Exhaustive Swimming Research Articles

Structural characterization and anti-fatigue mechanism based on the gut-muscle axis of a polysaccharide from Zingiber officinale.

This study aimed to characterize the structure of polysaccharide ZOPA extracted from Zingiber officinale and its purified form (ZOPA-1), and to investigate their anti-fatigue mechanisms based on the gut-muscle axis. The study found that the backbone of ZOPA-1 is primarily composed of →3,4)-α-Glcp-1→ and →4,6)-α-Glcp-(1→ linkages, with →4)-α-Glcp(1→ serving as its side chain. In exhaustive swimming experiments with mice, both crude ZOPA and purified ZOPA-1 demonstrated significant anti-fatigue effects, including enhanced glycogen storage, improved antioxidant capacity, reduced accumulation of metabolic waste products, and regulated energy metabolism in the gastrocnemius muscles. These effects may be mediated through the activation of the Keap1-Nrf2/ARE and AMPK/PGC-1α signaling pathways. Furthermore, ZOPA and ZOPA-1 modulated the intestinal flora of mice, increasing diversity, altering abundance, and regulating short-chain fatty acid concentrations, suggesting a potential role of the gut-muscle axis in mediating the anti-fatigue effects. This study provides valuable insights into the complex interplay between polysaccharides, the gut-muscle axis, and exercise-induced fatigue.

Effects of Shugan Tiaoshen acupuncture on anxiety-like behavior and PKC/ERK/CREB pathway in the bed nucleus of the stria terminalis in rats with post-traumatic stress disorder

To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the spirit) on the protein kinase C/extracellular signal-regulated kinase/cAMP response element-binding protein (PKC/ERK/CREB) signaling pathway in the bed nucleus of the stria terminalis (BNST) of rats with post-traumatic stress disorder (PTSD), and to explore the mechanism of acupuncture on alleviating anxiety and fear in PTSD. Fifty SPF-grade male SD rats were randomly divided into a blank group (10 rats) and a PTSD model group (40 rats). The PTSD model was induced by using a combination of closed electric shock and forced exhaustive swimming. Thirty successfully modeled rats were randomly assigned to a model group, a medication group, and an acupuncture group, with 10 rats in each group. The rats in the medication group were treated with paroxetine hydrochloride solution by gavage, once daily for 12 consecutive days. The rats in the acupuncture group were treated with acupuncture at "Baihui" (GV 20) and bilateral "Neiguan" (PC 6), "Shenmen" (HT 7), "Taichong" (LR 3). "Baihui" (GV 20) was needled daily, while the other acupoints were alternately needled on the left side on odd days and the right side on even days, once daily for 12 consecutive days. Anxiety and fear behaviors changes were assessed by using the open field test and elevated plus maze test. Histological changes in the BNST were observed by using HE staining and Nissl staining. The expression of PKC, phosphorylated PKC (p-PKC), ERK1/2, phosphorylated ERK1/2 (p-ERK1/2), and p-CREB proteins in the BNST were detected by using Western blot. Compared with the blank group, the model group showed decreased time and total distance spent in the center of the open field and on the open arms of the elevated plus maze (P<0.05); the BNST tissues in the model group exhibited a reduced number of neurons, disorganized cell arrangement, cell shrinkage, nuclear condensation, abnormal neuronal structure, uneven Nissl staining, and reduced Nissl bodies. The model group showed increased protein expression of p-PKC and p-PKC/PKC ratio (P<0.05) and decreased protein expression of p-ERK1/2, p-CREB, and p-ERK1/2/ERK1/2 ratio (P<0.05). Compared with the model group, the medication group and the acupuncture group showed increased time and total distance spent in the center of the open field and on the open arms of the elevated plus maze (P<0.05); the BNST tissues showed increased number of neurons, more organized cell arrangement, improved neuronal structure, and increased Nissl bodies; the medication group and the acupuncture group also showed decreased p-PKC protein expression and p-PKC/PKC ratio (P<0.05) and increased p-ERK1/2, p-CREB protein expression, and p-ERK1/2/ERK1/2 ratio (P<0.05). Shugan Tiaoshen acupuncture could alleviate anxiety and fear behaviors in PTSD rats, and improve neuronal damage in the BNST. The mechanism may be related to the regulation of the PKC/ERK/CREB signaling pathway in the BNST.

Influence of Ajuga turkestanica and Asparagus racemosus Phytoextracts on the Effectiveness of Aerobic–Anaerobic Training Regime

In this work, we study the effect of Asparagus racemosus (EAR) and Ajuga turkestanica (EAT) dry extracts at a dose of 100 mg/kg in comparison with a Rhaponticum carthamoides extract (ERC) on the effectiveness of an aerobic–anaerobic training regimen in female mice in a triple-weight loaded exhaustive swim test with a 10% load of body weight, as well as on the level of malondialdehyde and catalase activity in blood hemolysate, cardiac and skeletal striated muscle tissue, and liver homogenate. The results obtained indicate a reduced severity of lipid peroxidation under the influence of dry EAR and EAT extracts, thus pointing to the antioxidant activity of the extracts. In the conducted triple-weight loaded exhaustive swim test, a statistically significant increase in the duration of swimming No. 3 and the test index was noted in both groups compared to the control. Therefore, it can be concluded that the studied extracts have a positive effect on the first-phase recovery processes.

Anti-fatigue effect of pigeon meat hydrolysate on exercise mice and its underlying mechanism: Related to oxidative stress and energy metabolism

With the acceleration of the pace in modern society, fatigue caused by high-intensity physical work, long-term heavy mental work and lack of sleep has become a widespread and noticeable health problem. In this study, pigeon meat hydrolysate (PMH) with good antioxidant activity was prepared and the anti-fatigue effects of fractions in PMH with different molecular weights (MW) on exercise mice and the underlying mechanism were investigated. Results showed that mice gavaged with PMH and its fractions exhibited improved exhaustive swimming time when compared to the Control, with fraction at MW 1–5 kDa (PP2) showed the highest improvement. Meanwhile, PP2 decreased the levels of blood lactate acid (BLA) and blood urea nitrogen (BUN), and increased the contents of muscle and liver glycogen. And the activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in myocyte of mice were significantly enhanced, with the outflow of creatine kinase (CK) reduced. PP2 also exhibited significant antioxidant activity by increasing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and reducing the production of malondialdehyde (MDA), especially at relative higher dosages (M-PP2 and H-PP2). Metabolomics study indicated that the differential metabolites between PP2 and the Control group in liver tissues of mice were mainly related to the energy metabolism and central nervous system regulation pathways. All these results demonstrated that PP2 fraction in PMH at a dosage higher than 0.5 mg/g of mice body weight could significantly enhance the exercise endurance of mice and exert excellent anti-fatigue ability via alleviating oxidative stress and modulating energy metabolism in mice.

Preparation, Characterization, and In Vivo Anti‐Fatigue Evaluation of Octacosanol Nanoemulsions

ABSTRACTOctacosanol (OCT) is a natural aliphatic alcohol with multiple activities, but the poor solubility limited its wide applications. In this study, OCT nanoemulsions were prepared by a low‐energy emulsification method. The particle size, polydispersity index, and Zeta potential of OCT nanoemulsions were 12.59 nm, 0.131, and −10.54 mV, respectively. OCT nanoemulsions could keep stable up to 180 days at 4°C with particle size ranging from 12.61 to 16.57 nm. In addition, OCT nanoemulsions could remain stable upon exposure to autoclaving, acid–base (pH 2–8), freeze–thaw, ultraviolet (UV) irradiation, and low concentrations of ions. The grid test time and exhaustive swimming time of the OCT nanoemulsions group increased by 70% and 40% compared with the exercise control group, indicating that OCT nanoemulsions could enhance the muscle strength and endurance performance of mice. Compared with the exercise control group, the muscle glycogen, liver glycogen, superoxide dismutase (SOD), and glutathione peroxidase (GSH‐Px) levels of the OCT nanoemulsions group increased by 97%, 45%, 62%, and 20%, while the blood lactic acid and lactate dehydrogenase levels of the OCT nanoemulsions group decreased by 33% and 22%, respectively, suggesting that OCT nanoemulsions had the anti‐fatigue effect. Hematoxylin and eosin staining showed that OCT nanoemulsions could repair muscle damages induced by excessive exercise. These findings could pave the way for the development of OCT nanoemulsions with high stability and anti‐fatigue potential.

Establishment of a dexamethasone-induced zebrafish skeletal muscle atrophy model and exploration of its mechanisms

BackgroundSkeletal muscle atrophy is one of the main side effects of high-dose or continuous use of glucocorticoids (such as dexamethasone). However, there are limited studies on dexamethasone-induced skeletal muscle atrophy in zebrafish and even fewer explorations of the underlying molecular mechanisms. This study aimed to construct a model of dexamethasone-induced skeletal muscle atrophy in zebrafish and to investigate the molecular mechanisms. MethodsZebrafish soaked in 0.01 % dexamethasone solution for 10 days. Loli Track (Denmark) and Loligo Swimming Respirometer were used to observe the effect of dexamethasone on swimming ability. The effects of dexamethasone on zebrafish skeletal muscle were observed by Transmission electron microscopy, H&E, and wheat germ agglutinin techniques. Enriched genes and signaling pathways were analyzed using Transcriptome sequencing. Further, the levels of mitochondrial and endoplasmic reticulum-related proteins were examined to investigate possible mechanisms. Results0.01 % dexamethasone reduced zebrafish skeletal muscle mass (p < 0.05), myofibre size and cross-sectional area (p < 0.001), and increased protein degradation (ubiquitination and autophagy) (p < 0.05). In addition, 0.01 % dexamethasone reduced the swimming ability of zebrafish, as evidenced by the reluctance to move, fewer movement trajectories, decreased total distance traveled (p < 0.001), average velocity of movement (p < 0.001), oxygen consumption (p < 0.001), critical swimming speed (p < 0.01) and increased exhaustive swimming time (p < 0.001). Further, 0.01 % dexamethasone-induced mitochondrial dysfunction (decreased mitochondrial biogenesis, disturbs kinetic homeostasis, increased autophagy) and endoplasmic reticulum stress. Conclusions0.01 % dexamethasone induces skeletal muscle atrophy and impairs the swimming ability of zebrafish through mitochondrial dysfunction and endoplasmic reticulum stress.

Anti-fatigue effect of an enzymatically derived deer velvet extract through muscle damage recovery and improvement of antioxidant levels

Ethnopharmacological relevanceDeer velvet (DV) has been extensively used in traditional Oriental medicine to treat various diseases. Its pharmacological spectrum encompasses tonicity, longitudinal bone growth of adolescence, blood retention, hemopoiesis facilitation, enhancement of organ function, physical function improvement, and augmentation of physical vitality. Among its myriad effects, DV notably exhibits anti-fatigue properties; however, its specific mode of action is yet to be fully elucidated. Aim of the studyThis study was undertaken to investigate the anti-fatigue and exercise performance-enhancing effects of YC-1101(HENKIV®), an enzymatically derived DV extract, in C2C12 cell lines and forced swimming mouse models. Materials and methodsThe effect of YC-1101 on increasing cell growth and lowering lactate dehydrogenase (LDH) activity was assessed in C2C12. The antioxidative effects of YC-1101 and its mechanistic underpinnings were also evaluated in C2C12 cells. Moreover, mice were subjected to an exhaustive swimming test subsequent to 3 weeks of YC-1101 extract administration. Fatigue-associated biochemical parameters, such as LDH activity and lactate, superoxide dismutase, glutathione peroxidase, and malondialdehyde levels, were measured in serum and muscle tissues. ResultsYC-1101 significantly promoted myoblast growth and reduced LDH activity, indicative of a cell-proliferative effect. Notably, free radical scavenging assays and analysis of reactive oxygen species production and antioxidant-related mRNA expression corroborated the significant involvement of YC-1101 in antioxidation, an important mechanism in anti-fatigue processes. Furthermore, animal experiments demonstrated prolonged swimming endurance and inhibition of muscle LDH accumulation in forced swimming mouse models. Serum biochemical analysis further revealed significant modulation of the expression of anti-fatigue-related biomarkers. Various bioactive low-molecular-weight DV peptides were enriched in YC-1101 compared to YHC-BE-2038 (a DV extract without enzymatic digestion). The anti-fatigue effect of YC-1101 was significantly stronger than that of YHC-BE-2038. ConclusionsThese findings suggest the potential of YC-1101 as a nutraceutical adjunct in ameliorating fatigue, concurrently facilitating muscle damage recovery, and exerting antioxidant effects via the nuclear factor E2-related factor 2-Kelch-like ECH-associated protein-1 pathway. It can be assumed that the complex action of low-molecular-weight DV peptides produced during the enzymatic degradation process was effective, and the further research is needed.

Enhancing the anti-fatigue effect of ginsenoside extract by Bifidobacterium animalis subsp. lactis CCFM1274 fermentation through biotransformation of Rb1, Rb2 and Rc to Rd

The conversion of major ginsenosides into minor ginsenosides has been demonstrated to promote their absorption in vivo and enhance their bioavailability and bioactivity. In this study, we aimed to screen the strain that transforms the less efficient glycosylated ginsenosides (Rb1, Rc, and Rb2) into the highly efficient de-glycosylated form (Rd). The anti-fatigue ability and corresponding mechanism of fermented ginsenoside extracts (F-GE) from Rd-producing bacteria were evaluated using an exercise-induced model. Our results showed that Bifidobacterium animalis subsp. lactis CCFM1274 was capable of converting Rb1, Rc, and Rb2 into Rd in vitro. The anti-fatigue activity of ginsenoside extracts (GE) was significantly increased by CCFM1274 fermentation, characterized by an improvement in exhaustive swimming time (7.2 ± 0.8 to 10.7 ± 1.8 min) and histopathological changes. Moreover, F-GE treatment showed superior effects than GE in reducing the content of blood lactic acid (16.3 ± 3.6 to 13.7 ± 1.0 mmol/L), blood urea nitrogen (9.4 ± 0.6 to 5.2 ± 1.1 mmol/L), and malondialdehyde (9.3 ± 1.3 to 7.7 ± 2.1 nmol/mg), increasing the level of glycogen (1.1 ± 0.3 to 1.4 ± 0.3 mg/g), and superoxide dismutase activity (429.8 ± 107.8 to 671.3 ± 95.1 U/mg), which were associated with the upregulation of MCT1, LDHB, PDK4, GLUT4, Nrf2, and HO-1. Therefore, CCFM1274, which improved the bioactivity of ginsenoside, exhibited unique applicative potential for ginseng-based products to alleviate exercise fatigue.

Pre-exercise supplementation with curcuma xanthorrhiza roxb has minimal impact on red blood cell parameters but reduces oxidative stress: a preliminary study in rats.

This study examined the effects of longterm pre-exercise Curcuma xanthorriza Roxb supplementation on red blood cell indices along with circulating malondialdehyde (MDA) and superoxide dismutase (SOD) levels in response to endurance exercise to address previously inconsistent findings. Male Wistar rats (Rattus norvegicus; n = 20, aged 12-16 weeks) were divided equally into an exercise-only group (C) and three groups supplemented with Curcuma extract at dosages of 6.75 (T1), 13.50 (T2), and 20.25 mg (T3). Curcuma extract supplementation was administered for 28 d immediately prior to exercise. Following 28 d of exhaustive swimming, the hematocrit and erythrocyte count increased by 15% (p = 0.06). Pre-exercise Curcuma supplementation did not significantly affect mean corpuscular volume or mean corpuscular hemoglobin concentration. Longterm exercise intervention resulted in elevated MDA levels by 41% (p <0.001), while Curcuma supplementation (13.50 mg) attenuated this increase by 16.6% (p = 0.09). Additionally, Curcuma supplementation resulted in a dose-dependent increase in SOD levels, with an 82.6% increase observed at 20.25 mg (p = 0.028). Our preliminary findings indicated that pre-exercise supplementation with Curcuma extract had a negligible effect on changes in red blood cell markers, but it mitigated the increase in oxidative stress induced by exercise training. Our future research direction will involve applying the findings to humans.

The Antioxidant and Anti-Fatigue Effects of Rare Ginsenosides and γ-Aminobutyric Acid in Fermented Ginseng and Germinated Brown Rice Puree.

γ-aminobutyric acid (GABA) and rare ginsenosides are good antioxidant and anti-fatigue active components that can be enriched via probiotic fermentation. In this study, ginseng and germinated brown rice were used as raw materials to produce six fermented purees using fermentation and non-fermentation technology. We tested the chemical composition of the purees and found that the content of GABA and rare ginsenoside (Rh4, Rg3, and CK) in the puree made of ginseng and germinated brown rice (FGB) increased significantly after fermentation. The antioxidant activity of the six purees was determined using cell-free experiments, and it was found that FGB had better ferric-ion-reducing antioxidant power (FRAP) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging rates, exhibiting better antioxidant effects. We then evaluated the antioxidant effect of FGB in HepG2 cells induced by H2O2 and found that FGB can reduce the generation of reactive oxygen species (ROS) in HepG2 cells and increase the membrane potential level, thereby improving oxidative damage in these cells. In vivo experiments also showed that FGB has good antioxidant and anti-fatigue activities, which can prolong the exhaustive swimming time of mice and reduce the accumulation of metabolites, and is accompanied by a corresponding increase in liver glycogen and muscle glycogen levels as well as superoxide dismutase and lactate dehydrogenase activities. Finally, we believe that the substances with good antioxidant and anti-fatigue activity found in FGB are derived from co-fermented enriched GABA and rare ginsenosides.

Effects of progesterone administered to maternal rats during the teratogenesis-sensitive period through different routes on neurobehavior and gut microbiota in offspring

Objective: Progesterone (P4) is the optimal agent for luteal support in assisted reproductive technologies. Despite the availability of various formulations, the impacts of P4 treatment administered through different routes on offspring growth remain unevaluated. This study aimed to investigate and compare the effects of P4 administration through three different routes in pregnant rats during the teratogenesis-sensitive period on fertility outcomes and the behavior, plasma P4 and pregnenolone levels, and alterations in gut microbiota in the filial generation (F1) of offspring. Methods: Female rats that mated successfully were randomly classified into four groups: Group 1, the normal control group; Group 2, the IG group, in which utrogestan was administered via intragastric gavage; Group 3, the IM group, in which P4 was administered via intramuscular injection; and Group 4, the VAGIN group, in which P4 sustained-release vaginal gel was administered through the vagina. Except for the control group, P4 was administered in other groups through their respective routes for 13 consecutive days daily during the teratogenic-sensitive gestation period (days 6–18). The fertility outcomes of the maternal rats were observed, and open-field and three-chamber social preference tests were conducted to assess anxiety and social behavior, along with an exhaustive swimming experiment to evaluate the motor endurance of the offspring. Plasma P4 and pregnenolone levels in the offspring were measured, and fecal samples were assessed using gut microbiota sequencing and subsequent bioinformatics analysis. Results: No significant alterations in fertility outcomes were observed through three P4 administration routes—intragastric gavage, intramuscular injection, and vaginal administration—in rats. However, in behavioral experiments in offspring, a significant increase was observed in swimming time in the IG group than in the control group (P = 0.013). Furthermore, the offspring in the IG group exhibited a marked decrease in non-social behaviors compared with the control group (P = 0.030). No significant behavioral changes were observed in the F1 offspring in the open-field test. Additionally, the offspring in the IG group exhibited a significant elevation in plasma pregnenolone levels compared with the control group (P = 0.019) 30 days after birth. No notable differences in the α-diversity of gut microbiota were observed among the groups. However, significant differences in β-diversity were observed in both the IG and IM groups compared with the control group, indicating that P4 treatment via the two routes exhibited a significant impact on the gut microbiota composition of F1 offspring. Distinct differences were observed in the gut microbiota of the offspring among the three P4 treatment groups, with 22, 28, and 33 differential bacterial taxa identified in the IG, IM, and VAGIN groups, respectively, using linear discriminant effect size analysis, whereas Olivella appeared exclusively in the control group rather than in the P4 treatment groups. Conclusion: Oral administration of P4 to maternal rats during the teratogenesis-sensitive period enhanced motor endurance and plasma pregnenolone levels and altered the composition of the gut microbiota in the offspring. Our findings demonstrated different effects on offspring growth when P4 is administered orally, intramuscularly, or vaginally.

Ginkgo Biloba Bioactive Phytochemicals against Age-Related Diseases: Evidence from a Stepwise, High-Throughput Research Platform.

The seeds of ginkgo biloba L (GB) have been widely used worldwide. This study investigated the bioefficacies of whole GB seed powder (WGP) retaining the full nutrients of ginkgo against aging, atherosclerosis, and fatigue. The experimental results indicated that WGP lowered brain monoamine oxidase and serum malondialdehyde levels, enhanced thymus/spleen indexes, and improved learning ability, and delayed aging in senescent mice. WGP regulated lipid levels and prevented atherosclerosis by reducing triglycerides, lowering low-density lipoprotein cholesterol, increasing high-density lipoprotein cholesterol, and decreasing the atherosclerosis index. WGP improved exercise performance by reducing blood lactate accumulation and extending exhaustive swimming and climbing times, improved energy storage by increasing muscle/liver glycogen levels, and relieved physical fatigue. Network pharmacology analysis revealed 270 potential targets of WGP that play roles in cellular pathways related to inflammation inhibition, metabolism regulation, and anti-cellular senescence, etc. Protein-protein interaction analysis identified 10 hub genes, including FOS, ESR1, MAPK8, and SP1 targets. Molecular docking and molecular dynamics simulations showed that the bioactive compounds of WGP bound well to the targets. This study suggests that WGP exerts prominent health-promoting effects through multiple components, targets, and pathways.

Effects of nano-Rhodiola rosea combined with treadmill exercise on anti-exercise fatigue in rats.

To explore the potential strategies and mechanisms for enhancing the bioavailability of Rhodiola rosea. 36 Sprague-Dawley rats (8-weeks-old) were randomly assigned to six groups (n = 6 per group). Groups I and II received nano-dose forms of R. rosea, groups III and IV received normal dose form of R. rosea, and groups V and VI served as distilled water control groups. Groups II, IV, and VI were combined with moderate -intensity treadmill exercise. Each group received a daily gavage with 0.5 mL of nano -R. rosea solution (0.01 mg/mL), normal R. rosea solution, and distilled water. All rats were subjected to exhaustive swimming after 4 weeks. Outcome measures include GSH-px activity, T-AOC activity, MDA content, hepatic glycogen content, and T-SOD activity. For plasma MDA content, group I was lower than group III (p < 0.01) and group V (p < 0.01), group II was lower than group III (p < 0.01), group VI was higher than group II (p < 0.05) and group IV (p < 0.05). For plasma T-AOC activity, group II was higher than group VI (p < 0.01). For plasma GSH-px activity, group I was lower than group IV (p < 0.05), groups II, III, and IV were higher than group V (p < 0.05), and group V was lower than that of group VI (p < 0.05). For T-SOD activity of quadriceps muscle, groups I and III were higher than that in group V (p < 0.05). R. rosea has a positive effect on anti-exercise fatigue in rats, with the nano-dosage form of R. rosea showing more significant efficacy than the normal form especially combined with aerobic exercise.

A Flavonoid Concentrate from Moringa Oleifera Lam. Leaves Extends Exhaustive Swimming Time by Improving Energy Metabolism and Antioxidant Capacity in Mice.

Moringa oleifera Lam. leaves contain various nutrients and bioactive compounds. The present study aimed to assess the anti-fatigue capacity of a flavonoids concentrate purified from M. oleifera Lam. leaves. The total flavonoids in the purified extract were analyzed by ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC-MS/MS). The mice were supplemented with purified M. oleifera Lam. leaf flavonoid-rich extract (MLFE) for 14 days. The weight-loaded forced swimming test was used for evaluating exercise endurance. The 90-min non-weight-bearing swimming test was carried out to assess biochemical biomarkers correlated to fatigue and energy metabolism. UPLC-MS/MS analysis identified 83 flavonoids from MLFE. MLFE significantly increased the swimming time by 60%. Serum lactate (9.9 ± 0.9 vs. 8.9 ± 0.7), blood urea nitrogen (BUN) (8.8 ± 0.8 vs. 7.2 ± 0.5), and nonesterified fatty acid (NEFA) (2.4 ± 0.2 vs. 1.7 ± 0.3) were significantly elevated; phosphoenolpyruvate carboxykinase (PEPCK), glucokinase (GCK), and nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression were significantly downregulated; and heme oxygenase 1 mRNA expression was significantly upregulated in muscle after swimming. MLFE supplement significantly decreased serum lactate (8.0 ± 1.0 vs. 9.9 ± 0.9), BUN (8.6 ± 0.4 vs. 8.9 ± 0.8), and NEFA (2.3 ± 0.4 vs. 2.4 ± 0.2) and increased the protein and mRNA expression of GCK, PEPCK, and Nrf2. The enhancement of glucose metabolism and antioxidant function by MLFE contributes partly to its anti-fatigue action.

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

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

Intracerebroventricular administration of the exercise hormone irisin or acute strenuous exercise alleviates epileptic seizure-induced neuroinflammation and improves memory dysfunction in rats

BackgroundStatus epilepticus is a common and potentially life-threatening neurological emergency with a high risk for cognitive and neurobiological impairment. Our aim was to evaluate the neuroprotective effects of centrally administered irisin and acute exhausting exercise against oxidative brain injury and memory dysfunction due to a pentylenetetrazole (PTZ)-induced single seizure. Male Sprague Dawley rats with intracerebroventricular (icv) cannulas were randomly divided into intraperitoneally (ip) saline-injected control and PTZ-injected (45 mg/kg) seizure groups. Both the control and PTZ groups were then treated with irisin (7.5 µg/kg, 2 µl, icv), saline (2 µl, icv) or were forced to an acute bout of strenuous exercise before the ip injection of saline (control) or PTZ. Seizures were evaluated using the Racine score. To evaluate memory performance, a passive avoidance test was performed before and after PTZ injection. Following euthanasia at the 24th hour of seizure induction, brain tissues were removed for histopathological examination and for evaluating oxidative damage, antioxidant capacity, and neurotransmitter levels.ResultsGlutamate/GABA imbalance observed in PTZ rats was corrected by irisin administration (p < 0.001/p < 0.01), while irisin prevented the generation of reactive oxygen species and lipid peroxidation (p < 0.05 − 0.001) and replenished the antioxidant catalase and glutathione levels (p < 0.01–0.01) in the cerebral tissue, and reduced the histologically evident neuronal injury due to a single seizure (p < 0.05 − 0.01). Irisin also delayed the onset of seizures (p < 0.05) and improved memory dysfunction (p < 0.05), but did not affect the severity of seizures. The acute exhaustive swimming exercise completed before PTZ-seizure depressed glutamate level (p < 0.001), maintained the oxidant/antioxidant balance, alleviated neuronal injury (p < 0.05 − 0.01) and upregulated cerebral BDNF expression (p < 0.05).ConclusionIn conclusion, acute high-intensity exercise or exogenously administered irisin provides neuroprotection by maintaining the balance of excitatory/inhibitory neurotransmitters and oxidant/antioxidant systems.

Uncovering the action mechanism of Shenqi Tiaoshen formula in the treatment of chronic obstructive pulmonary disease through network pharmacology, molecular docking, and experimental verification.

To reveal the potential underlying mechanism of the Shenqi Tiaoshen formula (, SQTS) in the treatment of chronic obstructive pulmonary disease (COPD) by utilizing network pharmacology, molecular docking, and experimental verification. Multiple open-source databases and research related to Traditional Chinese Medicine or compounds were employed to screen active ingredients and corresponding potential targets of the SQTS. The protein-protein interaction network screened hub genes, the relevant molecular mechanism and gene regulation were initially identified through the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis, and molecular docking was used to confirm further the interaction of the main components bound to the core targets. In vivo experiments on the COPD combined Qi-deficiency syndrome rat model were performed to verify the intervention effects and predicted potential molecular mechanisms of the SQTS. This study selected 156 active compounds and 326 candidate targets for treating COPD. Quercetin, Nobiletin, Kaempferol, Luteolin, Ginsenoside Rh2 and Formononetin were probably the main active compounds of SQTS in COPD treatment as they affected the most COPD-related targets, and interleukin-1 (IL-6), signal transducing activator of transcription 3 (STAT3), matrix metalloproteinase-9 (MMP9), vascular endothelial growth factor A (VEGFA), protein kinase B (AKT1), hypoxia-inducible factor-1α (HIF-1α), and forkhead box O3 (FoxO3) were identified as the hub genes associated with its therapeutic effect. KEGG analysis was mainly enriched in the signaling pathways closely related to inflammation, immunity and oxidative stress, such as HIF-1, tumor necrosis factor (TNF), phosphatidylinositol 3 kinase (PI3K)-AKT, FoxO, apoptosis, IL-17, and toll-like receptor. Molecular docking confirmed that the main active components shared a good affinity with the hub genes. In vivo experiments, the SQTS was found to improve the body weight, exhaustive swimming time, tail-hanging immobility time and struggle times, airway inflammation, lung functions, and inflammatory factors in the rat model of COPD. The up-regulation of p-PI3K, p-AKT, HIF-1α, FoxO3α, toll like receptor 4, VEGFA, Caspase 3, TNF-α, and IL-17 in COPD rats were down-regulated by SQTS, consistent with the network pharmacology results. This study provides evidence that the SQTS plays a critical role in anti-inflammation via suppressing immune inflammation and oxidative stress related pathways, indicating that the SQTS is a candidate herbal drug for further investigation in treating COPD.

The Contrasting Effects of Two Distinct Exercise Training Modalities on Exhaustive Exercise-Induced Muscle Damage in Mice May Be Associated with Alterations in the Gut Microbiota.

Exhaustive exercise is known to induce muscle damage characterized by inflammation and oxidative stress. Although "regular" and "weekend warrior" exercise regimens have been shown to confer comparable health benefits in human studies, such as reduced risks of all-cause, cardiovascular disease (CVD), and cancer mortality, their differential impacts on muscle damage post-exhaustive exercise remain unclear. This study aimed to compare the effects of long-term, moderate-intensity (LTMI) and short-term, high-intensity (STHI) training modalities, matched for total exercise volume, on gut microbiota, short-chain fatty acids (SCFAs), and exhaustive exercise-induced muscle damage in mice, as well as to evaluate the correlation between these factors. LTMI is considered a regular exercise regimen, while STHI shares some similarities with the "weekend warrior" pattern, such as promoting exercise intensity and condensing training sessions into a short period. Our findings indicate that LTMI training significantly enhanced the abundance of SCFA-producing bacteria, including Akkermansia, Prevotellaceae_NK3B31_group, Odoribacter, Alistipes, and Lactobacillus, thereby increasing SCFA levels and attenuating muscle damage following exhaustive swimming. In contrast, STHI training increased the abundance of opportunistic pathogens such as Staphylococcus and Bilophila, without altering SCFA levels, and was associated with exacerbated muscle damage. Moreover, we observed a significant negative correlation between the abundance of SCFA-producing bacteria and SCFA levels with the expression of inflammatory cytokines in the muscle of mice post-exhaustive exercise. Conversely, the abundance of Staphylococcus and Bilophila showed a notable positive correlation with these cytokines. Additionally, the effects of LTMI and STHI on exhaustive exercise-induced muscle damage were transmissible to untrained mice via fecal microbiota transplantation, suggesting that gut microbiota changes induced by these training modalities may contribute to their contrasting impacts on muscle damage. These results underscore the significance of selecting an appropriate training modality prior to engaging in exhaustive exercise, with implications for athletic training and injury prevention.

Sacubitril/valsartan ameliorates cardiac function and ventricular remodeling in CHF rats via the inhibition of the tryptophan/kynurenine metabolism and inflammation

Sacubitril/valsartan has been highly recognized as a treatment for Chronic heart failure (CHF). Its potential cardioprotective benefits and mechanisms, however, remain to be explored. Metabolomics can be used to identify the metabolic characteristics and related markers, as well as the influence of drugs, thereby opening up the new mechanism for sacubitril/valsartan therapy in CHF disease. In this study, the ligation of left anterior descending and exhaustive swimming were used to induce a rat model of CHF after myocardial infarction. The efficacy was appraised with echocardiography, serum NT-proBNP, and histopathologica. UPLC-Q/TOF–MS combined with multivariate statistical analysis approach were used to analyze the effect of sacubitril/valsartan on CHF rats. RT-qPCR and western blot were performed to investigate the tryptophan/kynurenine metabolism pathway. Accordingly, the basal cardiac function were increased, while the serum NT-proBNP and collagen volume fraction decreased in CHF rats with sacubitril/valsartan. Sacubitril/valsartan regulated the expression of kynurenine et.al 8 metabolomic biomarkers in CHF rats serum, and it contributed to the cardioprotective effects through tryptophan metabolism pathway. In addition, the mRNA and protein expression of the indoleamine 2,3-dioxygenase (IDO) in the myocardial tissue of CHF rats, were down-regulated by sacubitril/valsartan, which was the same with the IL-1β, IFN-γ, TNF-α, COX-2, and IL-6 mRNA expression, and IL-1β, IFN-γ, and TNF-α expression in serum. In conclusion, sacubitril/valsartan can ameliorate cardiac function and ventricular remodeling in CHF rats, at least in part through inhibition of tryptophan/kynurenine metabolism.

Ginseng total saponin improves red blood cell oxidative stress injury by regulating tyrosine phosphorylation and glycolysis in red blood cells

BackgroundOxidative stress is the main cause of many diseases, but because of its complex pathogenic factors, there is no clear method for treating it. Ginseng total saponin (GTS) an important active ingredients in Panax ginseng C.A. Mey (PG) and has potential therapeutic ability for oxidative stress due to various causes. However, the molecular mechanism of GTS in the treating oxidative stress damage in red blood cells (RBCs) is still unclear. PurposeThis study aimed to examine the protective effect of GTS on RBCs under oxidative stress damage and to determine its potential mechanism. MethodsThe oxidative stress models of rat RBCs induced by hydrogen peroxide (H2O2) and exhaustive swimming in vivo and in vitro was used. We determined the cell morphology, oxygen carrying capacity, apoptosis, antioxidant capacity, and energy metabolism of RBCs. The effect of tyrosine phosphorylation (pTyr) of Band 3 protein on RBCs glycolysis was also examined. ResultsGTS reduced the hemolysis of RBCs induced by H2O2 at the lowest concentration. Moreover, GTS effectively improved the morphology, enhanced the oxygen carrying capacity, and increased antioxidant enzyme activity, adenosine triphosphate (ATP) levels, and adenosine triphosphatase (ATPase) activity in RBCs. GTS also promoted the expression of membrane proteins in RBCs, inhibited pTyr of Band 3 protein, and further improved glycolysis, restoring the morphological structure and physiological function of RBCs. ConclusionsThis study shows, that GTS can protect RBCs from oxidative stress damage by improving RBCs morphology and physiological function. Changes in pTyr expression and its related pTyr regulatory enzymes before and after GTS treatment suggest that Band 3 protein is the main target of GTS in the treating endogenous and exogenous oxidative stress. Moreover, GTS can enhance the glycolytic ability of RBCs by inhibiting pTyr of Band 3 protein, thereby restoring the function of RBCs.