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High-altitude polycythemia (HAPC) occurs in high-altitude (HA) environments and involves an imbalance between erythropoiesis and eryptosis. Spleen/splenic macrophages are an important primary tissue/cell of eryptosis and iron recycling. However, the role of the spleen in the pathogenesis of HAPC and the effect of hypobaric hypoxia (HH) on the biology of the spleen and splenic macrophages are still unclear. We used a mouse hypobaric hypoxia (HH) exposure model to simulate anin vivostudy of 6000 m HA exposure. Forin vitrostudies, we used a primary splenic macrophage model treated with 1% hypoxia. We found that the HH-treated mouse model promoted erythropoiesis and led to erythrocytosis. In addition, HH exposure resulted in marked splenic contraction followed by splenomegaly for up to 14 days. HH exposure impaired the red blood cell (RBC) handling capacity of the spleen, which was caused by a decrease in splenic macrophages in the red pulp. Moreover, HH treatment for 7 and 14 days promoted iron mobilization and ferroptosis in the spleen, as reflected by the expression of metabolism-related proteins and ferroptosis-related proteins. All of the protein expression levels were similar to the gene expression levels in human peripheral blood mononuclear cells. Single-cell sequencing of the spleen further demonstrated a significant decrease in macrophages in the spleen 7 days after HH exposure. Inin vitrostudies, we confirmed that primary splenic macrophages decreased and induced ferroptosis following hypoxic treatment, which was reversed by pre-treatment with the ferroptosis inhibitor ferrostatin-1. Taken together, HH exposure induces splenic ferroptosis, especially in red pulp macrophages, which further inhibits the clearance of RBCs from the spleen. As such, it promotes the retention of RBCs in the spleen and causes splenomegaly, which may further lead to the persistent production of RBCs and ultimately to the development of HAPC.

Inonotus obliquus (Fr.) Pilat is an edible mushroom which is used to produce tea and syrup due to its medicinal properties.

An investigation of the fruiting bodies of edible mushroom Ganoderma lucidum produced 13 steroids, containing one new lanostane-type triterpene compound, named ganoderterpene A (1). Nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry data were used to deduce these structures. All the isolates were evaluated for their ability to suppress NO generation in BV-2 microglial cells treated with lipopolysaccharide (LPS) and exhibited moderate to strong inhibition effects, with IC50 values in the range 7.15-36.88 μM. Among the tested compounds, compound 1 exhibited the most marked activity with an IC50 value of 7.15 μM, and the structure-activity relationships were studied. This study showed that compound 1 significantly suppressed the activation of MAPK and TLR-4/NF-κB signaling pathways, as evidenced by an immunofluorescence assay and a molecular docking experiment. Furthermore, compound 1 effectively improved the LPS-induced mitochondrial membrane potential and apoptosis. These findings suggest that ganoderterpene A could exert protective effects in microglial cells from apoptosis by restraining the inflammatory response. Hence, G. lucidum could be used as a novel preventative agent for neurodegenerative disorders.

Sixteen metabolites, including seven C7-alkylated salicylaldehyde derivatives (1-7) and nine prenylated indole alkaloids (8-16), three of which are new, namely, asperglaucins A and B (1 and 2) and neoechinulin F (8), were separated from the endolichenic fungus Aspergillus chevalieri SQ-8. Asperglaucin A (1) represents an unusual phthalide-like derivative with a benzo[c]thiophen-1(3H)-one scaffold. All compounds were assessed in vitro for antibacterial, antineuroinflammatory, and antioxidant activities. Notably, asperglaucins A and B exhibited potent antibacterial activities against two plant pathogens Pseudomonas syringae pv actinidae (Psa) and Bacillus cereus, with an MIC value of 6.25 μM; further SEM analyses illustrated that the possible bacteriostatic mechanisms for compounds 1 and 2 were to alter the external structure of B. cereus and Psa, and to cause the rupture or deformation of the cell membranes, respectively, and the results suggest that compounds 1 and 2 may serve as potential promising candidates for lead compounds of agrochemical bactericides. Furthermore, compounds 6 and 10 significantly inhibited nitric oxide production with an IC50 value of ca. 12 μM, and the possible anti-inflammatory mechanisms involved were also studied by molecular docking. Finally, the tested phenolics 3-5 showed significant antioxidative effects. Thus, strain SQ-8 represents a novel resource of these bioactive metabolites to be utilized.

Two new sterpurane sesquiterpenoids named sterpurol D (1) and sterpurol E (2), and one skeletally new sesquiterpene, cryptomaraone (3), bearing a 5,6-fused bicyclic ring system, along with five known ones, sterpurol A (4), sterpurol B (5), paneolilludinic Acid (6), murolane-2α, 9β-diol-3-ene (7) and (–)-10,11-dihydroxyfarnesol (8) were isolated from an endolichenic fungus Cryptomarasmius aucubae. The structures of the new compounds were elucidated by analysis of NMR spectroscopic spectra and HRESIMS data. The absolute configurations of 1 and 2 were established by spectroscopic data analysis and comparison of specific optical rotation, as well as the biosynthetic consideration. Additionally, compounds 1, 2, 4–6, and 8 showed significant nitric oxide (NO) production inhibition in Lipopolysaccharide (LPS)-induced BV-2 microglial cells with the IC50 values ranging from 9.06 to 14.81 μM. Graphic Abstract

A tandem asymmetric Michael-addition/cyclization of cyclic 1,3-dicarbonyl compounds to β,γ-unsaturated α-ketoesters catalyzed by chiral phosphoric acid is presented. This protocol provides a facile approach for the construction of enantioenriched 9-alkyl tetrahydroxanthenones, an ubiquitous framework found in a number of natural products and pharmaceutical molecules, in high yields with good to high enantioselectivities.

Microbial transformations of two tetracyclic beyerane-type diterpenes, ent-16β-oxobeyeran-19-oic acid (1) and its chemical reduction product, ent-16β-hydroxybeyeran-19-oic acid (2), by the filamentous fungus Cunninghamella echinulata ATCC 8688a yielded eight metabolites (3-10). Incubation of the substrate 2 with C. echinulata afforded three new hydroxylated ones (3-5) along with two known ones (6-7), while incubation of 1 gave three known ones (8-10). The new compounds were characterized by 1D and 2D NMR as well as HRESIMS analysis, and the stereostructures of 3 and 4 were confirmed by X-ray crystallography. The bioreactions were involved not only in stereoselective incorporation of hydroxyl groups at inert positions C-7, -9, -12, and -14 of the two beyerane diterpenes but also in glucosidation at C-19 of 2. This is the first report on the biotransformation of the diterpenes by using C. echinulata. All compounds were assayed for their α-glucosidase inhibitory, neurotrophic, anti-inflammatory, and phytotoxic activity, and only in neurotrophic assay compounds, 2 and 9 were found to display nerve growth factor-mediated neurite-outgrowth promoting effects in PC12 cells; the others were inactive.

Herein, we developed an enantioselective addition of aliphatic aldehydes to 2-hydroxychalcone promoted by cooperative organocatalysts, giving access to hybrid flavonoids in excellent enantioselectivities. This reaction took advantage of cycloisomerization of 2-hydroxychalcone to form a transient flavylium under the irradiation of 24 W CFL, which was trapped by the in situ generated chiral enamine intermediate. The synergistic action of chiral phosphoric acid secured the excellent outcome of this reaction by ion-pairing with the transient flavylium.

An investigation of the fruiting bodies of edible mushroom

Sixteen metabolites, including seven C

With environmental pollution, residual hazards accumulate and severe drug resistance and many other problems appear; some highly toxic drugs have been banned, and antifungal agents are far from satisfactory. Natural products play an important role in the discovery and development of new pesticides. The natural product griseofulvin (1) has been known as an antifungal agent in the treatment of dermatomycoses for decades. In this study, a series of new griseofulvin derivatives were synthesized with good yields. Their structures were characterized by 1H and 13C nuclear magnetic resonance and high-resolution mass spectrometry (electrospray ionization). The antifungal activities of griseofulvin analogues were first evaluated against five phytopathogenic fungi ( Cytospora sp., Colletotrichum gloeosporioides, Botrytis cinerea, Alternaria solani, and Fusarium solani) in vitro. Of significance is that most of them showed excellent antifungal activities against C. gloeosporioides. The antifungal activities of the four best compounds (6a, 6c, 6e, and 6f) against C. gloeosporioides were further investigated in vivo using infected apples. The results suggested that compounds 6c, 6e, and 6f [half-maximal inhibitory concentration (IC50) = 47.25 ± 1.46, 49.44 ± 1.50, and 53.63 ± 1.74 μg/mL, respectively] were better than thiophanate-methyl (IC50 = 69.66 ± 6.07 μg/mL). Furthermore, comparative molecular field analysis was performed on the basis of the antifungal activity results of all 22 of the compounds against C. gloeosporioides in vitro. The three-dimensional coefficient contour plots revealed that the suitable bulky and electronegative acyl-substituted groups seem to be more favorable for increasing activity at the 4' position of griseofulvin. The structure-activity relationships were also discussed. Griseofulvin derivatives can be used for the development of highly effective and safe agricultural fungicides.

Eleven new cyathane diterpenoids, designated cyafricanins A–K (1−11), were isolated from the culture broth of the baisidiomycete Cyathus africanus (Nidulariaceae, Bird's nest fungi). Their structures were elucidated by comprehensive analysis of their NMR and HRESIMS data. Cyafricanins A (1) was found to possess an unusual 3,4-seco‑carbon skeleton. All compounds were evaluated for their neurotrophic activity in PC-12 cells and anti-neuroinflammatory activity in BV2 microglia cells. All of the diterpenoids showed nerve growth factor induced neurite outgrowth-promoting activity at concentration of 20 μM. Among them, cyafricanin B (2) and cyafricanin G (7) exhibited promising neurotrophic activity, and cyafricanin A (1) showed strong inhibitory effects on both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Furthermore, molecular docking studies revealed that cyafricanin A (1) showed strong interactions with the iNOs protein in the active cavity.

Bioactivity-guided isolation of the cultures of the endophytic fugus Xylaria sp. XC-16 residing in a deciduous tree Toona sinensis led to the discovery of four new allelochemicals (1-4), including three cytochalasins, epoxycytochalasin Z17 (1), epoxycytochalasin Z8 (2), and epoxyrosellichalasin (3), and an abietane-type diterpenoid, hydroxyldecandrin G (4), along with four known analogues, 10-phenyl-[12]-cytochalasins Z16 (5) and Z17 (6), cytochalasin K (7), and cytochalasin E (8). The structures of these compounds were elucidated by comprehensive spectroscopic methods, and their absolute configurations were determined by electronic circular dichroism (CD) and X-ray diffraction. All of the chemicals were tested for their allelopathic effects on turnip ( Raphanus sativus) and wheat ( Triticum aestivum). Notably, compounds 3, 4, and 7 strongly inhibited wheat shoot elongation, and compounds 5, 7, and 8 inhibited wheat root elongation, showing comparable IC50 values to the positive control glyphosate. Meanwhile, compound 8 was a potential inhibitor on turnip root elongation, with an IC50 value of 1.57 ± 0.21 μM, which was 50-fold more potent than glyphosate. Nevertheless, compounds 5 and 7 stimulated turnip shoot elongation at lower concentrations.

Herein, we disclose that carboxylate phosphabetaine can act as a competent organocatalyst for promoting the intramolecular ring opening of oxetanes, delivering oxazolidin-2-ones in good to excellent yields. 1H NMR studies and DFT calculations revealed that the carboxylate moiety of the phosphabetaine not only acts as a proton shuttle, but also provides crucial hydrogen bonding for the activation of the oxetane ring.

A tandem asymmetric Michael-addition/cyclization of cyclic 1,3-dicarbonyl compounds to β,γ-unsaturated α-ketoesters catalyzed by chiral phosphoric acid is presented. This protocol provides a facile approach for the construction of enantioenriched 9-alkyl tetrahydroxanthenones, an ubiquitous framework found in a number of natural products and pharmaceutical molecules, in high yields with good to high enantioselectivities.

Ganoderma resinaceum, as a traditional edible mushroom, has been widely reported to improve neurodegenerative diseases characterized by oxidative stress and inflammation. In this study, five new terpenoids, including four lanostane triterpenoids, named ganoresinoid A-D (1-4) and one meroterpenoid, named ganoresinoid E (5), along with 27 known compounds (6-32), were isolated from the fruiting bodies of edible mushroom G. resinaceum. These structures were identified by NMR, HRESIMS data analysis. All metabolites were evaluated for anti-inflammatory, antioxidative and anti-apoptosis activities. Among them, ganoresinoid A showed notably restrained nitric oxide (NO), IL-1β, IL-6 and TNF-α levels in LPS-activated BV-2 microglial cells via suppressing TLR-4/ NF-κB and MAPK signaling pathway. Simultaneously, ganoresinoid A remarkably alleviated LPS-induced apoptosis by means of the decrease of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). In addition, ganoresinoid A demonstrated antioxidant effects in H

Ganorbifates C–I, seven undescribed biosynthetically related polyoxygenated 3,4-seco-27-norlanostanoid congeners, were isolated from the edible mushroom, Ganoderma orbiforme. Ganorbifate C features a unique cyclobutene ring constructed at C19/C11, and both D and E incorporate an unusual cyclopropane ring formed by C-19/C-9 linkage. Their structures, including the absolute configurations, were determined by spectroscopic methods and ECD calculations. The proposed Norrish-Yang cyclization-based key biosynthetic pathway for ganorbifates C-E is revealed by density functional theory (DFT) calculations. The computational studies uncover the formation of both cyclobutene and cyclopropane rings in the isolates and the stereoselectivity centers of these steps are consistent with those in the natural products. All compounds exhibited NO generation inhibition in LPS-induced BV-2 microglial cells, among them ganorbifate C was the most promising one with the IC50 values of 4.37 μM.

Fifteen eremophilane sesquiterpenoids, including nine undescribed congeners, septeremophilane A–H, and chaetopenoid G, together with four conjugated unsaturated polyketide fatty acids, including an undescribed derivative, were isolated from cultures of the fungus Septoria rudbeckiae, a plant pathogenic fungus isolated from the halophyte Karelinia caspia. Septeremophilane A represents an unprecedented tetranor-eremophilane sesquiterpenoid with an α,β-unsaturated δ-lactone unit bearing a hemiacetal group, while septeremophilane B–H possesses a trinor-eremophilane skeleton. Their structures and absolute configurations were established based on spectroscopic data (NMR and HRESIMS), quantum chemical calculations and electronic circular dichroism (ECD) experiments. All metabolites were tested for nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-activated BV-2 microglial cells, while dendryphiellin D, septeremophilane D, and septeremophilane E were found to display significant inhibition, with IC50 values of 11.9 ± 1.0, 8.5 ± 0.1, and 6.0 ± 0.2 μM, respectively.

Chaga mushroom, Inonotus obliquus, was used as food and nutrient food and traditional herbs in Russia, China and Japan, with anti-inflammatory and anticancer activities. Chemical investigations of the fruiting bodies of Chaga were carried to uncover the bioactive metabolites. As a result, seven undescribed lanostane-type triterpenoids, namely inonotusols H–N, were isolated, and all lanostanoids remarkably inhibited NO production in lipopolysaccharide-stimulated BV-2 microglial cells. Of these, inonotusols I and L presented the most potent inhibitory effects on inducible nitric oxide synthase (iNOS) and NO production without any significant cytotoxicity. Molecular docking studies confirmed the capacity of inonotusols I and L to interact with iNOS protein. Structure-activity relationships were also discussed. These results indicated that the potential anti-inflammatory effects of inonotusols I and L in microglial BV-2 cells may be imparted through suppression of iNOS. These results may support the use of I. obliquus for food and medicinal application.

Herein, we report a tandem cycloisomerization/nucleophilic addition/cyclization of 2-amino chalcone with bifunctional nucleophiles driven by visible light. This cascade process is realized by the irradiation of a blue LED at room temperature, which provides a concise route to structurally diverse benzo[d][1,3]oxazocine scaffolds. Mechanistic studies show that the reaction is initiated with the E to Z isomerization of a C–C double bond upon the irradiation of visible light, followed by cyclization/rearomatization to generate a transient quinolinium intermediate, which is trapped by the nucleophile and cyclized to produce the polycyclic benzo[d][1,3]oxazocine.

Microbial transformations of two tetracyclic beyerane-type diterpenes

Two biosynthetically related new metabolites, eucalyptacid A (

Objective To evaluate the validity and reliability of simplified Chinese SF-36v2 questionnaire for assessment of life quality of people immigrating to high altitude at different time periods. Methods Two hundred and forty-eight Chinese young males, aged 16-36 years (mean 22.1 years), immigrating to an altitude of 4520m plateau for 0.3-10.8 years (mean 2.3 years), were selected by cluster sampling methods. The general demographic characteristics questionnaire and simplified Chinese SF-36v2 scale were investigated by self-administered questionnaire. Thirty-four subjects were randomly sampled and re-examined by questionnaire after 4 weeks. Results A total of 252 questionnaires were sent out, and a total of 248 valid questionnaires (98.4%) were collected. The scores of 8 scales in SF-36v2, including physical function (PF), role-physical (RP), bodily pain (BP), general health (GH), vitality (VT), social function (SF), role-emotional (RE) and mental health (MH), were 78.50±15.34, 63.30±39.65, 70.60±17.69, 56.40±18.21, 59.10±18.18, 85.70±18.90, 53.68±41.65, 59.35±13.61. The floor effects were 0 except for RP (17.80%) and RE (27.92%) and the ceiling effects were 5.08%, 40.11%, 3.55%, 0, 2.54%, 9.64%, 31.47%, 0. The split half reliability of SF-36v2 scale was 0.632-0.800, and the Cranbach's coefficient of α was 0.641-0.824, the test-retest reliability coefficient was 0.543-0.848. The success rate of set validity was 100%, and the total discriminant validity success rate was 95.36%. Factor analysis was used to extract 2 principal factors, which could explain 69.5% of the total variance. Conclusion The simplified Chinese SF-36v2 scale has good internal consistency, reliability and validity, and it can be used to assess the quality of life in different periods. DOI: 10.11855/j.issn.0577-7402.2017.11.13

Objective To investigate the effects of plateau hypoxia environment on the physiology and biochemistry indicators of troops executing different combat mission. Methods Troops included the soldiers in camp (station altitude 4030m and 4600m) and those soldiers in field training (altitude 4300m) for one month. Blood samples were collected and the physiology and biochemistry indicators were detected including heart rate (HR), blood pressure (BP), oxygen saturation (SpO2) and the concentrations of hemoglobin (Hb), serum total protein (TP), albumin (ALB) and globulin (GLB), the ratio of albumin and globulin (A/G), concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C), creatine kinase (CK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and AST/ALT. Results The HR was significantly higher in soldiers of field training (82.25±14.10 beats/min) than in soldiers stationed in camp (74.18±9.02 beats/min, P0.05). The concentration of Hb and the prevalence of plateau polycythemia were significantly higher in soldiers of field training (211.6±17.4g/L and 55.6%) than in soldiers stationed in camp (199.3±22.7g/L and 25.7%, P0.05). The concentration of serum LDH was significantly higher and the abnormality rate of LDH was also higher in soldiers of field training (273.70±136.74U/L and 72.7%) than in soldiers stationed in camp (205.19±77.94 U/L and 51.1%, P

Eucommia ulmoides (EU) Oliver seeds are rich in oil and serve as a potential edible oil, but little is known about its phytochemical substances. In this study, the sterol profiles of the supercritical CO2 fluid extracted EU seed oil and its contents were first evaluated by GC-MS analysis, and fifteen sterols and three triterpene alcohols were determined. β-sitosterol was detected as the most abundant phytosterol in the seed oil. Additionally, seven iridoid glycosides (1–7), namely aucubin (1), bartsioside (2), linaride (3), geniposidic acid (4), one dimer scyphiphin D (5), two trimers ulmoidoside A (6) and ulmoidoside B (7) were identified from the defatted seed flour, and the compound 3 was reported in E. ulmoides for the first time. Natural and two acetylated compounds (1–9) were evaluated for their inhibitory effects on NO production in the lipopolysaccharide (LPS)-stimulated microglial cells, and 1–3 exerted significant inhibition of NO generation with IC50 values of 3.60, 7.09, and 10.52 μM, respectively. The structure-activity relationships (SARs) of these iridoids indicated that OH groups on C-10 and C-6 were more effective and the COOH group at C-4 position was highly detrimental to the activity. The results suggest that the edible EU seeds could be a potential dietary source of aucubin and β-sitosterol for reducing the risk of neurodegenerative diseases.

As a typical model of hypoxia-induced excessive erythrocytosis, high altitude polycythemia (HAPC) results in microcirculation disturbance, aggravates tissue hypoxia and results in a severe clinical outcome, without any effective intervention methods except for returning to an oxygen-rich environment. The present study aimed to explore potential therapeutic targets which may participate in the recovery of HAPC by studying the mechanisms of reducing the hemoglobin (HB) concentration during re-oxygenation. A total of 14 and 13 subjects were recruited over a 5,300 m distance and 5,170 m area. The patients were classified into HAPC or control groups based on their HB value. Plasma samples were collected on the day when they finished their stay in plateau for a year, and on the 180th day following their reaching in plain. Metabolic profiling was conducted by UPLC-QTOF/MS. MetaboAnalyst platform was performed to explore the most perturbed metabolic pathways. A panel of differential metabolites were obtained in the recovery phase of HAPC and control groups. The present study identified the uniquely upregulated pentose phosphate pathway in HAPC subjects, along with a significantly decreased HB level. The findings were verified via a direct comparison between HAPC and control subjects at a high altitude. An increased pentose phosphate pathway was identified in control groups compared with HAPC subjects. An elevated pentose phosphate pathway may therefore participate in the recovery of HAPC, whereas a downregulated pentose phosphate pathway may contribute to hypoxia-induced erythrocytosis. The results of the present study provide potential therapeutic strategies and novel insights into the pathogenesis of hypoxia-induced polycythemia.

Objective To investigate the sleep status of troops stationed in highland areas, and approach its correlation with chronic mountain sickness (CMS). Methods Stratified-random sampling method was employed and 956 male soldiers stationed in plateau for more than 6 consecutive months were selected from a garrison troops as the study objects (plateau group), and 587 male soldiers from the same garrison troops stationed at plain areas without any experience of highland garrison were selected as the control group. Pittsburgh Sleep Quality Index (PSQI) was employed to collect the sleep status of the soldiers and CMS symptom questionnaire combined with physiological parameters was adopted to determine the existence of CMS and its severity. Physiological parameters and PSQI scores were studied and compared between soldiers in the plateau group as well as its two subgroups (healthy subgroup and CMS subgroup) and those in the control group. Correlation analysis between PSQI and CMS scores and physiological parameters, as well as between PSQI of sleep quality and CMS scores of soldiers stationed at plateau were carried out. Differences of PSQI scores and physiological parameters among the three CMS subgroups (healthy subgroup, mild subgroup and moderate and severe subgroup) were analyzed. Results The systolic blood pressure (SBP), heart rate (HR) and hemoglobin (Hb) concentration were significantly higher (P

Objective To study the concentration of minerals in hair between garrison and field training troops at high altitude. Method Weighing method was used to investigate the intakes of Zn, Fe, Cu, Ca, Mg and Mn of garrison in 4600m, 4030m and 3800m high altitude. Dietary Allowances for Military Personnel and Dietary Nutrition Reference Intake for Chinese Residents were used to evaluate the intakes of 6 minerals. The plateau force was divided into field and garrison training troops, and the concentration of Zn, Fe, Cu, Ca, Mg, Mn and Cr in their hair was tested through atomic absorption spectrometry. Results There were no differences of mineral content in hair among garrisons at different altitude. The content of Ca and Zn of garrison training troop was insufficient (69.5% and 77.8% of the military standard), but the content of Fe, Cu, Mg and Mn in hair was sufficient (103.7%, 275.0%, 81.1% and 162.2% of the military standard). The content of Fe and Zn in hair of garrison training troop was insufficient, but the content of Cu, Ca, Mg, Mn and Cr was sufficient. The content of Fe and Zn in hair of field training troop was insufficient. The content of Mg was moderate deficiency, and it's content was significantly lower than Mg in hair of garrison soldiers (P

Hypoxic preconditioning (HPC) is well‑known to exert a protective effect against hypoxic injury; however, the underlying molecular mechanism remains unclear. The present study utilized a serum metabolomics approach to detect the alterations associated with HPC. In the present study, an animal model of HPC was established by exposing adult BALB/c mice to acute repetitive hypoxia four times. The serum samples were collected by orbital blood sampling. Metabolite profiling was performed using ultra‑performance liquid chromatography‑quadrupole time‑of‑flight mass spectrometry (UPLC‑QTOFMS), in conjunction with univariate and multivariate statistical analyses. The results of the present study confirmed that the HPC mouse model was established and refined, suggesting significant differences between the control and HPC groups at the molecular levels. HPC caused significant metabolic alterations, as represented by the significant upregulation of valine, methionine, tyrosine, isoleucine, phenylalanine, lysophosphatidylcholine (LysoPC; 16:1), LysoPC (22:6), linoelaidylcarnitine, palmitoylcarnitine, octadecenoylcarnitine, taurine, arachidonic acid, linoleic acid, oleic acid and palmitic acid, and the downregulation of acetylcarnitine, malate, citrate and succinate. Using MetaboAnalyst 3.0, a number of key metabolic pathways were observed to be acutely perturbed, including valine, leucine and isoleucine biosynthesis, in addition to taurine, hypotaurine, phenylalanine, linoleic acid and arachidonic acid metabolism. The results of the present study provided novel insights into the mechanisms involved in the acclimatization of organisms to hypoxia, and demonstrated the protective mechanism of HPC.