, consequently providing a theoretical foundation for the valuable utilization of sea cucumber intestines.

Polysaccharides derived from natural edible and medicinal sources as agents targeting exercise-induced fatigue: A review.

Exercise-induced fatigue (EF) is a common occurrence during prolonged endurance and excessive exercise and is mainly caused by energy depletion, harmful metabolite accumulation, oxidative stress, and inflammation. EF usually leads to a reduction in initiating or maintaining spontaneous activities and muscle performance and ultimately results in a decrease in the quality of life of people who engage in physical work. Therefore, the interest in investigating EF-targeting agents with minimal side effects and good long-term efficacy has substantially increased. Natural edible and medicinal polysaccharides have shown positive anti-EF effects, but the relevant reviews are rare. This review comprehensively summarizes studies on natural polysaccharides from edible and medicinal sources that can relieve EF and improve physical performance from the past decade, focusing on their sources, monosaccharide compositions, anti-EF effects, and possible molecular mechanisms. Most of these anti-EF polysaccharides are heteropolysaccharides and are mainly composed of glucose, arabinose, galactose, rhamnose, xylose, and mannose. In EF animal models, the polysaccharides exert positive EF-alleviating effects through energy supply, metabolic regulation, antioxidation, anti-inflammation, and gut microbiota remodeling. However, further studies are still needed to clarify the anti-EF effects of these polysaccharides on human beings. In summary, the present review expects to provide scientific data for the future research and development of natural polysaccharide-based anti-EF drugs, dietary supplements, and health-care products for specific fatigue groups.

Effect and Mechanism of Action of Epimedii Folium Polysaccharides on Mice with Exercise-induced Fatigue Based on p38 MAPK/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study the effects of Epimedii Folium polysaccharides on mice with exercise-induced fatigue and explore its possible mechanism of action. MethodICR male mice screened by swimming training were randomly divided into a control group， model group， vitamin C group， and low， medium， and high dose groups of Epimedii Folium polysaccharides， with eight mice in each group. The exercise-induced fatigue model was established by weight-bearing swimming training in each group except for the control group. After two weeks of weight-bearing swimming， the Epimedii Folium polysaccharide groups were given 100， 200， 400 mg∙kg-1 of Epimedii Folium polysaccharides by gavage， and the vitamin C group was given 200 mg∙kg-1 of vitamin C by gavage. The control group and the model group were given equal amounts of saline for 14 d. At the end of the experimental period， the body mass of the mice in each group and the time of last swimming due to exhaustion were recorded. Serum urea nitrogen （BUN）， lactic acid （LA）， lactate dehydrogenase （LDH）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidation （GSH-Px）， myoglycogen （MG） in skeletal muscle， hepatic glycogen （HG） in the liver were detected by kits. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in muscle tissue. Western blot was used to detect the protein expression of p38 mitogen-activated protein kinase （p38 MAPK）， phosphorylation （p）-p38 MAPK， extracellular signal-regulated kinase1/2 （ERK1/2）， nuclear factor-κB （NF-κB）， p-NF-κB， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in muscle tissue. The immunofluorescence （IF） method was used to detect the expression of tumor necrosis factor-α （TNF-α） in skeletal muscle tissue of mice in each group. ResultCompared with the control group， the body mass of mice in the model group decreased， and the time of last swimming due to exhaustion decreased （P<0.01）. In addition， there were significantly higher serum levels of the fatigue metabolites LA， LDH， BUN， and lipid peroxidation product MDA （P<0.01） and decreased levels of MG， HG， SOD， and GSH-Px （P<0.01）. The protein expressions of p-p38 MAPK， ERK1/2， p-NF-κB， IL-1β， IL-6， and TNF-α in skeletal muscle tissue were significantly higher than those of the control group （P<0.01）. Compared with the model group， the body mass and time of last swimming due to exhaustion of the mice in the low， medium， and high dose groups of Epimedii Folium polysaccharides and the vitamin C group were increased （P<0.05， P<0.01）， and the contents of LA， LDH， BUN， and MDA were significantly decreased （P<0.05， P<0.01）. The levels of MG， HG， SOD， and GSH-Px increased （P<0.05， P<0.01）， and the protein expression levels of p-p38 MAPK， ERK， p-NF-κB， IL-1β， IL-6， and TNF-α in skeletal muscle tissue decreased （P<0.05， P<0.01）. ConclusionEpimedii Folium polysaccharides can play a role in alleviating exercise-induced fatigue by inhibiting the p38 MARK/NF-κB signaling pathway， thereby reducing the accumulation of metabolites， improving the activity of antioxidant enzymes， increasing the glycogen content of the body， and reducing inflammation in skeletal muscle.

Aqueous Extract of Brassica rapa L.'s Impact on Modulating Exercise-Induced Fatigue via Gut-Muscle Axis.

Exercise-induced fatigue is a common physiological response to prolonged physical activity, often associated with changes in gut microbiota and metabolic responses. This study investigates the potential role of Brassica rapa L. in modulating these responses. Using an animal model subjected to chronic exercise-induced stress, we explored the effects of Brassica rapa L. on fatigue-related biomarkers, energy metabolism genes, inflammatory responses, intestinal integrity, and gut microbiota composition. Our findings revealed that Brassica rapa L. exhibits significant antioxidant activity and effectively modulates physiological responses to fatigue. It influences gene expression related to the tricarboxylic acid (TCA) cycle in muscle tissue through the AMPK/PGC-1α/TFAM signaling pathway. Furthermore, Brassica rapa L. has been found to alleviate inflammation by inhibiting lipopolysaccharide (LPS) infection and suppressing the activation of the NF-κB pathway. It also maintains intestinal integrity and controls Gram-negative bacterial growth. A correlation analysis identified several pathogenic bacteria linked with inflammation and energy metabolism, as well as beneficial probiotic bacteria associated with improved energy metabolism and reduced inflammation. These findings underscore Brassica rapa L.'s potential for managing prolonged exercise-induced fatigue, paving the way for future therapeutic applications. The results highlight its impact on gut microbiota modulation and its role in nutrition science and sports medicine.

Research on sweat metabolomics of athlete's fatigue induced by high intensity interval training.

Objective: Sweat is an important specimen of human metabolism, which can simply and non-invasively monitor the metabolic state of the body, and its metabolites can be used as biomarkers for disease diagnosis, while the changes of sweat metabolites before and after exercise-induced fatigue are still unclear. Methods: In this experiment, high-performance chemical isotope labeling liquid chromatography-mass spectrometry (LC-MS) was used to metabolomic 28 sweat samples before and after exercise-induced fatigue of 14 long-distance runners, also IsoMS PRO and SPSS22.0 software were used to analyze the metabolite changes and differential metabolic pathways. Results: A total of 446 metabolites with high confidence were identified, and the sweat metabolome group before and after high-intensity interval exercise-induced fatigue was obvious, among which the upregulated differential metabolites mainly included hypoxanthine, pyruvate, several amino acids, etc., while the downregulated differential metabolites mainly included amino acid derivatives, vitamin B6, theophylline, etc. Conclusion: The change of hypoxanthine concentration in sweat can be used as a good biomarker for the diagnosis of exercise-induced fatigue, while the change of pyruvate content in sweat can be used as a discriminant index for the energy metabolism mode of the body before and after exercise. The main metabolic pathways involved in differential metabolites produced before and after HIIT exercise-induced fatigue are purine metabolism and amino acid metabolism.

Effects of high-definition transcranial direct current stimulation on the cortical-muscular functional coupling and muscular activities of ankle dorsi-plantarflexion under running-induced fatigue.

Transcranial direct current stimulation (tDCS) can improve motor control performance under fatigue. However, the influences of tDCS on factors contributing to motor control (e.g., cortical-muscular functional coupling, CMFC) are unclear. This double-blinded and randomized study examined the effects of high-definition tDCS (HD-tDCS) on muscular activities of dorsiflexors and plantarflexors and CMFC when performing ankle dorsi-plantarflexion under fatigue. Twenty-four male adults were randomly assigned to receive five sessions of 20-min HD-tDCS targeting primary motor cortex (M1) or sham stimulation. Three days before and 1 day after the intervention, participants completed ankle dorsi-plantarflexion under fatigue induced by prolonged running exercise. During the task, electroencephalography (EEG) of M1 (e.g., C1, Cz) and surface electromyography (sEMG) of several muscles (e.g., tibialis anterior [TA]) were recorded synchronously. The corticomuscular coherence (CMC), root mean square (RMS) of sEMG, blood lactate, and maximal voluntary isometric contraction (MVC) of ankle dorsiflexors and plantarflexors were obtained. Before stimulation, greater beta- and gamma-band CMC between M1 and TA were significantly associated with greater RMS of TA (r = 0.460-0.619, p = 0.001-0.024). The beta- and gamma-band CMC of C1-TA and Cz-TA, and RMS of TA and MVC torque of dorsiflexors were significantly higher after HD-tDCS than those at pre-intervention in the HD-tDCS group and post-intervention in the control group (p = 0.002-0.046). However, the HD-tDCS-induced changes in CMC and muscle activities were not significantly associated (r = 0.050-0.128, p = 0.693-0.878). HD-tDCS applied over M1 can enhance the muscular activities of ankle dorsiflexion under fatigue and related CMFC.

Dopamine Release Impairments Accompany Movement Vigor Deficiency in an Exercise-Induced Fatigue Mouse Model.

Fatigue is a common symptom in neurological diseases with a complex cause, involving the influence of events occurring in both the central and peripheral nervous systems. When people suffer from fatigue, a general decline in their movement performance typically occurs. The neural representation of dopamine signaling in the striatum plays a crucial role in movement regulation. Movement vigor is regulated by dopamine-dependent neuron activity in the striatum. However, whether exercise-induced fatigue alters stimulated dopamine release and further affects movement vigor has not been described. Here, for the first time, we used fast-scan cyclic voltammetry to demonstrate the effect of exercise-induced fatigue on stimulated dopamine release in the striatum in combination with a fiber photometry system to observe the excitability of striatal neurons. The movement vigor of mice was reduced, and after fatigue, the balance of excitability of striatal neurons regulated by dopamine projections was disturbed, which was induced by a reduction in dopamine release. Additionally, D2DR regulation may serve as a targeted intervention to alleviate exercise-induced fatigue and promote fatigue recovery.

Repeated Inhalation of Peppermint Essential Oil Improves Exercise Performance in Endurance-Trained Rats.

Peppermint essential oil, being natural and safe, with antioxidant and anti-inflammatory properties, has long been a research interest in relieving fatigue and improving exercise performance. However, the related studies report controversial results, and the mechanisms remain unclear. Here we found that inhalation of peppermint essential oil significantly extended the exhaustion time in rats subjected to 2-week weight-bearing swimming training. Sprague-Dawley rats were subjected to a 2-week weight-loaded forced swimming regimen. Prior to each swimming session, the rats were administered peppermint essential oil via inhalation. An exhaustive swimming test was performed at the end of the protocol. Rats treated with essential oil had significantly extended time to exhaustion compared with exercised rats without essential oil treatment. In addition, treated rats also showed reduced oxidative damage induced by endurance exercise. Notably, the rats receiving two-week essential oil inhalation while not subjected to swimming training did not show improved exercise performance. The findings demonstrate that repeated inhalation of peppermint essential oil enhances the effects of endurance training and improves exercise performance partially by preventing oxidative damage.

Fatiguing freestyle swimming modifies miRNA profiles of circulating extracellular vesicles in athletes.

Extracellular vesicles (EVs) are secreted by various tissues and cells under normal physiological or pathological conditions. Exercise-induced EVs may be involved in the adaptation of exercise-induced fatigue. The 1500-m freestyle is the longest pool-based swimming event in the Olympic Games, and there is a paucity of information regarding changes in the miRNA profiles of circulating EVs after a single session of fatiguing swimming. In this study, 13 male freestyle swimmers conducted a fatiguing 1500-m freestyle swimming session at the speed of their best previously recorded swimming performance. Fasting venous blood was collected before and after the swimming session for analysis. 70 miRNAs from the circulating EVs were found to be differentially expressed after the fatiguing 1500-m freestyle swimming session, among which 45 and 25 miRNAs were up-regulated and down-regulated, respectively. As for the target genes of five miRNAs (miR-144-3p, miR-145-3p, miR-509-5p, miR-891b, and miR-890) with the largest expression-fold variation, their functional enrichment analysis demonstrated that the target genes were involved in the regulation of long-term potentiation (LTP), vascular endothelial growth factor (VEGF), glutathione metabolism pathway, dopaminergic synapse, signal transmission, and other biological processes. In summary, these findings reveal that a single session of fatiguing swimming modifies the miRNAs profiles of the circulating EVs, especially miR-144-3p, miR-145-3p, miR-509-5p, miR-891b, and miR-890, which clarifies new mechanisms for the adaptation to a single session of fatiguing exercise from the perspective of EV-miRNAs.

Acupoint Catgut Embedding Improves Lipid Metabolism in Exercise-Induced Fatigue Rats via the PPAR Signaling Pathway.

To improve the phenomenon of exercise-induced fatigue that often occurs during horse racing, we previously studied the improvement in exercise tolerance by acupoint catgut embedding preconditioning in an exercise-induced fatigue rat model. We found that acupoint catgut embedding pretreatment effectively improved animal exercise tolerance. Here, by combining transcriptomics and metabolomics, we aimed to explore the underlying mechanisms of this improvement. We used blood biochemical detection combined with ELISA to detect triglyceride (TG), total cholesterol (TC), lactate dehydrogenase (LDH), high-density lipoprotein (HDL), alanine transaminase (ALT), aspartate aminotransferase (AST), and glucose (GLU), arachidonic acid (AA), and free fatty acid (FFA) content and found that acupoint embedding can correct FFA, AA, TG, LDH, and AST in the blood. We used RT-qPCR to measure the expression of genes in tissue from the quadriceps femoris muscle. We found that solute carrier family 27 member 2 (Slc27a2), fatty acid binding protein 1 (Fabp1), apolipoprotein C3 (Apoc3), and lipoprotein lipase (Lpl) genes in the peroxisome proliferator-activated receptor (PPAR) signaling pathway were important. The regulation of lipid metabolism through the PPAR signaling pathway was important for improving the exercise endurance of rats in our exercise-induced fatigue model. Therefore, we conclude that acupoint catgut embedding can not only promote body fat decomposition and reduce lactic acid accumulation but also promote the repair of tissue damage and liver damage caused by exercise fatigue. Acupoint catgut embedding regulates the PPAR signaling pathway by upregulating Lpl expression and downregulating Slc27a2, Fabp1, and Apoc3 expression to further improve body fat metabolism.

Exploring the mechanism of moxibustion in myocardial protection of rats with long-term fatigue exercise based on the classical pyroptosis pathway / 针灸推拿医学（英文版）

Objective: To explore the possible mechanism of moxibustion in myocardial protection of rats undergoing long-term fatigue exercise based on observing the classical pyroptosis pathway mediated by nuclear factor kappa-B (NF-κB)/nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/cysteinyl aspartate specific proteinase 1 (Caspase-1).Methods: A total of 50 specific-pathogen-free male Sprague-Dawley rats were bought. Ten unqualified rats were excluded, and the remaining 40 rats were divided into a normal group, a normal + Shenque (CV8) group, a model group, a model + non-meridian non-point group, and a model + Shenque (CV8) group according to the random number table method, with 8 rats in each group. Except for rats in the normal group and the normal + Shenque (CV8) group, rats in the other three groups were trained with an incline running table exercise protocol to create a long-term fatigue exercise model, 1 h/time, once a day for 5 d with 2 d off, for a total of 8 weeks. Rats in the normal group received no modeling or intervention. Rats in the normal + Shenque (CV8) group were not modeled but received mild moxibustion at Shenque (CV8); those in the model group were modeled only without intervention; those in the model + non-meridian non-point group received moxibustion at non-meridian and non-point spots after the modeling; those in the model + Shenque (CV8) group received moxibustion at Shenque (CV8) after modeling. The above moxibustion interventions were performed for 15 min/time once daily, for 5 d with 2 d off per week and a total of 8 weeks. Blood was collected from the femoral artery 4 h after the last exercise, and the serum interleukin (IL)-1β and IL-18 levels were measured. The NF-κB, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, and gasdermin D (GSDMD) expression levels were detected by Western blotting. Myocardial morphology and pyroptosis were observed by hematoxylin-eosin (HE) staining and electron microscopy. Results: The HE staining results showed that the myocardial cells in the model group and the model + non-meridian non-point group were disorganized with blurred transverse lines, widened interstitial spaces, interstitial edema, and inflammatory cell infiltration. The structure of myocardial cells in the model + Shenque (CV8) group was clearly visible, with slightly widened interstitial spaces and occasional infiltration of inflammatory cells in the interstitium. Compared with the normal group, the serum IL-1β and IL-18 levels were increased, and myocardial NF-κB, NLRP3, ASC, Caspase-1, and GSDMD expression levels were elevated in the model group and the model + non-meridian non-point group (P<0.01). Compared with the model group, the above indicators did not change significantly in the model + non-meridian non-point group, while all the above indicators were decreased in the model + Shenque (CV8) group (P<0.01). Compared with the model + non-meridian non-point group, all the above biochemical indicators were decreased in the model + Shenque (CV8) group (P<0.01). Transmission electron microscopy showed that the mitochondria number was increased in the model group and the model + non-meridian non-point group, some of the mitochondrial lumen was irregularly enlarged, the cell membrane structure was unclear, and chromatin was aggregated. The mitochondria number was increased, the swelling was reduced, and the nuclear membrane structure was more intact in the model + Shenque (CV8) group. Conclusion: Moxibustion at Shenque (CV8) regulates the NF-κB/NLRP3/Caspase-1 pathway and reduces the pyroptosisin the myocardium of rats with long-term fatigue exercise, thus reducing the myocardial injury caused by long-term fatigue exercise.

Alleviation of Cognitive and Physical Fatigue with Enzymatic Porcine Placenta Hydrolysate Intake through Reducing Oxidative Stress and Inflammation in Intensely Exercised Rats.

Intense exercise is reported to induce physical and cognitive fatigue, but few studies have focused on treatments to alleviate fatigue. We hypothesized that the oral supplementation of enzymatic porcine placenta hydrolysate (EPPH) prepared using protease enzymes could alleviate exercise-induced fatigue in an animal model. The objectives of the study were to examine the hypothesis and the action mechanism of EPPH in relieving physical and cognitive fatigue. Fifty male Sprague−Dawley rats aged 8 weeks (body weight: 201 g) were classified into five groups, and rats in each group were given oral distilled water, EPPH (5 mg nitrogen/mL) at doses of 0.08, 0.16, or 0.31 mL/kg body weight (BW)/day, or glutathione (100 mg/kg BW/day) by a feeding needle for 5 weeks, which were named as the control, L-EPPH, M-EPPH, H-EPPH, or positive-control groups, respectively. Ten additional rats had no intense exercise with water administration and were designated as the no-exercise group. After 2 weeks, the rats were subjected to intense exercise and forced swimming trial for 30 min once per week for an additional 4 weeks. At 5 min after the intense exercise, lactate concentrations and lactate dehydrogenase (LDH) activity in the serum and the gastrocnemius muscle were higher in the control group, whereas M-EPPH and H-EPPH treatments suppressed the increase better than in the positive-control (p < 0.05). Intense exercise decreased glycogen content in the liver and gastrocnemius muscle, and M-EPPH and H-EPPH inhibited the decrement (p < 0.05). Moreover, lipid peroxide contents in the gastrocnemius muscle and liver were higher in the control group than in the M-EPPH, H-EPPH, positive-control, and no-exercise groups (p < 0.05). However, antioxidant enzyme activities such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were opposite to the lipid peroxide contents. Hypothalamic corticosterone and hippocampal mRNA expressions of tumor necrosis factor (TNF)-α and IL-1ß were higher. However, hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression and protein contents were lower in the control group than in the positive-control group. M-EPPH, H-EPPH, and positive-control suppressed the changes via activating hippocampal cAMP response element-binding protein phosphorylation, and H-EPPH showed better activity than in the positive-control (p < 0.05). In conclusion, EPPH (0.16−0.31 mL/kg BW) intake reduced exercise-induced physical and cognitive fatigue in rats and could potentially be developed as a therapeutic agent for relieving fatigue in humans.

Establishment and identification of an animal model of long-term exercise-induced fatigue.

In competitive sports, the training load is close to the human physiological limit, which will inevitably lead to exercise-induced fatigue. If fatigue cannot be recovered in time, it will eventually lead to excessive training and affect sport performance. Therefore, fatigue has become an important part of the physical function assessment for athletes. This paper will review animal models of long-term exercise-induced fatigue, modeling schemes of mice under treadmill and swimming training, phenotypes of long-term exercise-induced fatigue (e.g., nervous system damage, myocardial cell damage, bone mineral density changes, and skeletal muscle damage), and fatigue indicators. The relationship between physiological indicators and biomarkers and long-term exercise-induced fatigue is analyzed to promote exercise-induced fatigue monitoring. This paper attempts to provide a reference for the selection of animal models of long-term exercise-induced fatigue and provide a new theoretical basis for medical supervision and recovery of exercise-induced fatigue.

The use of traditional Chinese medicines in relieving exercise-induced fatigue.

Exercise-induced fatigue is a non-pathological fatigue and indicated by a reduction of muscle performance that is caused by excessive physical activity. It seriously affects the daily lives of people, in particular athletes, military personnel, and manual laborers. In recent years, increasing attention has been paid to improving the adverse effect of exercise-induced fatigue on people's daily activities. Thus, studies and applications of traditional Chinese medicines (TCMs) in relieving exercise-induced fatigue have become the focus because of their good curative effects with fewer side effects. This review aims to document and summarize the critical and comprehensive information about the biological processes of exercise-induced fatigue, and to know the types of TCMs, their active components, and possible molecular mechanisms in alleviating exercise-induced fatigue. The peripheral and central mechanisms that cause exercise-induced fatigue have been summarized. A total of 47 exercise-induced fatigue relief TCMs have been collected, mostly including the types of visceral function regulation and emotional adjustment TCMs. Polysaccharides, terpenes, flavonoids/polyphenols are demonstrated to be the major bioactive components. The underlying molecular mechanisms are mainly related to the improvement of energy metabolism, elimination of excess metabolites, inhibition of oxidative stress and inflammatory response, regulation of HPA axis and neurotransmitters. Although current results are obtained mostly from animal models, the clinic trials are still insufficient, and a very few TCMs have been reported to possess potential hepatotoxicity. These findings still offer great reference value, and the significant efficacy in relieving exercise-induced fatigue is impossible to ignore. This review is expected to give insights into the research and development of new TCMs-derived drugs and health care products in relieving exercise-induced fatigue.

Trilobatin, a Naturally Occurring Food Additive, Ameliorates Exhaustive Exercise-Induced Fatigue in Mice: Involvement of Nrf2/ARE/Ferroptosis Signaling Pathway.

Nrf2-mediated oxidative stress is a promising target of exhaustive exercise-induced fatigue (EEIF). Trilobatin (TLB) is a naturally occurring food additive with antioxidant effect and Nrf2 activation potency. The present study aimed to investigate the effect of TLB on EEIF and elucidate its underlying mechanism. Our results showed that TLB exerted potent anti-EEIF effect, as reflected by the rope climbing test and exhaustive swimming test. Moreover, TLB also effectively reduced the levels of lactate, creatine kinase, and blood urea nitrogen, and increased liver glycogen and skeletal muscle glycogen in mice after EEIF insult. Additionally, TLB also balanced the redox status as evidenced by decreasing the generation of reactive oxygen species and improving the antioxidant enzyme activities including superoxide dismutase, catalase, and glutathione peroxidase, as well as the level of glutathione both in the tissue of muscle and myocardium. Furthermore, TLB promoted nuclear factor erythroid 2-related factor 2 (Nrf2) from the cytoplasm to the nucleus, and upregulated its downstream antioxidant response element (ARE) including quinone oxidoreductase-1 and heme oxygenase-1. Intriguingly, TLB also upregulated the GPx4 protein expression and reduced iron overload in mice after EEIF insult. Encouragingly, the beneficial effect of TLB on EEIF-induced oxidative stress and ferroptosis were substantially abolished in Nrf2-deficient mice. In conclusion, our findings demonstrate, for the first time, that TLB alleviates EEIF-induced oxidative stress through mediating Nrf2/ARE/ferroptosis axis.

Orosomucoid: a promising biomarker for the assessment of exercise-induced fatigue triggered by basic combat training.

BACKGROUND: Orosomucoid (ORM) is a positive acute phase protein verified to be upregulated in various forms of exercise-induced fatigued (EIF) rodents. However, its association with EIF among human beings remained unknown. This study aimed to explore the association between serum ORM and EIF triggered by military basic combat training (BCT). METHODS: The degree of EIF were measured by Borg's Rating of Perceived Exertion Scale (Borg-RPE-Scale®) as RPE score after BCT. Fifty-three male recruits were classified into three groups according to the RPE score: (1) group 1 (slight fatigue group): RPE score after BCT < 13; (2) group 2 (moderate fatigue group): RPE score after BCT = 13 or 14; (3) group 3 (severe fatigue group): RPE score after BCT > 14. The levels of blood ORM, lactate (LAC), cortisol and C-reactive protein (CRP) were determined before and after BCT. The diagnostic value of ORM was evaluated by receiver operating characteristic (ROC) curve analysis and logistic regression. RESULTS: After BCT, the level of LAC, CRP, and cortisol increased among all groups, but the changes had no significant between-group difference (all p > 0.05). The level of ORM had a specific significant increase in group 3 (p = 0.039), and the changes of ORM (ΔORM) had significant difference among groups (p = 0.033). ROC curve analysis showed that the estimated area under ROC curve for ΔORM was 0.724 (p = 0.009) with the recommended optimal cut-off value as 0.2565 mg/mL. Logistic analysis showed that recruits with ΔORM ≥ 0.2565 mg/mL had higher odds for suffering from severe EIF, 5.625 times (95% CI 1.542-20.523, p = 0.009) as large as those with ΔORM < 0.2565 mg/mL. CONCLUSION: ORM might be a promising biomarker of severe EIF triggered by BCT among male recruits. Its potential optimal cut-off value regarding ΔORM was recommended to be 0.2565 mg/mL.

Effect of Normobaric Oxygen Inhalation Intervention on Microcirculatory Blood Flow and Fatigue Elimination of College Students After Exercise.

Objective: To explore the effect of normobaric oxygen inhalation intervention on microcirculatory blood flow of college students after exercise and the impact of the elimination of exercise-induced fatigue, to provide a theoretical and methodological reference for the rapid elimination of fatigue of college students after endurance exercise. Methods: Forty-eight male non-sports majors of Hubei University for nationalities were randomly divided into the control group (n = 24) and intervention group (n = 24). The subjects in both groups completed the same exercise program twice (running 3,000 m on the treadmill at maximum speed). After running, the issues in the intervention group inhaled portable oxygen for 30 min, and the control group recovered naturally. Microcirculatory blood flow (MBP), blood flow velocity (AVBC), blood flow concentration (CMBC), muscle oxygen saturation (SmO2), heart rate (HR), blood lactic acid (BLA), blood urea (BU), and creatine kinase (CK) were measured before exercise, immediately after exercise and 30 min after exercise. Results: 1) MBP and AVBC had interaction between groups and time before and after exercise, MBP and AVBC immediately after exercise in the intervention group were significantly higher than those before exercise and 30 min after exercise, and 30 min after exercise in the intervention group were significantly higher than those in the control group. 2) SmO2, HR, BLA, BU, and CK had interaction between groups and time, and SmO2 immediately after exercise in the intervention group was significantly lower than that before exercise and 30 min after exercise, but significantly higher than that in the control group at 30 min after exercise. The HR and BLA immediately after exercise in the intervention group were significantly higher than those before exercise and 30 min after exercise, but significantly lower than those in the control group at 30 min after exercise, and the BU and CK in the intervention group were significantly higher than those before exercise, but significantly lower than those in the control group at 30 min after exercise. Conclusion: Normobaric oxygen inhalation for 30 min after exercise can delay the decrease of microcirculatory blood flow, increase muscle oxygen saturation, and promote the recovery of heart rate, blood lactic acid, blood urea and creatine kinase. Therefore, normobaric oxygen inhalation for 30 min after exercise can be used as an effective means to promote the elimination of exercise-induced fatigue after endurance running.

A Comparative Study on Relieving Exercise-Induced Fatigue by Inhalation of Different Citrus Essential Oils.

Citrus essential oils (CEOs) possess physiological functions due to diverse aroma components. However, evidence for the effects of CEOs on exercise performance and exercise-induced fatigue is limited. The CEOs with discrepancies in components may exert different effects on the amelioration of exercise-induced fatigue. In this study, sweet orange (Citrus sinensis L.) essential oil (SEO), lemon (Citrus limon Osbeck) essential oil (LEO), and bergamot (Citrus bergamia Risso and Poit) essential oil (BEO) were chosen to explore the effect on amelioration of exercise-induced fatigue. Our results demonstrated that SEO and LEO increased the swimming time by 276% and 46.5%, while BEO did not. Moreover, the three CEOs exerted varying effects on mitigating exercise-induced fatigue via inhibiting oxidative stress, protecting muscle injury, and promoting glucose-dependent energy supply. Accordingly, BEO showed the best efficiency. Moreover, the GC-MS and Pearson correlation analysis of BEO showed that the contents of the major components, such as (±)-limonene (32.9%), linalyl butyrate (17.8%), and linalool (7.7%), were significantly positively correlated with relieving exercise-induced fatigue.

A New Tool for Rapid Assessment of Acute Exercise-Induced Fatigue.

Background: There are limited sensitive evaluation methods to distinguish people's symptoms of peripheral fatigue and central fatigue simultaneously. The purpose of this study is to identify and evaluate them after acute exercise with a simple and practical scale. Methods: The initial scale was built through a literature review, experts and athlete population survey, and a small sample pre-survey. Randomly selected 1,506 students were evaluated with the initial scale after exercise. Subjective fatigue self-assessments (SFSA) were completed at the same time. Results: The Acute Exercise-Induced Fatigue Scale (AEIFS) was determined after performing a factor analysis. In the exploratory factor analysis, the cumulative variance contribution rate was 65.464%. The factor loadings of the total 8 questions were 0.661-0.816. In the confirmatory factor analysis, χ2/df = 2.529, GFI = 0.985, AGFI = 0.967, NFI = 0.982, IFI = 0.989, CFI = 0.989, and RMSEA = 0.048. The Cronbach's alpha coefficient for the scale was 0.872, and it was 0.833 for peripheral fatigue and 0.818 for central fatigue. The intra-class correlation coefficient for the scale was 0.536, and the intra-class correlation coefficients for peripheral fatigue and central fatigue were 0.421 and 0.548, respectively. The correlation coefficient between the total score of the AEIFS and the SFSA score was 0.592 (p < 0.01). Conclusion: Our results demonstrate that the AEIFS can distinguish peripheral fatigue and central fatigue and can also reflect their correlation. This scale can be a useful evaluation tool not only for measuring fatigue after acute exercise but also for guiding reasonable exercise, choosing objective testing indicators, and preventing sports injuries resulting from acute exercise-induced fatigue.