Considerations for exerkine research focusing on the response to exercise training

García-Hermoso and colleagues1 recently published a systematic literature review and meta-analysis on exercise training-induced changes in exerkine concentrations in type 2diabetes mellitus patients,providing a contemporary view on how exerkines respond to exercise training.That review prompted us to highlight 2 additional considerations that should be taken into account when studying the response of exerkines to exercise training.Firstly,whether exerkines can exhibit discordant responses to acute exercise compared to exercise training,and secondly,the need to consider the residual effects of the most recent exercise bout.

Concerns about the application of resistance exercise with blood-flow restriction and thrombosis risk in hemodialysis patients

Background:Hemodialysis(HD) per se is a risk factor for thrombosis.Considering the growing body of evidence on blood-flow restriction(BFR) exercise in HD patients,identification of possible risk factors related to the prothrombotic agent D-dimer is required for the safety and feasibility of this training model.The aim of the present study was to identify risk factors associated with higher D-dimer levels and to determine the acute effect of resistance exercise(RE) with BFR on this molecule.Methods:Two hundred and six HD patients volunteered for this study(all with a glomerular filtration rate of <15 mL/min/1.73 m2).The RE+BFR session consisted of 50% arterial occlusion pressure during 50 min sessions of HD(intradialytic exercise).RE repetitions included concentric and eccentric lifting phases(each lasting 2 s) and were supervised by a strength and conditioning specialist.Results:Several variables were associated with elevated levels of D-dimer,including higher blood glucose,citrate use,recent cardiovascular events,recent intercurrents,higher inflammatory status,catheter as vascular access,older patients(>70 years old),and HD vintage.Furthermore,RE+BFR significantly increases D-dimer after 4 h.Patients with borderline baseline D-dimer levels(400-490 ng/mL) displayed increased risk of elevating D-dimer over the normal range(≥500 ng/mL).Conclusion:These results identified factors associated with a heightened prothrombotic state and may assist in the screening process for HD patients who wish to undergo RE+BFR.D-dimer and/or other fibrinolysis factors should be assessed at baseline and throughout the protocol as a precautionary measure to maximize safety during RE+BFR.

Efficacy of exercise rehabilitation for managing patients with Alzheimer's disease

Alzheimer's disease(AD) is a progressive and degenerative neurological disease characterized by the deterioration of cognitive functions. While a definitive cure and optimal medication to impede disease progression are currently unavailable, a plethora of studies have highlighted the potential advantages of exercise rehabilitation for managing this condition. Those studies show that exercise rehabilitation can enhance cognitive function and improve the quality of life for individuals affected by AD. Therefore, exercise rehabilitation has been regarded as one of the most important strategies for managing patients with AD. Herein, we provide a comprehensive analysis of the currently available findings on exercise rehabilitation in patients with AD, with a focus on the exercise types which have shown efficacy when implemented alone or combined with other treatment methods, as well as the potential mechanisms underlying these positive effects. Specifically, we explain how exercise may improve the brain microenvironment and neuronal plasticity. In conclusion, exercise is a cost-effective intervention to enhance cognitive performance and improve quality of life in patients with mild to moderate cognitive dysfunction. Therefore, it can potentially become both a physical activity and a tailored intervention. This review may aid the development of more effective and individualized treatment strategies to address the challenges imposed by this debilitating disease, especially in low-and middle-income countries.

Treadmill exercise improves hippocampal neural plasticity and relieves cognitive deficits in a mouse model of epilepsy

Epilepsy frequently leads to cognitive dysfunction and approaches to treatment remain limited.Although regular exercise effectively improves learning and memory functions across multiple neurological diseases,its application in patients with epilepsy remains controversial.Here,we adopted a 14-day treadmill-exercise paradigm in a pilocarpine injection-induced mouse model of epilepsy.Cognitive assays confirmed the improvement of object and spatial memory after endurance training,and electrophysiological studies revealed the maintenance of hippocampal plasticity as a result of physical exercise.Investigations of the mechanisms underlying this effect revealed that exercise protected parvalbumin interneurons,probably via the suppression of neuroinflammation and improved integrity of blood-brain barrier.In summary,this work identified a previously unknown mechanism through which exercise improves cognitive rehabilitation in epilepsy.

Impact of stage-specific limb function exercises guided by a selfmanagement education model on arteriovenous fistula maturation status

BACKGROUND The exercise of limb function is the most economical and safe method to promote the maturation of arteriovenous fistula(AVF).However,due to the lack of a uni-fied exercise standard in China,many patients have insufficient awareness of the importance of AVF,leading to poor effectiveness of limb function exercise.The self-management education model can effectively promote patients to take pro-active health-related actions.This study focuses on the characteristics of patients during the peri-AVF period and conducts a phased limb function exercise under the guidance of the self-management education model to observe changes in fac-tors such as the maturity of AVF.AIM To assess the impact of stage-specific limb function exercises,directed by a self-management education model,on the maturation status of AVFs.METHODS This study is a randomized controlled trial involving 74 patients with forearm AVFs from the Nephrology Department of a tertiary hospital in Sichuan Province,China.Patients were randomly divided into an observation group and a control group using a random number table method.The observation group underwent tailored stage-specific limb func-tion exercises,informed by a self-management education model which took into account the unique features of AVF at various stages,in conjunction with routine care.Conversely,the control group was given standard limb function exercises along with routine care.The assessment involves the maturity of AVFs post-intervention,post-operative complications,and the self-management level of the fistula in both groups patients.Analyses were conducted using SPSS version 23.0.Count data were represented by frequency and percentage and subjected to chi-square test comparisons.Measurement data adhering to a normal distribution were presented as mean±SD.The independent samples t-test was utilized for inter-group comparisons,while the paired t-test was used for intra-group comparisons.For measurement data not fitting a normal distribution,the median and interquartile range were presented and analyzed using the Wilcoxon rank sum test.RESULTS At the 8-wk postoperative mark,the observation group demonstrated significantly higher scores in AVF symptom recognition,symptom prevention,and self-management compared to the control group(P<0.05).However,the variance in symptom management scores between the observation and control groups lacked statistical signi-ficance(P>0.05).At 4 wk after the operation,the observation group displayed a superior vessel diameter and depth from the skin of the drainage vessels in comparison to the control group(P<0.05).While the observation group did manifest elevated blood flow rates in the drainage vessels relative to the control group,this distinction was not statistically significant(P>0.05).By the 8-wk postoperative interval,the observation group outperformed the control group with notable enhancements in blood flow rates,vessel diameter,and depth from the skin of drainage vessels(P<0.01).Seven days following the procedure,the observation group manifested significantly diminished limb swelling and an overall reduced complication rate in contrast to the control group(P<0.05).The evaluation of infection,thrombosis,embolism,arterial aneurysm stenosis,and incision bleeding showed no notable differences between the two groups(P>0.05).By the 4-wk postoperative juncture,complications between the observation and control groups were statistically indistinguishable(P>0.05).CONCLUSION Stage-specific limb function exercises,under the guidance of a self-management education model,amplify the capacity of AVF patients to discern and prevent symptoms.Additionally,they expedite AVF maturation and miti-gate postoperative limb edema,underscoring their efficacy as a valuable method for the care and upkeep of AVF in hemodialysis patients.

Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise

Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

Exercise training mode effects on myokine expression in healthy adults:A systematic review with meta-analysis

Background:The benefits of exercise are well known;however,many of the underlying molecular mechanisms are not fully understood.Skeletal muscle secretes myokines,which mediate muscleorgan crosstalk.Myokines regulate satellite-cell proliferation and migration,inflammatory cascade,insulin secretion,angiogenesis,fatty oxidation,and cancer suppression.To date,the effects of different exercise modes(namely,aerobic and resistance exercise)on myokine response remain to be elucidated.This is crucial considering the clinical implementation of exercise to enhance general health and wellbeing and as a medical treatment.Methods:A systematic search was undertaken in PubMed,MEDLINE,CINAHL,Embase,SPORTDiscus,andWeb of Science in April 2023.Eligible studies examining the effects of a single bout of exercise on interleukin15(IL-15),irisin,secreted protein acidic and rich in cysteine(SPARC),oncostatinM(OSM),and decorin were included.A random-effects meta-analysis was also undertaken to quantify the magnitude of change.Results:Sixty-two studies were included(n=1193).Overall,exercise appeared to induce small to large increases in myokine expression,with effects observed immediately after to 60 min post-exercise,although these were mostly not statistically significant.Both aerobic and resistance exercise resulted in changes in myokine levels,without any significant difference between training modes,and with the magnitude of change differing across myokines.Myokine levels returned to baseline levels within 180 min to 24 h post-exercise.However,owing to potential sources of heterogeneity,most changes were not statistically significant,indicating that precise conclusions cannot be drawn.Conclusion:Knowledge is limited but expanding with respect to the impact of overall and specific effects of exercise on myokine expression at different time points in the systemic circulation.Further research is required to investigate the effects of different exercise modes at multiple time points on myokine response.

Impact of Exercise Atmosphere on Adolescents’Exercise Behavior:Chain Mediating Effect of Exercise Identity and Exercise Habit

Appropriate physical exercise has a positive impact on adolescents’physical and mental health,but there is a serious lack of physical exercise among Chinese adolescents.How to shape their exercise behavior(EB)has become an important task in promoting their development.A questionnaire survey was conducted using stratified cluster random sampling on three middle schools by class in Zhejiang Province,China to investigate the impact of exercise atmosphere(EA)on adolescents’exercise behavior and the mediating role of exercise identity(EI)and exercise habit(EH).806 adolescents were investigated by the Exercise Atmosphere Scale(EAS),Exercise-Identity Scale(EIS),Self-Report Habit Index(SRHI),and Physical Activity Rating Scale(PARS-3).The results show that:There is a significant positive correlation between each two of exercise atmosphere,exercise identity,exercise habit,and exercise behavior(p<0.05).Exercise atmosphere could not only directly affect adolescents’physical exercise behavior but can also indirectly affect their physical exercise behavior through the mediating effect of exercise identity and exercise habit,involving three mediating pathways,namely,the mediating path through exercise identity,the mediating pathway through exercise habit and the chain mediating pathway through exercise identity and exercise habit.The direct effect of exercise atmosphere on exercise behavior was 0.459(p<0.01),accounting for 62.62% of the total effect of 0.733,and its indirect effect was 0.274,accounting for 37.28% of the total effect.To a certain extent,the mediating effect model reveals the mechanism of exercise atmosphere affecting exercise behavior and has a certain reference value for promoting adolescents’exercise behavior.We should start by creating an exercise atmosphere,cultivating exercise identity,and enhancing exercise habits to help teenagers form active physical exercise behaviors.

The emerging role of exercise as a cancer treatment

Over the past few decades,exercise oncology has emerged as an important subfield within exercise science.Over that time,substantial progress has been made in understanding the role of exercise in people newly diagnosed with cancer,actively being treated for cancer,and recovering after cancer treatments.

An Innovative Approach towards Selecting Aerobic and Coordinative Exercises in Clinical Practice for Children and Young People with ADHD

A growing body of studies and systematic reviews show evidence of the beneficial effects of physical exercise on core symptoms of ADHD. Furthermore, studies indicate that physical exercise as an adjuvant can enhance the effects of medication in the treatment of ADHD. Aerobic and coordinative exercises improve executive functioning through their effect on neurocognitive domains that are implicated in ADHD. It is postulated that through their specific modus operandi, aerobic exercise, by raising cortical arousal levels, improves impaired alerting functions whereas coordinative exercises improve the regulation of inhibitory control through the involvement of a higher variety of frontal-dependent cognitive processes. The increasing use of routine neurocognitive testing with continuous performance tests (CPT), such as the QbTest, at clinical assessments for ADHD allows for an innovative approach to identify the assessment impairments in alerting function and inhibition control that are related to ADHD and accordingly choose aerobic or coordinative physical exercise in a more targeted fashion.

Could near infrared spectroscopy be the new weapon in our understanding of the cerebral and muscle microvascular oxygen demand during exercise?

Near-infrared spectroscopy(NIRS)has been increasingly utilized in both sport and health sciences to assess various physiological parameters related to exercise performance.1 NIRS methods coupled with the recent development of portable and wearable devices suitable for field-based measurements have revolutionized the study of exercise physiology and the determinants of exercise performance by providing real-time,non-invasive,and spatially localized measurements of tissue oxygenation dynamics.

Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

Impact of exercise on markers of B cell-related immunity:A systematic review

Background:B cells represent a crucial component of adaptive immunity that ensures long-term protection from infection by generating pathogen-specific immunoglobulins.Exercise alters B cell counts and immunoglobulin levels,but evidence-based conclusions on potential benefits for adaptive immunity are lacking.This systematic review assessed current literatures on the impact of acute exercise and exercise training on B cells,immunoglobulins,and markers of secretory immunity in human biofluids.Methods:According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines,MEDLINE,Web of Science,and Embase were searched on March 8,2023.Non-randomized controlled trials and crossover trials investigating the impact of acute exercise or exercise training on B cell counts and proportions,immunoglobulin levels,salivary flow rate,or secretory immunoglobulin A secretion rate were included.Quality and reporting of exercise training studies were assessed using the Tool for the Assessment of Study Quality and reporting in Exercise.Study characteristics,outcome measures,and statistically significant changes were summarized tabularly.Results:Of the 67 eligible studies,22 applied acute exercise and 45 applied exercise training.All included outcomes revealed significant alterations over time in acute exercise and exercise training context,but only a few investigations showed significant differences compared to control conditions.Secretory and plasma immunoglobulin A levels were most consistently increased in response to exercise training.Conclusion:B cell-related outcomes are altered by acute exercise and exercise training,but evidence-based conclusions cannot be drawn with high confidence due to the large heterogeneity in populations and exercise modalities.Well-designed trials with large sample sizes are needed to clarify how exercise shapes B cell-related immunity.

Anticancer effects of exercise:Insights from single-cell analysis

A recent special topic in the Journal of Sport and Health Science reported the health benefits conferred by traditional and innovative m-health exercise and multimodal programs with respect to several types of cancer.1 A possible mechanism behind this protective effect could be enhanced cancer immunosurveillance.

Non-coding RNAs in exercise immunology:A systematic review

Regular physical exercise has been recognized as a potent modulator of immune function,with its effects including enhanced immune surveillance,reduced inflammation,and improved overall health.While strong evidence exists that physical exercise affects the specific expression and activity of non-coding RNAs(ncRNAs)also involved in immune system regulation,heterogeneity in individual study designs and analyzed exercise protocols exists,and a condensed list of functional,exercise-dependent ncRNAs with known targets in the immune system is missing from the literature.A systematic review and qualitative analysis was used to identify and categorize ncRNAs participating in immune modulation by physical exercise.Two combined approaches were used:(a)a systematic literature search for“ncRNA and exercise immunology”,(b)and a database search for microRNAs(miRNAs)(miRTarBase and DIANA-Tarbase v8)aligned with known target genes in the immune system based on the Reactome database,combined with a systematic literature search for“ncRNA and exercise”.Literature searches were based on PubMed,Web of Science,and SPORTDiscus;and miRNA databases were filtered for targets validated by in vitro experimental data.Studies were eligible if they reported on exercise-based interventions in healthy humans.After duplicate removal,95 studies were included reporting on 164 miRNAs,which were used for the qualitative synthesis.Six studies reporting on long-noncoding RNAs(lncRNAs)or circular RNAs were also identified.Results were analyzed using ordering tables that included exercise modality(endurance/resistance exercise),acute or chronic interventions,as well as the consistency in reported change between studies.Evaluation criteria were defined as“validated”with 100%of≥3 independent studies showing identical direction of regulation,“plausible”(≥80%),or“suggestive”(≥70%).For resistance exercise,upregulation of miR-206 was validated while downregulation of miR-133a appeared plausible.For endurance exercise,15 miRNAs were categorized as validated,with 12 miRNAs being consistently elevated and 3 miRNAs being downregulated,most of them after acute exercise training.In conclusion,our approach provides evidence that miRNAs play a major role in exercise-induced effects on the innate and adaptive immune system by targeting different pathways affecting immune cell distribution,function,and trafficking as well as production of(anti-)inflammatory cytokines.miRNAs miR-15,miR-29c,miR-30a,miR-142/3,miR-181a,and miR-338 emerged as key players in mediating the immunomodulatory effects of exercise predominantly after acute bouts of endurance exercise.

Immune consequences of exercise in hypoxia:A narrative review

Immune outcomes are key mediators of many health benefits of exercise and are determined by exercise type,dose(frequency/duration,intensity),and individual characteristics.Similarly,reduced availability of ambient oxygen(hypoxia)modulates immune functions depending on the hypoxic dose and the individual capacity to respond to hypoxia.How combined exercise and hypoxia(e.g.,high-altitude training)sculpts immune responses is not well understood,although such combinations are becoming increasingly popular.Therefore,in this paper,we summarize the impact on immune responses of exercise and of hypoxia,both independently and together,with a focus on specialized cells in the innate and adaptive immune system.We review the regulation of the immune system by tissue oxygen levels and the overlapping and distinct immune responses related to exercise and hypoxia,then we discuss how they may be modulated by nutritional strategies.Mitochondrial,antioxidant,and anti-inflammatory mechanisms underlie many of the adaptations that can lead to improved cellular metabolism,resilience,and overall immune functions by regulating the survival,differentiation,activation,and migration of immune cells.This review shows that exercise and hypoxia can impair or complement/synergize with each other while regulating immune system functions.Appropriate acclimatization,training,and nutritional strategies can be used to avoid risks and tap into the synergistic potentials of the poorly studied immune consequences of exercising in a hypoxic state.

Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

Comparison of Nutrition Practices, Knowledge and Exercise between Pregnant Women in China and Zambia

Purpose: The aim of this study is to compare how Chinese and Zambian pregnant women respond to nutrition and exercise. Methods: This is a cross-sectional study with data that was conducted in Chingola City, Zambia, and Hangzhou City, China, using an online survey between September 1, 2023 and February 28, 2024. The subjects were divided into two groups (the China group and the Zambia group) according to their nationality. Results: A total of 210 participants were included through a questionnaire survey, 104 from China and 106 from Zambia. In terms of nutrient supplementation and whether to choose takeout weekly, 100% of Chinese pregnant women chose yes, while 100% of Zambian pregnant women chose no (P 0.05). The proportion of pregnant women in the China group choosing moderate or intense activities was higher than that in the Zambia group. In terms of daily exercise time, the proportion of Chinese pregnant women choosing 13 - 30 minutes or 30 - 60 minutes was significantly higher than that of Zambian pregnant women (P Conclusion: From the findings in our study, it can be observed that although pregnancy is an experience that many women may go through, lifestyle habits during pregnancy can vary from culture to culture or ethnicity.

COVID-19 vaccination produces exercise-responsive SARS-CoV-2 specific T-cells regardless of infection history

Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.Methods:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine.All major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb serology.Results:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise.However,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner.Both groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens.nAbs increased significantly during exercise only in the hybrid immunity group.Conclusion:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.

The Effect and Mechanism of Fructus lycii on Improvement of Exercise Fatigue Using a Network Pharmacological Approach with in vitro Experimental Verification

Objective This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue.Methods A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii.Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis.Results Six potential active components,namely quercetin,β-sitosterol,stigmasterol,7-Omethylluteolin-6-C-beta-glucoside_qt,atropine,and glycitein,were identified to have potency in improving exercise fatigue via multiple pathways,such as the PI3K-Akt,neuroactive ligand-receptor interaction,IL-17,TNF,and MAPK signaling pathways.The immunofluorescence results indicated that quercetin,a significant active component in Fructus lycii,increased the mean staining area of 2-NBDG,TMRM,and MitoTracker,and decreased the area of CellRox compared to the control.Furthermore,the protein expression levels of p-38 MAPK,p-MAPK,p-JNK,p-PI3K,and p-AKT markedly increased after quercetin treatment.Conclusion Fructus lycii might alleviate exercise fatigue through multiple components and pathways.Among these,quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress.The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.