Anti-fatigue Effects Research Articles

Anti-fatigue effects of fermented soybean protein peptides in mice.

Bioactive protein hydrolysates and peptides are believed to help counteract and ameliorate physical fatigue. Fermented soybean protein peptides (FSPPs) were prepared by protease hydrolysis and microbial fermentation. The present study aimed to evaluate the anti-fatigue properties of FSPPs. The forced swimming time in the FSPP group was 35.78% longer than the control group, the oxygen-resistant survival time of the FSPP group was significantly prolonged and the prolongation rate was 31.00%. In addition, FSPPs decreased the lactic acid (LD), blood urea nitrogen (BUN) and creatine kinase (CK) concentration by 27.47%, 25.93% and 21.70%, respectively, after treatment, while increasing the levels of liver glycogen and muscle glycogen by 93.35% and 67.31%, respectively. FSPPs can significantly increase gut microbiota diversity and regulate the species richness of gut microbiota. The results of real-time polymerase chain reaction (RT-PCR) and western blotting showed that FSPPs activate p-AMPK/PGC1-α and PI3K/Akt/mTOR signaling pathways. These results indicate that treatment with FSPPs induces anti-fatigue effects, which may be due to the mediating muscle protein synthesis and participation in skeletal muscle hypertrophy, providing energy for muscle cells. FSPPs may have potential applications in the food industry as functional material additives. © 2021 Society of Chemical Industry.

High-degree hydrolysis sea cucumber peptides improve exercise performance and exert antifatigue effect via activating the NRF2 and AMPK signaling pathways in mice

In this study, the antifatigue potential of two sea cucumber peptides (SCP), with low hydrolysis degree (SCP-1) and high hydrolysis degree (SCP-2) derived from Acaudina leucoprocta was investigated. SCP-2 had a lower molecular weight, shorter peptide length, and higher proportion of identified sequences related to branched chain amino acids than SCP-1. Both SCP-1 and SCP-2 significantly improved exercise performance and exerted antifatigue effects in comparison to the negative control group (NC). The mice group received SCP-2 treatment showed better antifatigue effects than that of SCP-1 by prolonging exhaustive swimming time, increasing forelimb grip strength, reducing metabolite accumulation, relieving muscle injury, enhancing muscle glycogen and energy metabolism. Besides, these two treatments significantly modulated the protein relative levels of oxidative stress and mitochondrial function by regulating the NRF2 and AMPK signaling pathways. Conclusively, the study’s findings suggested that SCP could possibly be used as a green functional ingredient to overcome fatigue.

Anti-fatigue effect of hypericin in a chronic forced exercise mouse model

Ethnopharmacological relevanceHypericum perforatum L. is a traditional Chinese medicine used to sooth the liver, relieve depression, reduce body temperature, reduce sweating, and stimulate lactation. HP was extracted from Hypericum perforatum L. Aim of studyThe antifatigue effects of hypericin were assessed in a series of experiments. Materials and methodsSix-to eight-week-old male ICR mice were raised in our lab. Mice were subjected to swimming training for 2 h, 6 days/week for 6 weeks. One hour prior to each swimming session, intraperitoneal injection of saline or HP (2 or 4 mg/kg) was performed. ResultsCompared with the fatigue model control group, HP was found to significantly increase the swimming time in forced swimming tests. The molecular mechanisms underlying the antifatigue effects were further revealed by analysing energy metabolism, the oxidant–antioxidant system and the inflammatory response. HP normalized changes in BLA, LDH, BUN, and CK, LG in the liver. In addition, multiple assays have confirmed that HP improved the MDA, T-AOC, GSH-PX and SOD activity, and the relevant signalling pathways involved in the antifatigue effects were clarified. Furthermore, HP improves the expression of pro- and anti-inflammatory cytokines in skeletal muscle. ConclusionThese results suggested that the anti-chronic fatigue effects of HP are likely achieved by normalizing energy metabolism and attenuating oxidative and inflammatory responses. Consequently, this study supports HP use in the clinic to alleviate chronic fatigue.

Anti-fatigue effect of quercetin on enhancing muscle function and antioxidant capacity.

The aim of this study was to evaluate the anti-fatigue effect of quercetin in mice. Three-week-old male BALB/c mice, fed with/without 0.005% quercetin for 6weeks, were randomly divided into two experimental sets (loaded swimming and non-loading swimming tests). Our data indicated that dietary quercetin supplementation prolonged the exhaustive swimming time. In addition, lactic acid (LD) and blood urea nitrogen (BUN) levels, lactate dehydrogenase (LDH) and creatine kinase (CK) activities in serum were significantly decreased, while the levels of non-esterified free fatty acids (NEFA) in serum and the content of liver glycogen and muscle glycogen were significantly enhanced in dietary quercetin supplementation group. Furthermore, dietary quercetin supplementation significantly enhanced the glutathione peroxidase (GPx) and catalase (CAT) activities in serum, liver and gastrocnemius muscle and enhanced the total superoxide dismutase (T-SOD) activity in gastrocnemius muscle, but decreased the malondialdehyde (MDA) content and reactive oxygen species (ROS) level. Meanwhile, dietary quercetin supplementation affected the mRNA expression of regulators factors involved in muscle damage and inflammation, glucose metabolism and gluconeogenesis, muscle mitochondrial fatty acid β-oxidation and antioxidant related genes. Together, our data confirm that dietary quercetin supplementation can promote anti-fatigue capacity by promoting the antioxidant capacity and glycogen storage, as well as enhancing muscle function. PRACTICAL APPLICATIONS: Quercetin is a natural polyphenolic flavonoid substance. Here we confirm that quercetin has anti-fatigue activity. Our study indicates that quercetin may be used as natural anti-fatigue functional food or drugs.

Gynostemma pentaphyllum extract and its active component gypenoside L improve the exercise performance of treadmill-trained mice.

BACKGROUND/OBJECTIVESThe effectiveness of natural compounds in improving athletic ability has attracted attention in both sports and research. Gynostemma pentaphyllum (Thunb.) leaves are used to make traditional herbal medicines in Asia. The active components of G. pentaphyllum, dammarane saponins, or gypenosides, possess a range of biological activities. On the other hand, the anti-fatigue effects from G. pentaphyllum extract (GPE) and its effective compound, gypenoside L (GL), remain to be determined.MATERIALS/METHODSThis study examined the effects of GPE on fatigue and exercise performance in ICR mice. GPE was administered orally to mice for 6 weeks, with or without treadmill training. The biochemical analysis in serum, glycogen content, mRNA, and protein expressions of the liver and muscle were analyzed.RESULTSThe ExGPE (exercise with 300 mg/kg body weight/day of GPE) mice decreased the fat mass percentage significantly compared to the ExC mice, while the ExGPE showed the greatest lean mass percentage compared to the ExC group. The administration of GPE improved the exercise endurance and capacity in treadmill-trained mice, increased glucose and triglycerides, and decreased the serum creatine kinase and lactate levels after intensive exercise. The muscle glycogen levels were higher in the ExGPE group than the ExC group. GPE increased the level of mitochondrial biogenesis by enhancing the phosphorylation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein and the mRNA expression of nuclear respiratory factor 1, mitochondrial DNA, peroxisome proliferator-activated receptor-δ, superoxide dismutase 2, and by decreasing the lactate dehydrogenase B level in the soleus muscle (SOL). GPE also improved PGC-1α activation in the SOL significantly through AMPK/p38 phosphorylation.CONCLUSIONSThese results showed that GPE supplementation enhances exercise performance and has anti-fatigue activity. In addition, the underlying molecular mechanism was elucidated. Therefore, GPE is a promising candidate for developing functional foods and enhancing the exercise capacity and anti-fatigue activity.

Antifatigue effects of Hechong (Tylorrhynchus heterochaetus) through modulation of Nrf2/ARE- mediated antioxidant signaling pathway

This study was to evaluate the antifatigue effect of T. heterochaetus and explore the underlying mechanism of action. T. heterochaetus extract was treated to mice for 28 days. On the 28th day, after weight loaded swimming test. The levels of antioxidant enzymes and levels of pro- and anti-inflammatory cytokines in the liver and muscles of exercised mice were evaluated. mRNA and protein expression levels of Nrf2, SOD, HO-1, and Keap-1 were evaluated using RT-PCR and western blot analysis. The low (2.70 mg/0.5 ml/20 g) and medium (5.41 mg/0.5 ml/20 g) dose enhanced the activities of antioxidant enzymes like SOD, CAT and GPx in the liver and skeletal muscle thereby enhancing the antifatigue effect. The low and medium doses showed good anti-inflammatory effects by evaluating the levels of pro and anti-inflammatory cytokines such as TNF-α, IL-1β, IL-6, and IL-10 both in the liver and skeletal muscle. Furthermore, RT-PCR and western blot analysis showed increased expression of HO-1, SOD, Nrf2, and decreased expression of Keap-1 gene and proteins in liver and skeletal muscle of T. heterochaetus treated group mice. The current results indicate that T. heterochaetus exert the antifatigue effect through attenuating oxidative stress injury and inflammatory responses through the Nrf2/ARE-mediated signaling pathway.

Effectiveness of human-origin Lactobacillus plantarum PL-02 in improving muscle mass, exercise performance and anti-fatigue

Gut microbiota is very important for energy metabolism and regulation, which in turn affect the health and physiological functions of the host, and provide energy required for exercise. Supplementation with probiotics may be one of the ways to change the gut microbiota. In recent years, many studies have shown that probiotic supplementation can effectively improve sports performance. In this study, we screened Lactobacillus plantarum (PL-02), a probiotic of human-origin, from the intestines of 2008 Olympic women's 48 kg weightlifting gold medalist and explored the role of PL-02 in improved exercise endurance performance, reduced fatigue biochemical parameters, and changes in body composition. Male Institute of Cancer Research (ICR) mice were assigned to 0, 2.05 × 109, 4.10 × 109 and 1.03 × 1010 CFU/kg/day groups and were fed by oral gavage once daily for 4 weeks. The results showed that 4 weeks of PL-02 supplementation could significantly increase muscle mass, muscle strength and endurance performance, and hepatic and muscular glycogen storage. Furthermore, PL-02 could significantly decrease lactate, blood urea nitrogen (BUN), ammonia, and creatine kinase (CK) levels after exercise (p < 0.05). We believe that PL-02 can be used as a supplement to improve exercise performance and for its anti-fatigue effect.

Safety and antifatigue effect of Korean Red Ginseng capsule: A randomized, double-blind and placebo-controlled clinical trial

BackgroundIn physical activity or labor, the human body is in a state of high intensity stress, and all parts or physiological functions of the body respond positively to maintain or balance the need for movement. The human body has many physiological changes in the process of movement, and fatigue is the external manifestation of various complex changes inside the human body. Fatigue is also a physiological mechanism of self-protection after the body reaches a certain level of activity, which can prevent the occurrence of life-threatening excessive functional failure. The generation of fatigue is a very complex process, and its mechanism has not been concluded yet. Therefore, it is an important work to search and screen the effective components of natural plants that have anti-fatigue effect and to explore their mechanism. MethodsThis was a 8-week, randomized, double-blind, placebo-controlled clinical trial. A total of 110 subjects who passed physical examination were included according to the scheme design, and randomly divided into a test group which was given KRG and a placebo control group. The calculation is carried out according to the standard of sub-high-intensity exercise test. ResultsThere was no adverse effect on safety index of subjects after taking red ginseng capsule. After KRG treatment, subjective strength grade is significant lower than placebo treatment. Blood lactic acid content is significantly get lower after trial in KRG group, and significant lower than placebo group. Creatine phosphokinase(CK) content is significantly get lower after trial in KRG group, and significant lower than placebo group. ConclusionAccording to the criterion in the test scheme, the result shows that KRG is helpful on relieving physical fatigue.

Korean Red Ginseng Ameliorates Fatigue via Modulation of 5-HT and Corticosterone in a Sleep-Deprived Mouse Model.

Central fatigue, which is neuromuscular dysfunction associated with neurochemical alterations, is an important clinical issue related to pathologic fatigue. This study aimed to investigate the anti-central fatigue effect of Korean red ginseng (KRG) and its underlying mechanism. Male BALB/c mice (8 weeks old) were subjected to periodic sleep deprivation (SD) for 6 cycles (forced wakefulness for 2 days + 1 normal day per cycle). Simultaneously, the mice were administered KRG (0, 100, 200, or 400 mg/kg) or ascorbic acid (100 mg/kg). After all cycles, the rotarod and grip strength tests were performed, and then the changes regarding stress- and neurotransmitter-related parameters in serum and brain tissue were evaluated. Six cycles of SD notably deteriorated exercise performance in both the rotarod and grip strength tests, while KRG administration significantly ameliorated these alterations. KRG also significantly attenuated the SD-induced depletion of serum corticosterone. The levels of main neurotransmitters related to the sleep/wake cycle were markedly altered (serotonin was overproduced while dopamine levels were decreased) by SD, and KRG significantly attenuated these alterations through relevant molecules including brain-derived neurotropic factor and serotonin transporter. This study demonstrated the anti-fatigue effects of KRG in an SD mouse model, indicating the clinical relevance of KRG.

Assessing the Potential of Nutraceuticals as Geroprotectors on Muscle Performance and Cognition in Aging Mice.

Aging and frailty are associated with a decline in muscle force generation, which is a direct consequence of reduced muscle quantity and quality. Among the leading contributors to aging is the generation of reactive oxygen species, the byproducts of terminal oxidation. Their negative effects can be moderated via antioxidant supplementation. Krill oil and astaxanthin (AX) are nutraceuticals with a variety of health promoting, geroprotective, anti-inflammatory, anti-diabetic and anti-fatigue effects. In this work, we examined the functional effects of these two nutraceutical agents supplemented via pelleted chow in aging mice by examining in vivo and in vitro skeletal muscle function, along with aspects of intracellular and mitochondrial calcium homeostasis, as well as cognition and spatial memory. AX diet regimen limited weight gain compared to the control group; however, this phenomenon was not accompanied by muscle tissue mass decline. On the other hand, both AX and krill oil supplementation increased force production without altering calcium homeostasis during excitation-contraction coupling mechanism or mitochondrial calcium uptake processes. We also provide evidence of improved spatial memory and learning ability in aging mice because of krill oil supplementation. Taken together, our data favors the application of antioxidant nutraceuticals as geroprotectors to improve cognition and healthy aging by virtue of improved skeletal muscle force production.

The anti-fatigue potential of water-soluble polysaccharides of Semen cassiae on BALB/c mice.

Fatigue syndrome is a major health problem that affects the voluntary activities of an individual. Particularly, exercise-induced fatigue has become a serious concern in people's health. Since polysaccharides from various medicinal plants have been reported for anti-fatigue effect, the current study deals with the anti-fatigue potential of water-soluble polysaccharides of the Chinese medicinal plant Semen cassiae (Cassia obtusifolia L.) in BALB/c mice. Water-soluble polysaccharides from Semen cassiae were extracted using aqueous solvent (water). An orthogonal test design was employed for the optimization of polysaccharide extraction. The conditions optimized through this design unveiled the raw materials to solvent ratio as 1:30. The optimal temperature and time duration were found to be 80°C and 3.5 h, respectively. The yield of soluble polysaccharides at these specified conditions was 5.42%. Strikingly, the water-soluble polysaccharide from S. cassiae exhibited strong anti-fatigue activity at 100 mg/kg in BALB/c mice. S. cassiae polysaccharide extended the weight-loaded swimming duration in BALB/c mice. In addition, it ameliorated the level of antioxidant enzymes (SOD, GPX) while decreased the blood urea nitrogen, creatine phosphokinase, triglyceride, lactic acid, lactate dehydrogenase, and malondialdehyde levels in blood serum. Moreover, the assessment of the immunomodulatory effect of S. cassia polysaccharides unveiled the enhancement of B-cell and T-cell lymphocytes, denoting the positive effect on physical immunity.

Inflammation Disturbed the Tryptophan Catabolites in Hippocampus of Post-operative Fatigue Syndrome Rats via Indoleamine 2,3-Dioxygenas Enzyme and the Improvement Effect of Ginsenoside Rb1.

AimPost-operative fatigue syndrome (POFS) is a common complication that prolongs the recovery to normal function and activity after surgery. The aim of the present study was to explore the mechanism of central fatigue in POFS and the anti-fatigue effect of ginsenoside Rb1.MethodWe investigated the association between inflammation, indoleamine 2,3-dioxygenase (IDO) enzyme, and tryptophan metabolism in the hippocampus of POFS rats. A POFS rat model was induced by major small intestinal resection. Rats with major small intestinal resection were administered ginsenoside Rb1 (15 mg/kg) once a day from 3 days before surgery to the day of sacrifice, or with saline as corresponding controls. Fatigue was assessed with the open field test (OFT) and sucrose preference test (SPT). ELISA, RT-PCR, Western blot, immunofluorescence, and high-performance liquid chromatography (HPLC) were used to test the inflammatory cytokines; p38MAPK, NF-κB/p65, and IDO enzyme expressions; and the concentrations of tryptophan, kynurenine, and serotonin, respectively.ResultOur results showed that POFS was associated with increased expressions of inflammatory cytokines and p38MAPK and higher concentrations of kynurenine and tryptophan on post-operative days 1 and 3; a lower serotonin level on post-operative day 1; and an enhanced translocation of NF-κB/p65 and the IDO enzyme on post-operative days 1, 3, and 5. Ginsenoside Rb1 had an improvement effect on these.ConclusionInflammatory cytokines induced by large abdominal surgery disturb tryptophan metabolism to cause POFS through the activation of the p38MAPK–NF-κB/p65–IDO pathway in the hippocampus. Ginsenoside Rb1 had an anti-fatigue effect on POFS by reducing inflammation and IDO enzyme.

Anthocyanins in Lycium ruthenicum Murray reduce nicotine withdrawal-induced anxiety and craving in mice

Lycium ruthenicum Murray is widely used in traditional Chinese medicine and is believed to have antimicrobial, antioxidant, and anti-fatigue effects. Anthocyanins are considered to be one of the main active components. The previous work by our research team found that the anthocyanins in Lycium ruthenicum extract (ALRM) produce a stable anti-anxiety effect. The mechanisms of action include reducing the level of corticotropin-releasing factor (CRF) as well as regulating extracellular signal-regulated kinase/mitogen activation, protein kinase (ERK/MAPK) pathways, and others, all of which are related to the mechanisms of nicotine addiction. To investigate the effects of ALRM on anxiety and craving behavior after nicotine withdrawal, the components of ALRM were analyzed using the UPLC-Orbitrap MS method. The effects of ALRM on anxiety behavior induced by nicotine withdrawal were investigated in mice using the elevated plus maze (EPM) and light–dark box (LDB) tests. The effects of ALRM on craving behavior after nicotine withdrawal were further investigated using the conditional place preference (CPP) test. The EPM and LDB tests demonstrated that ALRM could alleviate the anxiety behavior induced by nicotine withdrawal and reduce nicotine craving in mice. Based on the identified ALRM components, the network pharmacology method was used to predict the mechanism of ALRM alleviating anxiety after nicotine withdrawal in mice. It was speculated that ALRM was involved in the production and transmission of dopamine, choline, and other nervous system functions and exhibited a potential role in treating nicotine addiction.

Characterisation, Chain Conformation and Antifatigue Effect of Steamed Ginseng Polysaccharides With Different Molecular Weight.

Two polysaccharides were obtained from steamed ginseng via ultrafiltration, and their physical–chemical properties, solution properties and antifatigue activities were studied. WSGP-S3 and WSGP-G3 were acid heteropolysaccharides with the molecular weights of 2.03 × 104 and 4.86 × 104, respectively. They were composed of different molar ratios of the monosaccharides Rha, GlcA, GalA, Glc, Gal, and Ara. The results of size-exclusion chromatography–multiangle laser light scattering analysis, Conge red staining and Circular dichroism spectroscopy revealed that WSGP-S3 exhibited a random conformation of branched clusters in solution. By contrast, WSGP-G3 exhibited an ordered conformation, including helix-like conformations in aqueous solution. Antifatigue activity tests proved that WSGP-S3 markedly prolonged the exhaustive swimming time of fatigued mice; increased liver and muscle glycogen levels and superoxide dismutase, catalase, glutathione peroxidase activities and decreased blood lactic acid, nitrogen and malondialdehyde levels compared with the control treatment. Moreover, it enhanced spleen cell proliferation in fatigued mice. By contrast, WSGP-G3 had no significant effect on fatigued mice. The results showed that WSGP-S3 might have a major contribution to the antifatigue effects of steamed ginseng polysaccharides and could be a potential anti-fatigue polysaccharide.

Dietary Supplementation of Octacosanol Improves Exercise-Induced Fatigue and Its Molecular Mechanism.

Several publications report that octacosanol (OCT) has different biological functions. This study was designed to evaluate the antifatigue effect and molecular mechanism of octacosanol (200 mg/(kg day)) in forced exercise-induced fatigue models of trained male C57BL/6 mice. Results showed that octacosanol ameliorated the mice's autonomic activities, forelimb grip strength, and swimming endurance, and the levels of liver glycogen (LG), muscle glycogen (MG), blood lactic acid (BLA), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were also regulated. Gene analysis results showed that treatment with OCT upregulated 29 genes, while 38 genes were downregulated in gastrocnemius tissue. Gene ontology (GO) analyses indicated that these genes enriched functions in relation to myofibril, contractile fiber, and calcium-dependent adenosinetriphosphatase (ATPase) activity. Octacosanol supplementation significantly adjusted the messenger RNA (mRNA) and protein expression levels related to fatigue performance. Octacosanol has an observably mitigating effect in exercise-induced fatigue models, and its molecular mechanism may be related to the regulation of tripartite motif-containing 63 (Trim63), periaxin (Prx), calcium voltage-gated channel subunit α1 H (Cacna1h), and myosin-binding protein C (Mybpc3) expression.

Effects of taurine and ginseng extracts on energy metabolism during exercise and their anti-fatigue properties in mice.

BACKGROUND/OBJECTIVESGinseng extract (GSE) and taurine (TR) are widely used antifatigue resources in functional foods. However, the mechanism underlying the antifatigue effects of GSE and TR are still unclear. Hence, we investigated whether GSE and TR have synergistic effects against fatigue in mice.MATERIALS/METHODSL6 cells were treated with different concentrations of TR and GSE, and cell viability was determined using 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium. Oxidative stress was analyzed by immunocytochemistry using MitoTracker™ Red FM and an anti-8-oxoguanine antibody. Respiratory gas analysis was performed to investigate metabolism. Expression of an activated protein kinase was analyzed using immunohistochemistry. Gene expression of cluster of differentiation 36 and pyruvate dehydrogenase lipoamide kinase isozyme 4 was measured using reverse transcription–polymerase chain reaction. Mice were orally administered TR, GSE, or their combination for 30 days, and then fatigue-related parameters, including lactate, blood urea nitrogen, and glycogen, were measured after forced swimming.RESULTSTR and GSE reduced oxidative stress levels in hydrogen peroxide-stimulated L6 cells and enhanced the oxygen uptake and lipid metabolism in mice after acute exercise. After oral administration of TR or GSE for 30 days, the fatigue-related parameters did not change in mice. However, the mice administered GSE (400 mg/kg/day) alone for 30 days could swim longer than those from the other groups. Further, no synergistic effect was observed after the swimming exercise in mice treated with the TR and GSE combination for 30 days.CONCLUSIONSTaken together, our data suggest that TR and GSE may exert antifatigue effects in mice after acute exercise by enhancing oxygen uptake and lipid oxidation.

Ingredients, Functionality, and Safety of the Japanese Traditional Sweet Drink Amazake

The sweet drink amazake is a fermented food made from Aspergillus oryzae and related koji molds in Japan. There are two types of drinks called amazake, one made from koji (koji amazake) and the other made from sake lees, a by-product of sake (sakekasu amazake). The sweetness of koji amazake is from glucose, derived from starch broken down by A. oryzae amylase. The other, sakekasu amazake, depends on added sugar. The main components are glucose and sucrose, but they also contain more than 300 other ingredients. Koji amazake contains oligosaccharides and ergothioneine, and sakekasu amazake has a resistant protein and α-ethyl glucoside, which are characteristic ingredients of each amazake. However, there are also common ingredients such as glycosylceramide. Functionality is known to include anti-fatigue, bowel movement, skin barrier, and other effects on human health. In particular, the bowel movement-improving effects have been well studied for both amazakes. These functions result from ingesting approximately 100 mL per day, but human clinical trials have clarified that this amount has no effect on blood glucose levels and weight gain. In the future, the identification of substances associated with each function is required.

Metabolomics study on the intervention effect of Radix Salviae Miltiorrhizae extract in exercise-induced exhaustion rat using gas chromatography coupled to mass spectrometry

The metabolomics approach based on the gas chromatography coupled to mass spectrometry (GC-MS) was adopted to explore the underlying mechanism of the anti-fatigue effect of Radix Salviae Miltiorrhizae (RSM), a famous herbal medicine in China used for multiple biological functions, in load-weighted swimming test in rat, combined with biochemical parameters evaluations. As a result, the metabolomics study followed by orthogonal partial least-square (OPLS) analysis could differentiate metabolic profiling between the control and exhaustive exercise group, showing the rats underwent an obvious metabolic perturbation, whereas RSM treatment restored scores plot close to normal and showed regulatory effects on the muscle metabolic profiles. The changed metabolic pathways of the potential biomarkers in response to the effect of RSM treatment for exhaustive exercise rats included in glucose metabolism (glucose, lactic acid, alanine), glutathione metabolism (glycine, glutamate, 5-oxo-proline), TCA cycle (succinic acid), arginine biosynthesis (glutamine, ornithine, urea), glyoxylate and dicarboxylate metabolism (serine, glycine), oxidative stress (taurine) and purine metabolism (inosine). In addition, intervention of RSM increased hepatic glycogen, muscle glycogen and serum glucose, and decreased triglyceride and blood urea nitrogen levels, indicating RSM treatment may regulate energy metabolism by increasing the rate of fat utilization, decrease the protein and carbohydrate utilization. Furthermore, RSM reduced exhaustive exercise-induced accumulation of the lipid peroxidation byproduct malonaldehyde and elevated antioxidants' levels, including reduced glutathione and superoxide dismutase, which might be a positive reflection of improved oxidant-antioxidant balance. Moreover, RSM could protect against exercise-induced muscle damage by attenuating creatine kinase release. In summary, RSM provided a good anti-fatigue effect by regulating energy metabolism, oxidant-antioxidant balance, and the endogenous metabolites in the exercising muscle. This study demonstrates that metabolomics is an effective tool for the estimation of the potential anti-fatigue effect of RSM and for the illustration of its pharmacological mechanism.

Discovery of the signal pathways and major bioactive compounds responsible for the anti-hypoxia effect of Chinese cordyceps

Ethnopharmacological relevanceHypoxia will cause an increase in the rate of fatigue and aging. Chinese cordyceps, a parasitic Thitarodes insect-Ophiocordyceps sinensis fungus complex in the Qinghai-Tibet Plateau, has long been used to ameliorate human conditions associated with aging and senescence, it is principally applied to treat fatigue, night sweating and other symptoms related to aging, and it may play the anti-aging and anti-fatigue effect by improving the body's hypoxia tolerance. Aims of the studyThe present study investigated the anti-hypoxia activity of Chinese cordyceps and explore the main corresponding signal pathways and bioactive compounds. Materials and methodsIn this study, network pharmacology analysis, molecular docking, cell and whole pharmacodynamic experiments were hired to study the major signal pathways and the bioactive compounds of Chinese cordyceps for anti-hypoxia activity. Results17 pathways which Chinese cordyceps acted on seemed to be related to the anti-hypoxia effect, and “VEGF signal pathway” was one of the most important pathway. Chinese cordyceps improved the survival rate and regulated the targets related VEGF signal pathway of H9C2 cells under hypoxia, and also had significant anti-hypoxia effects to mice. Chorioallantoic membrane model experiment showed that Chinese cordyceps and the main constituents of (9Z,12Z)-octadeca-9,12-dienoic acid and cerevisterol had significant angiogenic activity in hypoxia condition. ConclusionBased on the results of network pharmacology and molecular docking analysis, cell and whole pharmacodynamic experiments, promoting angiogenesis by regulating VEGF signal pathway might be one of the mechanisms of anti-hypoxia effect of Chinese cordyceps, (9Z, 12Z)-octadeca-9,12-dienoic acid and cerevisterol were considered as the major anti-hypoxia bioactive compounds in Chinese cordyceps.

The Effect of Lactobacillus plantarum CQPC02 on Fatigue and Biochemical Oxidation Levels in a Mouse Model of Physical Exhaustion.

Chinese Sichuan pickle is a fermented food rich in microorganisms. Microorganisms have the potential to become an important new form of potent future therapeutic capable of treating human disease. Selecting vitamin C as a positive control, a lactic acid bacteria (Lactobacillus plantarum CQPC02, LP-CQPC02) isolated from Sichuan pickle was given to mice over 4 weeks to investigate the effect of CQPC02 on fatigue levels and biochemical oxidation phenomena in exercise-exhausted Institute of Cancer Research (ICR) mice. The fatigue model was established by forced swimming of mice, the levels of hepatic glycogen, skeletal muscle glycogen, lactic acid, blood urea nitrogen and free fatty acid were measured by physicochemical methods, serum serum creatine kinase (CK), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) levels were measured by kits, the histopathological changes in the livers of mice were observed by H&E slicing, and the mRNA changes in the livers and skeletal muscles were observed by quantitative polymerase chain reaction (qPCR). Both vitamin C and LP-CQPC02 increased swimming exhaustion time. The concentration of LP-CQPC02 and exhaustion time were positively correlated. LP-CQPC02 also increased liver glycogen, skeletal muscle glycogen and free fatty acid content in mice and reduced lactic acid and blood urea nitrogen content in a dose-dependent manner. As walnut albumin antioxidant peptide concentration increased, levels of mouse CK, AST, and AST gradually decreased. LP-CQPC02 increased SOD and CAT levels and decreased MDA levels in a dose-dependent fashion. LP-CQPC02 up-regulated expression of mRNA encoding copper/zinc-superoxide dismutase (Cu/Zn-SOD), manganese-superoxide dismutase (Mn-SOD), and CAT in swimming exhaustion mouse liver tissue. LP-CQPC02 also up-regulated alanine/serine/cysteine/threonine transporter 1 (ASCT1) expression while down-regulating syncytin-1, inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α) expression in swimming exhaustion mouse skeletal muscle. Overall, LP-CQPC02 had a clear anti-fatigue and anti-oxidation effect. This suggests that LP-CQPC02 can be developed as a microbiological therapeutic agent.