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Abstract The World Health Organization determined cardiovascular disease to be the leading cause of death globally; atherosclerosis is the primary cause of the high morbidity and mortality rates. Regular physical activity is an effective strategy for maintaining endothelial health and function to prevent the development of atherosclerosis. Obesity is also a crucial risk factor for atherosclerotic progression in combination with various complications and systemic inflammation. Physiological homeostasis is modulated by the intestinal microbiota, but the mechanisms through which exercise attenuates atherosclerosis through the microbiota have not been elucidated. Therefore, we investigated the effects of endurance exercise on atherosclerosis induced by a Western diet (WD) and apolipoprotein E (ApoE) knockout in terms of microbiota parameters and metabolites. Genetically modified ApoE knockout mice (C57BL/6-Apoe em1Narl /Narl, ApoEKO) and wild-type mice (C57BL6/J) were divided into the following four groups (n = 6), namely, wild-type mice fed a chow diet (WT CD), ApoEKO mice fed a chow diet (ApoE CD), ApoEKO mice fed a WD (ApoE WD), and ApoEKO mice fed a WD and performing endurance exercise (ApoE WD EX), for a 12-week intervention. The WD significantly induced obesity and atherosclerotic syndrome in the ApoE WD group. Severe atherosclerotic lesions and arterial thickness were significantly elevated and accompanied by increases in VCAM-1, MCP-1, TNF-α, and IL-1β for immune cell chemotaxis and inflammation during atherosclerotic pathogenesis in the ApoE WD group. In addition, dysbiosis in the ApoE WD group resulted in the lowest short-chain fatty acid (SCFA) production. Endurance exercise intervention (ApoE WD EX) significantly alleviated atherosclerotic syndrome by reducing obesity, significantly inhibiting VCAM-1, MCP-1, TNF-α, and IL-1β expression, and increasing the production of SCFAs. Modulation of the microbiota associated with inflammation, such as Desulfovibrio, Tyzzerella, and Lachnospiraceae_ge, and increased SCFA production, particularly through an abundance of Rikenellaceae and Dubosiella, were also observed after exercise intervention. Endurance exercise can alleviate WD-induced atherosclerosis through the amelioration of obesity, inflammation, and chemotaxis signaling, which are modulated by the microbiota and derived SCFAs.

Abstract Background Non-alcoholic fatty liver disease (NAFLD), which is growing more common in the Western world, has become the main cause of chronic liver disease and is strongly associated with metabolism syndromes. NAFLD can indicate a wide spectrum of hepatic pathologies, ranging from simple hepatic steatosis and inflammatory non-alcoholic steatohepatitis to more severe stages of fibrosis and cirrhosis. Moreover, evidence has demonstrated that physical inactivity and westernized dietary habits may facilitate the development of NAFLD. Lipid modulation and metabolism could be important factors in the development of steatosis. Lipid species, characterized using a lipidomic approach with untargeted analysis, could provide potential biomarkers for the pathogenesis of NAFLD or therapeutic applications. Thus, in this study, the effects of exercise on the improvement of NAFLD were further investigated from a lipidomic perspective through the aspects of lipid regulation and metabolism. Methods Wild type (WT) C57BL/6 J and C57BL/6-ApoE em1Narl /Narl mice were assigned to one of four groups: WT mice fed a normal chow diet (CD), apolipoprotein E (ApoE) knockout mice fed a normal CD, ApoE knockout mice fed a high-fat diet (HFD), and ApoE knockout mice fed a HFD and provided with swimming exercise. The treatments (e.g., normal diet, HFD, and exercise) were provided for 12 consecutive weeks before the growth curves, biochemistry, fat composition, pathological syndromes, and lipid profiles were determined. Results Exercise significantly reduced the HFD-induced obesity (weight and fat composition), adipocyte hypertrophy, liver lipid accumulation, and pathological steatosis. In addition, exercise ameliorated HFD-induced steatosis in the process of NAFLD. The lipidomic analysis revealed that the changes in plasma triglyceride (14:0/16:0/22:2), phosphatidic acid (18:0/17:2), and phosphatidylglycerol (16:0/20:2) induced by the administration of the HFD could be reversed significantly by exercise. Conclusions The 12-week regular exercise intervention significantly alleviated HFD-induced NAFLD through modulation of specific lipid species in plasma. This finding could elucidate the lipids effects behind the hepatic pathogenesis with exercise.

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Introduction: Obesity, which can result from disease, genetics, nutrition, lifestyle, and insufficient physical activity, substantially increases an individual’s risk of complications and comorbidities. Exercise can be an effective strategy for achieving an energy balance and physiological fitness as part of obesity management. Additionally, probiotics, which are isolated from food and the environment, are being rapidly developed and have functional benefits for mitigating various metabolic dysfunctions associated with obesity. The potentially positive physiological and functional effects of exercise, probiotics, and exercise combined with probiotics should be elucidated in a model of diet-induced obesity. Methods: Bifidobacterium longum subsp. longum OLP-01 (OLP-01) was isolated from an elite Olympic-level athlete who exhibited physiological adaptations to peripheral fatigue caused by exercise training. In this current study, ICR strain mice were fed a high-fat diet (HFD) for 4 weeks to replicate an obesity model. The mice were divided into 5 groups according to the diet administered: control with normal diet, only HFD, HFD + exercise, HFD + OLP, and HFD + exercise + OLP groups. They were administered the probiotic and/or treadmill exercise training for 5 weeks, and their growth curve, physical activity, physiological adaptation, biochemical parameters, body composition, and glucose tolerance were assessed. Results: Compared with only exercise or only probiotics, a combination of probiotics and exercise significantly improved the weight, glucose tolerance, fat composition, and exercise-related oxidative stress of mice. Regular and programmed exercise with sufficient rest may be crucial to obesity improvement, and a combination of probiotics and exercise may synergistically assist obesity management and health promotion. Conclusion: OLP-01 probiotics combined with exercise training can be employed as a strategy for treating obesity. However, the exact regulatory mechanisms underlying this effect, possibly involving microbiota and associated metabolites, warrant further investigation.

BackgroundOsteoporosis and immune-associated disorders are highly prevalent among menopausal women, and diet control and exercise exert beneficial effects on physiological modulation in this population. A controlled diet with a low fat content and a balanced caloric intake improves menopausal health, but the health effects of excessive fructose consumption on menopausal women are yet to be confirmed. In addition, whole-body vibration (WBV), a safe passive-training method, has been shown to have multiple beneficial effects on metabolism regulation, obesity, and bone health.MethodsThe ovariectomized (OVX) C57BL/6J model was used to verify the effects of WBV combined with a high-fructose diet (HFrD) for 16 weeks on physiological modulation and immune responses. The mice were randomly allocated to sham, OVX, OVX+HFrD, and OVX+HFrD+WBV groups, which were administered with the indicated ovariectomy, dietary and WBV training treatments. We conducted growth, dietary intake, glucose homeostasis, body composition, immunity, inflammation, histopathology, and osteoporotic assessments (primary outcomes).ResultsOur results showed that the isocaloric HFrD in OVX mice negated estrogen-deficiency–associated obesity, but that risk factors such as total cholesterol, glucose intolerance, osteoporosis, and liver steatosis still contributed to the development of metabolic diseases. Immune homeostasis in the OVX mice was also negatively affected by the HFrD diet, via the comprehensive stimulation of T cell activation, causing inflammation. The WBV intervention combined with the HFrD model significantly ameliorated weight gain, glucose intolerance, total cholesterol, and inflammatory cytokines (interferon gamma [IFN-γ], interleukin [IL]-17, and IL-4) in the OVX mice, although osteoporosis and liver steatosis were not affected compared to the negative control group. These findings indicate that an isocaloric high-fructose diet alone may not result in menopausal obesity, but that some deleterious physiological impacts still exist.ConclusionThe WBV method may modulate the physiological impacts of menopause and the HFrD diet, and should be considered as an alternative exercise prescription for people with poor compliance or who are unable or unwilling to use traditional methods to improve their health. In future studies, using the WBV method as a preventive or therapeutic strategy, combined with nutritional interventions, medication, and other exercise prescriptions, may prove beneficial for maintaining health in menopausal women.

Complementary and alternative medicines (CAMs) are widely applied and accepted for therapeutic purposes because of their numerous benefits. Negative ion treatment belongs to one of the critical categories defined by the National Center for CAM, with such treatment capable of air purification and ameliorating emotional disorders (e.g., depression and seasonal affective disorder). Negative ions can be produced naturally and also by a material with activated energy. Exercise-induced muscle damage (EIMD) often occurs due to inadequate warm up, high-intensity exercise, overload, and inappropriate posture, especially for high-intensive competition. Few studies have investigated the effects of negative ion treatment on muscular injury in the sports science field. In the current study, we enrolled badminton athletes and induced muscle damage in them through eccentric exercise in the form of a high-intensity squat program. We evaluated the effects of negative ion patches of different intensities at three points (preexercise, postexercise, and recovery) by analyzing physiological indexes (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-10, creatine kinase [CK], and lactate dehydrogenase [LDH] levels) and performing a functional assessment (a countermovement jump [CMJ] test). We found that a high-intensity negative ion patch could significantly reduce the levels of TNF-α, an injury-associated inflammatory cytokine, and related markers (CK and LDH). In addition, muscular overload-caused fatigue could be also ameliorated, as indicated by the functional CMJ test result, and related muscular characteristics (tone and stiffness) could be effectively improved. Thus, the negative ion treatment could effectively improve physiological adaption and muscular fatigue recovery after EIMD in the current study. The negative ion patch treatment can be further integrated into a taping system to synergistically fulfill exercise-induced damage protection and functional elevation. However, the effects of this treatment require further experimental validation.

Eccentric contraction can easily cause muscle damage and an inflammatory response, which reduces the efficiency of muscle contraction. Resveratrol causes anti-inflammatory effects in muscles, accelerates muscle repair, and promotes exercise performance after contusion recovery. However, whether resveratrol provides the same benefits for sports injuries caused by eccentric contraction is unknown. Thus, we explored the effects of resveratrol on inflammation and energy metabolism. In this study, mice were divided into four groups: a control group, an exercise group (EX), an exercise with low-dose resveratrol group (EX + RES25), and an exercise with high-dose resveratrol group (EX + RES150). The results of an exhaustion test showed that the time before exhaustion of the EX + RES150 group was greater than that of the EX group. Tumour necrosis factor-α (Tnfα) mRNA expression was lower in the EX + RES150 group than in the EX group. The energy utilisation of the EX + RES150 group was greater than that of the EX + RES25 group in different muscles. High-dose resveratrol intervention decreased Tnfα mRNA expression and enhanced the mRNA expressions of sirtuin 1, glucose transporter 4, AMP-activated protein kinase α1, and AMP-activated protein kinase α2 in muscles. These results revealed that high-dose resveratrol supplementation can reduce inflammation and oxidation and improve energy utilisation during short-duration high-intensity exercise.

Atherosclerosis is the preliminary cause of coronary artery disease, one of the diseases that account for the largest number of fatal mortalities. Physical activity is an effective strategy to restrain atherosclerosis from deterioration. Evidence indicated that changes in the proteomic profile are highly associated with atherosclerosis development, but the mechanism behind exercise for atherosclerosis amelioration has not yet been investigated from a proteomics perspective. Hence, the proteomic profiles could further elucidate the systematic effects of exercise intervention on ApoE knockout atherosclerotic model and high-fat-diet intervention. In the current study, Apoeem1Narl/Narl mice were randomly allocated into a normal diet (ND), Western diet (WD), and WD with 12-week exercise intervention (WD EX) groups. The plasma proteome between WD and WD EX groups demonstrate the significant difference, and ten major pathways, including cardiovascular disease (CVD)–hematological disease, inflammatory disease, infectious diseases, inflammatory response, cell-to-cell signaling and interaction, connective tissue disorders_inflammatory disease, metabolic disease_organismal injury and abnormalities, cell-to-cell signaling and interaction, connective tissue disorders_inflammatory disease, and endocrine system disorders_gastrointestinal disease, etc., were generated by the IPA analysis. The 15 proteins (MYOCD, PROS1, C2, SERPINA10, CRP, F5, C5, CFB, FGG, CFH, F12, PRDX2, PROZ, PPIA, and HABP2) critically involved in CVD–hematological disease pathway showed significant difference between WD and WD EX groups. In current study, exercise could significantly alleviate the significantly elevated C5 and inflammation induced by the WD group in accordance with amelioration of atherosclerosis. Therefore, exercise could mitigate chemotaxis through the modulation of the C5 level and innate immunity, thereby alleviating the pathogenesis of atherosclerosis in Western-diet-induced obese mice.

Overtraining in athletes usually causes profound and lasting deleterious effects on the maintenance of health and exercise capacity. Here, we established an overtraining animal model to investigate the physiological modulation for future strategic applications in vivo. We subjected C57BL/6 mice to exhaustive treadmill exercises daily for 8 weeks (the exhaustive exercise group). Next, the physiological and psychological outcomes were compared with the regular exercise and sedentary groups. Outcome measures included growth, glucose tolerance, exercise metabolism profiles, cytokine levels, intestinal tight junction gene expression, and psychological behavioral changes. Our results revealed that overtraining negatively affected the physiological and psychological changes in the current model. The exhaustive exercise group exhibited significantly lower endurance performance and imbalanced energy expenditure, causing a decrease in body fat mass and slowing down the growth curve. In addition, the inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, and interleukin-1β) and immune cells (neutrophils and monocytes) were significantly elevated after successive exhaustive exercise interventions. Furthermore, overtraining-induced stress resulted in increased anxiety status and decreased food intake. Our findings reinforce the idea that an imbalance between exercise and recovery can impair health and performance maintenance after overtraining. This study highlights the maladaptation of overtraining and provides an animal model to determine the effectiveness of possible strategies, including nutrition and monitoring, for treatment and prevention of overtraining syndromes in future studies.

Regular exercise prevents lipid abnormalities and conditions such as diabetes mellitus, hypertension, and obesity; it considerably benefits sedentary individuals. However, individuals exhibit highly variable responses to exercise, probably due to genetic variations. Animal models are typically used to investigate the relationship of intrinsic exercise capacity with physiological, pathological, psychological, behavioral, and metabolic disorders. In the present study, we investigated differential physiological adaptations caused by intrinsic exercise capacity and explored the regulatory molecules or mechanisms through multiomics approaches. Outbred ICR mice (n = 100) performed an exhaustive swimming test and were ranked based on the exhaustive swimming time to distinguish intrinsically high- and low-capacity groups. Exercise performance, exercise fatigue indexes, glucose tolerance, and body compositions were assessed during the experimental processes. Furthermore, the gut microbiota, transcriptome, and proteome of soleus muscle with intrinsically high exercise capacity (HEC) and low exercise capacity (LEC) were further analyzed to reveal the most influential factors associated with differential exercise capacities. HEC mice outperformed LEC mice in physical activities (exhaustive swimming and forelimb grip strength tests) and exhibited higher glucose tolerance than LEC mice. Exercise-induced peripheral fatigue and the level of injury biomarkers (lactate, ammonia, creatine kinase, and aspartate aminotransferase) were also significantly lower in HEC mice than in LEC mice. Furthermore, the gut of the HEC mice contained significantly more Butyricicoccus than that of the LEC mice. In addition, transcriptome data of the soleus muscle revealed that the expression of microRNAs that are strongly associated with exercise performance-related physiological and metabolic functions (i.e., miR-383, miR-107, miR-30b, miR-669m, miR-191, miR-218, and miR-224) was higher in HEC mice than in LEC mice. The functional proteome data of soleus muscle indicated that the levels of key proteins related to muscle function and carbohydrate metabolism were also significantly higher in HEC mice than in LEC mice. Our study demonstrated that the mice with various intrinsic exercise capacities have different gut microbiome as well as transcriptome and proteome of soleus muscle by using multiomics approaches. The specific bacteria and regulatory factors, including miRNA and functional proteins, may be highly correlated with the adaptation of physiological functions and exercise capacity.

The wide diversity in gut microbiota that is found among individuals is affected by factors including environment, genetics, dietary habits, and lifestyle after birth. The gastrointestinal tract, the largest and most complicated in vivo ecosystem, is a natural habitat for microbe colonization. Gut microbiota acts as “metabolic organ” that interacts with the human host symbiotically and performs an important role in maintaining health. In addition to the above factors, microbiota distributions/proportions are affected by exercise and other forms of physical activity. However, diet, lifestyle, and nutritional supplementation may impede the actual analytic relationship in practice. Therefore, the purpose of this study is to understand the effects of several microbiota on physical fitness, exercise performance, energy metabolism, and biochemistries using the concept of gnotobiote based on a germ-free model. The microbes Eubacterium rectale, Lactobacillus plantarum TWK10, and Clostridium coccoides were separately inoculated into gnotobiotic animal models. Fecal analysis was regularly done for the entire duration of the experiment. The exercise capacities were measured repeatedly with and without aerobic exercise training using an exhaustive swimming test. Various fatigue-associated biochemical variables, including lactate, ammonia, glucose, lactic dehydrogenase (LDH), and creatine kinase (CK) were also measured to assess physiological adaption. In addition, metabolic phenotype was applied to record basal metabolic rate, diet, behavior, and activities. Body composition, glycogen content, and histopathology were further evaluated to assess the gnotobiotic effects. E. rectale engendered capacities, physiological adaption, and physical activities that were significantly better than other two microbes, possible due to energy regulation and bioavailability. In addition, L. plantarum TWK10 and C. coccoides were found to significantly increase the basal metabolic rate and to alter the body compositions, although no exercise capacity benefit was found in the gnotobiotic models. The E. rectale and L. plantarum gnotobiotic animals all showed normal histological observations with the exception of the C. coccoides gnotobiote, which showed the pathological observation of hepatic necrosis. The gnotobiotic model directly demonstrates the interactions between microbes and hosts, which are especially relevant and applicable to the field of sports science. This study supports the development of beneficial microbiota for application to exercise and fitness, which is an emerging area of health promotion.

Tomato is a globally famous food and contains several phytonutrients including lycopene, β-carotene, anthocyanin, and flavonoids. The increased temperature used to produce tomato juice, ketchup, tomato paste and canned tomato enhances the bioactive composition. We aimed to verify the beneficial effects of processed tomato juice from Kagome Ltd. (KOT) on hypolipidemic action in hamsters with hyperlipidemia induced by a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet (HCD)). Male Golden Syrian hamsters were randomly divided into two groups for treatment: normal (n = 8), standard diet (control); and experimental (n = 32), HCD. The 32 hamsters were further divided into four groups (n = 8 per group) to receive vehicle or KOT by oral gavage at 2787, 5573, or 13,934 mg/kg/day for six weeks, designated the HCD-1X, -2X and -5X groups, respectively. The efficacy and safety of KOT supplementation was evaluated by lipid profiles of serum, liver and feces and by clinical biochemistry and histopathology. HCD significantly increased serum levels of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio, hepatic and fetal TC and TG levels, and degree of fatty liver as compared with controls. KOT supplementation dose-dependently decreased serum TC, TG, LDL-C levels, LDL-C/HDL-C ratio, hepatic TC and TG levels, and fecal TG level. Our study provides experiment-based evidence to support that KOT may be useful in treating or preventing the onset of hyperlipidemia.

A triathlon is an extremely high-intensity exercise and a challenge for physiological adaptation. A triathlete’s microbiome might be modulated by diet, age, medical treatments, lifestyle, and exercise, thereby maintaining aerobiosis and optimum health and performance. Probiotics, prebiotics, and synbiotics have been reported to have health-promoting activities (e.g., immunoregulation and cancer prevention). However, few studies have addressed how probiotics affect the microbiota of athletes and how this translates into functional activities. In our previous study, we found that Lactobacillus plantarum PS128 could ameliorate inflammation and oxidative stress, with improved exercise performance. Thus, here we investigate how the microbiota of triathletes are altered by L. plantarum PS128 supplementation, not only for exercise performance but also for possible physiological adaptation. The triathletes were assigned to two groups: an L. plantarum 128 supplement group (LG, 3 × 1010 colony-forming units (CFU)/day) and a placebo group (PG). Both groups continued with their regular exercise training for the next 4 weeks. The endurance performance, body composition, biochemistries, blood cells, microbiota, and associated metabolites were further investigated. PS128 significantly increased the athletes’ endurance, by about 130% as compared to the PG group, but there was no significant difference in maximal oxygen consumption (VO2max) and composition between groups. The PS128 supplementation (LG) modulated the athlete’s microbiota with both significant decreases (Anaerotruncus, Caproiciproducens, Coprobacillus, Desulfovibrio, Dielma, Family_XIII, Holdemania, and Oxalobacter) and increases (Akkermansia, Bifidobacterium, Butyricimonas, and Lactobacillus), and the LG showed lower diversity when compared to the PG. Also, the short-chain fatty acids (SCFAs; acetate, propionate, and butyrate) of the LG were significantly higher than the PG, which might be a result of a modulation of the associated microbiota. In conclusion, PS128 supplementation was associated with an improvement on endurance running performance through microbiota modulation and related metabolites, but not in maximal oxygen uptake.

Moderate to severe psoriasis, an immune-mediated inflammatory disease, adversely affects patients’ lives. Cyclosporin A (CsA), an effective immunomodulator, is used to treat psoriasis. CsA is ineffective at low doses and toxic at high doses. Acarbose (Acar), a common antidiabetic drug with anti-inflammatory and immunomodulatory effects, reduces imiquimod (IMQ)-induced psoriasis severity. Combinations of systemic drugs are generally more efficacious and safer than higher doses of single drugs. We observed that mice treated with a combination of Acar (250 mg/kg) and low-dose CsA (10 or 20 mg/kg) exhibited significantly milder IMQ-induced psoriasis-like dermatitis and smoother back skin than those treated with Acar (250 mg/kg), low-dose CsA (10 or 20 mg/kg), or IMQ alone. The combination therapy significantly reduced serum and skin levels of Th17-related cytokines (interleukin (IL)-17A, IL-22, and IL-23) and the Th1-related cytokine tumor necrosis factor-α (TNF-α) compared with Acar, low-dose CsA, and IMQ alone. Additionally, the combination therapy significantly reduced the percentages of IL-17- and IL-22-producing CD4+ T-cells (Th17 and Th22 cells, respectively) and increased that of Treg cells. Our data suggested that Acar and low-dose CsA in combination alleviates psoriatic skin lesions by inhibiting inflammation. The findings provide new insights into the effects of immunomodulatory drugs in psoriasis treatment.

Probiotics exert multiple health benefits, including gastrointestinal health, immunoregulation, and metabolic disease improvement, by modulating microbiota to maintain eubiosis via the hypothalamic–pituitary–adrenal (HPA) and brain–gut–microbiome axes. Physiological fatigue, mental stress, and gastrointestinal discomfort under the demands of athletic performance as well as immunosuppression are common during endurance training and competition. Limited studies investigated the functional effects of probiotic supplementation on endurance training. Bifidobacterium longum subsp. Longum OLP-01 (OLP-01), isolated from an elite Olympic athlete, was combined with a six-week exercise training program with gradually increasing intensity. In this study, Institute of Cancer Research (ICR) mice were assigned to sedentary, exercise, OLP-01, or exercise + OLP-01 groups and administered probiotic and/or treadmill exercise training for six weeks to assess exercise performance, physiological adaption, and related metabolites. The exercise + OLP-01 group demonstrated higher performance in terms of endurance and grip strength, as well as improved fatigue-associated indexes (lactate, ammonia, creatine kinase (CK), lactate dehydrogenase (LDH), and glycogen content), compared with the other groups. OLP-01 supplementation significantly ameliorated inflammation and injury indexes (platelet/lymphocyte ratio (PLR), aminotransferase (AST), and CK) caused by prolonged endurance exercise test. Moreover, acetate, propionate, and butyrate levels were significantly higher in the exercise + OLP-01 group than in the sedentary and OLP-01 groups. Athletes often experience psychological and physiological stress caused by programed intensive exercise, competition, and off-site training, often leading to poor exercise performance and gastrointestinal issues. Functional OLP-01 probiotics are considered to be a nutritional strategy for improving physiological adaption, oxidative stress, inflammation, and energy balance to ensure high physical performance. Based on these results, probiotics combined with exercise training is a potential strategy for ensuring high physical performance of athletes, which should be further investigated through microbiota validation.

Low-osmolality carbohydrate–electrolyte solution (LCS) ingestion can replace losses from exercise-induced dehydration, but the benefits of LCS ingestion strategy after exhaustive endurance exercise (EEE) remain unknown. The present study evaluated the effects of LCS ingestion on dehydration, oxidative stress, renal function, and aerobic capacity after EEE. In our study with its double-blind, crossover, counterbalanced design, 12 healthy male participants were asked to consume LCS (150 mL four times per hour) or placebo (water) 1 h before and 1 h after EEE. All participants completed a graded exercise test to exhaustion on a treadmill for the determination of maximal oxygen consumption ( V ˙ O 2 max ), applied to further intensity calibration, and then completed the EEE test. The average heart rate, maximal heart rate, running time to exhaustion, and peak oxygen uptake (VO2peak) were recorded during the exercise period. The participants’ body weight was recorded at different time points before and after the EEE to calculate the dehydration rate. Blood samples were drawn at baseline and before, immediately after, 1 h after, and 2 h after EEE to determine indicators of oxidative stress and renal function. The results indicated that the dehydration rates in participants with LCS ingestion at 15 min, 30 min, and 45 min after EEE were significantly lower than in participants with placebo ingestion (−1.86 ± 0.47% vs. −2.24 ± 0.72%; −1.78 ± 0.50% vs. −2.13 ± 0.74%; −1.54 ± 0.51% vs. −1.94 ± 0.72%, respectively; p < 0.05). In addition, the concentration of catalase in participants with LCS ingestion immediately after EEE was significantly higher than in participants with placebo ingestion (2046.21 ± 381.98 nmol/min/mL vs. 1820.37 ± 417.35 nmol/min/mL; p < 0.05). Moreover, the concentration of protein carbonyl in participants with LCS ingestion immediately after EEE was slightly lower than in participants with placebo ingestion (2.72 ± 0.31 nmol carbonyl/mg protein vs. 2.89 ± 0.43 nmol carbonyl/mg protein; p = 0.06). No differences were noted for other variables. Our findings conclude that LCS ingestion can effectively avoid fluid loss and oxidative stress after EEE. However, LCS ingestion had no benefits for renal function or aerobic capacity.

Probiotics have been rapidly developed for health promotion, but clinical validation of the effects on exercise physiology has been limited. In a previous study, Lactobacillus plantarum TWK10 (TWK10), isolated from Taiwanese pickled cabbage as a probiotic, was demonstrated to improve exercise performance in an animal model. Thus, in the current study, we attempted to further validate the physiological function and benefits through clinical trials for the purpose of translational research. The study was designed as a double-blind placebo-controlled experiment. A total of 54 healthy participants (27 men and 27 women) aged 20−30 years without professional athletic training were enrolled and randomly allocated to the placebo, low (3 × 1010 colony forming units (CFU)), and high dose (9 × 1010 CFU) TWK10 administration groups (n = 18 per group, with equal sexes). The functional and physiological assessments were conducted by exhaustive treadmill exercise measurements (85% VO2max), and related biochemical indices were measured before and after six weeks of administration. Fatigue-associated indices, including lactic acid, blood ammonia, blood glucose, and creatinine kinase, were continuously monitored during 30 min of exercise and a 90 min rest period using fixed intensity exercise challenges (60% VO2max) to understand the physiological adaptation. The systemic inflammation and body compositions were also acquired and analyzed during the experimental process. The results showed that TWK10 significantly elevated the exercise performance in a dose-dependent manner and improved the fatigue-associated features correlated with better physiological adaptation. The change in body composition shifted in the healthy direction for TWK10 administration groups, especially for the high TWK10 dose group, which showed that body fat significantly decreased and muscle mass significantly increased. Taken together, our results suggest that TWK10 has the potential to be an ergogenic aid to improve aerobic endurance performance via physiological adaptation effects.

We aimed to verify the beneficial effects of probiotic strain Lactobacillus reuteri 263 (Lr263) on hypolipidemic action in hamsters with hyperlipidemia induced by a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet (HCD)). Male Golden Syrian hamsters were randomly divided into two groups: normal (n = 8), standard diet (control), and experimental (n = 32), a HCD. After a two-week induction followed by a six-week supplementation with Lr263, the 32 hyperlipidemic hamsters were divided into four groups (n = 8 per group) to receive vehicle or Lr263 by oral gavage at 2.1, 4.2, or 10.5 × 109 cells/kg/day for 6 weeks, designated the HCD, 1X, 2X and 5X groups, respectively. The efficacy and safety of Lr263 supplementation were evaluated by lipid profiles of serum, liver and feces and by clinical biochemistry and histopathology. HCD significantly increased serum levels of total cholesterol (TC), triacylglycerol (TG) cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio, hepatic and fetal TC and TG levels, and degree of fatty liver as compared with controls. Lr263 supplementation dose dependently increased serum HDL-C level and decreased serum TC, TG, LDL-C levels, LDL-C/HDL-C ratio, hepatic TC and TG levels, and fecal TG level. In addition, Lr263 supplementation had few subchronic toxic effects. Lr263 could be a potential agent with a hypolipidemic pharmacological effect.

Curcumin (CCM) is a well-known phytocompound and food component found in the spice turmeric and has multifunctional bioactivities. However, few studies have examined its effects on exercise performance and physical fatigue. We aimed to evaluate the potential beneficial effects of CCM supplementation on fatigue and ergogenic function following physical challenge in mice. Male ICR mice were divided into four groups to receive vehicle or CCM (180 μg/mL) by oral gavage at 0, 12.3, 24.6, or 61.5 mL/kg/day for four weeks. Exercise performance and anti-fatigue function were evaluated after physical challenge by forelimb grip strength, exhaustive swimming time, and levels of physical fatigue-associated biomarkers serum lactate, ammonia, blood urea nitrogen (BUN), and glucose and tissue damage markers such as aspartate transaminase (AST), alanine transaminase (ALT), and creatine kinase (CK). CCM supplementation dose-dependently increased grip strength and endurance performance and significantly decreased lactate, ammonia, BUN, AST, ALT, and CK levels after physical challenge. Muscular glycogen content, an important energy source for exercise, was significantly increased. CCM supplementation had few subchronic toxic effects. CCM supplementation may have a wide spectrum of bioactivities for promoting health, improving exercise performance and preventing fatigue.

Bacteroides fragilis (BF) are Gram-negative anaerobe symbionts present in the colon. Recent studies have reported the beneficial role of BF in maintaining intestinal homeostasis, stimulating host immunologic development, and preventing infectious colitis caused by pathogenic bacteria. Our previous studies showed that monocolonization of germ-free mice with BF significantly reduced colon inflammations and damage.In order to investigate the Toll-like receptor-2 (TLR2), TLR4, and interleukin 10 (IL-10) molecular signaling pathways involved in BF-mediated prevention of dextran sulfate sodium (DSS)-induced colitis. The wild-type (WT), TLR4, TLR2, and IL-10 knockout (-/-) germ-free mice grown were with or without BF colonization for 28 days, and then administered 1% DSS in drinking water for 7 day to induce acute ulcerative colitis.We compared phenotypes such as weight loss, disease activity, intestinal histological scores, and immunohistochemistry for inflammatory cells. Unlike WT and TLR4-/- mice, the severity of DSS-colitis did not improve in TLR2-/- animals after BF colonization. The BF enhanced anti-inflammatory cytokines IL-10 expression and inhibited pro-inflammatory-related tumor necrosis factor (TNF-α) and IL-6 mRNA expression in both WT and TLR4-/- mice. In contrast, the failed to up-regulated IL-10 and down-regulated the TNF-α and IL-6 in BF colonization TLR2-/- mice. In addition, we further perform IL-10-/- mice to clarify whether the BF through TLR2 /IL-10 pathway to alleviate DSS-colitis. There were no significant differences in colitis severity and pro-inflammatory related genes expression in the IL-10-/- mice with or without BF colonization.These results indicate the disease-preventing effects of BF in acute DSS-induced colitis may occur through the TLR2/IL-10 signal pathway.

Chicken essence (CE) is a liquid nutritional supplement made from cooking whole chickens. In traditional Chinese medicine, CE is used to support health, promote healing, increase metabolism, and relieve fatigue. However, few studies have examined the effect of CE on exercise performance and physical fatigue. We aimed to evaluate the potential beneficial effects of CE on fatigue and ergogenic functions following physical challenge in mice. Male ICR mice were divided into four groups to receive vehicle or CE by oral gavage at 0, 845, 1690, or 4225 mg/kg/day for 4 weeks. Exercise performance and anti-fatigue function were evaluated by forelimb grip strength, exhaustive swimming time, and levels of physical fatigue-related biomarkers serum lactate, ammonia, glucose, and creatine kinase (CK) after physical challenge. CE supplementation dose-dependently elevated endurance and grip strength. CE supplementation significantly decreased lactate, ammonia, and CK levels after physical challenge. Tissue glycogen content, an important energy source for exercise, was significantly increased with CE supplementation. In addition, CE supplementation had few subchronic toxic effects. The supplementation with CE can have a wide spectrum of bioactivities on health promotion, performance improvement and anti-fatigue.

Adipocyte differentiation and the extent of subsequent fat accumulation are closely related to the occurrence and progression of diseases such as insulin resistance and obesity. Black soybean koji (BSK) is produced by the fermentation of black soybean with Aspergilllus awamori. Previous study indicated that BSK extract has antioxidative and multifunctional bioactivities, however, the role of BSK in the regulation of energy metabolism is still unclear. We aimed to investigate the effect of glucose utilization on insulin-resistant 3T3-L1 preadipocytes and adipogenesis-related protein expression in differentiated adipocytes with BSK treatment. Cytoxicity assay revealed that BSK did not adversely affect cell viability at levels up to 200 µg/mL. The potential for glucose utilization was increased by increased glucose transporter 1 (GLUT1), GLUT4 and protein kinase B (AKT) protein expression in insulin-resistant 3T3-L1 cells in response to BSK treatment. Simultaneously, BSK inhibited lipid droplet accumulation in differentiated 3T3-L1 cells. The inhibitory effect of adipogenesis was associated with downregulated peroxisome proliferator-activated receptor g (PPARγ) level and upregulated Acrp30 protein expression. Our results suggest that BSK extract could improve glucose uptake by modulating GLUT1 and GLUT4 expression in a 3T3-L1 insulin-resistance cell model. In addition, BSK suppressed differentiation and lipid accumulation in mature 3T3-L1 adipocytes, which may suggest its potential for food supplementation to prevent obesity and related metabolic abnormalities.

Astragalus membranaceus (AM) is a popular “Qi-tonifying” herb with a long history of use as a Traditional Chinese Medicine with multiple biological functions. However, evidence for the effects of AM on exercise performance and physical fatigue is limited. We evaluated the potential beneficial effects of AM on ergogenic and anti-fatigue functions following physiological challenge. Male ICR strain mice were randomly assigned to four groups (n = 10 per group) for treatment: (1) sedentary control and vehicle treatment (vehicle control); (2) exercise training with vehicle treatment (exercise control); and (3) exercise training with AM treatment at 0.615 g/kg/day (Ex-AM1) or (4) 3.075 g/kg/day (Ex-AM5). Both the vehicle and AM were orally administered for 6 weeks. Exercise performance and anti-fatigue function were evaluated by forelimb grip strength, exhaustive swimming time, and levels of serum lactate, ammonia, glucose, and creatine kinase after 15-min swimming exercise. Exercise training combined with AM supplementation increased endurance exercise capacity and increased hepatic and muscle glycogen content. AM reduced exercise-induced accumulation of the byproducts blood lactate and ammonia with acute exercise challenge. Moreover, we found no deleterious effects from AM treatment. Therefore, AM supplementation improved exercise performance and had anti-fatigue effects in mice. It may be an effective ergogenic aid in exercise training.

Obesity has become an epidemic worldwide. It is a complex metabolic disorder associated with many serious complications and high morbidity. Rice bran is a nutrient-dense by product of the rice milling process. Asia has the world’s highest rice production (90% of the world’s rice production); therefore, rice bran is inexpensive in Asian countries. Moreover, the high nutritional value of the rice bran suggests its potential as a food supplement promoting health improvements, such as enhancing brain function, lowering blood pressure, and regulating pancreatic secretion. The present study evaluated the anti-obesity effect of rice bran in rats with high-energy diet (HED)-induced obesity. Male Sprague−Dawley rats were randomly divided into one of five diet groups (n = 10 per group) and fed the following for eight weeks: Normal diet with vehicle treatment, HED with vehicle, rice bran-0.5X (RB-0.5X) (2% wt/wt rice bran), RB-1.0X (4% wt/wt rice bran), and RB-2.0X (8% wt/wt rice bran). Rice bran (RB-1.0X and RB-2.0X groups) markedly reduced obesity, including body weight and adipocyte size. In addition, treating rats with HED-induced obesity using rice bran significantly reduced the serum uric acid and glucose as well as the liver triglyceride (TG) and total cholesterol (TC). Furthermore, administration of an HED to obese rats significantly affected hepatic lipid homeostasis by increasing phosphotidylcholine (PC; 18:2/22:6), diacylglycerol (DG; 18:2/16:0), DG (18:2/18:1), DG (18:1/16:0), cholesteryl ester (CE; 20:5), CE (28:2), TG (18:0/16:0/18:3), and glycerol-1-2-hexadecanoate 3-octadecanoate. However, the rice bran treatment demonstrated an anti-adiposity effect by partially reducing the HED-induced DG (18:2/18:1) and TG (18:0/16:0/18:3) increases in obese rats. In conclusion, rice bran could act as an anti-obesity supplement in rats, as demonstrated by partially reducing the HED-induced DG and TG increases in obese rats, and thus limit the metabolic diseases associated with obesity and the accumulation of body fat and hepatic lipids in rats.

Calendula officinalis, Ribes nigrum, and Vaccinium myrtillus (CRV) possess a high phenolic compound content with excellent antioxidant activity. Dietary antioxidants can reduce exercise-induced oxidative stress. Consumption of large amounts of phenolic compounds is positively correlated with reduction in exercise-induced muscle damage. Research for natural products to improve exercise capacity, relieve fatigue, and accelerate fatigue alleviation is ongoing. Here, CRV containing a large total phenolic content (13.4 mg/g of CRV) demonstrated antioxidant activity. Ultra-performance liquid chromatography quantification revealed 1.95 ± 0.02 mg of salidroside in 1 g of CRV. In the current study, CRV were administered to mice for five weeks, and the antifatigue effect of CRV was evaluated using the forelimb grip strength test; weight-loaded swimming test; and measurement of fatigue-related biochemical indicators, such as blood lactate, ammonia, glucose, blood urea nitrogen (BUN), and creatine kinase (CK) activity; and muscle and liver glycogen content. The results indicated that in CRV-treated mice, the forelimb grip strength significantly increased; weight-loaded swimming time prolonged; their lactate, ammonia, BUN, and CK activity decreased, and muscle and liver glucose and glycogen content increased compared with the vehicle group. Thus, CRV have antifatigue activity and can increase exercise tolerance.

Menopause is associated with changes in body composition (a decline in lean body mass and an increase in total fat mass), leading to an increased risk of metabolic syndrome, nonalcoholic fatty liver disease, and heart disease. A healthy diet to control body weight is an effective strategy for preventing and treating menopause-related metabolic syndromes. In the present study, we investigated the effect of long-term feeding of edible oils (soybean oil (SO), tea seed oil (TO), and lard oil (LO)) on female ovariectomized (OVX) mice. SO, TO, and LO comprise mainly polyunsaturated fatty acids (PUFA), monounsaturated fatty acids (MUFA), and saturated fatty acids (SFA), respectively. However, there have been quite limited studies to investigate the effects of different fatty acids (PUFA, MUFA, and SFA) on physiological adaption and metabolic homeostasis in a menopausal population. In this study, 7-week-old female Institute of Cancer Research (ICR) mice underwent either bilateral laparotomy (sham group, n = 8) or bilateral oophorectomy (OVX groups, n = 24). The OVX mice given a high-fat diet (HFD) were randomly divided into three groups: OVX+SO, OVX+TO, and OVX+LO. An HFD rich in SO, TO, or LO was given to the OVX mice for 12 weeks. Our findings revealed that the body weight and relative tissues of UFP (uterus fatty peripheral) and total fat (TF) were significantly decreased in the OVX+TO group compared with those in the OVX+SO and OVX+LO groups. However, no significant difference in body weight or in the relative tissues of UFP and TF was noted among the OVX+SO and OVX+LO groups. Furthermore, mice given an HFD rich in TO exhibited significantly decreased accumulation of liver lipid droplets and adipocyte sizes of UFP and brown adipose tissue (BAT) compared with those given an HFD rich in SO or LO. Moreover, replacing SO or LO with TO significantly increased oral glucose tolerance. Additionally, TO improved endurance performance and exhibited antifatigue activity by lowering ammonia, blood urea nitrogen, and creatine kinase levels. Thus, tea seed oil (TO) rich in MUFA could prevent obesity, reduce physical fatigue, and improve exercise performance compared with either SO (PUFA)- or LO(SFA)-rich diets in this HFD-induced obese OVX mice model.

A triathlon, which consists of swimming, bicycling, and running, is a high-intensity and long-term form of exercise that can cause injuries such as muscular damage, inflammation, oxidative stress, and energy imbalance. Probiotics are thought to play an important role in disease incidence, health promotion, and nutrient metabolism, but only a few studies have focused on physiological adaptations to exercise in sports science. Previous studies indicated that Lactobacillus supplementation could improve oxidative stress and inflammatory responses. We investigate the effects of Lactobacillus plantarum PS128 supplementation on triathletes for possible physiological adaptation. The triathletes were assigned to one of two groups with different exercise intensity stimulations with different time-points to investigate the effects of body compositions, inflammation, oxidative stress, performance, fatigue, and injury-related biochemical indices. L. plantarum PS128 supplementation, combined with training, can significantly alleviate oxidative stress (such as creatine kinase, Thioredoxin, and Myeloperoxidase indices) after a triathlon (p < 0.05). This effect is possibly regulated by a 6⁻13% decrease of indicated pro-inflammation (TNF-α, IL-6, and IL-8) cytokines (p < 0.05) and 55% increase of anti-inflammation (IL-10) cytokines (p < 0.05) after intensive exercise stimulation. In addition, L. plantarum PS128 can also substantially increase 24⁻69% of plasma-branched amino acids (p < 0.05) and elevate exercise performance, as compared to the placebo group (p < 0.05). In conclusion, L. plantarum PS128 may be a potential ergogenic aid for better training management, physiological adaptations to exercise, and health promotion.

Isolated soy protein (ISP) is a well-known supplement and has been reported to improve health, exercise performance, body composition, and energy utilization. ISP exhibits multifunctional bioactivities and also contains branched-chain amino acids (BCAAs), which have been confirmed to positively affect body weight (BW) regulation and muscle protein synthesis. The combined effects of BCAA supplements and exercise in older postmenopausal women with osteoporosis, sarcopenia, and obesity have been inadequately investigated. Therefore, in this study, we evaluated the potential beneficial effects of soy protein supplementation and exercise training on postmenopausal mice. Forty mice (14 weeks old) with ovariectomy-induced osteosarcopenic obesity were divided into five groups (n = 8), namely sham ovariectomy (OVX, control), OVX, OVX with ISP supplementation (OVX+ISP), OVX with exercise training (ET, OVX+ET), and OVX with ISP and ET (OVX+ISP+ET). The mice received a vehicle or soy protein (3.8 g/kg BW) by oral gavage for four weeks, and the exercise performance (forelimb grip strength and exhaustive swimming time) was evaluated. In the biochemical profiles, we evaluated the serum glucose level and tissue damage markers, such as lactate, ammonia, glucose, blood urine nitrogen (BUN), and creatinine phosphate kinase (CPK). The body composition was determined by evaluating bone stiffness and muscle mass. All data were analyzed using one-way repeated measures analysis of variance. The physical performance of the OVX+ISP+ET group did not differ from that of the other groups. The OVX+ISP+ET group exhibited lower levels of serum lactate, ammonia, CPK, and BUN as well as economized glucose metabolism after an acute exercise challenge. The OVX+ISP+ET group also exhibited higher muscle mass and bone strength than the OVX group. Our study demonstrated that a combination of ISP supplementation and exercise reduced fatigue and improved bone function in OVX mice.

Ixora parviflora, a species of the Rubiaceae, is rich in polyphenols and flavonoids, and has been traditionally used as a folk medicine. An I. parviflora extract (IPE) has great antioxidant activity in vitro, including a scavenging effect on superoxide radicals, reducing power, and ferrous ion-chelating ability. However, whether IPE is efficacious against oxidative damage in vivo is not known. The purpose of this study was to determine the protective effects of IPE treatment on hepatic oxidative stress and antioxidant defenses after exhaustive exercise in mice. Fifty male C57BL/6 mice (6 week old) were randomly divided into five groups and designated a sedentary control with vehicle (C), and exhaustive exercise with vehicle (IPE0), low dosage (IPE10), medium dosage (IPE50) and high dosage (IPE100) of IPE at 0, 10, 50, and 100 mg/kg, respectively. After a single bout of exhaustive swimming exercise challenge, levels of blood ammonia and creatine kinase (CK), and hepatic superoxide dismutase (SOD) protein expression, thiobarbituric acid-reactive substance (TBARS), and gp91phox, p22phox, and p47phox subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expressions in the IPE0 group were significantly affected compared to those of the C group, but they were all significantly inhibited by the IPE treatments. Results of the present in vivo study in mice indicate that I. parviflora extract possesses antioxidative and hepatoprotective potential following exhaustive exercise.

Resveratrol (RES) is a well-known phytocompound and food component which has antioxidative and multifunctional bioactivities. However, there is limited evidence for the effects of RES on physical fatigue and exercise performance. The purpose of this study was to evaluate the potential beneficial effects of trans-RES on fatigue and ergogenic functions following physiological challenge. Male ICR mice from four groups (n = 8 per group) were orally administered RES for 21 days at 0, 25, 50, and 125 mg/kg/day, which were respectively designated the vehicle, RES-25, RES-50, and RES-125 groups. The anti-fatigue activity and exercise performance were evaluated using forelimb grip strength, exhaustive swimming time, and levels of serum lactate, ammonia, glucose, and creatine kinase (CK) after a 15-min swimming exercise. The exhaustive swimming time of the RES-25 group (24.72 ± 7.35 min) was significantly (p = 0.0179) longer than that of vehicle group (10.83 ± 1.15 min). A trend analysis revealed that RES treatments increased the grip strength. RES supplementation also produced dose-dependent decreases in serum lactate and ammonia levels and CK activity and also an increase in glucose levels in dose-dependent manners after the 15-min swimming test. The mechanism was related to the increased energy utilization (as blood glucose), and decreased serum levels of lactate, ammonia, and CK. Therefore, RES could be a potential agent with an anti-fatigue pharmacological effect.

Several studies have been shown that accelerated apoptosis is involved in post-exercise lymphocytopenia and tissue damage after high-intensity exercise. Ganoderma tsugae (GT) is one of the well-known medicinal mushrooms that possess various pharmacological functions. This mushroom has traditionally been used for health promotion purposes. This study investigates the hepatoprotective effects of GT on exhaustive exercise-induced liver damage. Twenty-four male Sprague-Dawley rats were randomly divided into four groups and designated as exhaustive exercise only (E), exhaustive exercise with low dosage (EL), medium dosage (EM) and high dosage (EH) GT at 0, 0.1875, 0.9375 and 1.875 g/kg/day, respectively. After 30 days all rats were euthanized immediately after an exhaustive running challenge on a motorized treadmill. The rat livers were immediately harvested. Evidence of apoptotic liver cell death was revealed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and caspases mediated cascade events. DNA fragmentation, an apoptosis process, can be examined using TUNEL assay. A few TUNEL-positive hepatocytes, compared to the exercise only group, were observed in the livers from exhaustive animals supplemented with GT. Immunoblot analysis also showed that caspase-6-mediated specific cleavage of lamin A/C was increased significantly in the livers of group E, but was significantly decreased in the EM and EH groups. Our observations demonstrate that GT possesses anti-apoptotic and hepatoprotective potential after exhaustive exercise.

Pumpkin (Cucurbita moschata) is a popular and nutritious vegetable consumed worldwide. The overall purpose of this study was to evaluate the effects of C. moschata fruit extract (CME) on anti-fatigue and ergogenic functions following physiological challenges. Male ICR mice from four groups designated vehicle, CME-50, CME-100 and CME-250, respectively (n = 8 per group in each test) were orally administered CME for 14 days at 0, 50, 100 and 250 mg/kg/day. The anti-fatigue activity and exercise performance were evaluated using exhaustive swimming time, forelimb grip strength, as well as levels of plasma lactate, ammonia, glucose, and creatine kinase after an acute swimming exercise. The resting muscular and hepatic glycogen was also analyzed after 14-day supplementation with CME. Trend analysis revealed that CME treatments increased grip strength. CME dose-dependently increased 5% body weight loaded swimming time, blood glucose, and muscular and hepatic glycogen levels. CME dose-dependently decreased plasma lactate and ammonia levels and creatine kinase activity after a 15-min swimming test. The mechanism was relevant to the increase in energy storage (as glycogen) and release (as blood glucose), and the decrease of plasma levels of lactate, ammonia, and creatine kinase. Therefore, CME may be potential for the pharmacological effect of anti-fatigue.

The comprehensive studies done on resveratrol (RES) support that this polyphenol has multiple bioactivities and is widely accepted for dietary supplementation. Furthermore, regular exercise is known to have benefits on health and is considered as a form of preventive medicine. Although the vast majority of prior studies emphasize the efficacy of aerobic exercise in promoting physiological adaptions, other types of exercise, such as resistance exercise and high-intensity interval training (HIIT), may achieve similar or different physiological outcomes. Few studies have looked into the effectiveness of a combinational, synergistic approach to exercise using a weight-loading ladder climbing animal platform. In this study, ICR mice were allocated randomly to the RES and training groups using a two-way ANOVA (RES × Training) design. Exercise capacities, including grip strength, aerobic performance, and anaerobic performance, were assessed and the physiological adaptions were evaluated using fatigue-associated indexes that were implemented immediately after the exercise intervention. In addition, glycogen levels, muscular characteristics, and safety issues, including body composition, histopathology, and biochemistry, were further elucidated. Synergistic effects were observed on grip strength, anaerobic capacities, and exercise lactate, with significant interaction effects. Moreover, the training or RES may have contributed significantly to elevating aerobic capacity, tissue glycogen, and muscle hypertrophy. Toxic and other deleterious effects were also considered to evaluate the safety of the intervention. Resistance exercise in combination with resveratrol supplementation may be applied in the general population to achieve better physiological benefits, promote overall health, and promote participation in regular physical activities.

The present study evaluated the potential beneficial effect of kefir (KF) against fatigue. Furthermore, the composition of the gut microbiota is related to health benefits in the host; therefore, the study also investigated the effect of KF on the gut microbiota composition. Male ICR mice from four groups (n = 8 per group) were orally administered KF once daily for four weeks at 0, 2.15, 4.31, and 10.76 g/kg/day and were designated as the vehicle, KF-1X, KF-2X, and KF-5X groups, respectively. The gut microbiota was analyzed using 16S rRNA gene sequencing. The results showed a significant clustering of cecum after treatment in the vehicle, KF-1X, KF-2X, and KF-5X groups. The KF-2X and KF-5X groups showed a decreased Firmicutes/Bacteroidetes ratio compared with the vehicle group. In addition, anti-fatigue activity and exercise performance were evaluated on the basis of exhaustive swimming time, forelimb grip strength, and levels of serum lactate, ammonia, glucose, blood urea nitrogen (BUN), and creatine kinase (CK) after a swimming exercise. The exhaustive swimming time for the KF-1X, KF-2X, and KF-5X groups was significantly longer than that for the vehicle group, and the forelimb grip strength of the KF-1X, KF-2X, and KF-5X groups was also significantly higher than that of the vehicle group. KF supplementation also decreased serum lactate, ammonia, BUN, and CK levels after the swimming test. However, tissue glycogen content, an important energy source for exercise, increased significantly with KF supplementation. Thus, KF supplementation can alter the gut microbiota composition, improve performance, and combat physical fatigue.

Thiamine, named as vitamin B1, is an important cofactor for the critical enzymes regarding to glucose metabolism, like transketolase, pyruvate dehydrogenase, and alpha-ketoglutarate dehydrogenase. The thiamine tetrahydrofurfuryl disulfide (TTFD) is a derivative of thiamine with higher bioavailability and solubility than thiamine and has been widely applied to health maintenance and disease therapy. Higher physical activities are associated with higher thiamine supplements for efficient energy metabolism. Furthermore, the effective dose of TTFD, beneficial to exercise physiological adaption and performance, still be further validated and the safety evaluation were also an important issue to be considered for potential application. ICR (Institute of Cancer Research) strain mice were allocated as 0, 50, 100, and 500 mg/kg dose groups and administrated by oral gavage consecutively for 6 weeks. Physical activities including grip strength and aerobic endurance were measured. Various fatigue-associated biochemical variables such as lactate, glucose, blood urine nitrogen (BUN) or creatine kinase (CK), were also assessed. The levels of liver and muscle glycogen were measured as an indicator of energy storage at the end of the experiment. Toxicity assessments for long-term supplementation were also further evaluated for safety consideration. TTFD supplementation significantly increased the endurance and grip strength and demonstrated beneficial effects on lactate production and clearance rate after an acute exercise challenge. The TTFD supplementation significantly mitigated the BUN and CK indexes after extended exercise and elevated the glycogen content in the liver and muscle tissues. According to body composition, biochemical and histopathological data, daily administration of TTFD for over 6 weeks (subacute toxicity) also demonstrated reasonable safety results for long-term and adequate supplementation. The toxicity of TTFD were also considered as safety for long-term supplementation with indicated doses. Furthermore, the TTDF could be applied to not only the health promotion but also improvement of exercise physiological adaption and the TTFD could be further considered as potential ergogenic aids combined with different nutrient strategy.

Nonalcoholic fatty liver disease (NAFLD) is a serious liver disorder associated with the accumulation of fat and inflammation. The objective of this study was to determine the gut microbiota composition that might influence the progression of NAFLD. Germ-free mice were inoculated with feces from patients with nonalcoholic steatohepatitis (NASH) or from healthy persons (HL) and then fed a standard diet (STD) or high-fat diet (HFD). We found that the epididymal fat weight, hepatic steatosis, multifocal necrosis, and inflammatory cell infiltration significantly increased in the NASH-HFD group. These findings were consistent with markedly elevated serum levels of alanine transaminase, aspartate transaminase, endotoxin, interleukin 6 (IL-6), monocyte chemotactic protein 1 (Mcp1), and hepatic triglycerides. In addition, the mRNA expression levels of Toll-like receptor 2 (Tlr2), Toll-like receptor 4 (Tlr4), tumor necrosis factor alpha (Tnf-α), Mcp1, and peroxisome proliferator-activated receptor gamma (Ppar-γ) significantly increased. Only abundant lipid accumulation and a few inflammatory reactions were observed in group HL-HFD. Relative abundance of Bacteroidetes and Firmicutes shifted in the HFD-fed mice. Furthermore, the relative abundance of Streptococcaceae was the highest in group NASH-HFD. Nevertheless, obesity-related Lactobacillaceae were significantly upregulated in HL-HFD mice. Our results revealed that the gut microbiota from NASH Patients aggravated hepatic steatosis and inflammation. These findings might partially explain the NAFLD progress distinctly was related to different compositions of gut microbiota.

Pseudomonas aeruginosa exotoxin A (PEA) causes severe hepatotoxicity in experimental animals and is useful in investigations of immune-mediated liver injury. However, strain differences in the sensitivity to PEA-induced hepatotoxicity in rats remains be elucidated. In this study, we determined the severity of PEA-induced hepatotoxicity in six genetically different rat strains. Male LE (Long Evans), Wistar, F344, WKY, BN/SsN and LEW rats were administered a single intravenous injection of PEA (20 μg/kg). Significantly elevated serum ALT and AST levels, massive necrosis and hemorrhage, and numerous TUNEL-positive hepatocytes were observed in BN/SsN rats. In contrast, low levels of ALT and AST as well as mild changes in liver histopathology were observed in Wistar and F344 rats. Moderate levels of hepatic injuries were observed in LE, WKY, and LEW rats. Pro-inflammatory cytokines including TNF-α, IL-2 and IL-6 serum levels were markedly increased in BN/SsN rats compared to Wistar and F344 rats. However, the hepatic levels of low density lipoprotein receptor-related protein (LRP), which functions as the PEA receptor, were not significantly different in each strain. Taken together, we suggest that BN/SsN is the most sensitive rat strain, whereas Wistar and F344 were the most resistant rat strains to PEA-induced liver damage. The different genetic background of rat strains plays an important role in the susceptibility to PEA-induced epatotoxicity that may depend on immune-regulation but not LRP receptor levels.

SCOPE: Traditional medicinal herbs are increasingly used as alternative therapies in patients with inflammatory diseases. Here we evaluated the effect of Wedelia chinensis, a medicinal herb commonly used in Asia, on the prevention of dextran sulfate sodium (DSS)-induced acute colitis in mice. General safety and the effect of different extraction methods on the bioactivity of W. chinensis were also explored. METHODS AND RESULTS: C57BL/6 mice were administrated hot water extract of fresh W. chinensis (WCHF) orally for one week followed by drinking water containing 2% DSS for nine days. WCHF significantly attenuated the symptoms of colitis including diarrhea, rectal bleeding and loss of body weight; it also reduced the shortening of colon length and histopathological damage caused by colonic inflammation. Among four W. chinensis extracts prepared using different extraction techniques, WCHF showed the highest anti-colitis efficacy. Analyses of specific T-cell regulatory cytokines (TNF-α, IL-4, IFN-γ, IL-17, TGF-β, IL-12) revealed that WCHF treatment can suppress the Th1 and Th17, but not Th2, responses in colon tissues and dendritic cells of DSS-induced colitis mice. A 28-day subacute toxicity study showed that daily oral administration of WCHF (100, 500, 1000 mg/kg body weight) was not toxic to mice. CONCLUSION: Together, our findings suggest that specific extracts of W. chinensis have nutritional potential for future development into nutraceuticals or dietary supplements for treatment of inflammatory bowel disease.

Chili pepper is used as a food, seasoning and has been revered for its medicinal and health claims. It is very popular and is the most common spice worldwide. Capsaicin (CAP) is a major pungent and bioactive phytochemical in chili peppers. CAP has been shown to improve mitochondrial biogenesis and adenosine triphosphate (ATP) production. However, there is limited evidence around the effects of CAP on physical fatigue and exercise performance. The purpose of this study was to evaluate the potential beneficial effects of CAP on anti-fatigue and ergogenic functions following physiological challenge. Female Institute of Cancer Research (ICR) mice from four groups (n = 8 per group) were orally administered CAP for 4 weeks at 0, 205, 410, and 1025 mg/kg/day, which were respectively designated the vehicle, CAP-1X, CAP-2X, and CAP-5X groups. The anti-fatigue activity and exercise performance was evaluated using forelimb grip strength, exhaustive swimming time, and levels of serum lactate, ammonia, glucose, BUN (blood urea nitrogen) and creatine kinase (CK) after a 15-min swimming exercise. The grip strength and exhaustive swimming time of the CAP-5X group were significantly higher than other groups. CAP supplementation dose-dependently reduced serum lactate, ammonia, BUN and CK levels, and increased glucose concentration after the 15-min swimming test. In addition, CAP also increased hepatic glycogen content, an important energy source for exercise. The possible mechanism was relevant to energy homeostasis and the physiological modulations by CAP supplementation. Therefore, our results suggest that CAP supplementation may have a wide spectrum of bioactivities for promoting health, performance improvement and fatigue amelioration.

Resveratrol (RES) has antioxidative, anti-inflammatory, anticancer, antidiabetic, antiasthmatic, antalgic, and anti-fatigue activities. Exercise training (ET) improves frailty resulting from aging. This study evaluated the effects of a combination of RES supplementation and ET on the exercise performance of aged mice. C57BL/6J mice (16 months old) were randomly divided into four groups: an older control group (OC group), supplementation with RES group (RES group), ET group (ET group), and a combination of ET and RES supplementation group (ET+RES group). Other 10-week-old mice were used as a young control group (Y-Ctrl group). In this study, exercise performance was evaluated using forelimb grip strength and exhaustive swimming time, as well as levels of plasma lactate, ammonia, glucose, and creatine kinase after an acute swimming exercise. Our results showed that the forelimb grip strength of mice in the ET+RES group was significantly higher than those in the OC, RES, and ET groups (by 1.3-, 1.2-, and 1.1-fold, respectively, p < 0.05), and exhibited no difference with the Y-Ctrl group. The endurance swimming test showed that swimming times of the ET and ET+RES groups were significantly longer than those of the OC and RES groups. Moreover, plasma lactate and ammonia levels of the ET + RES group after acute swimming exercise were significantly lower compared to the OC group (p < 0.05). Thus, it was suggested that by combining RES supplementation with ET for 4 weeks, the muscle strength and endurance performance of aged mice were significantly improved compared to the single intervention with either RES or ET alone. This combination might help shorten the extent of deterioration accompanying the aging process.

The resistant carbohydrates, inulin, and Fibersol-2, belong to soluble dietary fibers and are considered important prebiotics that maintain biological functions, including glucose homeostasis, lipid regulation, colon disease prevention, and prebiotics characteristics. However, few studies have investigated Fibersol-2 alone or in combination with inulin to assess a pooled effect on modulation of hyperlipidemia. We aimed to investigate the effects of this combined supplement (defined as InF) on hamsters fed a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet, HCD) to induce hyperlipidemia. A total of 40 male hamsters were randomly assigned to five groups (n = 8 per group) for treatment: standard diet, vehicle (control); or vehicle or InF supplementation by oral gavage at 0, 864, 1727, or 2591 mg/kg/day for eight weeks, designated HCD, InF-1X, InF-2X, and InF-3X groups, respectively. The hypolipidemic efficacy and safety of InF supplementation was assessed by serum lipid indexes, hepatic and fecal lipid content, and histology. InF supplementation significantly improved serum levels of triacylglycerol (TG) and low-density lipoprotein cholesterol (LDL-C) and the ratio of LDL-C/HDL-C after two-week treatment, and reduced serum total cholesterol (TC) levels after four-week administration. After eight-week supplementation, InF supplementation dose-dependently improved serum levels of TC, TG, HDL-C, and LDL-C; LDL-C/HDL-C ratio; and hepatic TC and TG levels. It inhibited TC absorption by feces elimination. Our study provides experiment-based evidence to support that this prebiotics remedy may be useful in preventing or treating hyperlipidemia.