Anti-fatigue Activity Research Articles

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

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

Investigation of the polysaccharides synthesis enhancement mechanism from Agaricus bitoquis (Quél.) Sacc Chaidam and its fermentation regulation technology system based on multi-omics technologies

The polysaccharides (PS) of Agaricus bitoquis (Quél.) Sacc. Chaidam (ABSC) had attracted the attention of researchers due to their strong anti hypoxia, antioxidant, and anti fatigue activities. Therefore, this article focuses on studying the regulatory channels of exogenous additives-Lycium ruthenicum Murr. Anthocyanin (LRA) to delay fungus cell aging and promote the incremental synthesis of PS from ABSC, and optimizing the regulation system for pilot fermentation experiments. The joint analysis of Ultra High Performance Liquid Chromatography-Quadrupole-Time of Flight Mass Spectrometry (UHPLC-Q-TOFMS) and RNA sequencing (RNA-seq) database elucidates that at the molecular level, the crude extract of LRA inhibits the Telecommunications Association (TCA) cycle, transferring carbon metabolism to the synthesis of polysaccharide precursors (UDP-glucose, UDP-galactose, etc.), promoting the synthesis of PS, promoting the formation of key antioxidant substances (including flavonoids such as quercetin and alginate), improving cell membrane fluidity (saturated fatty acid to unsaturated conversion) and enhancing the degradation of toxic substances (oxidized glutathione), thereby promoting the anti-aging activity and PS synthesis ability of mycelial cells; LRA-adding could enhance the activity in the pilot fermentation of ABSC, which make the mycelia biomass, EPS and IPS production were significantly increased (89.04 %, 65.46 % and 37.64 % respectively) compared with the untreatment control. Based on the optimal fermentation system of PS synthesized in mycelium by adding LRA, Logistic, Gauss, and Asymptotic kinetic equations were used to describe the cell growth, product synthesis and regulatory substrate consumption from ABSC. The correlation coefficients of three models were all above 0.95, indicating a good fit between the experimental values and predicted value, this indicated ABSC fermentation kinetics model could better simulate the actual production process and provide theoretical data for the industrial production of polysaccharides. The results demonstrated that the present proposed LRA intensification approach could be useful to boost up the fermentation of ABSC, which possibly applied to yield increase and fermentation product acquisition of macrofungi.

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

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

Bioactive Peptides from Marine Organisms.

Marine organisms represent promising bioactive peptide resources with diverse biological activities such as antioxidant, antimicrobial, antihypertensive, anti-fatigue, and immunoregulatory activities. Despite many studies on marine bioactive peptides, there is a dearth of comprehensive review articles on the emerging trends that encompass the production techniques and the biological applications of marine bioactive peptides. In this review, we summarize the major research and findings related to marine bioactive peptides, encompassing aspects of their production, purification, biological activities, nanotechnology-based strategies, and their potential applications. Enzymatic hydrolysis currently stands out as the most commonly used method for producing marine bioactive peptides; the downstream purification process often includes a combination of multiple purification techniques. Due to their diverse biological properties, marine peptides have garnered considerable interest for industrial applications as active ingredients in the food, pharmaceutical, and cosmetics industries. Additionally, the incorporation of encapsulation strategies such as nano emulsion, nanoliposome, and microemulsions holds promise for significantly enhancing the bioavailability and bioactivity of marine peptides. Future research should also prioritize the systematic identification and validation of the potential health benefits of marine peptides by both in vitro and in vivo animal models, along with the conduct of human clinical trials.

Research on the Anti-Fatigue Effects and Mechanisms of Arecoline in Sleep-Deprived Mice.

This research aims to estimate the anti-fatigue effects of arecoline and explore its underlying mechanisms using a murine model of central fatigue precipitated by sleep deprivation (SD). Seventy-two male C57BL/6 mice were randomly assigned to six groups: a control group, an SD-induced fatigue model group, a group that received Rhodiola Rosea capsules (2.5 mg/kg), and three arecoline groups, which were administered at low, medium, and high doses (10, 20, and 40 mg/kg, respectively). Following 28 days of continuous administrations, the effects of arecoline on mouse fatigue-related behaviors were assessed by behavioral tests, including grip strength, rotarod performance, and weight-bearing swimming endurance. The release levels of the related biochemical markers were measured by enzyme-linked immunosorbent assays (ELISAs). Western blotting was employed to quantify the expression levels of nuclear factor erythroid 2-related factor (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase 1 (HO-1), sequestosome-1 (p62), and NADPH quinone oxidoreductase 1 (NQO1) in the gastrocnemius muscle. Arecoline administration notably enhanced grip strength, delayed the onset of fatigue as evidenced by extended latencies in rotarod tests, and increased the duration of weight-bearing swimming in mice. In the elevated plus maze, arecoline obviously decreased both the number of entries and the total distance traveled in the open arms. Arecoline markedly decreased the contents of creatine kinase, blood urea nitrogen, lactate dehydrogenase, triglycerides, and cholesterol in the serum, while it elevated the levels of total testosterone, lactate dehydrogenase, and immunoglobulin G. Furthermore, it significantly increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase in the gastrocnemius muscle, reduced malondialdehyde levels, augmented hippocampal SOD and CAT activity, and elevated glycogen stores in both liver and muscle tissues. Neurotransmitter levels showed significant increases, cytokine levels were markedly reduced, and the expressions of Nrf2, Keap1, NQO1, p62, and HO-1 in brain tissues were significantly upregulated. This study demonstrates that arecoline has anti-fatigue activity, and the specific mechanisms are associated with elevating glucose and lipid metabolism levels, relieving oxidative stress damage, inhibiting neuroinflammatory response, and regulating neurotransmitter levels and the Keap1/Nrf2/HO-1 signaling pathway. The research provides a new direction for arecoline's potential in preventing and improving fatigue.

Anti-fatigue activity on male mice of 70% ethanol and aqueous extract of Rusa unicolor antler from East Kalimantan

Energy supply issues, ATP+PC, anaerobic glycolysis, product accumulation, lactic acid, mechanical failure of muscles to contractions and nervous system changes contribute to fatigue. The goal of this study was to determine whether 70% ethanol and aqueous extracts of Rusa unicolor antler from East Kalimantan, Indonesia, can reduce fatigue in male mice. A total of sixty-four male mice aged 2-3 months (20-30 g) were randomly assigned to eight groups (negative control, positive control and 3 doses of treatments for each extract). After that, the swimming endurance time was assessed, and blood glucose levels were measured before and after the test. Mice's tiredness is demonstrated by their head remaining submerged for 4-7 s while their tails and legs are stretched. One-way ANOVA was used to statistically analyze the data. The results showed that there were significant differences between all treatments with the negative control group (p<0.05). At a dose of 1.3 mg/kg BW of 70% ethanol and aqueous extract of Rusa unicolor antlers were able to maintain the stamina of male mice in swimming for 2 hrs 37 mins. Both extracts improve endurance training, delay tiredness, and promote recovery after exercise. Hence, Rusa unicolor antler extract can significantly improve athletic ability and facilitate recovery after exercise in male mice by increasing endurance training capacity and delaying tiredness.

Systematical Investigation on Anti-Fatigue Function and Underlying Mechanism of High Fischer Ratio Oligopeptides from Antarctic Krill on Exercise-Induced Fatigue in Mice.

High Fischer ratio oligopeptides (HFOs) have a variety of biological activities, but their mechanisms of action for anti-fatigue are less systematically studied at present. This study aimed to systematically evaluate the anti-fatigue efficacy of HFOs from Antarctic krill (HFOs-AK) and explore its mechanism of action through establishing the fatigue model of endurance swimming in mice. Therefore, according to the comparison with the endurance swimming model group, HFOs-AK were able to dose-dependently prolong the endurance swimming time, reduce the levels of the metabolites (lactic acid, blood urea nitrogen, and blood ammonia), increase the content of blood glucose, muscle glycogen, and liver glycogen, reduce lactate dehydrogenase and creatine kinase extravasation, and protect muscle tissue from damage in the endurance swimming mice. HFOs-AK were shown to enhance Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities and increase ATP content in muscle tissue. Meanwhile, HFOs-AK also showed significantly antioxidant ability by increasing the activities of superoxide dismutase and glutathione peroxidase in the liver and decreasing the level of malondialdehyde. Further studies showed that HFOs-AK could regulate the body's energy metabolism and thus exert its anti-fatigue effects by activating the AMPK signaling pathway and up-regulating the expression of p-AMPK and PGC-α proteins. Therefore, HFOs-AK can be used as an auxiliary functional dietary molecules to exert its good anti-fatigue activity and be applied to anti-fatigue functional foods.

A non-antibiotic erythromycin derivative improves muscle endurance by regulating endogenous anti-fatigue protein orosomucoid in mice.

At present, there are no official approved drugs for improving muscle endurance. Our previous research found acute phase protein orosomucoid (ORM) is an endogenous anti-fatigue protein, and macrolides antibiotics erythromycin can elevate ORM level to increase muscle bioenergetics and endurance parameters. Here, we further designed, synthesized and screened a new erythromycin derivative named HMS-01, which lost its antibacterial activity in vitro and in vivo. Data showed that HMS-01 could time- and dose-dependently prolong mice forced-swimming time and running time, and improve fatigue index in isolated soleus muscle. Moreover, HMS-01 treatment could increase the glycogen content, mitochondria number and function in liver and skeletal muscle, as well as ORM level in these tissues and sera. In Orm-deficient mice, the anti-fatigue and glycogen-elevation activity of HMS-01 disappeared. Therefore, HMS-01 might act as a promising small molecule drug targeting ORM to enhance muscle endurance.

Integration of Metabolomics with Network Pharmacology Deciphers the Anti-Fatigue Activity Mechanisms of the Extract of Mirabilis himalaica Root.

Fatigue, a common symptom in both diseased and healthy individuals, is a biological phenomenon characterized by a sense of extreme physical or mental exhaustion. To explore novel drugs and food sources of anti-fatigue, the hydroalcoholic extract of the root of Mirabilis himalaica (MH extract) is evaluated as anti-fatigue agents in this work, and clarifies that the mechanism of MH intervention in fatigue symptoms, and distribution of the anti-fatigue constituents in the plant of Mirabilis himalaica is examined. The results show that the MH extract have a significantly anti-fatigue effect via the pharmacological experiment and biochemical indicators. The network pharmacology, metabolomics, molecular docking, and pharmacology are integrated to determine that boeravinone A, B, and E are the pharmacoperones of anti-fatigue. Moreover, the compounds of boeravinone are present only in the root and not in the leaf and stem of the Mirabilis himalaica, which validates that root of Mirabilis himalaica is historically and officially utilized medicinal parts.

Evaluation of medicinal and nutritional effectiveness of abelmoschus esculentus L

Plants that have been used under the name of traditional treatment for many years have been supported by recent studies. We use plant species as bioactive phytochemicals in many areas of our lives. In addition to being used in cosmetics, food, medical, and industrial applications, it is a potential product for preventing diseases with the compounds found in its structures. Okra (Abelmoschus esculentus L.) with its bioavailability and phytochemical compounds has an important place among such plants. Okra is a vegetable plant that grows in tropical and subtropical environments and belongs to the family Malvaceae. Okra, which is thought to be of African origin, is an edematous plant, especially for Pakistan and India. Okra has various uses with its seed, flower, leaf, bark, and stem parts. It is mostly used as a fresh and green soft vegetable. The edible parts are rich in carbohydrates, protein, fatty acids, fiber, vitamins, and minerals. Due to these compositions, it plays a vital role in human nutrition. Okra seeds are a potential source of oil with concentrations between 20% and 40% decoctions, containing up to 47.4% linoleic acid. Its seeds are rich in linoleic acid. It is also known to be rich in high-quality protein in terms of essential amino acid content. The soft and edible parts become mucilaginous after cooking. Carbohydrates are usually found in the form of mucilage. In recent years, more attention has been paid to the use of metabolites found and obtained in some parts of plants, such as seeds, leaves, and bark, in medical fields and their effects on human health. The different parts of the okra plant (mucilage, seeds, and pods) contain some important bioactive components that give it its medicinal properties. These bioactive components of okra have been studied for their potential effects on various chronic diseases such as type 2 diabetes, cancer, and cardiovascular and digestive system diseases, as well as their anti-fatigue, liver detoxification, and antibacterial activities under the influence of polyphenols, which allow it to have antioxidant properties in its content. In general, okra is recognized as an important food product with various nutritional values and potential health benefits, easy to procure, and low cost.

O/W nanoemulsions encapsulated octacosanol: Preparation, characterization and anti-fatigue activity

Octacosanol has various biological effects such as antioxidant, hypolipidemic and anti-fatigue. However, poor solubility has limited the application of octacosanol in food. The aim of this study was to prepare octacosanol nanoemulsions with better solubility, stability and safety and to investigate in vivo anti-fatigue effect. The food-grade formulation of the octacosanol nanoemulsions consisted of octacosanol, olive oil, Tween 80, glycerol and water with 0.1 %, 1.67 %, 23.75 %, 7.92 % and 66.65 % (w/w), respectively. The nanoemulsions had an average particle size of 12.26 ± 0.76 nm and polydispersity index of 0.164 ± 0.12, and showed good stability under different pH, cold, heat, ionic stress and long-term storage conditions. The results of animal experiments showed that the octacosanol nanoemulsions significantly prolonged the fatigue tolerance time, alleviated the fatigue-related biochemical indicators, and weakened the oxidative stress. Meanwhile, octacosanol nanoemulsions upregulated hepatic glycogen levels. Taken together, these findings suggested that octacosanol nanoemulsions have promising applications as anti-fatigue functional foods.

Whey protein hydrolysate maintains the homeostasis of muscle metabolism in exercise mice and releases potential anti-fatigue peptides after gastrointestinal digestion

Whey protein hydrolysate (WPH) has been proven to possess anti-fatigue effects, but its regulatory mechanism on muscle metabolism in exercise mice is unclear. In the present study, the effects of WPH on muscle metabolites in mice before and after exercise were explored using metabolomics techniques. Results showed that 34 muscle metabolites were significantly altered by exercise in the WPH group, which was less than 71 in the WP group and 101 in the control group. Specifically, supplementation of WPH significantly increased the levels of amino acid and carbohydrate metabolites (i.e., 1-methylhistamine, guanidoacetic acid, melibiose, and xylulose 5-phosphate) pre-exercise, thereby delaying energy depletion and maintaining metabolic homeostasis during exercise. Furthermore, simulated gastrointestinal digestion (SGID), peptidomics and bioinformatics tools were employed to screen potential peptides in WPH. A total of 37 peptides with 2–5 residues in WPH were resistant to SGID (peak intensity > 105). Among them, YGLF showed favorable potentials in physicochemical property, bioavailability, bioactivity, SwissTargetPrediction, and molecular docking. In addition, the anti-fatigue activity of YGLF was evaluated in vivo. YGLF (100 mg/kg) significantly increased the contents of glucose, glycogens, and amino acids and decreased the levels of lactate and urea nitrogen in mice after exercise. These findings may serve as a reference for the screening of anti-fatigue peptides.

Polysaccharides from Artemisia argyi leaves: Environmentally friendly ultrasound-assisted extraction and antifatigue activities

Artemisia argyi leaf polysaccharide (AALPs) were prepared through ultrasound-assisted extraction (UAE), and their antifatigue activities were evaluated. Extraction was optimized using response surface methodology (RSM), which yielded the following optimal UAE conditions: ultrasonication power of 300 W, extraction temperature of 51 °C, liquid:solid ratio of 20 mL/g, and ultrasonication time of 47 mins. The above optimal conditions resulted in the maximum extraction rate of 10.49 %. Compared with hot water extraction (HWE), UAE supported higher yields and total sugar, uronic acid, and sulfate contents of AALPs. Meanwhile, AALP prepared through UAE (AALP-U) exhibited higher stability due to its smaller particle size and higher absolute value of zeta potential than AALP prepared through HWE (AALP-H). In addition, AALP-U demonstrated stronger antioxidant activity than AALP-H. In forced swimming tests on mice, AALP-U could significantly prolong swimming time with a dose-dependent effect, increase liver and muscle glycogen levels, and improve other biochemical indices, thus showing great potential for application in functional food.

Anti-fatigue activity of methyl dihydrojasmonate and linalool in a rat model evaluated by a novel index for neuro-immune and oxidative stress interactions

Avoiding fatigue is a long-standing challenge in both healthy and diseased individuals. Establishing objective standard markers of fatigue is essential to evaluate conditions in spatiotemporally different locations and individuals and identify agents to fight against fatigue. Herein, we introduced a novel method for evaluating fatigue using nervous system markers (including dopamine, adrenaline, and noradrenaline), various cytokine levels (such as interleukin [IL]-1β, tumor necrosis factor [TNF]-α, IL-10, IL-2, IL-5 and IL-17A), and oxidative stress markers (such as diacron-reactive oxygen metabolites [d-ROMs] and biological antioxidant potential [BAP]) in a rat fatigue model. Using this method, the anti-fatigue effects of methyl dihydrojasmonate (MDJ) and linalool, the fragrance/flavor compounds used in various products, were assessed. Our method evaluated the anti-fatigue effects of the aforementioned compounds based on the changes in levels of the nerves system markers, cytokines, and oxidative stress markers. MDJ exerted more potent anti-fatigue effects than linalool. In conclusion, the reported method could serve as a useful tool for fatigue studies and these compounds may act as effective therapeutic agents for abrogating fatigue symptoms.

A comprehensive review of Siraitia grosvenorii (Swingle) C. Jeffrey: chemical composition, pharmacology, toxicology, status of resources development, and applications.

Siraitia grosvenorii (Swingle) C. Jeffrey (S. grosvenorii), a perennial indigenous liana from the Cucurbitaceae family, has historically played a significant role in southern China's traditional remedies for various ailments. Its dual classification by the Chinese Ministry of Health for both medicinal and food utility underscores its has the potential of versatile applications. Recent research has shed light on the chemical composition, pharmacological effects, and toxicity of S. grosvenorii. Its active ingredients include triterpenoids, flavonoids, amino acids, volatile oils, polysaccharides, minerals, vitamins, and other microconstituents. Apart from being a natural sweetener, S. grosvenorii has been found to have numerous pharmacological effects, including alleviating cough and phlegm, preventing dental caries, exerting anti-inflammatory and anti-allergic effects, anti-aging and anti-oxidative, hypoglycemic, lipid-lowering, anti-depression, anti-fatigue, anti-schizophrenic, anti-Parkinson, anti-fibrotic, and anti-tumor activities. Despite its versatile potential, there is still a lack of systematic research on S. grosvenorii to date. This paper aims to address this gap by providing an overview of the main active components, pharmacological efficacy, toxicity, current status of development and application, development dilemmas, and strategies for intensive exploitation and utilization of S. grosvenorii. This paper aims to serve as a guide for researchers and practitioners committed to exploiting the biological resources of S. grosvenorii and further exploring its interdisciplinary potential.

A comparative study of the anti-fatigue activity of extracts from different parts of Cistanche tubulosa (Schenk) Wight

ObjectiveTo evaluate the anti-fatigue effects of different extracts from Cistanche tubulosa (Schenk) Wight (C. tubulosa, Rou Cong Rong), focusing on central and exercise-induced fatigue in mice. This study investigated the pharmacological effects of the total oligosaccharides, polysaccharides, and phenylethanoid glycosides (CPhGs) extracted from C. tubulosa. MethodsModels of sleep deprivation and forced swimming fatigue were established to simulate central and exercise-induced fatigue. The mice were treated with different extracts of C. tubulosa, and their effects were assessed using behavioral tests to measure exercise capacity, learning, and memory function. Biochemical analyses were performed to evaluate the changes in serum and brain neurotransmitter levels, liver and muscle glycogen storage, and various fatigue-related biomarkers. ResultsThis study found that treatment with C. tubulosa extract improved exercise capacity, learning, and memory in mice. Total oligosaccharides from C. tubulosa enhanced adrenocorticotropic hormone, cholinesterase, and thyroid-stimulating hormone levels, reduced cortisol levels in central fatigue models, and ameliorated biochemical markers of exercise-induced fatigue, including lowering lactic acid, blood urea nitrogen, and malondialdehyde levels. Among the tested extracts, the total oligosaccharides showed the most comprehensive anti-fatigue effects. ConclusionThe anti-fatigue effects of C. tubulosa, particularly those of its total oligosaccharides, are pronounced in both central and exercise-induced fatigue. These effects are mediated by the regulation of neurotransmitter levels, enhancement of glycogen storage, and improvement of antioxidant enzyme activity, suggesting potential therapeutic benefits in fatigue-related conditions.

Bao Yuan decoction alleviates fatigue by restraining inflammation and oxidative stress via the AMPK/CRY2/PER1 signaling pathway

Ethnopharmacological relevanceBaoyuan Decoction (BYD) was initially recorded in the classic of “Bo Ai Xin Jian” in the Ming dynasty. It is traditionally used for treating weakness and cowardice, and deficiency of vital energy. In researches related to anti-fatigue effects, the reciprocal regulation of AMPK and circadian clocks likely plays an important role in anti-fatigue mechanism, while it has not yet been revealed. Therefore, we elucidated the anti-fatigue mechanism of BYD through AMPK/CRY2/PER1 pathway. Aim of the studyTo investigate the effect and mechanism of BYD in reducing fatigue, using pharmacodynamics, network pharmacology and transcriptomics through the AMPK/CRY2/PER1 signaling pathway. Materials and methodsFirstly, the chemical constituents of BYD were qualitatively identified by UHPLC-Q-Exactive Orbitrap/MS, establishing a comprehensive strategy with an in-house library, Xcalibur software and Pubchem combined. Secondly, a Na2SO3-induced fatigue model and 2,2′-Azobis (2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative stress model were developed to evaluate the anti-fatigue and anti-oxidant activities of BYD using AB zebrafish. The anti-inflammatory activity of BYD was evaluated using CuSO4-induced and tail cutting-induced Tg (lyz: dsRed) transgenic zebrafish inflammation models. Then, target screening was performed by Swiss ADME, GeneCards, OMIM and DrugBank databases, the network was constructed using Cytoscape 3.9.0. Transcriptome and network pharmacology technology were used to investigate the related signaling pathways and potential mechanisms after treatment with BYD, which were verified by real-time quantitative PCR (RT-qPCR). ResultsIn total, 114 compounds from the water extract of BYD were identified as major compounds. Na₂SO₃-induced fatigue model and AAPH-induced oxidative stress model indicated that BYD has significant anti-fatigue and antioxidant effects. Meanwhile, BYD showed significant anti-inflammatory effects on CuSO4-induced and tail cutting-induced zebrafish inflammation models. The KEGG result of network pharmacology showed that the anti-fatigue function of BYD was mainly effected through AMPK signaling pathway. Besides, transcriptome analysis indicated that the circadian rhythm, AMPK and IL-17 signaling pathways were recommended as the main pathways related to the anti-fatigue effect of BYD. The RT-qPCR results showed that compared with a model control group, the treatment of BYD significantly elevated the expression mRNA of AMPK, CRY2 and PER1. ConclusionHerein, we identified 114 chemical constituents of BYD, performed zebrafish activity validation, while demonstrated that BYD can relieve fatigue by AMPK/CRY2/PER1 signaling pathway through network pharmacology and transcriptome.

Sedum aizoon L.: a review of its history, traditional uses, nutritional value, botany, phytochemistry, pharmacology, toxicology, and quality control.

In China, Russia, Mongolia, Japan, North Korea, and Mexico, Sedum aizoon L. (S. aizoon) is used as an edible plant. Up to now, over 234 metabolites, including phenolic acids, flavonoids, triterpenes, phytosterols, and alkaloids, among others, have been identified. In addition to its antioxidant, anti-inflammatory, anti-fatigue, antimicrobial, anti-cancer, and hemostatic activities, S. aizoon is used for the treatment of cardiovascular disease. This paper provides an overview of the history, botany, nutritional value, traditional use, phytochemistry, pharmacology, toxicology, and quality control of S. aizoon.

Phytochemistry and antifatigue activities of Carica papaya leaf from geothermal, coastal and urban areas, Indonesia.

Fatigue, a condition of lack of energy and motivation resulting in the feeling of extreme tiredness or exhaustion, is usually prevented and treated with ergogenic aids, such as in the form of nutritional supplements. Papaya (Carica papaya) may be a potential candidate for ergogenic aids, considering its healthy secondary metabolite properties and number of metabolite compounds that could be affected by the location where the plant growing. The aim of this study was to identify the phytochemicals of papaya leaves from three different locations: geothermal, coastal, and urban areas in Aceh province, Indonesia. Concentrations of papaya leaf with the highest number of secondary metabolite compounds were tested in rats to measure blood lactate acid concentrations after strenuous exercise. The number of chemical compounds identified from the three locations was 24 compounds; 23 compounds and 17 compounds, respectively. The highest concentration of chemical compounds that have antifatigue activity contained in all papaya leaf samples were neophytadiene, linolenic acid, gamma tocopherol, hexadecanoic acid, vitamin E, carpaine, octadecatrienoic acid, nor lean-12-ene, squalene, and phytol. Furthermore, most of the compounds' highest concentrations were found in papaya leaves from the coastal area and, therefore, tested on the animal model. Treatment was provided in 12 male rats with different doses of papaya powder supplements for 15 days. The results showed that lactic acid levels of rats received a dose of 400 mg/kg of papaya leaf extract reduced the lactic acid concentration (p=0.014) compared with the control group. This study highlights that papaya leaves from the coastal area have the most potential activities as ergogenic herbal aid and were able to reduce lactic acid levels in rats after strenuous exercise.

Vicatia thibetica de Boiss: Botany, Traditional Uses, Phytochemistry, Quantitative Analysis, and Pharmacology.

Vicatia thibetica de Boiss is a common Tibetan medicine used for both medicine and food, belonging to the family Apiaceae. This plant has the functions of dispelling wind, removing dampness, dispersing cold, and relieving pain. It has great development potential and application prospects in food development and medicinal value. The related references on botany, traditional uses, phytochemistry, quantitative analysis, and pharmacology of V. thibetica de Boiss had been retrieved from both online and offline databases, including PubMed, ScienceDirect, Web of Science, Elsevier, Willy, SpringLink, SciFinder, Google Scholar, Baidu Scholar, ACS publications, SciHub, Scopus, and CNKI. V. thibetica de Boiss exerts nourishing, appetizing, and digestive effects according to the theory of Tibetan medicine. Phytochemical reports have revealed that V. thibetica de Boiss contains flavonoids, coumarins, sterols, and organic acids. Meanwhile, the quantitative analysis of the chemical constituents of V. thibetica de Boiss has been done by means of UPLC-Q-TOF-MS. It has also been found that V. thibetica de Boiss possesses multiple pharmacological activities, including anti-fatigue, anti-oxidant, anti-aging, and non-toxic activities. This paper has comprehensively summarized botany, traditional uses, phytochemistry, quantitative analysis, and pharmacology of V. thibetica de Boiss. It will not only provide an important clue for further studying V. thibetica de Boiss, but also offer an important theoretical basis and valuable reference for in-depth research and exploitation of this plant in the future.