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Cordyceps sinensis promotes exercise endurance capacity of rats by activating skeletal muscle metabolic regulators
Abstract
Cordyceps sinensis is a traditional Chinese medicine used for promotion of health, longevity and athletic power. However, the molecular mechanism for anti-fatigue activity and physical fitness has not yet been reported.
The present study was conducted to evaluate the exercise endurance promoting activities of fungal traditional Chinese medicine (FTCM) Cordyceps sinensis cultured whole mycelium (CS) and the underlying mechanisms.
CS was orally supplemented (200mg/kg body weight/day) to rats for 15days with or without swimming exercise along with exercise and placebo groups.
Both CS supplementation and supplementation concurrent with exercise improved exercise endurance by 1.79- (P<0.05) and 2.9-fold (P<0.01) respectively as compared to placebo rats. CS supplementation concurrent with exercise also increased the swimming endurance by 1.32-fold (P<0.05) over the exercise group. To study the molecular mechanism of the observed effect, we measured the expression levels of endurance responsive skeletal muscle metabolic regulators AMPK, PGC-1α and PPAR-δ as well as endurance promoting and antioxidant genes like MCT1, MCT4, GLUT4, VEGF, NRF-2, SOD1 and TRX in red gastrocnemius muscle. Our results indicate that CS supplementation significantly upregulates the skeletal muscle metabolic regulators, angiogenesis, better glucose and lactate uptake both in exercised and non-exercised rats. We have also observed increased expression of oxidative stress responsive transcription factor NRF-2 and its downstream targets SOD1 and TRX by CS supplementation.
CS supplementation with or without exercise improves exercise endurance capacity by activating the skeletal muscle metabolic regulators and a coordinated antioxidant response. Consequently, CS can be used as a potent natural exercise mimetic.
... Their training protocol consisted of 30 min of swimming per day, gradually increasing in duration until it reached 1 h. The swimming took place in an acrylic plastic pool measuring 90 cm × 45 cm × 45 cm, filled with water up to 60 cm and maintained at a temperature between 34 and 36 • C. In the meantime, the non-exercise groups received the same dosages of vehicles, crude extract, and maltodextrin but were kept in cages with only 3 cm of water to avoid potential stress or deleterious effects [16]. ...
... High-intensity training seems to impact creatinine more than moderate-intensity exercise [8]. Creatinine is not a perfect marker of muscle damage, as other markers like creatine kinase (CK) might be more reliable [16]. Age, sex, diet, and pre-existing conditions can also influence creatinine levels [17]. ...
... This study investigated the effects of sweet cassava extract and maltodextrin on exercise endurance in rats. While maltodextrin at 500 mg/kg significantly improved swimming times in both trained and untrained rats, mirroring findings from Ogawa et al. [4], Fukuda et al. [5], Costa et al. [7], and Kumar et al. [16], the crude extract had no such effect, contrasting with Nishii et al. [6]. Both supplements, however, increased glycogen levels in liver and muscle, potentially explaining the endurance boost. ...
The effects of maltodextrin and crude extract from sweet cassava on exercise endurance were examined in the male Wistar rat. The rats were randomly assigned to either an exercise training group or a non-exercise training group. Both groups were further divided into subgroups that received either a control, crude extract (250 or 500 mg/kg), or maltodextrin (250 or 500 mg/kg) orally once daily for 16 days. The time to the point of exhaustion after weight-loaded forced swimming was measured on day 16. Body weight gain, relative organ weight, biochemical parameters, and liver and gastrocnemius muscle glycogen content were also determined. Maltodextrin at a dose of 500 mg/kg significantly increased the time to the point of exhaustion compared to all other groups. Maltodextrin and crude extract with both doses significantly increased liver and gastrocnemius muscle glycogen content compared to the control group. There were no significant differences in glucose, BUN, triglyceride, or insulin levels between the groups. Crude extract at a dose of 250 mg/kg significantly increased AST and ALT levels, and LDH levels significantly increased in the exercise training group. Creatinine levels were significantly higher in the exercise training group compared to the non-exercise training group. Exercise boosted antioxidant enzymes, glycogen, and reduced damaging free radicals in the rats. Maltodextrin and crude extract further amplified this effect by activating AMPK and PGC-1α, suggesting that they combat fatigue through an antioxidant pathway linked to AMPK. These findings suggest that maltodextrin and crude extract from sweet cassava may have the potential to enhance exercise endurance. They may increase glycogen storage in the liver and gastrocnemius muscle, potentially through improved glycogen reserves and glycogen sparing effects. Further studies are needed to elucidate the mechanisms underlying these effects.
... Chronic exercise training has been widely studied in a range of tissues in the rat model. Studies [36][37][38][39][40] investigated changes in skeletal muscle Nrf2 protein content after a training period between 6 and 14 weeks. Collectively, similar exercise duration and intensity sessions (45-90 min/day, 25-30 m/min treadmill running or forced swimming, 4-6 days/week) were evaluated. ...
... Sahin et al. (2016) [37] and [40] report an increase of~25% in Nrf2 protein content after 6 weeks of exercise while Strobel et al. (2011) [38] reported an increase of~50% after 14 weeks of exercise. Of note, Kumar et al. (2011) [39] did find an increase in Nrf2 protein content of~100% after exercising rats 60 min/day, 6 days/week for 6 weeks. However, the mode of exercise, swimming, was different to treadmill studies [37,38,40], suggesting that exercise mode may have an impact on upregulation of Nrf2 protein in whole muscle tissue. ...
... Sahin et al. (2016) [37] and [40] report an increase of~25% in Nrf2 protein content after 6 weeks of exercise while Strobel et al. (2011) [38] reported an increase of~50% after 14 weeks of exercise. Of note, Kumar et al. (2011) [39] did find an increase in Nrf2 protein content of~100% after exercising rats 60 min/day, 6 days/week for 6 weeks. However, the mode of exercise, swimming, was different to treadmill studies [37,38,40], suggesting that exercise mode may have an impact on upregulation of Nrf2 protein in whole muscle tissue. ...
Chronic metabolic health diseases are increasing worldwide placing strain on healthcare systems and importantly, impacting individuals’ quality of life. It is well established that many chronic diseases are associated with inflammation and oxidative stress. Exercise is a known strategy to manage and treat inflammation in animals and humans. Understanding the mechanisms which cause acute and chronic changes to systems via various exercise protocols may provide insights into how we can better clinically manage patients with inflammatory and oxidative stress associated diseases. Nrf2 is a basic leucine transcription factor which regulates the expression of antioxidant proteins to protect against damage caused by electrophilic or oxidative stress. The aim of this narrative review is to provide an overview of the literature which has investigated the relationship between acute and chronic exercise training and Nrf2 protein, mRNA and Nrf2-ARE binding activity. This narrative review presents analysis of twenty-nine articles presenting studies using animals and humans. Findings from animal models suggest that exercise increases all molecular aspects of the Nrf2-ARE pathway in all tissues studied. It was noted that there seems to be an age-related decline in Nrf2 protein upregulation with exercise training. In humans, however, there is a lack of evidence to support this claim.
... Based on previous studies, the bioactivities of OS and OSM were found as immunomodulation [3], anti-inflammation [4], anti-tumor [5], antioxidation [6], cardiovascular-protection [6], anti-fibrosis [7], and regulating male reproductive function [8]. Besides, the evidences for exercise-endurance promotion and anti-fatigue activities of OS were demonstrated, and it meditated upregulation of some metabolic regulators, such as AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1), and peroxisome proliferator activated receptor (PPAR), in the skeletal muscle [9]. Recently, it was reported that cordycepin, one nucleotide derivatives in OS, could activate AMPK in HepG2 cells and then decrease intracellular lipid accumulation [10]. ...
... Many phytochemicals, i.e. polysaccharide, glycopeptide, showed powerful immunomodulatory, anti-inflammatory, and antioxidative activities [30,31,32,33]. Furthermore, Ophiocordyceps sinensis revealed the improvement of an exercise endurance capacity of rats by activating not only the skeletal muscle metabolic regulators but also a coordinated antioxidative response [9]. ...
... Surprisingly, the OSM use in this study also decreased the liver TG levels, but it did not enhance (p>0.05) the TG output in feces, so it may not be related to lipase activities. Probably, the decreased liver TG levels by OSM treatment may be related to the energy expenditure in hepatic or other tissues like skeletal muscle [9]. It has been proclaimed the Cordymin, a compound in OS, could enhance the mitochondria biogenesis in livers [40,41]. ...
... Kumar and coworkers studied the antifatigue activity of C. sinensis in the molecular level and found that C. sinensis could enhance muscle endurance by promoting the expression of skeletal muscle key metabolic regulators AMPK, PGC-1 , and PPAR-( Figure 1) [39]. These genes could induce marked changes in skeletal muscle metabolism, including increases in glycogen breakdown, glycolysis, glucose uptake, and oxidation of fatty acid, together with many changes in gene expression promoting endurance [40]. ...
... Meanwhile, Kumar et al. [39] also found that C. sinensis was capable of stimulating the expression of lactate monocarboxylate transporter MCT1 and glucose transporter GLUT4 Skeletal metabolic regulators PPAR- PGC-1 Figure 1: A possible mechanism with skeletal muscle metabolic regulators and transporters for the muscle endurance enhancement with a medicinal mushroom C. sinensis (adapted from [39]). ...
... Meanwhile, Kumar et al. [39] also found that C. sinensis was capable of stimulating the expression of lactate monocarboxylate transporter MCT1 and glucose transporter GLUT4 Skeletal metabolic regulators PPAR- PGC-1 Figure 1: A possible mechanism with skeletal muscle metabolic regulators and transporters for the muscle endurance enhancement with a medicinal mushroom C. sinensis (adapted from [39]). ...
Fatigue is the symptom of tiredness caused by physical and/or psychological stresses. As fatigue is becoming a serious problem in the modern society affecting human health, work efficiency, and quality of life, effective antifatigue remedies other than pharmacological drugs or therapies are highly needed. Mushrooms have been widely used as health foods, because of their various bioactive constituents such as polysaccharides, proteins, vitamins, minerals, and dietary fiber. This paper reviews the major findings from previous studies on the antifatigue effects, the active components of mushrooms, and the possible mechanisms. Many studies have demonstrated the antifatigue effects of edible and medicinal mushrooms. These mushrooms probably mitigate human fatigue through effects on the functional systems, including the muscular, cardiovascular, hormone, and immune system. The bioactive constituents that contribute to the antifatigue effects of mushrooms may include polysaccharides, peptides, nucleosides, phenolic compounds, and triterpenoids. Further research is still needed to identify the active ingredients and to investigate their mechanism of action on the antifatigue effects. Since most previous studies have been carried out in animal models, more human trials should be performed to verify the antifatigue function of edible and medicinal mushrooms.
... If that is in fact the case, there may be potential for synergistic effects between exercise training and Nrf2 activating compounds. There are some recent data in support of this and those are presented in section 6 of this review [27,28]. For those interested in a more detailed background on mechanisms of Nrf2 activation we refer readers to an excellent recent review in this area [16]. ...
... The effect of regular exercise training on the Nrf2 response has been studied more extensively than acute exercise. A comparison of these studies is outlined in Table 2. Regardless of duration (4-24 weeks) or training regimen (traditional moderate intensity or high-intensity interval training), regular aerobic exercise in rodent models has consistently been shown to activate Nrf2 signaling across multiple tissues including skeletal muscle, kidney, brain, liver, testes, prostate, and myocardium [27,42,43,[54][55][56][57][58][59][60][61][62][63]. ...
... The combined effect of supplementation and exercise was significantly greater in all tissues for Nrf2 expression with similar patterns observed for inducible HO-1. Sprague-Dawley rats supplemented with a known Nrf2 activator, Cordyceps sinensis [80], during a 15-day swimming program increased Nrf2 protein expression and phase II enzyme expression to levels significantly higher than those measured with exercise alone [27]. This area warrants further research. ...
The primary aim of this review is to summarize the current literature on the effects of acute exercise and regular exercise on nuclear factor erythroid 2-related factor 2 (Nrf2) activity and downstream targets of Nrf2 signaling. Nrf2 (encoded in humans by the NFE2L2 gene) is the master regulator of antioxidant defenses, a transcription factor that regulates expression of more than 200 cytoprotective genes. Increasing evidence indicates that Nrf2 signaling plays a key role in how oxidative stress mediates the beneficial effects of exercise. Episodic increases in oxidative stress induced through bouts of acute exercise stimulate Nrf2 activation and when applied repeatedly, as with regular exercise, leads to upregulation of endogenous antioxidant defenses and overall greater ability to counteract the damaging effects of oxidative stress. The evidence of Nrf2 activation in response to exercise across variety of tissues may be an important mechanism of how exercise exerts its well-known systemic effects that are not limited to skeletal muscle and myocardium. Additionally there are emerging data that results from animal studies translate to humans.
... The mechanisms underlying these effects are complex and involve multiple factors, including increased energy production, reduced oxidative stress, and activation of key signaling pathways such as the AMPK and PGC-1α pathways. Additional studies are required to clarify the specific molecular pathways through which these supplements exert their effects and to identify the optimal regimen for maximizing performance gains [9,10]. ...
... Following the experiment, the liver and muscle glycogen contents were measured using a modified version of a previously described method [10]. Blood samples for glucose, insulin, and free fatty acid levels were collected for biochemical analyses. ...
Ginseng and L-carnitine are natural compounds often used as dietary supplements to enhance athletic performance. However, their combined effects on exercise endurance remain unclear. Objectives: This study aimed to investigate the effects of ginseng extract and L-carnitine supplementation on exercise endurance in a rat model. Methods: Male Wistar rats were divided into 10 groups (n = 5 per group): control, ginseng extract (250 and 500 mg/kg/day), L-carnitine (250 and 500 mg/kg/day), and combined treatment. Half of the groups underwent a 16-day exercise training program of swimming without loading. Exercise endurance was assessed using a tail-suspended forced swimming test. Relative organ weight, glycogen content, blood biochemistry, and gene expression were analyzed. Results: Both ginseng extract and L-carnitine supplementation significantly increased exercise endurance, particularly in the exercise group. Ginseng extract and L-carnitine also increased liver glycogen content and upregulated the expression of AMPKα1 and PGC-1α genes in the liver and muscle. In addition, both supplements reduced oxidative stress by decreasing MDA levels and increasing SOD activity. Conclusions: Ginseng extract and L-carnitine supplementation may enhance exercise endurance by improving energy metabolism, reducing oxidative stress, and upregulating key genes involved in mitochondrial biogenesis.
... Several in vivo studies on rodents have investigated the effects of Cordyceps on physiological, neurobiological, and behavioral changes induced by stress [93][94][95][102][103][104][105][106][107]. Koh et al. (2003) observed changes in the weight of four glands (thymus, spleen, and adrenal and thyroid glands) in rats that were supplemented with a hot water fraction of Cordyceps sinensis mycelia for 8 days, and reported that the supplement counteracted the effects of 2 days of stress in the tested animals [103]. ...
... Such an interpretation would explain the contradictory results regarding the involvement of the serotonergic system in the effects of C. sinensis. Indeed, evidence from several rodent [106][107][108] and human [109,110] studies indicates the ability of Cordyceps spp. to counteract the physiological effects of exertion/effort. The only other study investigating the effect of Cordyceps mushrooms on streptozotocin-induced diabetes in the context of stress-coping was performed with Ophiocordyceps formosana [111]. ...
Dietary interventions for people suffering from major depressive disorder (MDD) are an ongoing field of research. In this article, we present a comprehensive background for understanding the possibility of using edible medicinal mushrooms as an adjunctive treatment for MDD. We start with a brief history of MDD, its diagnosis, epidemiology and treatment, and the effects of diet on depression symptoms, followed by a review of neurobiological, behavioral, and clinical studies of medicinal mushrooms. We specifically highlight the results of preclinical and clinical studies on dietary supplementation with three selected mushroom species: Lion’s mane (Hericium erinaceus), Caterpillar mushroom (Cordyceps militaris), and Lingzhi/Reishi (Ganoderma lucidum). Preliminary small-sample clinical studies suggest that Lion’s mane can influence well-being of humans. In the case of Reishi, the results of clinical studies are equivocal, while in the case of Caterpillar Mushroom, such studies are underway. Edible mushrooms contain 5-hydroxy-L-tryptophan (5-HTP), which is a direct precursor of serotonin—a neurotransmitter targeted in pharmacotherapy of MDD. Therefore, in light of the well-recognized role of stress as a pathogenic factor of MDD, we also describe the neurobiological mechanisms of the interaction between stress and serotonergic neurotransmission; and summarize the current state of knowledge on dietary supplementation with 5-HTP in MDD.
... •Increase in levels of serum insulin •Reduction in the levels of blood and liver lipid, and improvement of the glutamate pyruvate transaminase and antioxidant activity Yamaguchi et al., 2000a;Yamaguchi et al., 2000b;Chiou et al., 2000;Koh et al., 2003;Won et al., 2009;Gao et al., 2011;Guo et al., 2011; Anti-fatigue and antidepressant activity •Activating AMPK and protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways and regulating serum hormone level (Zhang et al., 1995;Xiao et al., 1999;Dai et al., 2001;Chen S et al. (2010); Kumar et al., 2011;Yan et al., 2012;Yan et al., 2013;Song et al., 2015;Geng et al., 2017) Aphrodisiac potential ...
... Such observations confirmed the anti-fatigue effects of C. sinensis polysaccharides Yan et al., 2012). To explore the underlying mechanisms behind the exercise endurance promoting activities of C. sinensis, Kumar et al. (2011) reported that such beneficial effects are mediated by upregulation of skeletal metabolic regulators AMPK, peroxisome proliferator-activated receptor gamma (PGC)-1 and peroxisome proliferator-activated receptors (PPAR)-as well as activation of NF-E2-related factor 2 (NRF-2)antioxidant responsive element (ARE) pathway that reduces exercise-induced oxidative stress and inflammation. To other species, i.e. C. guangdongensis has also been reported that it exhibits anti-fatigue effect as evident by the longest swimming time in mice . ...
In recent decades, interest in the Cordyceps genus has amplified due to its immunostimulatory potential. Cordyceps species, its extracts, and bioactive constituents have been related with cytokine production such as interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor (TNF)-α, phagocytosis stimulation of immune cells, nitric oxide production by increasing inducible nitric oxide synthase activity, and stimulation of inflammatory response via mitogen-activated protein kinase pathway. Other pharmacological activities like antioxidant, anti-cancer, antihyperlipidemic, anti-diabetic, anti-fatigue, anti-aging, hypocholesterolemic, hypotensive, vasorelaxation, anti-depressant, aphrodisiac, and kidney protection, has been reported in pre-clinical studies. These biological activities are correlated with the bioactive compounds present in Cordyceps including nucleosides, sterols, flavonoids, cyclic peptides, phenolic, bioxanthracenes, polyketides, and alkaloids, being the cyclic peptides compounds the most studied. An organized review of the existing literature was executed by surveying several databanks like PubMed, Scopus, etc. using keywords like Cordyceps, cordycepin, immune system, immunostimulation, immunomodulatory, pharmacology, anti-cancer, anti-viral, clinical trials, ethnomedicine, pharmacology, phytochemical analysis, and different species names. This review collects and analyzes state-of-the-art about the properties of Cordyceps species along with ethnopharmacological properties, application in food, chemical compounds, extraction of bioactive compounds, and various pharmacological properties with a special focus on the stimulatory properties of immunity.
... Although there have been numerous studies investigating the independent ergogenic effects of Rhodiola [28][29][30][31][32][33] and Cordyceps [34][35][36][37] in the literature, the results obtained here are still controversial among studies using varied experimental models. Short-term Rhodiola extracts (600-1500 mg/day for 3-30 days) have been demonstrated to exhibit ergogenic benefits among varied experimental models [28][29][30]. ...
... Short-term Rhodiola extracts (600-1500 mg/day for 3-30 days) have been demonstrated to exhibit ergogenic benefits among varied experimental models [28][29][30]. On the other hand, few studies have reported the positive ergogenic benefits of Cordyceps (1000-4000 mg/day for 21 days to 12 weeks) on enhancing exercise performance in both animal and human models [34][35][36][37]. These findings thus indicate the possibility of combining these two herbal-based ingredients to improve exercise adaptations. ...
Rhodiola crenulata (R) and Cordyceps sinensis (C) are commonly used herbs that promote health in traditional Chinese medicine. These two herbs have also been shown to exhibit anti-inflammation and antioxidant functions. Regular endurance training reveals potent endurance capacity, body composition improvement, and metabolic-related biomarker benefits. However, it is not known whether the combination of Rhodiola crenulata and Cordyceps sinensis (RC) supplementation during endurance training provides additive health benefits. The purpose of this study was to investigate the effects of 8-week endurance training plus RC supplementation on body composition, oxidative stress, and metabolic biomarkers in young sedentary adults.
Methods:
Fourteen young sedentary adults (8M/6F) participated in this double-blind randomized controlled study. Participants were assigned to exercise training with placebo groups (PLA, n = 7, 4M/3F; age: 21.4 ± 0.4 years) and exercise training with the RC group (RC, 20 mg/kg/day; n = 7, 4M/3F; age: 21.7 ± 0.4 years). Both groups received identical exercise training for eight weeks. The body composition, circulating oxidative stress, and blood metabolic biomarkers were measured before and after the 8-week intervention.
Results:
Improvement in body composition profiles were significantly greater in the RC group (body weight: p = 0.044, BMI: p = 0.003, upper extremity fat mass: p = 0.032, lower extremity muscle mass: p = 0.029, trunk fat mass: p = 0.011) compared to the PLA group after training. The blood lipid profile and systemic oxidative stress makers (thiobarbituric reactive substanceand total antioxidant capacity) did not differ between groups. Although endurance training markedly improved endurance capacity and glycemic control ability (i.e., fast blood glucose, insulin, and HOMA index), there were no differences in these variables between treatments.
Conclusions:
In this preliminary investigation, we demonstrated that an 8-week RC supplementation (20 mg/kg/day) faintly enhanced endurance training-induced positive adaptations in body composition in young sedentary individuals, whereas the blood lipid profile and systemic oxidative stress states were not altered after such intervention.
... Today, the fungus is used to treat male impotence and boost libido, which earned it the nickname 'Himalayan Viagra'. Recent studies show that cordyceps indeed possesses a wide range of beneficial effects on cells, animals, and humans [1][2][3], including increased energy and testosterone levels [5,6]. ...
... The kinetics of the binding is described by Equation 3. Some literature reports cite very high sensitivities for certain immunoassays [5][6][7][8]. ...
The caterpillar fungus Ophiocordyceps sinensis is a medicinal mushroom increasingly used as a dietary supplement for various health conditions, including fatigue, chronic inflammation, and male impotence. Here, we propose strategies to address the existing challenges related to the study and commercial production of this mysterious fungus.
... The reduction of lactic acid is the reason of reduction in exhaustion and stress, and thus improves physical performance and increases the stamina. By using swimming test the similar results were found in a rat study [37,38] . Now, researchers believe that Cordyceps is the best known multimedicine or complete energy package (dietary supplements) or booster for increasing physical stamina. ...
... [55] : Adenosine (33), cordycepin (34), guanosine(35), dideoxyadenosine (36), N6-(2-hydroxyethyl) adenosine(37), inosine(38), thymidine(39), uridine ...
Yarsagumba (Cordyceps sinensis) is one of the world rarest fungal species that parasites on the body of a caterpillar of a moth and found underground of alpine grass at high altitude. The Cordyceps sinensis is known as " summer plant and winter insect " or " half-caterpillar-half-mushroom ". This fungus used for various medicinal purposes, caring diseases and specially used as a food product in China and south Asian countries. It contains various biologically active pharmacophores which helps to maintain the health and body. Reports say that, the regular use of Cordyceps, is very useful for sportsperson to maintain their body balance, endurance, strength, and to make healthy body weight etc. On the basis of scientific and manmade facts, we tried to summarise, why Cordyceps is recommended to sport person as a physical booster. It contains various bioactive pharmacophores including essential oil, which are medicinally important. Thus body always looks for such type of dietary supplements.
... In I/R hearts, the activation of AMPK is an adaptive response of the heart; it provides ATP to protect myocardial tissue from damage during hypoxia [32,33,34]. Exercise training stimulates myocardial AMPK to regulate cellular metabolism [35,36], and different exercise intensities and durations also elicit the stimulation of AMPK. ...
... All of the results are expressed as the means ± SEMs. I/R, 30 min of ischemia and 120 min of reperfusion; I/R + ME, moderate intensity exercise for 8 wk before I/R; I/R + HE, high intensity exercise for 8 wk before I/R; I/R + AE, acute exercise before I/R; I/R + ME+ nor-BNI, moderate intensity exercise for 8 wk before I/R plus nor-BNI (2.0 mg/kg); I/R + HE + nor-BNI, high intensity exercise for 8 wk before I/R plus nor-BNI (2.0 mg/kg); I/R + AE + nor-BNI; acute exercise before I/R plus nor-BNI (2.0 mg/kg); I/R + ME + Compound C, moderate intensity exercise for 8 wk before I/R plus Compound C (20 mg/kg); I/R + HE + Compound C, high intensity exercise for 8 wk before I/R plus Compound C (20 mg/kg); I/R + AE + Compound C, acute exercise before I/R plus Compound C (20 mg/kg); I/R + ME + Akt inhibitor, moderate intensity exercise for 8 wk before I/R plus Akt inhibitor (0.3 mg/kg); I/R + HE + Akt inhibitor, high intensity exercise for 8 wk before I/R plus Akt inhibitor (0.3 mg/kg); I/R + AE + Akt inhibitor, acute exercise before I/R plus Akt inhibitor (0.3 mg/kg); I/R + ME + L-NAME, moderate intensity exercise for 8 wk before I/R plus L-NAME (30 mg/kg); I/R + HE + L-NAME, high intensity exercise for 8 wk before I/R plus L-NAME (30 mg/kg); I/R + AE + L-NAME, acute exercise before I/R plus L-NAME (30 mg/kg κ-opioid receptor and cardioprotection induced by exercise training AMPK to regulate the metabolism of myocardial tissue [35,36]. In this study, in agreement with previous studies [42,43,44], all three exercise training protocols with different intensities elevated the phosphorylation of AMPK. ...
The present study was designed to test the hypothesis that exercise training elicited a cardioprotective effect against ischemia and reperfusion (I/R) via the κ-opioid receptor (κ-OR)-mediated signaling pathway. Rats were randomly divided into four groups: the control group, the moderate intensity exercise (ME) group, the high intensity exercise (HE) group, and the acute exercise (AE) group. For the exercise training protocols, the rats were subjected to one week of adaptive treadmill training, while from the second week, the ME and HE groups were subjected to eight weeks of exercise training, and the AE group was subjected to three days of adaptive treadmill training and one day of vigorous exercise. After these protocols, the three exercise training groups were divided into different treatment groups, and the rats were subjected to 30 min of ischemia and 120 min of reperfusion. Changes in infarct size and serum cTnT (cardiac troponin T) caused by I/R were reduced by exercise training. Moreover, cardiac dysfunction caused by I/R was also alleviated by exercise training. These effects of exercise training were reversed by nor-BNI (a selective κ-OR antagonist), Compound C (a selective AMPK inhibitor), Akt inhibitor and L-NAME (a non-selective eNOS inhibitor). Expression of κ-OR and phosphorylation of AMPK, Akt and eNOS were significantly increased in the ME, HE and AE groups. These findings demonstrated that the cardioprotective effect of exercise training is possibly mediated by the κ-OR-AMPK-Akt-eNOS signaling pathway.
... In addition to moderate exercise, certain compounds can also promote Nrf2 activation. Several studies have reported the synergistic effect of exercise/physical activity and Nrf2-activating compounds [60,61]. Similarly, this study showed that the combination of exercise and YH had a greater effect on the elevation of Nrf2 levels compared to exercise and YH alone. ...
Background
Yeast hydrolysate (YH) has been shown to be effective in inhibiting fat accumulation. This study aimed to investigate the effects of YH and exercise on high-fat diet-induced obesity and their underlying mechanisms in C57BL/6J mice.
Methods
In this study, 6-week-old C57BL/6 mice were divided into 7 groups; a normal group fed a normal chow diet, an HFD group (CON) fed ad libitum, an exercise group (15m/min, 30min), an HFD supplemented with low dose of YH (100 mg/kg, YHL), an HFD supplemented with high dose of YH (200 mg/kg, YHH), and a combination of exercise and YHH group. After 12 weeks of HFD and YH administration, white adipocytes and liver tissue were analyzed.
Results
Both YH and exercise significantly reduced the weight of the body and adipose tissues; however, the greatest effect was observed when YH and exercise were combined. Similarly, most reduction in adipocyte size and fat formation in the liver was notable following the combination of YH and exercise. Furthermore, both YH and exercise effectively downregulated lipid synthesis genes, namely fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and HMG-CoA reductase (HMGCR), and SREBP1 and SREBP2 proteins. YH and/or exercise also significantly increased the mRNA levels of hormone sensitive lipase (HSL) and carnitine palmitoyltransferase 1 (CPT1), both of which are related to fatty acid oxidation. In addition, pAMPKα and PPARα levels were significantly increased by YH and exercise, with the greatest increase noted following the combination of YH and exercise. Additionally, YH and exercise combined caused the most significant increase in the antioxidant response, as evidenced by nuclear factor erythroid 2-related factor 2 (Nrf2) and superoxide dismutase 1 (SOD1) upregulation at protein and mRNA levels. Their combination also exhibited strongest suppression of inflammatory responses via the downregulation of NF-κB, TNF-α, and IL-1β at protein and mRNA levels. Collectively, YH and exercise combination showed an inhibitory effect on obesity, leading to decreased lipogenesis and increased lipolysis, with favorable regulation of antioxidant and inflammatory responses.
Conclusion
This study suggests the potential use of a combination of physical activity and YH supplementation to control obesity and related metabolic diseases.
... Studies also indicate that the polysaccharides of O. sinensis significantly upregulated metabolic regulators in both exercising and non-exercising skeletal muscles of rats, potentially due to the polysaccharides enhancing endurance and energy metabolism. These antioxidant properties may limit oxidative stress in skeletal muscles during exercise, thereby mitigating related cellular dysfunction and improving exercise endurance [36,37]. A previous study has also indicated that O. sinensis mycelium can enhance exercise coordination by increasing muscle endurance and reducing fatigue [38]. ...
Muscle atrophy, an age-related condition, presents a growing healthcare concern within the context of global population aging. While studies have investigated Hirsutella sinensis for its potential antifatigue properties, reports on its active components remain limited. This study evaluated the efficacy of H. sinensis mycelium extract on muscle health, utilizing a 1:1 water–ethanol preparation administered to C57BL/6 mice exhibiting acute hind leg atrophy. The results indicated no adverse effects, with significant improvements in muscle endurance and soleus muscle mass observed over a 14-day period. To further elucidate the mechanisms and effects of H. sinensis mycelium on dexamethasone-induced muscle atrophy, the water extract was fractionated into components of <3.5 kDa, 3.5–10 kDa, and >10 kDa using dialysis membranes. The investigation utilized a C2C12 cell atrophy model, induced by dexamethasone, to analyze the expression of relevant genes via qPCR. The results demonstrated that the <3.5 kDa and >10 kDa fractions significantly upregulated the expression of Myh2 and Myh7 genes while simultaneously downregulating the expression of MuRF-1 and Atrogin-1. It is noteworthy that the <3.5 kDa fraction exclusively enhanced MYHC protein expression and suppressed AMPK expression, as confirmed by Western blot analysis. This comprehensive pilot study suggests that the low-molecular-weight fraction of H. sinensis mycelium exhibits considerable potential for muscle mass preservation and atrophy mitigation. As a result, it offers a promising direction for the development of supplements aimed at addressing fatigue and preventing muscle atrophy.
... Due to the easy cultivation process and high cordycepin, Cordyceps militaris is grown at a large scale and is used for medicinal applications. As natural exercise promotes 4 Cordyceps also promotes blood flow and oxygen utilization and enhances the clearance of lactate 5 . This will allow the athletes to maintain a higher intensity of exercise, while the reduction in oxidation stress and clearance of lactate, leading to delay of fatigue [6][7][8] . ...
... A combination of Nrf2 activators, exercise, and metformin reduced diabetic complications (e.g., gain weight, water, calorie intake, blood glucose, insulin, and GLUT4 content) more efficiently than each treatment. 123,124,125 The combinations exhibited a greater impact on enhancing oxidative stress homeostasis by effectively activating Nrf2 signaling pathway and reducing the KEAP1 protein to a greater extent, but without considering the timing of Nrf2 activation. 126 The safety of the long-term effects of the combination therapy that includes Nrf2 activators is complicated by the role of Nrf2 in cancer onset and treatment. ...
Exercise has well-characterized therapeutic benefits in the management of type 2 diabetes mellitus (T2DM). Most of the beneficial effects of exercise arise from the impact of nuclear factor erythroid 2 related factor-2 (Nrf2) activation of glucose metabolism. Nrf2 is an essential controller of cellular anti-oxidative capacity and circadian rhythms. The circadian rhythm of Nrf2 is influenced by circadian genes on its expression, where the timing of exercise effects the activation of Nrf2 and the rhythmicity of Nrf2 and signaling, such that the timing of exercise has differential physiological effects. Exercise in the evening has beneficial effects on diabetes management, such as lowering of blood glucose and weight. The mechanisms responsible for these effects have not yet been associated with the influence of exercise on the circadian rhythm of Nrf2 activity. A better understanding of exercise-induced Nrf2 activation on Nrf2 rhythm and signaling can improve our appreciation of the distinct effects of morning and evening exercise. This review hypothesizes that activation of Nrf2 by exercise in the morning, when Nrf2 level is already at high levels, leads to hyperactivation and decrease in Nrf2 signaling, while activation of Nrf2 in the evening, when Nrf2 levels are at nadir levels, improves Nrf2 signaling and lowers blood glucose levels and increases fatty acid oxidation. Exploring the effects of Nrf2 activators on rhythmic signaling could also provide valuable insights into the optimal timing of their application, while also holding promise for timed treatment of type 2 diabetes.
... In a study, the effect of its extract on forced swimming ability in mice enhanced forced swimming ability by increasing fat utilization and delaying the accumulation of plasma lactate and ammonia. Cordyceps extracts also could prolong the mice swimming time [81]. ...
Caterpillar fungus (Cordyceps sinensis) has been widely used as a traditional Chinese medicine for several decades. It is essential to clarify the product composition, structural characteristics, and pharmacological functions of caterpillar fungus. In this review, we comprehensively and systematically summarized the various bioactive components isolated from caterpillar fungus, including nucleosides, d-mannitol, sterols, flavonoids, fatty acids, amino acids, vitamins, peptides, amides, proximate, and mineral composition. Meanwhile, peptides, nucleosides, and polysaccharides serve as the main active components in this genus, which possess immunomodulatory, antioxidant, anti-allergic, anti-tumor, anti-inflammatory, antibacterial, anti-malaria, and antifungal activities. Consequently, the active components of caterpillar fungus demonstrate a vital source of treatment for various diseases and can be used as possible leads for drug discovery. This article reviews the composition and pharmacological action of caterpillar fungus, which is the key to ensuring the safety and effectiveness of caterpillar fungus, and will be of interest for future research.
... Prior to data collection, our team hypothesized that previously established findings from animal models and mushroom consumption might reveal similar metabolic changes in a human cohort. Previous work has found that supplementation with Cordyceps sinensis significantly elevated proteins involved in mitochondrial synthesis and long chain fatty acid -oxidation in mice (14,21). Theoretically, this should increase some aspects of metabolic health (e.g., reduced BF% or elevated fat oxidation rates) and possibly reduced peripheral fatigue by lowering rates of carbohydrate oxidation while simultaneously reducing circulating lactate concentrations during exercise (16,26). ...
Hericium erinaceus (HE), also known as Lion's Mane mushroom, has been found to enhance cognition and metabolic flexibility in various animal models. To date however, only four studies exist in humans and none have evaluated the effects of HE on markers of metabolic flexibility or cognitive performance. A single-blind, placebo controlled, parallel-longitudinal study was used to determine the effects of HE on markers of metabolic flexibility and cognition. Twenty-four participants completed a graded exercise test on a cycle ergometer to analyze substrate oxidation rates and markers of cardiorespiratory fitness. Additionally, two dual-task challenges consisting of a Stroop Word Challenge interspersed with a Mental Arithmetic Challenge were performed, pre-post the graded exercise test, to evaluate markers of cognition in a pre-post fatigued state. Participants were stratified into two groups, receiving either 10 g of HE per day or placebo for 4-weeks in the form of two muffins identical in taste and appearance. Repeated-measures analysis of variance were conducted to evaluate potential interactions or main effects. Although group differences were noted at baseline, there were no significant interactions or main effects observed from HE ingestion for any dependent variable (all p > 0.05). Our data suggest that ingesting 10 g of HE per day for 4-weeks had no impact on metabolic flexibility and cognition in a college-age cohort. Due to the limited research on HE supplementation, future research is needed to establish an effective supplement dose and duration for potential physiological changes to be observed in humans.
... Importance of Cordiceps in sport and physical effort.Cordicepos increases endurance (Chiou et al., 2000;Koh et al., 2003), aerobic capacity , resistance to muscle fatigue in sedentary subjects (Nagata et al., 2006); improves cardiovascular activity in healthy runners (Nagata & Tajima, 2000); increases the capacity of resistance to effort (Kumar et al., 2011); and has antioxidant action in situations of exhausting physical exertion (Yan et al., 2014). ...
... Multiple research studies have shown that increased expression of AMPK and PGC-1⊍ pathways play an important role in resisting fatigue and promoting repair of damaged skeletal muscle. 56,57 Increased expression of AMPK and PI3K-Akt pathways facilitated the promotion of protein synthesis and the restoration of damaged muscle cells. Increasing expression of the gluconeogenic pathway promoted liver glycogen and muscle glycogen stores for rapid energy supply for exercise. ...
BACKGROUND
Corn peptides (CPs) are rich in branched‐chain amino acids such as leucine and have a variety of biological activities such as antioxidant and improved lipid distribution. In this article, we prepared CPs by enzymatic digestion of corn proteins and evaluated their anti‐fatigue activity.
RESULTS
We evaluated the anti‐fatigue effect of CPs through an exhaustive swimming experiment. The results showed that CPs were able to significantly reduce the rate of body weight gain and prolong the duration of exhaustive swimming. Besides, CPs reduced blood urea nitrogen (BUN) levels after exercise, while they significantly increased muscle glycogen and liver glycogen stores. They reduced muscle cell damage from exercise. In addition, CPs were effective in increasing AMPK, PGC‐1α and PI3K protein expression levels and promoting Akt phosphorylation. Correlation analysis showed that CPs increased the abundance of probiotics such as Lactobacillus and Akkermansia in the gut microflora.
CONCLUSION
CPs, which enhanced exercise performance in mice and could modulate gut microbial composition, had significant anti‐fatigue activity. © 2021 Society of Chemical Industry.
... Owing to these properties, it has been employed to treat various rehabilitation disorders such as arrhythmias, asthenia after severe illness, bronchitis, cancer, hyperglycaemia, hyperlipidaemia, hyposexuality, liver disease, lungs disorders, night sweating, renal dysfunction and renal failure etc. [4][5][6][7][8][9][10]. The Indian isolates of C. sinensis possess medicinal properties like anti-bacterial activity, anti-oxidant activities, anti-stress effect, anti-inflammatory, antimicrobial, muscular endurance, immune modulating effects, enhancement of neuromuscular activity, endurance enhancing activity [11][12][13][14][15][16] and tolerance activity to hypoxia at high altitude [15]. There are various HPLC methods that had been widely used in the determination of adenosine and cordycepin from C. sinensis or C. militaris [17,18,19]. ...
Cordyceps, a kind of precious natural crude drugs and edible mushrooms, were used as tonic food in East Asia area and enjoyed an extensive praise for its medicinal functions. Cordycepin exhibits various bio-activities, including anticancer, antibacterial, antiviral and immune regulation activities, and it's been a significant focus of research. However, the preparation of high-purity cordycepin remains challenging. Also, the molecular target with which cordycepin interacts to cause an antibacterial effect remains unknown. A simple and rapid isocratic chromatographic method (HPLC), optimum separation for (adenosine and cordycepin) analytes was achieved using the mixture of water and methanol as a mobile phase (85:15, v/v). The Photo-Diode Array Detector (DAD) WR, an auto injector, and a reverse phase column, Agilent Shield RP C18/4.6 × 150 mm, 4-micron and confirmation by LC/MSMS coupled with electrospray ionization (ESI) method for simultaneous separation and determination of adenosine and cordycepin in Cordyceps sinensis (Cs) and its substitutes was developed. Selective ion monitoring (SIM) mode ([M+/H]-at m/z 136, 267 and 252) was used for quantitative analysis of above components. The linearities for the 6 substances were studied in the range between 0.001 to 0.2 mg/L and the coefficients of determination (R 2) were always > 0.999. Matrix effects were also assessed by comparing the slopes obtained in solvent and matrix. The recoveries for all the substances at 3 different spike levels (0.05, 0.10 and 0.20 mg/L) were in the range 70.50-108% with RSDs < 5%. The instrumental limits of quantification were in the range 0.013-0.016 mg/L, while the reporting level of the method was 0.004 mg/L for all the aforementioned compounds. The nucleoside contents of types of natural Cs and its substitutes were determined and compared with this developed method.
... Yushu and Guoluo prefecture of Qinghai province and Naqu region of Tibet are the core natural distribution areas [4,5]. C. sinensis medicinal benefits include lung protection and kidney improvement [1,2], immunomodulation [2,6], antitumour effects [7], hepatoprotection [8], and increased endurance [9]. Some wild C. sinensis samples have a high arsenic content [10,11] and some samples do not comply with the limit standard of BS ISO 18664:2015 [12]. ...
The excessive arsenic content in wild Cordyceps sinensis has caused great concerns on human health. The toxicity of arsenic depends on its concentration, chemical form, and valence. The source studies of arsenic in C. sinensis are essential for safety evolution and quality control. We used ICP-MS and HPLC-ICP-MS methods to determine the total arsenic amount and the arsenic speciation. Synchrotron-based XANES and micro-XRF imaging techniques were used to characterize arsenic valence and distribution. The total arsenic amount range in wild C. sinensis samples was 5.77–13.20 μg/g with an average of 8.85 ± 2.5 μg/g. As(III) and As(V) were the main species in wild C. sinensis samples. The iAs only accounts for 4.47–11.42% of the extracted arsenic. Trivalent and pentavalent forms were the dominant chemical forms of arsenic. Besides, we found that arsenic was accumulated at the digestive tract of the host larva.
... In human athletes, Cordyceps sinensis L. showed improvement of the cardiovascular response in healthy runners (Nagata and Tajima 2000). Studies in rats have also shown an improvement in exercise endurance through the activation of skeletal muscle metabolism regulators and a coordinated antioxidant response (Kumar et al. 2011). However, despite some benefits, there is insufficient evidence for a role of Cordyceps sinensis L. supplementation in athletic performance, including a lack of studies evaluating the effects of supplementation on a sporting dog. ...
Sporting dog owner should realize that proper nutrition is one of the most important factors influencing the sports results achieved by the dog. In addition to the increased demand for energy and basic nutrients, particular attention should be paid to the adequate supply of vitamins and minerals, as well as dietary supplements. Therefore, the aim of the study was to characterize the importance of minerals, vitamins and functional additives in the nutrition of sporting dogs. The significant elements in the sporting dogs nutrition are calcium, phosphorus, potassium, sodium and magnesium. Micronutrients such as copper, iron, manganese, selenium and zinc are also very important. Of the vitamins in the sporting dogs nutrition, vitamins with antioxidant properties (vitamin E, vitamin C) are crucial, as well as vitamin D and B-group vitamins. Moreover, the diet of a sporting dog can also be enriched with functional additives that support the function of joints, muscles and circulatory system, as well as plants with an adaptogenic effect that improve the dog's immunity. Selecting the right amounts of individual additives so they fulfill their planned functions and are completely safe may be a problem. Since it should be remembered that both the deficiency and the excess of nutrients can be dangerous for the body.
... The results of the current study are in agreement with previous investigations that evaluated the influence of chronic exercise on Nrf2 in skeletal muscles. Kumar et al. (2011) showed an increase in the expression of Nrf2, SOD, and Trx induced by swimming exercise (2 weeks, 6 times per week) in skeletal muscle of healthy rats. In another study, Merry and Ristow (2016) demonstrated that following chronic exercise (60 min, 5 days/week, for 6 weeks), mice with impaired Nrf2 expression presented reduced antioxidant activity. ...
Cigarette smoke (CS) exposure reduces skeletal muscle function; however, the mechanisms involved have been poorly investigated. The current study evaluated the temporal effects of aerobic exercise training on oxidant and antioxidant systems as well as inflammatory markers in skeletal muscle of mice exposed to CS. Mice were randomly allocated to control, exercise, smoke, and smoke+exercise groups and 3 time points (4, 8, and 12 weeks; n = 12 per group). Exercise training and CS exposure were performed for 30 min/day, twice a day, 5 days/week for 4, 8, and 12 weeks. Aerobic exercise improved functional capacity and attenuated the increase in the cachexia index induced by CS exposure after 12 weeks. Concomitantly, exercise training downregulated tumor necrosis factor α concentration, glutathione oxidation, and messenger RNA (mRNA) expression of Keap1 (P < 0.01) and upregulated interleukin 10 concentration, total antioxidant capacity, and mRNA expression of Nrf2, Gsr, and Txn1 (P < 0.01) in muscle. Exercise increased mRNA expression of Hmox1 compared with the control after 12 weeks (P < 0.05). There were no significant differences between smoke groups for superoxide dismutase activity and Hmox1 mRNA expression. Exercise training improved the ability of skeletal muscle to adequately upregulate key antioxidant and anti-inflammatory defenses to detoxify electrophilic compounds induced by CS exposure, and these effects were more pronounced after 12 weeks.
NoveltyExercise attenuates oxidative stress in skeletal muscle from animals exposed to CS via Nrf2 and glutathione pathways.
Exercise is a helpful tool to control the inflammatory balance in skeletal muscle from animals exposed to CS.
These beneficial effects were evident after 12 weeks.
... Increasing evidence supports the notion that suppression of PGC-1α activity contributes to the development of AMD, because loss of PGC-1α induces ROS generation and mitochondrial damage. In contrast, elevated expression of PGC-1α promotes the mitochondrial antioxidant defense by increasing the expression of antioxidant genes, such as SOD2 and thioredoxin 1 (TRX1) [107]. Thioredoxininteracting protein can inhibit TRX activity and increase oxidative stress and destructive inflammation [108]. ...
Age-related macular degeneration (AMD) is a leading cause of severe visual loss and irreversible blindness in the elderly population worldwide. Retinal pigment epithelial (RPE) cells are the major site of pathological alterations in AMD. They are responsible for the phagocytosis of shed photoreceptor outer segments (POSs) and clearance of cellular waste under physiological conditions. Age-related, cumulative oxidative stimuli contribute to the pathogenesis of AMD. Excessive oxidative stress induces RPE cell degeneration and incomplete digestion of POSs, leading to the continuous accumulation of cellular waste (such as lipofuscin). Autophagy is a major system of degradation of damaged or unnecessary proteins. However, degenerative RPE cells in AMD patients cannot perform autophagy sufficiently to resist oxidative damage. Increasing evidence supports the idea that enhancing the autophagic process can properly alleviate oxidative injury in AMD and protect RPE and photoreceptor cells from degeneration and death, although overactivated autophagy may lead to cell death at early stages of retinal degenerative diseases. The crosstalk among the NFE2L2, PGC-1, p62, AMPK, and PI3K/Akt/mTOR pathways may play a crucial role in improving disturbed autophagy and mitigating the progression of AMD. In this review, we discuss how autophagy prevents oxidative damage in AMD, summarize potential neuroprotective strategies for therapeutic interventions, and provide an overview of these neuroprotective mechanisms.
... They can use oxygen and synthesize more ATP for continuous muscle contractions and become more resistant to fatigue (Lin et al., 2002). We are in the lineup with the result of T. matsutake and C. sinensis on the anti-fatigue effect which works by the mechanism through the AMPK linked pathway (Li et al., 2015;Kumar et al., 2011). Hence, we also believe that T. heterochaetus works by the same mechanism (Fig. 10). ...
Tylorrhynchus heterochaetus (Hechong in Chinese) has been used in Chinese traditional medicine for treating various diseases. This study was aimed to assess the anti-fatigue effect of T. heterochaetus on Kunming mice and its primary mechanism of action using forced running, rotating rod and weight-loaded swimming tests. Low (2.70 mg/0.5 mL/20 g), medium (5.41 mg/0.5 mL/20 g) and high (6.58 mg/0.5 mL/20 g) doses of T. heterochaetus aqueous extract were treated to mice for 28 days. Among the doses, the low and medium doses showed significant (p ≤ 0.05) anti-fatigue effect on the weight-loaded swimming test. Also, T. heterochaetus extract showed significant (p ≤ 0.05) effects on fatigue-related blood parameters by increasing the GLU, TG and LDH levels and decreasing the LA, CK and BUN levels. The levels of liver and skeletal muscle glycogen were also significantly (p ≤ 0.05) increased after treatment. Further, on Western blot analysis, it has been found that T. heterochaetus enhanced the expressions of AMPK and PGC-1α in the liver and skeletal muscles of mice. From the study, our outcomes suggest that T. heterochaetus possess an anti-fatigue effect through the AMPK-linked pathway and thereby it can regularize the energy metabolism.
... To demonstrate the impacts of PFEA on metabolic regulators PGC-1α and PPARα, we evaluated the mRNA expression levels of PGC-1α and PPARα in skeletal muscle (Kumar et al., 2011). As shown in Fig. 6, the PGC-1α and PPARα mRNA expression level were markedly increased in NC group, whereas, in PFEA treatment groups, such sharp increases have been significantly intensified. ...
Demands for anthocyanins are steadily growing due to their positive bioactivities in human health and food coloration. This study was performed to evaluate the characteristics of purified purple passion fruit epicarp anthocyanins (PFEA) as well as its anti-fatigue activity and underlying mechanisms in mice. The result showed that three major anthocyanins including cyanidin-3-O-glucoside, cyanidin-3-O-rutinoside and peonidin-3-O-glucoside were identified, and the total content of these anthocyanins was 710.40 mg/g in PFEA. PFEA significantly prolonged the weight-loaded forced swimming time, decreased lactate dehydrogenase (LDH), the blood lactate (BLA) and the blood urea nitrogen (BUN) levels, and increased the liver glycogen (LG) content. Meanwhile, PFEA could ameliorate fluctuates in oxidative stress biomarkers (MDA), antioxidant enzymes (SOD) and inflammatory cytokines (TNF-α, IL-1β, IL-6). Moreover, the mRNA expression of PGC-1α and PPARα in skeletal muscles were also up-regulated by PFEA treatment. In conclusion, these results showed that supplementing PFEA could relieve fatigue effects.
... Sacc. supplementation on lactate transporters MCT1 and MCT4 in red gastrocnemius muscles, and found a significant increase of the expression of MCT1 [101]. ...
It is a common phenomenon that people are in a sub-health condition and facing “unexplained fatigue”, which seriously affects their health, work efficiency and quality of life. Meanwhile, fatigue is also a common symptom of many serious diseases such as HIV/AIDS, cancer, and schizophrenia. However, there are still no official recommendations for the treatment of various forms of fatigue. Some traditional natural medicines are often used as health care products, such as ginseng, Cordyceps militaris (L.ex Fr.Link) and Rhodiola rosea L., and these have been reported to have specific anti-fatigue effects with small toxic and side effects and rich pharmacological activities. It may be promising treatment strategy for sub-health. In this review, we first outline the generation of fatigue. Furthermore, we put emphasis on the anti-fatigue mechanism, bioactive components, and clinic trials of natural medicines, which will contribute to the development of potential anti-fatigue agents and open up novel treatments for sub-health.
... The effect of regular exercise training on the Nrf2 response has been studied extensively and it has been found that, regardless of duration or training regimen, regular aerobic exercise in rodent models activates Nrf2 signaling across multiple tissues including skeletal [241] and cardiac muscle [242,243]. ...
Unaccustomed and/or exhaustive exercise generates excessive free radicals and reactive oxygen and nitrogen species leading to muscle oxidative stress-related damage and impaired contractility. Conversely, a moderate level of free radicals induces the body’s adaptive responses. Thus, a low oxidant level in resting muscle is essential for normal force production, and the production of oxidants during each session of physical training increases the body’s antioxidant defenses. Mitochondria, NADPH oxidases and xanthine oxidases have been identified as sources of free radicals during muscle contraction, but the exact mechanisms underlying exercise-induced harmful or beneficial effects yet remain elusive. However, it is clear that redox signaling influences numerous transcriptional activators, which regulate the expression of genes involved in changes in muscle phenotype. The mitogen-activated protein kinase family is one of the main links between cellular oxidant levels and skeletal muscle adaptation. The family components phosphorylate and modulate the activities of hundreds of substrates, including transcription factors involved in cell response to oxidative stress elicited by exercise in skeletal muscle. To elucidate the complex role of ROS in exercise, here we reviewed the literature dealing on sources of ROS production and concerning the most important redox signaling pathways, including MAPKs that are involved in the responses to acute and chronic exercise in the muscle, particularly those involved in the induction of antioxidant enzymes.
... Seven days of dosing in C57-Bl/6 mice (both 200 mg/kg and 400 mg/kg) demonstrated a higher hepatic bioenergy status (increased ATP) [9]. Twenty-eight days of cordyceps sinesis supplementation (100 mg/kg, 200 mg/kg and 400 mg/kg) in mice demonstrated longer swimming durations, increase hepatic and muscle glycogen, and decreased blood lactate compared to controls [10], while 15 days of Supplementation After Seven and Twenty-Eight Days supplementation (200 mg/kg) increased antioxidant response and improved endurance in rats [11]. ...
... The fungus contains several idiosyncratic secondary metabolites such as cordycepic acid, cordycepin, ergosterol, fatty acids, nucleobases, polyphenols, polysaccharides, steroids, terpenes and vitamins (Arora et al., 2008;Mamta et al., 2015;. The Indian isolates of C. sinensis possess medicinal properties like anti-bacterial activity, anti-oxidant activities, anti-stress effect, anti-inflammatory, antimicrobial, muscular endurance, immunomodulating effects, enhancement of neuromuscular activity, endurance enhancing activity (Kumar et al., 2011;Mamta et al., 2015;Meena et al., 2013;Negi et al., 2006;Rathor et al., 2014; and tolerance activity to hypoxia at high altitude . As mentioned by Thakur et al. (2011), the qualitative and quantitative fingerprinting of Indian isolates of C. sinensis has not been reported so far although several studies have been reported on its pharmacological activities (Thakur et al., 2011). ...
Cordyceps sinensis (C. sinensis) is well established as a traditional Chinese medicine (TCM) that has
been valued as a health food for centuries. It is an entomopathogenic fungus in Ascomycetes that naturally
occurs at high altitude in Himalayan region and has received considerable attention due to the abundance of
various biologically active compounds. Despite having reported health benefits and economic importance,
qualitative phytochemical analysis, proximate composition and proteome study of Indian isolates of C. sinensis
grown at high altitude remains untapped. In the present study, qualitative phytochemical analysis was carried
on powdered whole body of C. sinensis (CSWb) and its aqueous extract (CSAq) prepared by accelerated solvent
extraction technique which indicated the presence of several bioactive constituents such as alkaloids, amino
acids and proteins, carbohydrates, flavonoids and phenols, gums, mucilages and saponins. We evaluated chemical
composition of the Indian Himalayan medicinal mushroom C. sinensis in terms of its carbohydrate (55.68%)
content, crude fiber (6.40%), fat (1.80%), moisture (7.18%), protein (21.46%) and total ash (7.48%). Furthermore,
soluble protein identification of both CSWb and CSAq by SDS-PAGE followed by MALDI-TOF-TOF analysis revealed
the presence of various types of most abundant proteins such as P-type II A ATPase, TE1b [Blumeriagraminis f.
sp. hordei], Chitin synthase Chs [Penicilliummarneffei ATCC 18224], Serine/threonine-protein kinase CLA4,
DEHA2C06820p [Debaryomyceshansenii CBS767], YALI0E29887p [Yarrowialipolytica] etc. In conclusion, the
present study provides a comprehensive qualitative phytochemical analysis, proximate composition and proteome
study on Indian isolate of C. sinensis which could endorse its use as a functional food.
... On the contrary, the liver TG and TC contents of TAA-injected groups were higher (P < 0.05) than those of Control Regarding to effects of OSM on exercised rats, Ophiocordyceps sinensis improved an exercise endurance capacity by activating not only the skeletal muscle metabolic regulators but also a coordinated antioxidative response. 23 Altogether, the results revealed that OSM supplementation could consolidate the antioxidative system against extrinsic factor induced oxidative stress. ...
Thioacetamide (TAA), usually used as a fungicide to control the decay of citrus products, itself is not toxic to the liver, but its intermediates are able to increase oxidative stress in livers and further cause fibrosis. Ophiocordyceps sinensis mycelium (OSM) which contains 10% polysaccharides and 0.25% adenosine decreased (P < 0.05) the lipid accumulation and increased (P < 0.05) antioxidative capacity in livers of thioacetamide (TAA) injected rats. Meanwhile, the increased (P < 0.05) liver sizes, serum alanine transaminase (AST) and aspartate transaminase (ALT) values in thioacetamide (TAA)-injected rats were ameliorated (P < 0.05) by OSM supplementation. Moreover, the levels of proinflammatory cytokines, such as the tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were also reduced (P < 0.05). The fibrosis phenomena in pathological (Masson's trichrome and H&E stainings) and immunohistochemical [α-smooth actin (αSMA) and CD86/ED1] observations in TAA-treated rats were reduced (P < 0.05) by OSM cotreatment. The protective effect of OSM against TAA-induced liver inflammation/fibrosis may be via downregulations (P < 0.05) of TGF-β pathways and NFκB which further influenced (P < 0.05) the expressions of fibrotic and inflammatory genes (i. e., αSMA, Col1α, COX2). Therefore, OSM shows preventive effects on the development of TAA-induced hepatic fibrosis.
Background/Objectives: Growth in the aging world population is accompanied by an increase in comorbidities, profoundly impacting the quality of life of older people. This development has motivated a large effort to investigate the mechanisms underlying aging and the search for countermeasures. The most investigated strategies envisage the control of diet and physical exercise, which exploit both common and distinct mechanisms to promote health. Since the application of nutritional and exercise protocols to aged persons introduces several issues due to their disabled state, some strategies have been developed. The nutritional approach exploits a wide range of compounds, including calorie restriction mimetics, supplements, antioxidants, and others. In the context of exercise, in recent years, molecules able to provide similar effects to exercise, the so-called exercise mimetics, have been developed. Methods: To have a better perspective on exercise mimetics and their connection with nutrition, we performed a systematic search of the PubMed and Scopus databases using the term “exercise mimetics”. Results: In total, 97 research articles were selected and discussed. The present review provides evidence of the presence of multiple exercise-mimetic compounds and physical strategies that can target metabolic pathways, oxidative stress defense mechanisms, or myokine modulation. Conclusions: Interestingly, this review highlights that an important number of exercise mimetics are represented by products of natural origin and supplements assimilable with diet. This evidence provides a further link between exercise and nutrition and confers a central role on nutrition in the context of exercise mimetics.
Ethnopharmacological relevance: Cordyceps has a long medicinal history as a nourishing herb in traditional Chinese medicine (TCM). Ischemic cardio-cerebrovascular diseases (CCVDs), including cerebral ischemic/reperfusion injury (CI/RI) and myocardial ischemic/reperfusion injury (MI/RI), are major contributors to mortality and disability in humans. Numerous studies have indicated that Cordyceps or its artificial substitutes have significant bioactivity on ischemic CCVDs, however, there is a lack of relevant reviews.
Aim of the study: This review was conducted to investigate the chemical elements, pharmacological effects, clinical application and drug safety of Cordycepson ischemic CCVDs.
Materials and methods: A comprehensive search was conducted on the Web of Science, PubMed, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases using the keywords "Cordyceps", "Cerebral ischemic/reperfusion injury", and "Myocardial ischemic/reperfusion injury" or their synonyms. The retrieved literature was then categorized and summarized.
Results: The study findings indicated that Cordyceps and its bioactive components, including adenosine, cordycepin, mannitol, polysaccharide, and protein, have the potential to protect against CI/RI and MI/RI by improving blood perfusion, mitigating damage from reactive oxygen species, suppressing inflammation, preventing cellular apoptosis, and promoting tissue regeneration. Individually, Cordyceps could reduce neuronal excitatory toxicity and blood-brain barrier damage caused by cerebral ischemia. It can also significantly improve cardiac energy metabolism disorders and inhibit calcium overload caused by myocardial ischemia. Additionally, Cordyceps exerts a significant preventive or curative influence on the factors responsible for heart/brain ischemia, including hypertension, thrombosis, atherosclerosis, and arrhythmia.
Conclusion: This study demonstrates Cordyceps' prospective efficacy and safety in the prevention or treatment of CI/RI and MI/RI, providing novel insights for managing ischemic CCVDs.
Keywords: Cardio-cerebrovascular diseases; Cerebral ischemic/reperfusion injury; Chemical components; Chinese Cordyceps; Myocardial ischemic/reperfusion injury; Pharmacological activities.
Thioredoxin (Trx) is a compact redox-regulatory protein that modulates cellular redox state by reducing oxidized proteins. Trx exhibits dual functionality as an antioxidant and a cofactor for diverse enzymes and transcription factors, thereby exerting influence over their activity and function. Trx has emerged as a pivotal biomarker for various diseases, particularly those associated with oxidative stress, inflammation, and aging. Recent clinical investigations have underscored the significance of Trx in disease diagnosis, treatment, and mechanistic elucidation. Despite its paramount importance, the intricate interplay between Trx and cellular senescence—a condition characterized by irreversible growth arrest induced by multiple aging stimuli—remains inadequately understood. In this review, our objective is to present a comprehensive and up-to-date overview of the structure and function of Trx, its involvement in redox signaling pathways and cellular senescence, its association with aging and age-related diseases, as well as its potential as a therapeutic target. Our review aims to elucidate the novel and extensive role of Trx in senescence while highlighting its implications for aging and age-related diseases.
A third of the world’s population suffers from unexplained fatigue, hugely impacting work learning, efficiency, and health. The fatigue development may be a concomitant state of a disease or the side effect of a drug, or muscle fatigue induced by intense exercise. However, there are no authoritative guides or clinical medication recommendations for various fatigue classifications. Traditional Chinese medicines (TCM) are used as dietary supplements or healthcare products with specific anti-fatigue effects. Thus, TCM may be a potential treatment for fatigue. In this review, we outline the pathogenesis of fatigue, awareness of fatigue in Chinese and western medicine, pharmacodynamics mechanism, and substances. Additionally, we offer a comprehensive summary of fatigue and forecast the potential effect of novel herbal-based medicines against fatigue.
IntroductionNuclear factor erythroid-2-related factor 2 (Nrf2), is an inducible transcription factor that reduced in type 2 diabetes(T2D) and increases oxidative stress and then stimulating antioxidant expression. The purpose of this RCT was to investigate the effects of HIIT induced H2O2, Nrf2 changes on Glutathione Peroxidase (GPx), Glutathione Reductase (GR), Catalase (CAT) and superoxide dismutase (SOD) in T2D.Methods
Thirty-three male patients with T2D were randomly divided in 2 groups including to 12-weeks HIIT (10 rotations for 60 seconds (10 × 60s) set in constant watt mode at a pedal cadence of 80–100 revolutions/min) or a non-exercise control group. Nrf2, H2O2 and GPx, GR, Cat and SOD protein were measured in response to 12 weeks HIIT.ResultsLevels of Nrf2 and H2O2 showed high levels in HIIT with respect to control subjects after 12 weeks’ interventions (HIIT). Fasting plasma glucose (FPG) (p = 0.001), postprandial plasma glucose (PPG) (p = 0.001), glycated hemoglobin, (HbA1c) (p = 0.041), plasma total cholesterol (Tc) (p = 0.028), plasma triglyceride (TG) (p = 0.001), Na (p = 0.001), creatine kinase (Ck) (p = 0.035), alkaline phosphatase (ALP) (p = 0.025), hematocrit (Hct) (p = 0.008) and Cortisol (p = 0.001) were statistically significant in the T2D + HIITgroup. After 12 weeks’ interventions (HIIT), control group the Plasma CAT levels (p = 0.001) were found to be higher in HIIT group compared to control group.Conclusion
Our results provide evidence that HIIT causes an increase in oxidative stress levels, which ultimately the body responds to increased antioxidant levels. Therefore, it is suggested that these indicators (HIIT and H2O2, Nrf2) can be considered as a therapeutic target for type 2 diabetic patients.
Background & Aims
Edible mushrooms can be referred to as a “super food” and are recommended as a valuable constituent of the daily diet. Animal studies have suggested that mushroom intake can increase muscle endurance due to its abundant nutrients, and anti-inflammatory properties. However, no studies have explored the association between edible mushrooms consumption and muscle strength in the general population. We aimed to investigate the association of edible mushrooms consumption with handgrip strength (HGS) among Chinese adults.
Methods
A cross-sectional study was performed with 32,308 adults (17,290 men), in Tianjin, China. Mushrooms consumption was assessed via a self-administered food frequency questionnaire. Handgrip strength was measured using a handheld digital dynamometer. Analysis of covariance were used to evaluate the association between edible mushrooms consumption and handgrip strength.
Results
After adjusting potential confounding factors [age, body mass index, smoking status, alcohol-consumption status, education levels, employment status, household income, physical activity, family history of diseases (cardiovascular disease, hypertension, hyperlipidemia, and diabetes), metabolic syndromes, total energy intake, and dietary pattern], the least square means (95% confidence intervals) of HGS across consumption of edible mushrooms in males were 42.3 (41.0, 43.6) kg for ≤1 time/week, 43.4 (42.1, 44.6) kg for 2–3 times/week and 43.2 (41.9, 44.4) kg for ≥4 times/week (P for trend <0.001). In females, least square means were 25.1 (24.0, 26.2) kg for ≤1 time/week, 25.7 (24.7, 26.8) kg for 2–3 times/week and 25.7 (24.7, 26.8) kg for ≥4 times/week (P for trend <0.001). Similar associations were also observed for weight-adjusted HGS.
Conclusions
The study firstly revealed a positive association between edible mushrooms consumption and handgrip strength in both males and females. Further studies are needed to explore the casual relationship.
Trial registered
UMIN Clinical Trials Registry.
Reg No
UMIN000027174.
Trial Registration website
https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000031137.
Objective:
To investigate the effect of M3P (containing Deer antler, Cordyceps sinensis, Rhodiola rosea, and Panax ginseng); an herbal remedy with the function of tonifying Kidney (Shen) and invigorating Spleen (Pi), replenishing qi and nourishing blood; on fatigue alleviation, endurance capacity and toxicity.
Methods:
Swimming with weight-loading of 24 male ICR mice was used to evaluate the endurance capacity, and fatigue-related plasma biomarkers were determined. Mice were randomly assigned to control or M3P treatment groups with 6 mice for each group and were orally administered with M3P everyday for 8 weeks at doses 0, 10, 33 or 100 mg/kg. Swimming time to exhaustion was measured in a specialized water tank. Lliver and kidney functions, body weight, and hematological profile were determined to evaluate the safety and toxicity after long-term M3P administration.
Results:
M3P supplementation 100 mg/kg significantly increased swimming endurance time up to approximate 2.4 folds of controls (P<0.05). The plasma concentrations of cortisol and hepatic glycogen content were significantly increased in mice received M3P (P<0.05, P<0.01 respectively). The lactic acid level and blood glucose were not changed after M3P treatment (P>0.05). The liver and kidney functions muscle damage biomarker creatine, body weight, and hemograms were not altered in M3P supplementation (P>0.05).
Conclusion:
M3P supplementation may improve swimming endurance accompanied by increasing hepatic glycogen content and serum cortisol level without major toxicity.
Ophiocordyceps sinensis (Berk.) is a fungus closely related to medicinal mushroom, which belongs to the family Ophiocordycipitaceae. It is a well-known and rich herbal source of bioactive active constituents. The medicinal mushroom has garnered worldwide attention owing to its multifarious bioactivities. This mushroom grows on the larva of ghost moths (Hepialidae) and produces fruiting bodies, which serve as a vital natural source of medicine and supplementary diets. On account of the diverse pharmacological and bioactive constituents present in O. sinensis, it has been established as a potential antioxidant, anticancer, antibacterial, anti-proliferative, anti-inflammatory agent that has been successfully used for treating several health issues, including hypoxia-related problems encountered by mountaineers, pilgrims, tourists and soldiers occurring at high-altitude regions such as acute mountain sickness (AMS), high-altitude pulmonary edema (HAPE), high-altitude cerebral edema (HACE), frostbite, chilblains, hypothermia, etc. The most important pharmacologically active compounds present in the O. sinensis include nucleobases and its derivatives (adenosine, cordycepin, 3-deoxyadenosine, AMP, GMP, UMP, guanosine, uridine), polysaccharides (mannose, glucose, galactose, rhamnose, arabinose, xylose, galactose), proteins, peptides and steroids. This article focuses on the various research endeavors undertaken to scientifically establish the medicinal properties of O. sinensis, highlighting the various principally active compounds, their pharmacological action, drug designing and development and future perspective for various health benefits.
Introduction
Supplementation with Rhodiola Rosea (RR) and Cordyceps Sinensis (CS) has been shown to improve aerobic performance, but their influence on concurrent training (resistance training plus high intensity interval training) outcomes has not been established. The purpose of this study was to determine the effects of supplementation with a multi-ingredient performance supplement (MIPS) containing RR and CS during a 14-week training and testing program on body composition, weekly exercise training outcomes, overall training and performance outcomes, and hormone profiles.
Methods
Active college-aged men (N = 21) were stratified into either a MIPS or a placebo (PLA) group. Both groups completed 14 weeks of training and testing. Body composition, overall training outcomes, and blood sample collection occurred at weeks 0, 7, and 14, while training performance was evaluated weekly.
Results
Both groups improved (p < 0.05) percent body fat (-1.3%), bench press (+4%) and squat strength (+8%), with no difference between groups. Serum cortisol concentrations significantly decreased (-11%) but there were no differences between groups. No other changes in blood hormone profiles occurred. Weekly exercise performance data suggests that MIPS improved sprint performance, bench press lifting volume, and total workload, but this did not lead to improved overall training performance compared to PLA over the14-week study.
Conclusion
Despite MIPS improving certain aspects of weekly training performance, supplementation with MIPS for 14 weeks did not improve body composition, overall training and performance outcomes, or blood biomarkers of health in response to concurrent training in young men compared to PLA. This study was registered with clinicaltrials. gov (NCT02383017).
The genus Daphne belongs to the Thymeleaceae family and contains over 90 species that are distributed in Asia, Europe and parts of North Africa. The species of the genus Daphne are used in the traditional medicine of China, Tibet, Korea, and the Middle East for the treatment of various conditions. A broad range of studies has shown the significant biological potential of these species as sources of biologically and pharmacologically active compounds. Daphne species are a source of several classes of valuable phytochemicals such as coumarins, flavonoids, lignans, steroids and different classes of terpenes. The phytochemical diversity of this genus is demonstrated by over 350 secondary metabolites isolated from various species. The genus possesses a broad spectrum of biological activities including antibacterial, antifungal, antioxidant, analgesic, anti-inflammatory, cytotoxic, antiviral, abortive and haemostatic effects. A variety of bioactive secondary metabolites found in this genus may have potential use in pharmaceutical, cosmetic and food industries. Thus, species belonging to the genus Daphne can be considered an important source both for the treatment of various disorders, due to the presence of a plethora of bioactive constituents with potent bioactivities, and as possible leads in the discovery and synthesis of new medications.
Background and Objective
More and more people are facing the danger of fatigue with the fast-paced lifestyle. Fatigue symptoms are common in side effects of some diseases, such as cancer. The mechanism of fatigue is not definite up to now. Traditional Chinese medicine is often used for anti-fatigue with the unique efficacy, but the potential mechanism of Polygonati Rhizoma(PR) is not clear. This study attempts to explore the potential anti-fatigue mechanism of virtual screening for Polygonati Rhizoma based on network pharmacology.
Methods
The candidate compounds of PR and the known targets of fatigue were obtained from multiple professional databases. PharmMapper Server designed to identify potential targets for the candidate compounds. We constructed Herbal medicine-Compound-Disease-Target network and analyzed interactions. Protein-protein interaction network constructed through the Cytoscape software and analyzed by topological methods. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were carried out by DAVID Database. Finally, we constructed Compound-Target-Pathway network to illustrate the anti-fatigue mechanism of PR.
Results
This approach identified 12 active compounds and 156 candidate targets of PR. The top 10 annotation terms about GO and KEGG were obtained by enrichment analysis with 35 key targets. The interaction between E2F1 and PI3K-AKT plays a vital role in the anti-fatigue effect of PR due to this study.
Conclusions
This study shows that the anti-fatigue effect of PR has multi-component, multi-target and multi-pathway.
Objective:
To study the effect of Liuwei Dihuang Decoction () or Yukmijihwangtang (YJT) on endurance exercise by in vivo experiment.
Methods:
ICR mice were randomly divided into the control group (distilled water) and the YJT groups (1, 10, 100 mg/kg), 5 animals per group. YJT and distilled water were orally administered. The anti-fatigue effect of YJT was evaluated by open fifiled test (OFT), forced swimming test (FST), and tail suspension test (TST).
Results:
In the OFT, YJT signifificantly increased the total movement distance in a dose-dependent manner. Additionally, treatment with YJT signifificantly decreased immobility time in the FST and the TST. Various neurotransmitters such as norepinephrine (NE), serotonin (5-HT), dopamine (DA) levels were increased by FST. Administration of YJT down-regulated the expression levels of NE, 5-HT, 5-hydroxyindole-acetic acid (5-HIAA), and DA in the brain stem and hypothalamus of mice. Moreover, protein expression of HSP70 in mice liver and heart muscles was signifificantly increased in the YJT groups.
Conclusions:
YJT could ameliorate fatigue and enhance exercise tolerance through suppressing of brain monoamines including NE, 5-HT, 5-HIAA, and DA in FST mice model.
Sudden exposure to high altitude leads to various health related issues known as acute mountain sickness which arises due to decrease in partial pressure of oxygen and consequently, results in hypobaric hypoxia. Therefore, to ameliorate these health maladies, several studies have been carried out to explore the high altitude medicinal mushrooms for their biological and pharmacological activities; attributable to the presence of various active metabolites. Cordyceps sinensis (C. sinensis) is one of such mushrooms found at high altitude region. It is known for its medicinal importance and being an entomogenous fungus i.e. an assortment of insect and mushroom, possesses unique metabolite profile. It has been traditionally used as medicine and its various products are also available commercially, worldwide. Therefore, considering these facts, this chapter will divulgeorigin, bioactive constituents and its medicinal properties mainly pertaining to high altitude related ailments.
Key words: Cordycepssinensis, high altitude, bioactive constituents, medicinal mushrooms, antioxidant, hypoxia.
The genus Cordyceps has about 750 identified species which are distributed in many regions of the World, but mainly found in South Asia, Europe and North America. The species of the genus are highly priced and are widely used as food and medicine for the treatment of various ailments. This present review compiles literature information on the ethno-medicinal, phytochemistry and pharmacological properties of species in the genus Cordyceps. In addition, the review also suggest recommendations for the future researches. Thirty five Cordyceps species have been reported in the literature to have medicinal properties or has a report on the isolation of bioactive compounds. In vitro and in vivo research studies reporting the validation of the medicinal properties of some species were also reviewed. The phytochemical diversity of this genus was demonstrated with over 200 metabolites including nucleosides, sterols, cyclic peptides, flavonoids, dihydrobenzofurans, bioxanthracenes, polyketide, terpenes, alkaloids and phenolics isolated from various Cordyceps species. Cordyceps sinensis was identified as the most frequently used and most explored member of the Cordyceps genus. Cyclodepsipeptides, nucleosides and polysaccharides were identified as the most studied class of compounds from the genus and they show immunomodulatory, antioxidant, antitumor, cytotoxic, anti-inflammatory, anti-allergic, antidiabetic, analgesic, anti-HIV, antibacterial, antimalarial and antifungal activities. Thus, species belonging to the genus Cordyceps showcases an important source of treating various disorders due to the presence of bioactive constituents that displays potent bioactivities and could serve as possible leads in drug discovery.
Cordyceps sinensis (=Ophiocordyceps sinensis) and Ganoderma lucidum are 2 medicinal mushrooms that have been suggested to have the potential to enhance exercise capacity. We used a commercial supplement combining a traditional Chinese medicine and G. lucidum and tested its effects on human physical, aerobic, and anaerobic capacities. Physical education students (n = 96; 43 women, 53 men; mean ± standard deviation age, 26.3 ± 3.21 years) were randomly divided into 3 groups: low-dose treatment, high-dose treatment, and placebo. Participants received the supplement or the placebo for 28-33 days. Both before and after the intervention, the participants performed a graded maximum oxygen consumption (Vo2max) test on a treadmill and a Wingate anaerobic cycle test (on a different day). The following parameters were measured and recorded during the maximal graded treadmill test: heart rate, oxygen consumption, respiratory exchange ratio, and ventilation. The following parameters were calculated from the Wingate anaerobic cycle test: maximal anaerobic power, mean anaerobic power, and fatigue index. The supplements did not affect Vo2max or the physiological responses upon maximal exercise during the graded treadmill test. In a similar way, they had no effect on peak or mean power, or fatigue index, as measured by the Wingate anaerobic test. A borderline interaction indicated a somewhat lower heart rate at rest after treatment; however, post hoc analysis did not reveal any further statistically significant differences (P = 0.047; F = 3.169). The findings indicate that dual supplementation with C. sinensis and G. lucidum had no effect on Vo2max, on physiological responses at peak exercise load during a graded maximal treadmill test, or on the parameters of anaerobic capacity.
To determine the effects of a mushroom blend containing Cordyceps militaris on high-intensity exercise after 1 and 3 weeks of supplementation. Twenty-eight individuals (Mean ± standard deviation [SD]; Age = 22.7 ± 4.1 yrs; Height = 175.4 ± 8.7 cm; Weight = 71.6 ± 12.0 kg) participated in this randomized, repeated measures, double-blind, placebo-controlled design. Maximal oxygen consumption (VO2max), time to exhaustion (TTE), and ventilatory threshold (VT) were measured during a maximal graded exercise test on a cycle ergometer. Relative peak power output (RPP), average power output (AvgP), and percent drop (%drop) were recorded during a 3 minute maximal cycle test with resistance at 4.5% body weight. Subjects consumed 4 g·d−1 mushroom blend (MR) or maltodextrin (PL) for 1 week. Ten volunteers supplemented for an additional 2 weeks. Exercise tests were separated by at least 48 hours and repeated following supplementation periods. One week of supplementation elicited no significant time × treatment interaction for VO2max (p = 0.364), VT (p = 0.514), TTE (p = 0.540), RPP (p = 0.134), AvgP (p = 0.398), or %drop (p = 0.823). After 3 weeks, VO2max significantly improved (p = 0.042) in MR (+4.8 ml·kg−1·min−1), but not PL (+0.9 ml·kg−1·min−1). Analysis of 95% confidence intervals revealed significant improvements in TTE after 1- (+28.1 s) and 3 weeks (+69.8 s) in MR, but not PL, with additional improvements in VO2max (+4.8 ml·kg−1·min−1) and VT (+0.7 l·min−1) after 3 weeks. Acute supplementation with a Cordyceps militaris containing mushroom blend may improve tolerance to high-intensity exercise; greater benefits may be elicited with consistent chronic supplementation.
The entomopathogenic fungus Ophiocordyceps sinensis, formerly known as Cordyceps sinensis, has long been used as a traditional Chinese medicine for the treatment of many illnesses. In recent years its usage has increased dramatically because of the improvement of people's living standard and the emphasis on health. Such demands have resulted in over-harvesting of this fungus in the wild. Fortunately, scientists have demonstrated that artificially cultured and fermented mycelial products of O. sinensis have similar pharmacological activities to wild O. sinensis. The availability of laboratory cultures will likely to further expand its usage for the treatment of various illnesses. In this review, we summarize recent results on the pharmacological activities of the components of O. sinensis and their putative mechanisms of actions. Copyright © 2016 John Wiley & Sons, Ltd.
The skeletal muscle is the second more plastic tissue of the body - second to the nervous tissue only. In fact, both physical activity and inactivity contribute to modify the skeletal muscle, by continuous signaling through nerve impulses, mechanical stimuli and humoral clues. In turn, the skeletal muscle sends signals to the body, thus contributing to its homeostasis. We'll review here the contribute of physical exercise to the shaping of skeletal muscle, to the adaptation of its mass and function to the different needs imposed by different physical activities and to the attainment of the health benefits associated with active skeletal muscles. Focus will primarily be on the molecular pathways and on gene regulation that result in skeletal muscle adaptation to exercise.
Previous studies of oral supplementation with CordyMax (CM), a proprietary mycelial fermentation product of the Cordyceps sinensis, have demonstrated significant improvements in aerobic capacity in older humans and in exercise performance and metabolism in elite athletes (JACM 2001;7:231; FASEB 2002;16:A628). This randomized, double-blind clinical study further examined the effect of CM on endurance parameters in healthy, sedentary adults. Subjects (40-70 yrs old) received either CM (n=61) or placebo (P; n=70) for 12 weeks. VO2peak, respiratory exchange ratio (RER), time to complete a 1-mile walk (TMW), and work output (WO) by Jeukendrup bike test were examined at Weeks 0, 6, and 12. VO2peak was increased by 5.5% in CM (p=0.003), but by only 2.2% in P (NS). Exercise time to VO2peak was longer in CM (+5.4%, p=0.047), but no change in P. TMW was reduced by 29 sec in CM (p=0.05), but slightly increased in P (+19 sec, NS). WO was increased by 2.8% in CM (p=0.033), but fell in P (-5.6%, NS). RER was reduced by 2.1% in CM (p=0.018), but no change in P. Diastolic blood pressure was reduced by 3.2% in CM (p=0.045), but no change in P. Consistent with previous findings in healthy, elderly and athlete individuals, these data indicates that oral CM supplementation improves aerobic capability, exercise metabolism, and endurance performance in healthy, mid-age to elderly sedentary humans. Supported by a grant from Pharmanex.
Two species of the genus Cordyceps, namely, C. sinensis and C. militaris, are found in the high altitudes (4000-5000 m) and low altitudes (2500-2800 m), respectively, in the central Himalayan hills of India. The natural populations of C. sinensis and C. militaris have variations in color, shape, size, and number of stroma and have single or multiple stromae at one or both of the ends. The biochemical characterizations of in vitro-cultured mycelium vis-a-vis natural specimens of C sinensis contain almost the same concentrations of cordycepin, an important bioactive ingredient. This study was conducted to find the genetic similarity between the natural samples and the cultured ones, as well as to find the extent of genetic variability existing within natural populations. A total of 45 random primers were screened. Twenty random RAPID primers were selected for PCR amplification, and amplicon levels were scored. Primers showed a very high level of polymorphism. Out of a total of 362 bands detected, 87% were polymorphic. Genetic similarity indices ranged from 0.282 to 0.782, indicating a high level of diversity within natural samples. RAPD polymorphs were analyzed with a phenatic distance measure (Jacquard coefficient), and a dendrogram was constructed. Two genetically different groups of Cordyceps spp. were identified in the natural population, indicating intrageneric diversity. The in vitro-cultured mycelia of C. sinensis have only 5% genetic variability from their mother samples. This is a significant finding that in vitro-cultured C. sinensis can yield almost the same d-mannitol content that is being yielded by the natural samples. This study will be helpful in the reduction of the market price of C sinensis and will also contribute to the conservation of the dwindling natural population of this valuable medicinal species.
This review looks in depth at the history and medicinal value of the Cordyceps species, especially C. sinensis. The C. sinensis medicinal species, with a long history of use, has only been found growing from the head of one type of subterranean caterpillar, at high altitudes, in the Qinghai-Tibetan plateau. Because of this highly specific growth environment and restricted geographical distribution, C. sinensis has a long reputation of being the single-most expensive raw material used in Oriental Medicine. Due to environmental and ecological factors, the annual harvest has been steadily declining, while at the same time the worldwide demand has been increasing. This situation has driven Cordyceps spp. prices into an ever-increasing spiral over the last few years, driving research to determine ways of cultivating it to make it a more affordable material for commercial trade. Part of the goal of this research has been to understand the complex biological niche such an organism fills. This is a mushroom that is only found in cohabitation with the larvae of an insect, and it is this unique growth parameter that has made it challenging to produce Cordyceps spp. in artificial cultivation. Further complicating this cultivation issue is the rarefied atmosphere, mineral-rich soil, and low temperature in which Cordyceps naturally grows, resulting in a unique profile of secondary metabolites possessing interesting biological potential for medical exploitation, but which are not readily reproduced in normal laboratory cultivation. In this article, we attempt to unravel many of the mysteries of Cordyceps spp., detailing the history, medicinal uses, chemical composition, and cultivation of Cordyceps spp., with special attention to C. sinensis, the world's most costly medicinal mushroom.
Objective: Cordyceps sinensis (CS) is a popular natural Chinese herbal medicine for invigoration, health preservation and reducing
fatigue. Its natural substance has been prepared as a fermentation product of a specific strain of Cordyceps sinensis (Cs-4).
Our objective was to assess the effect of Cs-4 on the exercise capacity of the healthy elderly people in a randomized, double-blind,
placebo-controlled trial.Methods: Thirty-seven healthy, elderly Chinese subjects were randomly assigned to receive either Cs-4 (3 g/ day) or identical placebo
capsules. Their exercise performance was tested before and after 6 weeks of treatment with a symptom-limited, incremental
work rate protocol on a cycle ergometer. Maximum oxygen uptake (VO2max) was measured using a metabolic chart. Anaerobic thresholds (VO2θ) were identified by two observers using plots of both VCO2 vs VO2 and VE/VO2 vs time.Results: After taking Cs-4 for 6 weeks, VO2max (1.88 ±0.13 to 2.00 ±0.14 L/min;P = 0.050) and VO2θ (1.15 ±0.07 to 1.30 ±0.09 L/min;P = 0.012) were significantly increased, whereas after placebo application they were unchanged.Conclusion: These findings support the belief held in China that Cs-4 could improve oxygen uptake or aerobic capacity and ventilation
function and resistance to fatigue of elderly people in exercise.
The skeletal muscle is the second more plastic tissue of the body -second to the nervous tissue only. In fact, both physical activity and inactivity contribute to modify the skeletal muscle, by continuous signaling through nerve impulses, mechanical stimuli and humoral clues. In turn, the skeletal muscle sends signals to the body, thus contributing to its homeostasis. We'll review here the contribute of physical exercise to the shaping of skeletal muscle, to the adaptation of its mass and function to the different needs imposed by different physical activities and to the attainment of the health benefits associated with active skeletal muscles. Focus will primarily be on the molecular pathways and on gene regulation that result in skeletal muscle adaptation to exercise.
Hyperlipidemia is a major risk factor for cardiovascular diseases. In this study, we investigated the potential effects of cordycepin (3'-deoxyadenosine), a bioactive component of the fungus Cordyceps militaris, on hyperlipidemia. We found that in male Syrian golden hamsters fed a high-fat diet (HFD), daily administration of cordycepin effectively reduced the accumulation of serum total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-c) and suppressed HFD-associated increases in relative retroperitoneal fat. It also increased the levels of phospho-AMP-activated protein kinase (AMPK) and phospho-acetyl-CoA carboxylase (phospho-ACC) in liver and retroperitoneal adipose tissues. In HepG2 cells, cordycepin stimulated robust concentration- and time-dependent AMPK activation that correlated with the activation of ACC and the suppression of lipid biosynthesis. However, pretreatment with compound C, a specific inhibitor of AMPK, substantially abolished the effects of cordycepin on AMPK activation and lipid biosynthesis inhibition. These results indicate that cordycepin prevents hyperlipidemia via activation of AMPK. Experiments on abnormal metabolic mice indicated that cordycepin can also improve insulin sensitivity effectively.
Parasitic Cordyceps fungi, such as Cordyceps sinensis, is a parasitic complex of fungus and caterpillar, which has been used for medicinal purposes for centuries particularly in China, Japan and other Asian countries. This article gives a general idea of the latest developments in C. sinensis research, with regard to the active chemical components, the pharmacological effects and the research and development of products in recent years.
The common names for preparations include DongChongXiaCao in Chinese, winter worm summer grass in English. It has many bioactive components, such as 3'-deoxyadenosine, cordycepic acid and Cordyceps polysaccharides. It is commonly used to replenish the kidney and soothe the lung, and for the treatment of fatigue. It also can be used to treat conditions such as night sweating, hyposexuality, hyperglycaemia, hyperlipidaemia, asthenia after severe illness, respiratory disease, renal dysfunction, renal failure, arrhythmias and other heart disease and liver disease. Because of its rarity and outstanding curative effects, several mycelia strains have been isolated from natural Cordyceps and manufactured by fermentation technology, and are commonly sold as health food products. In addition, some substitutes such as C. militaris and adulterants also have been used; therefore, quality control of C. sinensis and its products is very important to ensure their safety and efficacy.
Recent research advances in the study of Cordyceps, including Cordyceps mushrooms, chemical components, pharmacological functions and developmental products, has been reviewed and discussed. Developing trends in the field have also been appraised.
The first suggestion that physical exercise results in free radical-mediated damage to tissues appeared in 1978, and the past three decades have resulted in a large growth of knowledge regarding exercise and oxidative stress. Although the sources of oxidant production during exercise continue to be debated, it is now well established that both resting and contracting skeletal muscles produce reactive oxygen species and reactive nitrogen species. Importantly, intense and prolonged exercise can result in oxidative damage to both proteins and lipids in the contracting myocytes. Furthermore, oxidants can modulate a number of cell signaling pathways and regulate the expression of multiple genes in eukaryotic cells. This oxidant-mediated change in gene expression involves changes at transcriptional, mRNA stability, and signal transduction levels. Furthermore, numerous products associated with oxidant-modulated genes have been identified and include antioxidant enzymes, stress proteins, DNA repair proteins, and mitochondrial electron transport proteins. Interestingly, low and physiological levels of reactive oxygen species are required for normal force production in skeletal muscle, but high levels of reactive oxygen species promote contractile dysfunction resulting in muscle weakness and fatigue. Ongoing research continues to probe the mechanisms by which oxidants influence skeletal muscle contractile properties and to explore interventions capable of protecting muscle from oxidant-mediated dysfunction.
The benefits of endurance exercise on general health make it desirable to identify orally active agents that would mimic or potentiate the effects of exercise to treat metabolic diseases. Although certain natural compounds, such as reseveratrol, have endurance-enhancing activities, their exact metabolic targets remain elusive. We therefore tested the effect of pathway-specific drugs on endurance capacities of mice in a treadmill running test. We found that PPARbeta/delta agonist and exercise training synergistically increase oxidative myofibers and running endurance in adult mice. Because training activates AMPK and PGC1alpha, we then tested whether the orally active AMPK agonist AICAR might be sufficient to overcome the exercise requirement. Unexpectedly, even in sedentary mice, 4 weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44%. These results demonstrate that AMPK-PPARdelta pathway can be targeted by orally active drugs to enhance training adaptation or even to increase endurance without exercise.
The effects of endurance training on the enzyme activity, protein content, and mRNA abundance of Mn and CuZn superoxide dismutase (SOD) were studied in various phenotypes of rat skeletal muscle. Female Sprague-Dawley rats were randomly divided into trained (T, n = 8) and untrained (U, n = 8) groups. Training, consisting of treadmill running at 27 m/min and 12% grade for 2 h/day, 5 days/wk for 10 wk, significantly increased citrate synthase activity (P < 0. 01) in the type I (soleus), type IIa (deep vastus lateralis, DVL), and mixed type II (plantaris) muscles but not in type IIb (superficial vastus lateralis, SVL) muscle. Mitochondrial (Mn) SOD activity was elevated by 80% (P < 0.05) with training in DVL. SVL and plantaris muscle in T rats showed 54 and 42% higher pooled immunoreactive Mn SOD protein content, respectively, than those in U rats. However, no change in Mn SOD mRNA level was found in any of the muscles. CuZn SOD activity, protein content, and mRNA level in general were not affected by training, except for a 160% increase in pooled CuZn SOD protein in SVL. Training also significantly increased glutathione peroxidase and catalase activities (P < 0.05), but only in DVL muscle. These data indicate that training adaptations of Mn SOD and other antioxidant enzymes occur primarily in type IIa fibers, probably as a result of enhanced free radical generation and modest antioxidant capacity. Differential training responses of mRNA, enzyme protein, and activity suggest that separate cellular signals may control pre- and posttranslational regulation of SOD.
The beneficial effects of a traditional Chinese medicine, Cordyceps sinensis (Cs), on mice with hypoferric anaemia were evaluated by NMR spectroscopy. Experimental hypoferric anaemia was induced in mice by feeding with an Fe-free diet for 6 weeks. They were then given extract from cultured Cs (200 mg/kg body weight daily, orally) and were placed on an Fe-containing recovery diet (35 mg Fe/kg diet) for 4 weeks. In vivo 31P and 2H NMR spectra acquired noninvasively and quantitatively at weekly intervals were used to evaluate hepatic energy metabolism and blood flow in the mice. During the 4-week Cs-extract treatment, consistent increases were observed in liver beta-ATP: inorganic phosphate value by liver 31P NMR spectroscopy, representing the high energy state, and in blood-flow rate as determined by 2H NMR spectroscopy of deuterated water (D2O) uptake after intravenous injection of D2O. The haematological variables (the packed cell volume and the haemoglobin level) and the hepatic intracellular pH, which was determined from the NMR chemical shift difference between the inorganic phosphate peak and the alpha-phosphate peak of ATP, were not significantly different between Cs-extract-treated and control mice. As blood flow and energy metabolism are thought to be linked, the Cs-extract-increased hepatic energy metabolism in the dietary hypoferric anaemic mice was concluded to be due to increased hepatic blood flow.
AMP-activated protein kinase (AMPK) is viewed as an energy sensor that acts to modulate glucose uptake and fatty acid oxidation
in skeletal muscle. Given that protein synthesis is a high energy-consuming process, it may be transiently depressed during
cellular energy stress. Thus, the intent of this investigation was to examine whether AMPK activation modulates the translational
control of protein synthesis in skeletal muscle. Injections of 5-aminoimidazole-4-carboxamide 1-β-d-ribonucleoside (AICAR) were used to activate AMPK in male rats. The activity of α1 AMPK remained unchanged in gastrocnemius muscle from AICAR-treated animals compared with controls, whereas α2AMPK activity was significantly increased (51%). AICAR treatment resulted in a reduction in protein synthesis to 45% of the
control value. This depression was associated with decreased activation of protein kinases in the mammalian target of rapamycin
(mTOR) signal transduction pathway as evidenced by reduced phosphorylation of protein kinase B on Ser473, mTOR on Ser2448, ribosomal protein S6 kinase on Thr389, and eukaryotic initiation factor eIF4E-binding protein on Thr37. A reduction in eIF4E associated with eIF4G to 10% of the control value was also noted. In contrast, eIF2B activity remained
unchanged in response to AICAR treatment and therefore would not appear to contribute to the depression in protein synthesis.
This is the first investigation to demonstrate changes in translation initiation and skeletal muscle protein synthesis in
response to AMPK activation.
To evaluate effects of CordyMax trade mark Cs-4, a mycelial fermentation product of Cordyceps sinensis, on improving glucose metabolism and insulin sensitivity.
An in vivo pharmacology study. Subjects and Study Interventions: Adult Wistar rats, male and female, were given CordyMax 250 or 500 mg/kg per day or placebo for 17 days by gavage.
Fasting blood glucose, fasting plasma insulin, glucose-insulin index, and oral glucose tolerance.
Rats fed Cs-4 at either 250 or 500 mg/kg showed significantly reduced fasting blood glucose after the 17-day treatment, by 27% and 24% from baselines respectively (both p < 0.001). Examination of fasting plasma insulin demonstrated a 37% decrease in the high dose treatment groups (p = 0.012). Glucose-insulin index, an index of insulin sensitivity, increased by 10% and 17% in both 250 and 500 mg/kg groups (p = 0.008 and p = 0.0001, respectively). Oral glucose tolerance tests showed significantly improved glucose tolerance at 0.5, 1.0, and 2.0 hours after oral administration of a bolus of glucose (the area under the glucose curve: p = 0.05-0.006), but no change at 5 hours.
CordyMax Cs-4 is effective in lowering basal blood glucose and plasma insulin, improving glucose metabolism by enhancing insulin sensitivity, and improving oral glucose tolerance.
The biochemical basis for the regulation of fibre-type determination in skeletal muscle is not well understood. In addition to the expression of particular myofibrillar proteins, type I (slow-twitch) fibres are much higher in mitochondrial content and are more dependent on oxidative metabolism than type II (fast-twitch) fibres. We have previously identified a transcriptional co-activator, peroxisome-proliferator-activated receptor-gamma co-activator-1 (PGC-1 alpha), which is expressed in several tissues including brown fat and skeletal muscle, and that activates mitochondrial biogenesis and oxidative metabolism. We show here that PGC-1 alpha is expressed preferentially in muscle enriched in type I fibres. When PGC-1 alpha is expressed at physiological levels in transgenic mice driven by a muscle creatine kinase (MCK) promoter, a fibre type conversion is observed: muscles normally rich in type II fibres are redder and activate genes of mitochondrial oxidative metabolism. Notably, putative type II muscles from PGC-1 alpha transgenic mice also express proteins characteristic of type I fibres, such as troponin I (slow) and myoglobin, and show a much greater resistance to electrically stimulated fatigue. Using fibre-type-specific promoters, we show in cultured muscle cells that PGC-1 alpha activates transcription in cooperation with Mef2 proteins and serves as a target for calcineurin signalling, which has been implicated in slow fibre gene expression. These data indicate that PGC-1 alpha is a principal factor regulating muscle fibre type determination.
It is purported that supplementation with Cordyceps Sinensis (CordyMax Cs-4) will improve oxidative capacity and endurance performance. The intent of this investigation was to examine the effects of CordyMax Cs-4 supplementation on VO<(2peak,) ventilatory threshold, and endurance performance in endurance-trained cyclists. Twenty-two male cyclists participated in 5 weeks of supplementation with CordyMax Cs-4 tablets (3 g/d). Training intensity was maintained by weekly documentation and reporting throughout the 5-week period. Subjects completed a VO(2peak) test and work-based time trial prior to and following the supplementation period. VO(2peak) was similar within and between placebo (PLA) and treatment (CS) groups prior to (59.9 +/- 5.9 vs. 59.1 +/- 5.4 ml/kg/min, respectively) and following (60.1 +/- 5.5 vs. 57.1 +/- 5.8 ml/kg/min, respectively) the supplementation period. Ventilatory threshold (VT) was measured at 72 +/- 10% of VO(2peak) in P and T prior to supplementation and did not change in either group following the supplementation. PLA completed the time trial in 61.4+/- 2.4 min compared to 62.1+/- 4.0 min in T. Time trial measurements did not differ between groups, nor did they change in response to supplementation. It is concluded that 5 weeks of CordyMax Cs-4 supplementation has no effect on aerobic capacity or endurance exercise performance in endurance-trained male cyclists.
Endurance exercise training can promote an adaptive muscle fiber transformation and an increase of mitochondrial biogenesis by triggering scripted changes in gene expression. However, no transcription factor has yet been identified that can direct this process. We describe the engineering of a mouse capable of continuous running of up to twice the distance of a wild-type littermate. This was achieved by targeted expression of an activated form of peroxisome proliferator-activated receptor delta (PPARdelta) in skeletal muscle, which induces a switch to form increased numbers of type I muscle fibers. Treatment of wild-type mice with PPARdelta agonist elicits a similar type I fiber gene expression profile in muscle. Moreover, these genetically generated fibers confer resistance to obesity with improved metabolic profiles, even in the absence of exercise. These results demonstrate that complex physiologic properties such as fatigue, endurance, and running capacity can be molecularly analyzed and manipulated.
Keap1-Nrf2-ARE signaling plays a significant role in protecting cells from endogenous and exogenous stresses. The development of Nrf2 knockout mice has provided key insights into the toxicological importance of this pathway. These mice are more sensitive to the hepatic, pulmonary, ovarian, and neurotoxic consequences of acute exposures to environmental agents and drugs, inflammatory stresses, as well as chronic exposures to cigarette smoke and other carcinogens. Under quiescent conditions, the transcription factor Nrf2 interacts with the actin-anchored protein Keap1, largely localized in the cytoplasm. This quenching interaction maintains low basal expression of Nrf2-regulated genes. However, upon recognition of chemical signals imparted by oxidative and electrophilic molecules, Nrf2 is released from Keap1, escapes proteasomal degradation, translocates to the nucleus, and transactivates the expression of several dozen cytoprotective genes that enhance cell survival. This review highlights the key elements in this adaptive response to protection against acute and chronic cell injury provoked by environmental stresses.
The present study examined the acute effects of a nutritional supplement intended to improve adenosine triphosphate (ATP) concentrations on vertical jump height, isometric strength of the leg extensors, leg extension endurance, and forearm flexion endurance.
Twenty-four healthy men (mean age +/- SD = 23 +/- 4 yrs, stature = 181 +/- 7 cm, and body mass = 82 +/- 12 kg) volunteered to complete a familiarization trial plus 2 randomly-ordered experimental trials separated by a 7-day washout period. Participants received either 6 (body mass < 91 kg) or 8 (body mass >/= 91 kg) tablets of the treatment (TR; 625 mg of adenylpyrophosphoric acid and calcium pyruvate, 350.8 mg of cordyceps sinensis extract and yohimbine hydrochloride) or placebo (PL; 980 mg of microcrystalline cellulose) 1 hour prior to the following tests: countermovement vertical jump (CVJ), forearm flexion repetitions to exhaustion, isometric maximal voluntary contractions (MVCs) of the leg extensors, and a 50-repetition maximal concentric isokinetic leg extension endurance test.
There were no differences between the TR and PL trials for CVJ height (P > 0.05), isometric MVC peak torque (P > 0.05), maximal concentric isokinetic peak torque (P > 0.05), percent decline during the leg extension endurance tests (P > 0.05), or repetitions to exhaustion during the forearm flexion endurance tests (P > 0.05).
These findings indicated no improvements in the measured variables as a result of ingesting this nutritional supplement. Future studies should examine whether chronic supplementation or a loading period is necessary to observe any ergogenic effects of this supplement.
Previous studies of oral supplementation with CordyMax (CM), a proprietary mycelial fermentation product of the Cordyceps sinensis, have demonstrated significant improvements in aerobic capacity in older humans and in exercise performance and metabolism in elite athletes (JACM 2001;7:231; FASEB 2002;16:A628). This randomized, double-blind clinical study further examined the effect of CM on endurance parameters in healthy, sedentary adults. Subjects (40-70 yrs old) received either CM (n=61) or placebo (P; n=70) for 12 weeks. VO2peak, respiratory exchange ratio (RER), time to complete a 1-mile walk (TMW), and work output (WO) by Jeukendrup bike test were examined at Weeks 0, 6, and 12. VO2peak was increased by 5.5% in CM (p=0.003), but by only 2.9% in P (NS). Exercise time to VO2peak was longer in CM (+4.1%, p=0.047), but no change in P. TMW was reduced by 29 sec in CM (p=0.05), but slightly increased in P (+19 sec, NS). WO was increased by 3.1% in CM (p=0.033), but fell in P (-4.9%, NS). RER was reduced by 2.1% in CM (p=0.018), but no change in P. Diastolic blood pressure was reduced by 5.2% in CM (p=0.045), but no change in P. Consistent with previous findings in healthy, elderly and athlete individuals, these data indicates that oral CM supplementation improves aerobic capability, exercise metabolism, and endurance performance in healthy, mid-age to elderly sedentary humans.
The purpose of this study was to examine the effectiveness of the cultured Cordyceps sinensis (Cs, supplement) powder during exhaustive running of human comparing with the placebo (control). These supplements were given to 36 male sedentary subjects over period of 2 weeks. During the exercise, following bio-signals were measured such as the respiratory variables (VO2, VCO2, VE), the blood pressure (BP), the heart rate (HR), and the lactic acid (LA). In addition, their storing urine for one night was inspected about the catecholamine (CA, Adr, NorA, Dop) and the cortisol hormone (17-KA-S and 17-OHCS) at the pre-and the post-ingesting with those supplements. The changing ratio calculating between the pre- and the post-variables of VO2/kg (5.2±0.1 & 4.8±0.1 ml), VE (12.0±0.2 & 11.0±0.2 L), and LA (6.1±2.1 & 5.2±2.6 mmol/dl) had decreased to lower percentages at the recovery period from the exercise test than those of CON, significantly (p<0.01). Futhermore, concentration of the total CA (1.19±0.51 & 1.29±0.49 mg/L), Adr (13.5±1.2 & 17.7±1.9μg/L), NorA (127.4±8.1 & 130.0±8.5μg/L), Dop (1.06±0.1 & 1.14±0.4mg/L), 17-OHCS/creatinine (4.42±0.30 & 4.2±0.31), and 17-KS-G/creatinine (3.18±0.09 & 3.06±0.07) showed changes of significant difference related to the placebo (p<0.05). There have been appeared an augmentation of the energy generation and the anti-fatigue ability intaking with this supplement during the exercise test. During this prolonged exercise, ingesting with this Cs might elicit the superior efficiency and the economical function on the energy metabolism.
In this study, the anti-fatigue effect of the purified polysaccharides from Cordycep were evaluated in mice. Swimming endurance experiment of mice were carried out after 21 days of polysaccharides from Cordyceps administration. And Body weight, blood lactic acid, serum blood urea nitrogen and tissue glycogen levels of mice were determined. Results showed that polysaccharides from Cordyceps extended the swimming endurance time of mice, effectively delayed the increasing of blood lactic acid, increasing the storage of liver and muscle glycogen. The dosage of 200 mg/kg was more effective than any other dosage. The results suggested that polysaccharides from Cordyceps had significant anti-fatigue effects on mice.
The objective of this study was to examine the effect of Cs-4 (Cordyceps sinensis) on exercise performance in healthy elderly subjects.
Twenty (20) healthy elderly (age 50-75 years) subjects were enrolled in this double-blind, placebo-controlled, prospective trial. The subjects were taking either Cs-4 333 mg or placebo capsules 3 times a day for 12 weeks.
Subjects received baseline screening including physical examination and laboratory tests. Maximal incremental exercise testing was performed on a stationary cycle ergometer using breath-by-breath analysis at baseline and at the completion of the study.
After receiving Cs-4 for 12 weeks, the metabolic threshold (above which lactate accumulates) increased by 10.5% from 0.83 +/- 0.06 to 0.93 +/- 0.08 L/min (p < 0.02) and the ventilatory threshold (above which unbuffered H(+) stimulates ventilation) increased by 8.5% from 1.25 +/- 0.11 to 1.36 +/- 0.15 L/min. Significant changes in metabolic or ventilatory threshold were not seen for the subjects in the placebo group after 12 weeks, and there were no changes in Vo(2) max in either group.
This pilot study suggests that supplementation with Cs-4 (Cordyceps sinensis) improves exercise performance and might contribute to wellness in healthy older subjects.
Training under hypoxia has several advantages over normoxic training in terms of enhancing the physical performance. Therefore, we tested the protective effect of hypoxia preconditioning by hypoxia mimetic cobalt chloride against exercise-induced oxidative damage in the skeletal muscles and improvement of physical performance.
Male Sprague-Dawley rats were randomly divided into four groups (n=8), namely control, cobalt-supplemented, training and cobalt with training. The red gastrocnemius muscle was examined for all measurements, viz. free radical generation, lipid peroxidation, muscle damage and antioxidative capacity.
Hypoxic preconditioning with cobalt along with training significantly increased physical performance (33%, P<0.01) in rats compared with training-only rats. Cobalt supplementation activated cellular oxygen sensing system in rat skeletal muscle. It also protected against training-induced oxidative damage as observed by an increase in the GSH/GSSG ratio (36%, P<0.001; 28%, P<0.01 respectively) and reduced lipid peroxidation (15%, P<0.01; 31%, P<0.01 respectively) in both trained and untrained rats compared with their respective controls. Cobalt supplementation along with training enhanced the expression of antioxidant proteins haem oxygenase-1 (HO-1; 1.2-fold, P<0.05) and metallothionein (MT; 4.8-fold, P<0.001) compared with training only. A marked reduction was observed in exercise-induced muscle fibre damage as indicated by decreased necrotic muscle fibre, decreased lipofuscin content of muscle and plasma creatine kinase level (16%, P<0.01) in rats preconditioned with cobalt.
Our study provides strong evidence that hypoxic preconditioning with cobalt chloride enhances physical performance and protects muscle from exercise-induced oxidative damage via GSH, HO-1 and MT-mediated antioxidative capacity.
This study was conducted to investigate the chemical component of the hot water (HW) fraction of mycelia of Cordyceps sinensis and its antifatigue and antistress effect against a stimulus in vivo using rats and mice. The growth of mycelia reached a maximum level of 31.6 g/l after 120 h of incubation. The main chemical composition of the HW fraction of mycelia of C. sinensis was found to be carbohydrate (78.9%) with 5% moisture. The swimming endurance capacity of mice orally administered with the HW fraction (150 and 300 mg/kg/d, respectively) was significantly prolonged from 75 to 90 min with a lessening of fatigue. When the HW fraction (150 mg/kg/d) was given to rats for 8 d including a 48 h stress period, the weight changes of the adrenal gland, spleen, thymus, and thyroid, which is an index of stress, were suppressed. The HW fraction also significantly inhibited the increase in total cholesterol and the decrease in alkaline phosphatase levels as biochemical parameters of immobilization stress in rats.
We examined the effects of a commercially marketed herbal-based formula purported to increase endurance on oxygen consumption (VO2) in 17 competitive category III/IV amateur cyclists [mean (SEM) age: 31.1 (1.8) yr; height: 178.5 (1.8) cm; weight: 77.1 (1.6) kg].
Each cyclist participated in two (pre/post) cycling tests progressing 25 W.4 min(-1) starting at 100 W administered in a randomized, placebo-controlled, double-blind fashion. The second trial was performed 14 d after the ingestion of a manufacturer recommended loading phase (4 d x 6 caps.d(-1)) and a maintenance phase (11 d x 3 caps.d(-1)). Three treatment capsules contained 1000 mg of Cordyceps sinensis (CS-4) and 300 mg Rhodiola rosea root extract as the primary ingredients; 800 mg of other ingredients included calcium pyruvate, sodium phosphate, potassium phosphate, ribose, and adenosine and 200 mcg of chromium.
Using a 2 x 2 ANOVA, we observed no significant treatment effect for any between or within group variables including peak VO2 [treatment 4.14 (0.2) L.min(-1); placebo 4.10 (0.2) L.min(-1)], time to exhaustion [treatment 38.47 (1.7) min; placebo 36.95 (1.8) min], peak power output (PO) [treatment 300.00 (12.1) W; placebo 290.63 (12.9) W], or peak heart rate. We also observed no differences for any subpeak exercise variable including the PO eliciting 2 mmol.L(-1) blood lactate (BLa) [treatment 201.00 (18.1) W; placebo 167.50 (19.2) W] and 4 mmol.L(-1) BLa [treatment 235.88 (15.8) W; placebo 244.78 (14.9) W], ventilatory threshold, respiratory compensation point, or Vo2 L.min(-1) gross efficiency at each stage.
A 2-wk ingestion schema of a commercial herbal-based formula is insufficient to elicit positive changes in cycling performance.
Cordyceps sinensis (Cs) and Rhodiola rosea (Rr) are herbs used in traditional Chinese medicine to treat a multitude of ailments as well as to enhance performance. The purpose of this research was to examine the effects of a formula containing Cs and Rr (Cs-Rr) on circulatory dynamics, specifically muscle tissue oxygen saturation (Sto(2)), in male subjects during maximal exercise. This study followed a double blind, randomized, placebo-treatment, pre-post test design. Capsules were administered to 8 subjects who were randomly assigned to 1 of 2 groups. The treatment group received Cs-Rr, and the control group received a placebo. All subjects performed 2 exercise stress tests to volitional fatigue on a cycle load ergometer. There were no significant (p </= 0.05) differences in Sto(2) slope, Sto(2) threshold (Sto(2T)), Vo(2)max, ventilatory threshold (V(T)), or time to exhaustion (T(E)) between or within the treatment or control group. In conclusion, Cs-Rr did not significantly enhance Sto(2).
Contraction induces marked metabolic changes in muscle, and the AMP-activated protein kinase (AMPK) is a good candidate to explain these effects. Recent work using a muscle-specific knockout of the upstream kinase, LKB1, has confirmed that the LKB1-->AMPK cascade is the signaling pathway responsible for many of these effects.
Recently, we reported that oxidative stress decreases D1 receptor numbers and G protein activation in renal proximal tubules (RPT), resulting in diminished natriuretic response to dopamine in old rats. We tested the hypothesis that exercise in old rats will decrease oxidative stress and restore natriuretic response to D1 receptor agonist, SKF 38393. Old (23 mo) rats were subjected to rest (sedentary) or to treadmill exercise followed by measurement of oxidative stress [malondialdehyde (MDA)], inflammation [C-reactive protein (CRP)], anti-inflammation (IL-10), antioxidant enzyme [superoxide dismutase (SOD)], and natriuretic response to SKF 38393. We found that MDA levels decreased and total SOD activity and Cu/ZnSOD protein increased in RPT of exercised rats. Exercise increased the nuclear levels of Nrf2 transcription factor (which binds to anti-oxidant response elements) in RPT. The levels of CRP decreased and IL-10 increased in RPT of exercised rats. Furthermore, exercise increased the basal bindings of [3H]SCH 23390 and [35S]GTPgammaS (indexes of D1 receptor number and G protein activation, respectively) together with D1 receptor and Galphaq proteins in RPT membranes. Moreover, SKF 38393 increased sodium excretion in exercised rats. Also, exercise decreased the levels of proteins in the urine of old rats. These results demonstrate that exercise decreases oxidative stress, inflammation, and proteinuria and increases anti-oxidant defense and D1 receptor function in old rats. Therefore, exercise may prove beneficial in preventing age-associated increases in oxidative stress, inflammation, and preserving kidney function, in general, and renal D1 receptor responsiveness, in particular.
Traditional Chinese medicines (TCM) are growing in popularity. However, are they effective? Cordyceps is not studied as systematically for bioactivity as another TCM, Ganoderma. Cordyceps is fascinating per se, especially because of the pathogenic lifestyle on Lepidopteron insects. The combination of the fungus and dead insect has been used as a TCM for centuries. However, the natural fungus has been harvested to the extent that it is an endangered species. The effectiveness has been attributed to the Chinese philosophical concept of Yin and Yang and can this be compatible with scientific philosophy? A vast literature exists, some of which is scientific, although others are popular myth, and even hype. Cordyceps sinensis is the most explored species followed by Cordyceps militaris. However, taxonomic concepts were confused until a recent revision, with undefined material being used that cannot be verified. Holomorphism is relevant and contamination might account for some of the activity. The role of the insect has been ignored. Some of the analytical methodologies are poor. Data on the "old" compound cordycepin are still being published: ergosterol and related compounds are reported despite being universal to fungi. There is too much work on crude extracts rather than pure compounds with water and methanol solvents being over-represented in this respect (although methanol is an effective solvent). Excessive speculation exists as to the curative properties. However, there are some excellent pharmacological data and relating to apoptosis. For example, some preparations are active against cancers or diabetes which should be fully investigated. Polysaccharides and secondary metabolites are of particular interest. The use of genuine anamorphic forms in bioreactors is encouraged.
Supplemental effects of Cordyceps sinensis extract on long distance runners
- T Hiyoshi
- F Akasu
- M Yoshisugu
- M Fujiwara
Hiyoshi, T., Akasu, F., Yoshisugu, M., Fujiwara, M., 1996. Supplemental effects of
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Fellingham Cordyceps sinensis (CordyMax Cs-4) supplementation does not improve endurance exercise performance
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Cordyceps sinensis-a high value medicinal fungus of Himalayan hills
- P S Negi
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medicinal fungus of Himalayan hills. DIBER technical pamphlet 1.
Effectiveness on ingestion with Cordyceps sinensis drinking during running exercise of humans
- A Nagata
- T Tajima
- S Moriyasu
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