[Effect of Erchen Decoction on liver mitochondrial function by inhibiting mTORC1/SREBP1/CAV1 pathway in mice with high-fat diet].

This study aims to investigate the effect of Erchen Decoction(ECD) on liver mitochondrial function in mice with a high-fat diet and its possible mechanism. A total of sixty C57BL/6J mice were randomly divided into a normal group, high-fat group, ECD group, mTORC1 activator(MHY) group, ECD+MHY group, and polyene phosphatidyl choline(PPC) group, with 10 rats in each group. The normal group was given a normal diet, and the other groups were fed a high-fat diet for 20 weeks. At the 17th week, the ECD group and ECD+MHY group were given ECD(8.7 g·kg~(-1)) daily, and the PPC group was given PPC(0.18 g·kg~(-1)) daily, while the remaining groups were given normal saline(0.01 mL·g~(-1)) daily for four weeks. In the 19th week, the MHY group and ECD+MHY group were injected intraperitoneally with MHY(5 mg·kg~(-1)) every other day for two weeks. During the experiment, the general conditions of the mice were observed. The contents of triglyceride(TG) and total cholesterol(TC) in serum were measured. Morphological changes in liver tissue were examined through HE and oil red O staining. The content of adenosine triphosphate(ATP) was determined using chemiluminescence, and mitochondrial membrane potential was assessed using a fluorescence probe(JC-1). Western blot was performed to detect the expression of rapamycin target protein complex 1(mTOR1), ribosomal protein S6 kinase B1(S6K), sterol regulatory element binding protein 1(SREBP1), and caveolin 1(CAV1). RESULTS:: revealed that compared with the normal group, the mice in the high-fat group exhibited significant increases in body weight and abdominal circumference(P<0.01). Additionally, there were significant increases in TG and TC levels(P<0.01). HE and oil red O staining showed that the boundaries of hepatic lobules were unclear; hepatocytes were enlarged, round, and irregularly arranged, with obvious lipid droplet deposition and inflammatory cell infiltration. The liver ATP content and mitochondrial membrane potential decreased significantly(P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 increased significantly(P<0.01), while the expression of CAV1 decreased significantly(P<0.01). Compared with the high-fat group, the body weight and TG content of mice in the ECD group and PPC group decreased significantly(P<0.05). Improvements were observed in hepatocyte morphology, lipid deposition, and inflammatory cell infiltration. Furthermore, there were significant increases in ATP content and mitochondrial membrane potential(P<0.05 or P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly in the ECD group(P<0.01), while CAV1 expression increased significantly(P<0.01). However, the indices mentioned above did not show improvement in the MHY group. When the ECD+MHY group was compared with the MHY group, there were significant reductions in body weight and TG contents(P<0.05). The morphological changes of hepatocytes, lipid deposition, and inflammatory cell infiltration were recovered. Moreover, there were significant increases in liver ATP content and mitochondrial membrane potential(P<0.05 or P<0.05). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly(P<0.01), while CAV1 expression increased significantly(P<0.01). In conclusion, ECD can improve mitochondrial function by regulating the mTORC1/SREBP1/CAV1 pathway. This mechanism may be involved in the resolution of phlegm syndrome and the regulation of lipid metabolism.

Acupuncture Ameliorated Behavioral Abnormalities in the Autism Rat Model via Pathways for Hippocampal Serotonin.

Purpose: Acupuncture can improve symptoms of autism spectrum disorder (ASD), but the potential mechanisms remain undefined. So, we aimed to explore the behavioral improvement of autism rat model after acupuncture and to describe the potential molecular mechanism underlying these changes. Patients and Methods: Wistar rats were intraperitoneally injected with VPA 12.5 days after conception, and their offspring were considered as good models of autism. Experimental rats were divided into three groups (wild-type (WT), n = 10; VPA, n = 10; and VPA_acupuncture, n = 10). VPA_acupuncture group rat received 4 weeks of acupuncture treatment (Shéntíng (GV24), and Bilateral Benshén (GB13)) on the 23rd day after birth. All rats were subjected to behavioral tests, including social interaction, open field, and Morris water maze tests. Afterwards, hippocampal tissues (left side) were removed and subjected to RNA sequencing (RNA-seq) analysis; ELISA was also used to detect the associated serotonin levels in the hippocampus. Results: Behavioral tests showed that acupuncture treatment improved spontaneous activity, aberrant social interaction, and alleviated impaired learning and memory in the VPA-induced rat model. Differentially expressed genes (DGEs) analysis showed 142 significantly differentially expressed genes between WT and VPA groups, and 282 between VPA and VPA_acupuncture rats. Htr2c and Htr1a, 5-HT receptor genes, were up-regulated in the VPA group compared with WT group. Additionally, Tph1, a rate-limiting enzyme gene of 5-HT synthesis, was up-regulated after acupuncture. These genes were confirmed to have the same trend of expression obtained by RT-qPCR and RNA seq. Furthermore, the concentration of serotonin in the hippocampus in the VPA group was significantly lower than the WT and VPA_acupuncture groups. Conclusion: Acupuncture improved abnormal behavioral symptoms in the VPA-induced rat model. Further experiments showed that the improvement of the serotonin system may be one of the main regulatory mechanisms of acupuncture for treating ASD.

Derivatives of sesquiterpenes, 2-furaldehyde, phenols, and alkaloids isolated from Taraxacum mongolicum.

Four new compounds (1-4), together with 23 known compounds (5-27), were isolated from the whole plant of Taraxacum mongolicum. Among them, one racemic mixture (4) was separated with a chiral HPLC column. Their structures were identified by spectroscopic evidence and mass spectrometry. The absolute configurations of compounds 1, 3, and 4 were determined via comparison of their calculated and experimental electronic circular dichroism (ECD) spectra. Compound 3 showed an inhibitory effect against aldose reductase with a 59.1% inhibition. Two known compounds (13 and 27) showed α-glucosidase inhibition of 51.5% and 56.0%, respectively.

Microbial communities that drive the degradation of flax pectin and hemicellulose during dew retting with Bacillus licheniformis HDYM-04 and Bacillus subtilis ZC-01 addition.

In this study, the combined addition of Bacillus licheniformis HDYM-04 and Bacillus subtilis ZC-01 to flax degradation increased the degradation rates of pectin (74.7 %) and pectinic acid (59.3 %) and increased the maximum activities of pectinase (610.66 ± 7.03 U/mL) and mannanase (656.97 ± 13.16 U/mL). 16S rRNA sequencing showed that the added bacterial agent (Bacillus) was the dominant bacterium, and its addition increased the relative abundance (RA) of Firmicutes and decreased the RA of Bacteroidetes. The core bacterial community linked to degradation (Firmicutes) was determined by RDA. Network analysis showed that the number of bacteria related to pectin and hemicellulose degradation increased with the addition of the bacteria combination. SEM analysis showed that Bacillus was positively correlated with the degradation of pectic substances. These results provide new ideas for improving the utilization of agricultural waste resources and promoting sustainable development in modern agriculture.

Underlying mechanism of Qiling Jiaogulan Powder in the treatment of broiler ascites syndrome.

Broiler ascites syndrome (AS), is a nutritional and metabolic disease that occurs in fast-growing commercial broiler chickens. AS can cause poor growth and a significant increase in the rate of broiler deaths, which has resulted in serious economic losses to the poultry industry. The classic traditional Chinese medicine Qiling Jiaogulan Powder (QLJP) has been demonstrated to have a certain therapeutic effect on broiler AS. However, its pharmacological mechanism remains to be elucidated. This study was performed to investigate the multitarget action mechanism of QLJP in the treatment of broiler AS based on network pharmacology analysis using a broiler AS model. First, all chemical components and targets of QLJP were obtained from the Traditional Chinese Medicine System Pharmacology Analysis Platform (TCMSP). Targets related to broiler AS were further obtained through the GeneCards database and the NCBI Gene sub-database. A protein-protein interaction (PPI) network was constructed. Then, enrichment analyses were performed to predict the potential mechanisms of QLJP in the treatment of broiler AS. Finally, the treatment effect of QLJP on AS was verified in a broiler AS model. Network pharmacology analysis generated 49 active ingredients and 167 core targets of QLJP, and a QLJP-single drug-target-disease network was successfully constructed. Gene enrichment analysis indicated that the core targets have played major roles in the Cell cycle, FOXO signaling pathways, etc. We demonstrated that QLJP improved clinical and organ damage symptoms and significantly reduced the ascites heart index in broilers with AS induced by administration of high-energy, high-protein diets and high-sodium drinking water in a low-temperature environment. QLJP may regulate lung oxidative stress, the cell cycle and apoptosis by activating the FOXO3a signaling pathway to interfere with the occurrence and development of AS in broilers. QLJP administration may be a good clinical strategy for the prevention and treatment of broiler AS.

Application Value of the CT Scan 3D Reconstruction Technique in Maxillofacial Fracture Patients.

Purpose The aim of the study was to explore the application value of computerized tomography (CT) scan 3D reconstruction technology in maxillofacial fracture patients. Methods A total of 80 maxillofacial fracture patients who underwent surgical treatment in Shijiazhuang People's Hospital from January 2019 to January 2020 were enrolled. All of them received 128-slice spiral CT scans before surgery, and the images were subjected to multiplanar reconstruction (MRP) and volume reconstruction (VR). Results A total of 181 fractures were found in 80 patients with maxillofacial fractures. The detection rates of axial CT, MRP, and VR were 77.90% (141/181), 93.92% (170/181), and 97.79% (177/181), respectively. The detection rates of the four inspection methods were statistically different. Taking the findings of surgical anatomy as the gold standard, the sensitivity of MRP and VR for the diagnosis of maxillofacial fractures was 90.06% (163/170) and 95.56% (174/177), with no significant difference. Conclusion CT scan 3D reconstruction technology has a high application value in the clinical diagnosis and treatment of maxillofacial fracture patients.

Discovery of Se-containing flavone in Se-enriched green tea and the potential application value in the immune regulation.

Selenium (Se)-enriched green tea has been recognized as a possible source of supplemental Se, while the structural and physiological activities of Se-containing flavone are still unclear. In this study, a Se-containing flavone was isolated from Se-enriched green tea by high-speed counter-current chromatography (HSCCC) and characterized through UHPLC-Q-Orbitrap, FT-IR and NMR. Results proved that HSeO3- can be combined with the alcohol hydroxyl of 2-phenylchromone in flavone and the content of Se-containing flavone in tea was 15690.4 µg L-1. Additionally, Se-containing flavone can effectively inhibit the production of nitric oxide (NO), and downregulate expression of TNF-α and IL-6. Compared with regular flavone extracted from green tea (43.24 pg mL-1), release of IL-10 was higher in Se-containing flavone group (53.37 pg mL-1), indicating that Se-containing flavone played an important role in the process of severe inflammatory injury. The results indicated that Se-containing flavone was an attractive natural ingredient for developing novel functional foods.

Pharmacological Effects of Gami-Yukmijihwang-Tang on the Lipopolysaccharide-Induced Hippocampus Oxidation and Inflammation via Regulation of Sirt6.

Yukmijihwang-Tang is widely used in traditional Korean medicine to treat age-related disorders. In the present study, we re-prescribed Gami-Yukmijihwang-Tang (YJT), which is slightly modified from Yukmijihwang-Tang by adding more medicinal plants to evaluate its pharmacological effects on underlying mechanisms against repeated lipopolysaccharide (LPS)-injection-induced neuroinflammation in the hippocampus regions. C57BL/6J male mice (16-24 weeks old) were divided into six groups: (1) the control group (DW with 0.9% saline injection), (2) LPS group (DW with LPS injection), YJT groups ((3) 100, (4) 200, or (5) 400 mg/kg of YJT with LPS injection), and (6) glutathione (GSH) group (100 mg/kg of GSH with LPS injection), respectively. Mice were orally administrated with various doses of YJT or glutathione (GSH) for the first five days. Neuroinflammation in the hippocampus region was induced by repeated injection of LPS during the last three days. As predicted, LPS not only increased oxidative stress-related markers including malondialdehyde, 4-hydroxynonenal, nitrotryptophan, and hydrogen peroxide, but also drastically enhanced inflammatory reactions including nitric oxide, inducible nitric oxide synthase, p65, and toll-like receptor 4, respectively. YJT administration, on the other hand, notably decreased the above pathological alterations by enhancement of antioxidant capacities such as superoxide dismutase and catalase activities. To explain the underlying pharmacological actions of YJT, we focused on a representative epigenetic regulator, a nicotinamide adenine dinucleotide + (NAD+)-dependent chromatin enzyme, Sirtuin 6 (Sirt6). Neuroinflammation in hippocampus regions depleted Sirt6 at the protein level and this alteration directly affected the nuclear factor erythroid 2-related factor (Nrf2)/hemeoxygenase (HO)-1 signaling pathway in the LPS group; however, YJT significantly recovered the Sirt6 protein levels, and it could recover the abnormal status of Nrf2/HO-1 signaling pathways in the hippocampus regions. Additionally, Sirt6 led to the up-regulation of GSH sub-enzymes of mRNA expression and protein levels of total GSH content. These findings suggest that YJT can protect against LPS-induced neuroinflammation and oxidative stress by regulating the Sirt6-related pathways and normalizing the GSH redox cycle.

Effect of traditional chinese medicine (TCM) and its fermentation using Lactobacillus plantarum on ceftriaxone sodium-induced dysbacteriotic diarrhea in mice.

BACKGROUND: Buzhongyiqi decoction (BD), Sijunzi decoction (SD), and Shenlingbaizhu decoction (SHD) have been extensively used clinically for the treatment of diseases caused by spleen-Qi deficiency and microbial fermentation has historically been utilized in traditional Chinese medicine (TCM). This study aimed to investigate the mitigative effect of TCM and fermented TCM (FTCM) with Lactobacillus plantarum (LP) on antibiotic-associated diarrhea, and to select an optimal formula and then identify its compounds. METHODS: Dysbacteriosis in mice was induced by ceftriaxone sodium (CS). The mice were then treated with LP, BD, SD, SHD, fermented BD, fermented SD (FSD), and fermented SHD. Diarrhea indexes, the abundances of gut bacteria, intestinal morphometrics, and mRNA expressions of genes related to intestinal barrier function were assessed. Then, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) were employed to identify and relatively quantify the compounds in the selected decoctions. RESULTS: CS significantly increased the fecal output weight, the total number of fecal output, and fecal water content, indicating the occurrence of diarrhea. Bacterial culture tests showed that the above symptoms were accompanied by the disruption of specific intestinal flora. TCM, LP, and FTCM alleviated the diarrhea index and recovered the intestinal microbiota. FTCM showed more advantageous than TCM or LP alone. The mRNA expressions of aquaporins (AQPs) and tight junctions (TJs) decreased by CS were enhanced by TCM, LP, and FTCM. In addition, through UHPLC-Q-TOF/MS, (S)-(-)-2-hydroxyisocaproic acid, L-methionine, 4-guanidinobutyric acid (4GBA), and phenyllactate (PLA) in SD and FSD were identified and relatively quantified. CONCLUSIONS: TCM, LP, and TCM fermented with LP alleviated CS-induced diarrhea symptoms, and improved the intestinal flora and barrier function. Four compounds including (S)-(-)-2-hydroxyisocaproic acid, L-methionine, 4GBA, and PLA in FSD, which were identified by UHPLC-Q-TOF/MS, might function in modulating intestinal flora and improving villi structure.

Two new sesquiterpene dimers isolated from the roots of Saussurea lappa (Yunmuxiang).

Two new sesquiterpene dimers, lappadimers A and B, were isolated from the roots of Saussurea lappa (Yunmuxiang). Their structures were established on the basis of spectroscopic methods. They were found to have potential anti-inflammatory activity at 10 µM and could reduce LPS-induced NO levels in murine macrophage, with inhibitory rates of 67% and 47%, respectively.

New quinones, a sesquiterpene and phenol compounds with cytotoxic activity from the aerial parts of Morinda umbellata L.

Eight previously undescribed compounds, two quinones (1-2), one sesquiterpene (3), and five phenol compounds (4-8), including three enantiomers (6a, 7a, and 8a), along with three corresponding known enantiomers (6b-8b) were isolated from the aerial parts of Morinda umbellata L. Their structures were elucidated by 1D and 2D NMR spectroscopy, X-ray diffraction, and experimental and calculated ECD spectra, respectively. Compound 5 was found to have weak cytotoxity, which inhibited the growth of seven human cancer cell lines (A2780, HeLa, MCF-7, BGC-823, H7420, Ketr3 and SW 1990) with IC50 values from 13.3 to 15.1 µM.

Water-soluble alkaloids isolated from Portulaca oleracea L.

Fifteen new water-soluble alkaloids were obtained from the fresh herbs of Portulaca oleracea L. The structures of 15 alkaloids 1-15 were established according to spectroscopic data, and the stereoconfigurations were determined based on experimental and calculated electronic circular dichroism (ECD) data and single crystal X-ray diffraction. Alkaloids 1-15 were found to display good anti-inflammatory activity at 10 µM and could significantly reduce the interleukin-6 (IL-6) and nitric oxide (NO) levels induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages.

[Advances in studies on structure and pharmacological activities of natural tirucallane-type triterpenoids].

The tirucallane-type triterpenoids, composed of six isoprene units, belong to a group of tetracyclic triterpenoids. Although the naturally-derived tirucallane-type triterpenoids were found in a small amount, the kind of compounds showed various structures, which consist of apo-type, linear said-chain-type and cyclolike said-chain-type and broad bioactivities, such as cytotoxicity, anti-inflammation, antioxidation and anti-plasmin, etc. This paper summarized origins, structures and bioactivities of tirucallane-type triterpenoids in recent ten years. The future research and exploration of tirucallane-type triterpenoids were discussed and prospected.

Inhibition of IL-6 expression by lignans and other constituents isolated from Schefflera rubriflora C. J. Tseng & G. Hoo.

Schefflera rubriflora, a plant native to Yunnan Province in China, is often used to treat ailments such as neuropathic pain, tracheitis, and cough. However, the active components imparting these pharmacological effects are largely unexplored. In this study, five novel lignans and three new derivatives of benzoid or pyran were isolated from the leaves and twigs of S. rubriflora. The structures of these compounds were determined by the comprehensive analyses of the 1D and 2D NMR spectra and ESI mass spectra and a comparison of the obtained data with those of the literature data. All the compounds were tested for the inhibition of IL-6 expression. Three of the isolated compounds could inhibit the expression by 52% to 72%.

[Reviews on natural monocyclic sesquiterpenoids and their bioactivities].

Sesquiterpenes are a class of terpenoids composed of three isoprene units( 15 carbons). Sesquiterpenoids possess a variety of different structures,including acyclic sesquiterpenes,monocyclic sesquiterpenoids,bicyclic sesquiterpenoids,tricyclic sesquiterpenoids,tetracyclic sesquiterpenoids and macrocyclic sesquiterpenoids. Among them,a large number of monocyclic sesquiterpenoids were isolated and display extensive bioactivities,such as cytotoxic,antioxidant,anti-inflammatory,antibacterial and other activities. In this review,we summarized the progress about the phytochemistry and biological activities of monocyclic sesquiterpenoids( a total of161 compounds) reported from 2014 to 2018( 5 years),including megastigmanes,monocyclofarnesol-type,bisabolane-type,germacrane-type,and other types of monocyclic sesquiterpenoids. Furthermore,several future research perspectives and development of sesquiterpenoids as potential therapeutic agents were discussed as well.

Cytotoxic quinones from the aerial parts of Morinda umbellata L.

Although Morinda umbellata L. has been used in numerous folk medicines, there is a lack of phytochemical studies on this plant. Sixteen undescribed quinones, namely, ten anthraquinones (umbellatas A-J), one naphthohydroquinone (umbellata K), one naphthohydroquinone dimer (umbellata L), and four dinaphthofuran quinones (umbellatas M-P), were isolated from the aerial parts of Morinda umbellata L. (Rubiaceae). The structures of all the isolated quinones were elucidated based on spectroscopic methods. Four of the unknown quinones (umbellatas A, H, K and M) showed potent cytotoxic effects against A431, A2780, NCI-H460, HCT116, HepG2, and MCF-7 human cancer cell lines with IC50 values of 1.3-7.1 µM. These results reveal potential lead compounds for the development of new anticancer agents.

Exploration in the Mechanism of Action of Licorice by Network Pharmacology.

Licorice is a popular sweetener and a thirst quencher in many food products particularly in Europe and the Middle East and also one of the oldest and most frequently used herbs in traditional Chinese medicine. As a wide application of food additive, it is necessary to clarify bioactive chemical ingredients and the mechanism of action of licorice. In this study, a network pharmacology approach that integrated drug-likeness evaluation, structural similarity analysis, target identification, network analysis, and KEGG pathway analysis was established to elucidate the potential molecular mechanism of licorice. First, we collected and evaluated structural information of 282 compounds in licorice and found 181 compounds that met oral drug rules. Then, structural similarity analysis with known ligands of targets in the ChEMBL database (similarity threshold = 0.8) was applied to the initial target identification, which found 63 compounds in licorice had 86 multi-targets. Further, molecular docking was performed to study their binding modes and interactions, which screened out 49 targets. Finally, 17 enriched KEGG pathways (p < 0.01) of licorice were obtained, exhibiting a variety of biological activities. Overall, this study provided a feasible and accurate approach to explore the safe and effective application of licorice as a food additive and herb medicine.

Anti-inflammatory terpenes from Schefflera rubriflora C. J. Tseng & G. Hoo with their TNF-α and IL-6 inhibitory activities.

The 95% ethanol extract and its EtOAc and n-BuOH fractions obtained from the leaves and twigs of Schefflera rubriflora C. J. Tseng & G. Hoo showed significant inhibitory activities (33.6%, 35.7% and 40.6%, respectively) against croton oil-induced ear inflammation in mice. Bioactivity-guided isolation and separation gave eight previously undescribed terpenes or terpene glycosides. Structural elucidation was based on UV, IR, and NMR spectroscopy, MS, experimental and calculated ECD data, and Mosher's method. To identify anti-inflammatory components from the extract, all the compounds were evaluated for tumor necrosis factor-α (TNF-α) and interleukine-6 (IL-6) inhibitory activities. Four undescribed compounds inhibited mRNA expression of TNF-α and IL-6 with IC50 values of 15.3-52.4 µM.

An in vitro validation of the therapeutic effects of Tougu Xiaotong capsule on tunicamycin-treated chondrocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Tougu Xiaotong capsule (TXC) is a Chinese herbal compound that belongs to a range of Chinese herbs functioning as 'kidney invigorators and liver softeners' commonly used to treat osteoarthritis (OA) in China. AIMS OF THE STUDY: The aims of the present study are to confirm the therapeutic effects of TXC in an OA cell model and to determine the mechanisms involved in such effects. MATERIALS AND METHODS: A tunicamycin (Tm)-exposed OA cell model was employed, and the effects of TXC were confirmed by observing cell viability and apoptosis. The reduced cell viability and increased apoptosis caused by Tm were improved by TXC, confirming the cellular protection of TXC. We then investigated the expression of biomarkers related to the endoplasmic reticulum (ER) stress pathway, including microRNA-211 (miR-211), a regulator in the ER stress pathway. RESULTS: Downregulation of X-box binding protein 1 (Xbp-1) and miR-211 expression following Tm administration was reversed by TXC. Moreover, the upregulation by Tm of the expression levels of binding immunoglobulin protein, Xbp-1, activating transcription factor 4, C/EBP-homologous protein, Caspase-9 and Caspase-3 was downregulated by TXC. These results indicated that the ER stress pathway-related mechanism may play a potential role in the therapeutic effects of TXC. CONCLUSIONS: The present study provides evidence of the therapeutic effects of TXC at the cell level and describes a cellular model for establishing the mechanisms of the effects of TXC used in the treatment of OA.

Distinct Effects of Repeated-Sprint Training in Normobaric Hypoxia and ß-Alanine Supplementation.

OBJECTIVE: The present study evaluated the effects of repeated-sprint training in normobaric hypoxia and ß-alanine supplementation (BA) on aerobic and anaerobic performance in recreationally active men. METHODS: Participants were randomly assigned to one of the following groups: normoxia/ß-alanine (NB, n = 11), normoxia/placebo (NP, n = 8), normobaric hypoxia/ß-alanine (HB, n = 10) and normobaric hypoxia/placebo (HP, n = 9). All participants completed 8 training sessions over 4 weeks on a cycle ergometer either in normobaric hypoxia (oxygen fraction: FiO2 = 14.2%) or normoxia (FiO2 = 20.9%). Participants were instructed to consume a daily dosage of 6.4 g of BA or placebo. Changes in performance in a graded exercise test, repeated-sprint test (RST), and 3-minute all-out test (3MT) were examined before and after training and supplementation. RESULTS: No between-group differences were observed for training volume or supplementation compliance. Anthropometric and hematological measures remained unchanged before and after intervention in all groups. A main effect of training condition was shown for oxygen consumption and power output at respiratory compensation point, average power output during the last sprint of the RST, heart rate recovery following the RST, and total work during the 3MT. These measures in the normobaric hypoxia groups were significantly (p < 0.05) higher than the normoxia groups, except for the heart rate recovery following the RST. A main effect of supplement was detected in anaerobic working capacity, with postintervention values in the BA groups being significantly (p < 0.05) higher than the placebo groups. CONCLUSIONS: Repeated-sprint training in hypoxia improved aerobic performance, exercise tolerance, cardiovascular recovery, and overall working capacity, while BA maintained the anaerobic working capacity. However, BA did not provide additional benefits with respect to attenuating fatigue or enhancing repeated-sprint performance.