Sweet potato leaf tips have high nutritional value,and exploring the differences in the metabolic profiles of leaf tips among different sweet potato varieties can provide information to improve their qualities.In this...Sweet potato leaf tips have high nutritional value,and exploring the differences in the metabolic profiles of leaf tips among different sweet potato varieties can provide information to improve their qualities.In this study,a UPLC-Q-Exactive Orbitrap/MS-based untargeted metabolomics method was used to evaluate the metabolites in leaf tips of 32 sweet potato varieties.Three varieties with distinct overall metabolic profiles(A01,A02,and A03),two varieties with distinct profiles of phenolic acids(A20 and A18),and three varieties with distinct profiles of flavonoids(A05,A12,and A16)were identified.In addition,a total of 163 and 29 differentially expressed metabolites correlated with the color and leaf shape of sweet potato leaf tips,respectively,were identified through morphological characterization.Group comparison analysis of the phenotypic traits and a metabolite-phenotypic trait correlation analysis indicated that the color differences of sweet potato leaf tips were markedly associated with flavonoids.Also,the level of polyphenols was correlated with the leaf shape of sweet potato leaf tips,with lobed leaf types having higher levels of polyphenols than the entire leaf types.The findings on the metabolic profiles and differentially expressed metabolites associated with the morphology of sweet potato leaf tips can provide useful information for breeding sweet potato varieties with higher nutritional value.展开更多
BACKGROUND Tong Xie Yao Fang is a representative traditional Chinese prescription for the treatment of liver and spleen deficiency,abdominal pain and diarrhea.It has a unique function in the treatment of gastrointesti...BACKGROUND Tong Xie Yao Fang is a representative traditional Chinese prescription for the treatment of liver and spleen deficiency,abdominal pain and diarrhea.It has a unique function in the treatment of gastrointestinal dysfunction including irritable bowel syndrome(IBS),is a common functional bowel disease.Its main symptoms are recurrent abdominal pain,diarrhea,constipation or alternations between diarrhea and constipation.There are obvious differences in metabolites between TCM syndromes.By comparing the body fluid metabolism maps of model animals,metabolomics can discover disease biomarkers,analyze the differences in metabolic pathways and understand the pathological process and the metabolic pathways of substances in the body.Thus,the evaluation of animal models tends to be comprehensive and objective.This may provide further understanding between the interaction between Tong Xie Yao Fang and the IBS model.AIM To evaluate the effect of Tong Xie Yao Fang on IBS rats by using metabolomics method.METHODS Wistar rats were used to establish IBS models,and then randomly divided into four groups:A model control group and three Tong Xie Yao Fang treatment groups(high,medium and low doses).A normal,non-IBS group was established.The rats were treated for 2 wk.On days 0 and 14 of the experimental model,urine was collected for 12 h and was analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry.Nine potential biomarkers were identified,and six major metabolic pathways were found to be related to IBS.RESULTS In the study of metabonomics,nine potential biomarkers including L-serine,4-methylgallic acid,L-threonine,succinylacetone,prolyl-hydroxyproline,valylserine,acetyl citrate,marmesin rutinoside and 5-hydroxy-L-tryptophan were identified in urine,which were assigned to amino acids,organic acids,succinyl and glycosides.Furthermore,the metabolic pathway of L-serine,L-threonine and 5-hydroxy-L-tryptophan was found in the Kyoto Encyclopedia of Genes and Genomes,which mainly involved the metabolism of cysteine and methionine,vitamin B6 metabolism,serotonin synapse,tryptophan metabolism,sphingolipid metabolism,digestion,absorption of protein and amino acid metabolism.These pathways are related to intestinal dysfunction,inflammatory syndrome,nervous system dysfunction and other diseases.CONCLUSION Tong Xie Yao Fang has pharmacological effects on IBS,and its mechanism may be related to the metabolism of the nine potential biomarkers identified above in urine.展开更多
In this work,a new pyrylium derivatization-assisted liquid chromatography-mass spectrometry(LC-MS)method was developed for metabolite profiling of the glutathione anabolic pathway(GAP)in cancer tissues and cells.The p...In this work,a new pyrylium derivatization-assisted liquid chromatography-mass spectrometry(LC-MS)method was developed for metabolite profiling of the glutathione anabolic pathway(GAP)in cancer tissues and cells.The pyrylium salt of 6,7-dimethoxy-3-methyl isochromenylium tetrafluoroborate(DMMIC)was used to label the amino group of metabolites,and a reductant of dithiothreitol(DTT)was employed to stabilize the thiol group.By combining DMMIC derivatization with LC-MS,it was feasible to quantify the 13 main metabolites on the GAP in complex biological samples,which had good linearity(R^(2)=0.99810.9999),precision(interday precision of 1.6%e19.0%and intraday precision of 1.4%e19.8%)and accuracy(83.4%-115.7%).Moreover,the recovery assessments in tissues(82.5%e107.3%)and in cells(98.1%e118.9%)with GSH-^(13)C2,^(15)N,and Cys-^(15)N demonstrated the reliability of the method in detecting tissues and cells.Following a methodological evaluation,the method was applied successfully to investigate difference in the GAP between the carcinoma and para-carcinoma tissues of esophageal squamous cell carcinoma(ESCC)and the effect of p-hydroxycinnamaldehyde(CMSP)on the GAP in KYSE150 esophageal cancer cells.The results demonstrate that the developed method provides a promising new tool to elucidate the roles of GAP in physiological and pathological processes,which can contribute to research on drugs and diseases.展开更多
Mud crab(Scylla paramamosain)is one of the most consumed crabs in China.Generally,it is believed that dead mud crabs are not edible.Herein,we investigated the postmortem metabolite profile changes of the muscle and he...Mud crab(Scylla paramamosain)is one of the most consumed crabs in China.Generally,it is believed that dead mud crabs are not edible.Herein,we investigated the postmortem metabolite profile changes of the muscle and hepatopancreas of mud crab associated with storage method using nuclear magnetic resonance-based metabolomics coupled with multivariate data analysis.Our results showed that postmortem changes of trimethylamine,organic acids(lactate,formate,and succinate),as well as ATP and its breakdown products are closely affected by the storage method.These metabolites can be used as indicators for monitoring loss of crab freshness.Furthermore,dead mud crabs preserved an edible quality at least for 4 h at room temperature,12h on ice,and 16 d at−20℃,strongly suggesting that dead crab consumption quality should be determined by freshness.They shouldn’t be discarded without considering the effects of different storage conditions on their freshness.展开更多
Objective:To profile the secondary metabolites and to evaluate the antidiabetic potential of hydroethanolic leaf extracts of Conocarpus lancifolius.Methods:The various hydroethanolic extracts of Conocarpus lancifolius...Objective:To profile the secondary metabolites and to evaluate the antidiabetic potential of hydroethanolic leaf extracts of Conocarpus lancifolius.Methods:The various hydroethanolic extracts of Conocarpus lancifolius leaf were prepared by ultrasonication assisted freezedrying.Total phenolic contents,flavonoid contents,antioxidant activity,α-glucosidase andα-amylase inhibitions of leaf extracts were determined.The metabolite profiling was accomplished by UHPLC-Q-TOF-MS/MS analysis.The antidiabetic assessment of the most potent extract was carried out by measuring the hypoglycemic and hypolipidemic effect in the high fat diet-fed diabetic albino mice.The blood glucose level,haemoglobin,total cholesterol,high-density lipoproteins(HDL)and low-density lipoproteins(LDL)were determined.Results:The 60%ethanolic extract exhibited the highest phenolic and flavonoid contents of(349.39±2.13)mg GAE/g dry extract and(116.95±2.34)mg RE/g dry extracts,respectively,and the highest DPPH scavenging activity with an IC50 value of(32.87±1.11)μg/mL.The IC50 values forα-glucosidase andα-amylase inhibitions were(38.64±0.93)μg/mL and(44.80±1.57)μg/mL,respectively.UHPLC-Q-TOF-MS/MS analysis confirmed the presence of gallic acid,ellagic acid,corilagin,kaempherol-3-O-rutinoside,caffeic acid derivative,isorhamnetin and galloyl derivatives in the 60%ethanolic extract.Plant extract at a dose of 450 mg/kg body weight reduced blood glucose level,total cholesterol,LDL and HDL,and increased haemoglobin in alloxan-induced diabetic mice,Conclusions:Conocarpus lancifolius leaves are proved as a good source of biologically functional metabolites and possess antidiabetic activity which may be further explored to treat diabetes.展开更多
In this report we have evaluated metabolite and RNA profiling technologies to begin to understand the natural variation in these biomolecules found in commercial-quality, conventional (non-GM) maize hybrids. Our analy...In this report we have evaluated metabolite and RNA profiling technologies to begin to understand the natural variation in these biomolecules found in commercial-quality, conventional (non-GM) maize hybrids. Our analyses focus on mature grain, the article of commerce that is most typically subjected to the rigorous studies involved in the comparative safety assessment of GM products. We have used a population of conventionally-bred maize hybrids that derive from closely related inbred parents grown under standard field conditions across geographically similar locations. This study highlights the large amount of natural variation in metabolites and transcripts across conventional maize germplasm grown under normal field conditions, and underscores the critical need for further extensive studies before these technologies can be seriously considered for utility in the comparative safety assessment of GM crops.展开更多
Ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC–Q-TOF/MS) was developed to identify the absorbed parent components and metabolites in rat bile, plasma and ...Ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC–Q-TOF/MS) was developed to identify the absorbed parent components and metabolites in rat bile, plasma and urine after oral administration of Radix Paeoniae Alba extract(RPAE).A total of 65 compounds were detected in rat bile, plasma and urine samples, including 11 parent compounds and 54 metabolites. The results indicated that glucuronidation, hydroxylation and methylation were the major metabolic pathways of the components of RPAE. Furthermore, the results of this work demonstrated that UPLC–Q-TOF/MS combined with MetaboLynx?software and mass defect filtering(MDF) could provide unique high throughput capabilities for drug metabolism study, with excellent MS mass accuracy and enhanced MSEdata acquisition. With the MSEtechnique, both precursor and fragment mass spectra can be simultaneously acquired by alternating between high and low collision energy during a single chromatographic run.展开更多
Objective:To evaluate the antioxidant potential and pancreatic lipase inhibitory action of optimized hydroethanolic extracts of Solanum nigrum.Methods:Optimized extraction for maximum recovery of metabolites was perfo...Objective:To evaluate the antioxidant potential and pancreatic lipase inhibitory action of optimized hydroethanolic extracts of Solanum nigrum.Methods:Optimized extraction for maximum recovery of metabolites was performed using a combination of freeze-drying and ultrasonication followed by determination of antioxidant and antiobesity properties.The ultra-high performance liquid chromatography equipped with mass spectrometry was used to analyze metabolite profiling of Solanum nigrum.Computational studies were performed using molecular docking and electrostatic potential analysis for individual compounds.The hypolipidemic potential of the most potent extract was assessed in the obese mice fed on fat rich diet.Results:The 80%hydroethanolic extract exhibited the highest extract yield,total phenolic contents,total flavonoid contents along with the strongest 2,2-diphenyl-1-picrylhydrazyl scavenging activity,total antioxidant power,and pancreatic lipase inhibitory properties.The 80%hydroethanolic extract not only regulated the lipid profile of obese mice but also restricted the weight gain in the liver,kidney,and heart.The 80%hydroethanolic extract also reduced alanine transaminase and aspartate transaminase concentrations in serum.The effects of plant extract at 300 mg/kg body weight were quite comparable with the standard drug orlistat.Conclusions:Solanum nigrum is proved as an excellent and potent source of secondary metabolites that might be responsible for obesity mitigation.展开更多
There is large usage of polybrominated diphenyl ethers(PBDEs) especially for decabromodiphenyl ether(BDE-209, Deca-BDE) in controlling the risks of fire. The toxicological effects of PBDEs are worth being concerned ab...There is large usage of polybrominated diphenyl ethers(PBDEs) especially for decabromodiphenyl ether(BDE-209, Deca-BDE) in controlling the risks of fire. The toxicological effects of PBDEs are worth being concerned about. Female SD rats were daily gavaged with BDE-209 ether at the dose of 100 mg/kg for 20 days. Histological observation was performed for the screening of the target organs for BDE-209 exposure. The distribution and metabolism of PBDEs in the exposed main organs were evidenced by HRGC-HRMS. Alterations of the endogenous metabolite concentrations in urine were investigated using metabonomic approaches based on1H NMR spectrum. Histopathological changes including serious edema in kidney, hepatocellular spotty necrosis and perivasculitis in liver indicated that BDE-209 caused potential influences on endogenous metabolism in the exposed liver and the kidney. BDE-209 was found to be highly accumulated in lipid, ovary, kidney and liver after 20 days' exposure. Occurrence of other lower brominated PBDEs in the rats demonstrated that reductive debromination process happened in vivo. Hydroxylated and methoxylated–BDEs, as metabolism products, were also detected in the rat tissues. A total of 12 different endogenous metabolites showed obvious alterations in urine from the exposed rats, indicating the disturbance of the corresponding internal biochemical processes induced by BDE-209 exposure. These findings in vivo suggested the potential health risk might be of concern due to the toxicological effects of BDE-209 as a ubiquitous compound in the environment.展开更多
Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal m...Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota.Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq.Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336–0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34–0.55),which were mainly involved in neurodevelopment.Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.展开更多
Soil salinity is known to improve cadmium(Cd)mobility,especially in arid soils.However,the mechanisms involved in how salt stress-associated metabolic profiles participate in mediating Cd transport in the soil-plant s...Soil salinity is known to improve cadmium(Cd)mobility,especially in arid soils.However,the mechanisms involved in how salt stress-associated metabolic profiles participate in mediating Cd transport in the soil-plant system remain poorly understood.This study was designed to investigate the effects of salinity-induced changes in soil metabolites on Cd bioavailability.Sodium salts in different combinations according to molar ratio(NaCl:Na_(2)SO_(4)=1:1;NaCl:Na_(2)SO_(4):NaHCO_(3)=1:2:1;NaCl:Na_(2)SO_(4):NaHCO_(3):Na_(2)CO_(3)=1:9:9:1;NaCl:Na_(2)SO_(4):NaHCO_(3):Na_(2)CO_(3)=1:1:1:1)were applied to the Cd-contaminated soils,which increased soil Cd availability by 22.36%and the Cd content in wheat grains by 36.61%,compared to the control.Salt stress resulted in soil metabolic reprogramming,which might explain the decreased growth of wheat plants and increased Cd transport from the soil into wheat tissues.For example,down-regulation of starch and sucrose metabolism reduced the production of sugars,which adversely affected growth;up-regulation of fatty acid metabolism allowed wheat plants to maintain a normal intracellular environment under saline conditions;up-regulation of the tricarboxylic acid(TCA)cycle was triggered,causing an increase in organic acid synthesis and the accumulation of organic acids,which facilitated the migration of soil Cd into wheat tissues.In summary,salt stress can facilitate Cd transport into wheat tissues by the direct effect of salt-based ions and the combined effect of altered soil physicochemical properties and soil metabolic profiles in Cd-contaminated soils.展开更多
Among the numerous fruit species of Baccaurea ramiflora Lour.,‘LR’(white flesh)and‘BR’(pink flesh)are two kinds of local strains with high edibility.In order to study the metabolic causes of taste differences,we p...Among the numerous fruit species of Baccaurea ramiflora Lour.,‘LR’(white flesh)and‘BR’(pink flesh)are two kinds of local strains with high edibility.In order to study the metabolic causes of taste differences,we performed the non-targeted metabonomics analysis of‘LR’and‘BR’using LC-MS/MS.541 metabolites were totally identified,and 45 kinds of metabolites(carbohydrates,fatty acids,flavonoids and terpenoids,etc.)were different between the two strains.The results indicate L-sorbose,D-(+)-glucose,citric acid,L-phenylalanine and oleamide,α-eleostearic acid were the main primary metabolites.The significant difference existed in pathways of unsaturated fatty acids between the studied two strains by pathway enrichment analysis.The results demonstrate that the different in composition,as well as the abundance of primary and secondary metabolites may be the potential causes of taste differences,which provides a new insight into the possible metabolic factors setting off the changing taste of B.ramiflora.展开更多
Circular RNAs(circRNAs)play a vital role in diabetic peripheral neuropathy.However,their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood.Here,we per...Circular RNAs(circRNAs)play a vital role in diabetic peripheral neuropathy.However,their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood.Here,we performed protein profiling and circRNA sequencing of sural nerves in patients with diabetic peripheral neuropathy and controls.Protein profiling revealed 265 differentially expressed proteins in the diabetic peripheral neuropathy group.Gene Ontology indicated that differentially expressed proteins were mainly enriched in myelination and mitochondrial oxidative phosphorylation.A real-time polymerase chain reaction assay performed to validate the circRNA sequencing results yielded 11 differentially expressed circRNAs.circ_0002538 was markedly downregulated in patients with diabetic peripheral neuropathy.Further in vitro experiments showed that overexpression of circ_0002538 promoted the migration of Schwann cells by upregulating plasmolipin(PLLP)expression.Moreover,overexpression of circ_0002538 in the sciatic nerve in a streptozotocin-induced mouse model of diabetic peripheral neuropathy alleviated demyelination and improved sciatic nerve function.The results of a mechanistic experiment showed that circ_0002538 promotes PLLP expression by sponging miR-138-5p,while a lack of circ_0002538 led to a PLLP deficiency that further suppressed Schwann cell migration.These findings suggest that the circ_0002538/miR-138-5p/PLLP axis can promote the migration of Schwann cells in diabetic peripheral neuropathy patients,improving myelin sheath structure and nerve function.Thus,this axis is a potential target for therapeutic treatment of diabetic peripheral neuropathy.展开更多
The raw and processed roots of Plygonum multiflorum Thunb(PM) are used to treat different diseases in clinical practice. In order to clarify the influence of processing, a comparative study of chemical substance analy...The raw and processed roots of Plygonum multiflorum Thunb(PM) are used to treat different diseases in clinical practice. In order to clarify the influence of processing, a comparative study of chemical substance analysis was carried out. As the xenobiotics with a high enough exposure in target organs being considered as the potential effective or toxicity components, an in vivo study was also implemented to characterize the constitutes and metabolites, and meanwhile, the factor of compatibility with black bean were also considered. As a result, a total of 148 compounds were detected in PM extracts and more than 40 compounds were only detected in the processed products, which were probably new components produced during the steaming process. In in vivo study, 7 prototype components and 66 metabolites were detected or tentatively identified, 24 of which were reported for the first time. Our results indicated that processing greatly changed the chemical composition of PM and influenced the disposition of the compounds in vivo. To the best of our knowledge, this was the first global comparative study of raw and processed PM. These results expanded our knowledge about the influence of processing of PM and provided the essential data for further efficacy or toxicity studies.展开更多
Chang-Kang-Fang(CKF)formula,a Traditional Chinese Medicine(TCM)prescription,has been widely used for the treatment of irritable bowel syndrome(IBS).However,its potential material basis and underlying mechanism remain ...Chang-Kang-Fang(CKF)formula,a Traditional Chinese Medicine(TCM)prescription,has been widely used for the treatment of irritable bowel syndrome(IBS).However,its potential material basis and underlying mechanism remain elusive.Therefore,this study employed an integrated approach that combined ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS)with network pharmacology to systematically characterize the phytochemical components and metabolites of CKF,as well as elucidating its underlying mechanism.Through this comprehensive analysis,a total of 150 components were identified or tentatively characterized within the CKF formula.Notably,six N-acetyldopamine oligomers from Cicadae Periostracum and eight resin glycosides from Cuscutae Semen were characterized in this formula for the first time.Meanwhile,149 xenobiotics(58 prototypes and 91 metabolites)were detected in plasma,urine,feces,brain,and intestinal contents,and the in vivo metabolic pathways of resin glycosides were elaborated for the first time.Furthermore,network pharmacology and molecular docking analyses revealed that alkaloids,flavonoids,chromones,monoterpenes,N-acetyldopamine dimers,p-hydroxycinnamic acid,and Cus-3/isomer might be responsible for the beneficial effects of CKF in treating IBS,and CASP8,MARK14,PIK3C,PIK3R1,TLR4,and TNF may be its potential targets.These discoveries offer a comprehensive understanding of the potential material basis and clarify the underlying mechanism of the CKF formula in treating IBS,facilitating the broader application of CKF in the field of medicine.展开更多
基金This work was supported by grants from the construction and operation of the Food Nutrition and Health Research Center of Guangdong Academy of Agricultural Sciences,China(XTXM 202205)the earmarked fund for CARS-10Sweetpotato,and the Guangdong Modern Agro-industry Technology Research System,China(2022KJ111).
文摘Sweet potato leaf tips have high nutritional value,and exploring the differences in the metabolic profiles of leaf tips among different sweet potato varieties can provide information to improve their qualities.In this study,a UPLC-Q-Exactive Orbitrap/MS-based untargeted metabolomics method was used to evaluate the metabolites in leaf tips of 32 sweet potato varieties.Three varieties with distinct overall metabolic profiles(A01,A02,and A03),two varieties with distinct profiles of phenolic acids(A20 and A18),and three varieties with distinct profiles of flavonoids(A05,A12,and A16)were identified.In addition,a total of 163 and 29 differentially expressed metabolites correlated with the color and leaf shape of sweet potato leaf tips,respectively,were identified through morphological characterization.Group comparison analysis of the phenotypic traits and a metabolite-phenotypic trait correlation analysis indicated that the color differences of sweet potato leaf tips were markedly associated with flavonoids.Also,the level of polyphenols was correlated with the leaf shape of sweet potato leaf tips,with lobed leaf types having higher levels of polyphenols than the entire leaf types.The findings on the metabolic profiles and differentially expressed metabolites associated with the morphology of sweet potato leaf tips can provide useful information for breeding sweet potato varieties with higher nutritional value.
基金Supported by the National Natural Science Foundation of China,No.81573870the Eighth Special Subsidy Project of China Post Doctoral Science Foundation,No.2015T80376+4 种基金Postdoctoral Science Research Developmental Foundation of China,No.2013M531079National Science Foundation of Heilongjiang Province,No.H2015020Heilongjiang University of Traditional Chinese Medicine Outstanding Innovative Talents Support Project(Outstanding Young Academic Leaders),Postdoctoral Science-Research Developmental Foundation of Heilongjiang Province,No.LBHQ12009Youth Academic Backbone Fund of Heilongjiang Province Education Department,No.1253G053Youth Science and Technology Project of Traditional Chinese Medicine Department of Heilongjiang Province,No.ZQG-034
文摘BACKGROUND Tong Xie Yao Fang is a representative traditional Chinese prescription for the treatment of liver and spleen deficiency,abdominal pain and diarrhea.It has a unique function in the treatment of gastrointestinal dysfunction including irritable bowel syndrome(IBS),is a common functional bowel disease.Its main symptoms are recurrent abdominal pain,diarrhea,constipation or alternations between diarrhea and constipation.There are obvious differences in metabolites between TCM syndromes.By comparing the body fluid metabolism maps of model animals,metabolomics can discover disease biomarkers,analyze the differences in metabolic pathways and understand the pathological process and the metabolic pathways of substances in the body.Thus,the evaluation of animal models tends to be comprehensive and objective.This may provide further understanding between the interaction between Tong Xie Yao Fang and the IBS model.AIM To evaluate the effect of Tong Xie Yao Fang on IBS rats by using metabolomics method.METHODS Wistar rats were used to establish IBS models,and then randomly divided into four groups:A model control group and three Tong Xie Yao Fang treatment groups(high,medium and low doses).A normal,non-IBS group was established.The rats were treated for 2 wk.On days 0 and 14 of the experimental model,urine was collected for 12 h and was analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry.Nine potential biomarkers were identified,and six major metabolic pathways were found to be related to IBS.RESULTS In the study of metabonomics,nine potential biomarkers including L-serine,4-methylgallic acid,L-threonine,succinylacetone,prolyl-hydroxyproline,valylserine,acetyl citrate,marmesin rutinoside and 5-hydroxy-L-tryptophan were identified in urine,which were assigned to amino acids,organic acids,succinyl and glycosides.Furthermore,the metabolic pathway of L-serine,L-threonine and 5-hydroxy-L-tryptophan was found in the Kyoto Encyclopedia of Genes and Genomes,which mainly involved the metabolism of cysteine and methionine,vitamin B6 metabolism,serotonin synapse,tryptophan metabolism,sphingolipid metabolism,digestion,absorption of protein and amino acid metabolism.These pathways are related to intestinal dysfunction,inflammatory syndrome,nervous system dysfunction and other diseases.CONCLUSION Tong Xie Yao Fang has pharmacological effects on IBS,and its mechanism may be related to the metabolism of the nine potential biomarkers identified above in urine.
基金We thank the Shanghai Municipal Committee of Science and Technology(Grant Nos.:20XD1423400,23ZR1460900 and 20DZ2201100)Shanghai Municipal Health Commission/Shanghai Municipal Administration of Traditional Chinese Medicine(Grant No.:ZY(2021e2023)-0501)+2 种基金Shanghai Science and Technology Development Fund from Central Leading Local Government(Grant No.:YDZX20223100001004)National Natural Science Foundation of China(Grant No.:21672249)Expenditure Budget Program of Shanghai University of Traditional Chinese Medicine(Grant Nos.:2020LK051,and 2021LK001).
文摘In this work,a new pyrylium derivatization-assisted liquid chromatography-mass spectrometry(LC-MS)method was developed for metabolite profiling of the glutathione anabolic pathway(GAP)in cancer tissues and cells.The pyrylium salt of 6,7-dimethoxy-3-methyl isochromenylium tetrafluoroborate(DMMIC)was used to label the amino group of metabolites,and a reductant of dithiothreitol(DTT)was employed to stabilize the thiol group.By combining DMMIC derivatization with LC-MS,it was feasible to quantify the 13 main metabolites on the GAP in complex biological samples,which had good linearity(R^(2)=0.99810.9999),precision(interday precision of 1.6%e19.0%and intraday precision of 1.4%e19.8%)and accuracy(83.4%-115.7%).Moreover,the recovery assessments in tissues(82.5%e107.3%)and in cells(98.1%e118.9%)with GSH-^(13)C2,^(15)N,and Cys-^(15)N demonstrated the reliability of the method in detecting tissues and cells.Following a methodological evaluation,the method was applied successfully to investigate difference in the GAP between the carcinoma and para-carcinoma tissues of esophageal squamous cell carcinoma(ESCC)and the effect of p-hydroxycinnamaldehyde(CMSP)on the GAP in KYSE150 esophageal cancer cells.The results demonstrate that the developed method provides a promising new tool to elucidate the roles of GAP in physiological and pathological processes,which can contribute to research on drugs and diseases.
基金Financial support from the 2025 Technological Innova-tion for Ningbo(No.2019B10010)China Agriculture Re-search System-CARS48+1 种基金K.C.Wong Magna Fund in Ningbo Universitythe Special research funding from the Marine Biotechnology and Marine Engineering Dis cipline Group in Ningbo University(No.422004582)are greatly acknowledged.
文摘Mud crab(Scylla paramamosain)is one of the most consumed crabs in China.Generally,it is believed that dead mud crabs are not edible.Herein,we investigated the postmortem metabolite profile changes of the muscle and hepatopancreas of mud crab associated with storage method using nuclear magnetic resonance-based metabolomics coupled with multivariate data analysis.Our results showed that postmortem changes of trimethylamine,organic acids(lactate,formate,and succinate),as well as ATP and its breakdown products are closely affected by the storage method.These metabolites can be used as indicators for monitoring loss of crab freshness.Furthermore,dead mud crabs preserved an edible quality at least for 4 h at room temperature,12h on ice,and 16 d at−20℃,strongly suggesting that dead crab consumption quality should be determined by freshness.They shouldn’t be discarded without considering the effects of different storage conditions on their freshness.
文摘Objective:To profile the secondary metabolites and to evaluate the antidiabetic potential of hydroethanolic leaf extracts of Conocarpus lancifolius.Methods:The various hydroethanolic extracts of Conocarpus lancifolius leaf were prepared by ultrasonication assisted freezedrying.Total phenolic contents,flavonoid contents,antioxidant activity,α-glucosidase andα-amylase inhibitions of leaf extracts were determined.The metabolite profiling was accomplished by UHPLC-Q-TOF-MS/MS analysis.The antidiabetic assessment of the most potent extract was carried out by measuring the hypoglycemic and hypolipidemic effect in the high fat diet-fed diabetic albino mice.The blood glucose level,haemoglobin,total cholesterol,high-density lipoproteins(HDL)and low-density lipoproteins(LDL)were determined.Results:The 60%ethanolic extract exhibited the highest phenolic and flavonoid contents of(349.39±2.13)mg GAE/g dry extract and(116.95±2.34)mg RE/g dry extracts,respectively,and the highest DPPH scavenging activity with an IC50 value of(32.87±1.11)μg/mL.The IC50 values forα-glucosidase andα-amylase inhibitions were(38.64±0.93)μg/mL and(44.80±1.57)μg/mL,respectively.UHPLC-Q-TOF-MS/MS analysis confirmed the presence of gallic acid,ellagic acid,corilagin,kaempherol-3-O-rutinoside,caffeic acid derivative,isorhamnetin and galloyl derivatives in the 60%ethanolic extract.Plant extract at a dose of 450 mg/kg body weight reduced blood glucose level,total cholesterol,LDL and HDL,and increased haemoglobin in alloxan-induced diabetic mice,Conclusions:Conocarpus lancifolius leaves are proved as a good source of biologically functional metabolites and possess antidiabetic activity which may be further explored to treat diabetes.
文摘In this report we have evaluated metabolite and RNA profiling technologies to begin to understand the natural variation in these biomolecules found in commercial-quality, conventional (non-GM) maize hybrids. Our analyses focus on mature grain, the article of commerce that is most typically subjected to the rigorous studies involved in the comparative safety assessment of GM products. We have used a population of conventionally-bred maize hybrids that derive from closely related inbred parents grown under standard field conditions across geographically similar locations. This study highlights the large amount of natural variation in metabolites and transcripts across conventional maize germplasm grown under normal field conditions, and underscores the critical need for further extensive studies before these technologies can be seriously considered for utility in the comparative safety assessment of GM crops.
文摘Ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC–Q-TOF/MS) was developed to identify the absorbed parent components and metabolites in rat bile, plasma and urine after oral administration of Radix Paeoniae Alba extract(RPAE).A total of 65 compounds were detected in rat bile, plasma and urine samples, including 11 parent compounds and 54 metabolites. The results indicated that glucuronidation, hydroxylation and methylation were the major metabolic pathways of the components of RPAE. Furthermore, the results of this work demonstrated that UPLC–Q-TOF/MS combined with MetaboLynx?software and mass defect filtering(MDF) could provide unique high throughput capabilities for drug metabolism study, with excellent MS mass accuracy and enhanced MSEdata acquisition. With the MSEtechnique, both precursor and fragment mass spectra can be simultaneously acquired by alternating between high and low collision energy during a single chromatographic run.
文摘Objective:To evaluate the antioxidant potential and pancreatic lipase inhibitory action of optimized hydroethanolic extracts of Solanum nigrum.Methods:Optimized extraction for maximum recovery of metabolites was performed using a combination of freeze-drying and ultrasonication followed by determination of antioxidant and antiobesity properties.The ultra-high performance liquid chromatography equipped with mass spectrometry was used to analyze metabolite profiling of Solanum nigrum.Computational studies were performed using molecular docking and electrostatic potential analysis for individual compounds.The hypolipidemic potential of the most potent extract was assessed in the obese mice fed on fat rich diet.Results:The 80%hydroethanolic extract exhibited the highest extract yield,total phenolic contents,total flavonoid contents along with the strongest 2,2-diphenyl-1-picrylhydrazyl scavenging activity,total antioxidant power,and pancreatic lipase inhibitory properties.The 80%hydroethanolic extract not only regulated the lipid profile of obese mice but also restricted the weight gain in the liver,kidney,and heart.The 80%hydroethanolic extract also reduced alanine transaminase and aspartate transaminase concentrations in serum.The effects of plant extract at 300 mg/kg body weight were quite comparable with the standard drug orlistat.Conclusions:Solanum nigrum is proved as an excellent and potent source of secondary metabolites that might be responsible for obesity mitigation.
基金supported by the National Natural Science Foundation of China(No.20621703,40590392)the Chinese Academy of Sciences(No.KZCX2-YW-420-21)the National Science and Technology Supporting Item(No.2007BAC27B02-1a)
文摘There is large usage of polybrominated diphenyl ethers(PBDEs) especially for decabromodiphenyl ether(BDE-209, Deca-BDE) in controlling the risks of fire. The toxicological effects of PBDEs are worth being concerned about. Female SD rats were daily gavaged with BDE-209 ether at the dose of 100 mg/kg for 20 days. Histological observation was performed for the screening of the target organs for BDE-209 exposure. The distribution and metabolism of PBDEs in the exposed main organs were evidenced by HRGC-HRMS. Alterations of the endogenous metabolite concentrations in urine were investigated using metabonomic approaches based on1H NMR spectrum. Histopathological changes including serious edema in kidney, hepatocellular spotty necrosis and perivasculitis in liver indicated that BDE-209 caused potential influences on endogenous metabolism in the exposed liver and the kidney. BDE-209 was found to be highly accumulated in lipid, ovary, kidney and liver after 20 days' exposure. Occurrence of other lower brominated PBDEs in the rats demonstrated that reductive debromination process happened in vivo. Hydroxylated and methoxylated–BDEs, as metabolism products, were also detected in the rat tissues. A total of 12 different endogenous metabolites showed obvious alterations in urine from the exposed rats, indicating the disturbance of the corresponding internal biochemical processes induced by BDE-209 exposure. These findings in vivo suggested the potential health risk might be of concern due to the toxicological effects of BDE-209 as a ubiquitous compound in the environment.
基金partly supported by grants from the National Natural Science Foundation of China(No:81372955)BiosTime Maternal and Infant Nutrition and Health Research Fund(2017FYH008)+1 种基金the Projects of Medical and Health Technology Development Program in Shandong Province(No:2016WS0309)Qingdao Outstanding Health Professional Development Fund(2020-2022,2022-2024)。
文摘Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota.Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq.Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336–0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34–0.55),which were mainly involved in neurodevelopment.Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.
基金supported by the National Natural Science Foundation of China(Nos.42177010 and 41877387)Fundamental Research Funds for Central Non-profit Scientific Institution(No.1610132021008).
文摘Soil salinity is known to improve cadmium(Cd)mobility,especially in arid soils.However,the mechanisms involved in how salt stress-associated metabolic profiles participate in mediating Cd transport in the soil-plant system remain poorly understood.This study was designed to investigate the effects of salinity-induced changes in soil metabolites on Cd bioavailability.Sodium salts in different combinations according to molar ratio(NaCl:Na_(2)SO_(4)=1:1;NaCl:Na_(2)SO_(4):NaHCO_(3)=1:2:1;NaCl:Na_(2)SO_(4):NaHCO_(3):Na_(2)CO_(3)=1:9:9:1;NaCl:Na_(2)SO_(4):NaHCO_(3):Na_(2)CO_(3)=1:1:1:1)were applied to the Cd-contaminated soils,which increased soil Cd availability by 22.36%and the Cd content in wheat grains by 36.61%,compared to the control.Salt stress resulted in soil metabolic reprogramming,which might explain the decreased growth of wheat plants and increased Cd transport from the soil into wheat tissues.For example,down-regulation of starch and sucrose metabolism reduced the production of sugars,which adversely affected growth;up-regulation of fatty acid metabolism allowed wheat plants to maintain a normal intracellular environment under saline conditions;up-regulation of the tricarboxylic acid(TCA)cycle was triggered,causing an increase in organic acid synthesis and the accumulation of organic acids,which facilitated the migration of soil Cd into wheat tissues.In summary,salt stress can facilitate Cd transport into wheat tissues by the direct effect of salt-based ions and the combined effect of altered soil physicochemical properties and soil metabolic profiles in Cd-contaminated soils.
基金Forestry Science and Technology Innovation Project of Guangdong province(2018KJCX023)National Science Foundation for Young Scientists of China(31801742)+2 种基金Guangdong Key Laboratory for Functional Substances in Medicinal Edible Resources and Healthcare Products(2021B1212040015)Science and Technology Major Project of Guangxi(Guike AA17204045-4)Science and Technology Project of Chongzuo,Guangxi(Chongkegong 2019029).
文摘Among the numerous fruit species of Baccaurea ramiflora Lour.,‘LR’(white flesh)and‘BR’(pink flesh)are two kinds of local strains with high edibility.In order to study the metabolic causes of taste differences,we performed the non-targeted metabonomics analysis of‘LR’and‘BR’using LC-MS/MS.541 metabolites were totally identified,and 45 kinds of metabolites(carbohydrates,fatty acids,flavonoids and terpenoids,etc.)were different between the two strains.The results indicate L-sorbose,D-(+)-glucose,citric acid,L-phenylalanine and oleamide,α-eleostearic acid were the main primary metabolites.The significant difference existed in pathways of unsaturated fatty acids between the studied two strains by pathway enrichment analysis.The results demonstrate that the different in composition,as well as the abundance of primary and secondary metabolites may be the potential causes of taste differences,which provides a new insight into the possible metabolic factors setting off the changing taste of B.ramiflora.
基金supported by the National Natural Science Foundation of China,Nos.81772094(to ZBC),81974289(to ZBC)the Key Research and Development Program of Hubei Province,No.2020BCB031(to ZBC)Natural Science Foundation of Hubei Province,No.2020CFB433(to YTL).
文摘Circular RNAs(circRNAs)play a vital role in diabetic peripheral neuropathy.However,their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood.Here,we performed protein profiling and circRNA sequencing of sural nerves in patients with diabetic peripheral neuropathy and controls.Protein profiling revealed 265 differentially expressed proteins in the diabetic peripheral neuropathy group.Gene Ontology indicated that differentially expressed proteins were mainly enriched in myelination and mitochondrial oxidative phosphorylation.A real-time polymerase chain reaction assay performed to validate the circRNA sequencing results yielded 11 differentially expressed circRNAs.circ_0002538 was markedly downregulated in patients with diabetic peripheral neuropathy.Further in vitro experiments showed that overexpression of circ_0002538 promoted the migration of Schwann cells by upregulating plasmolipin(PLLP)expression.Moreover,overexpression of circ_0002538 in the sciatic nerve in a streptozotocin-induced mouse model of diabetic peripheral neuropathy alleviated demyelination and improved sciatic nerve function.The results of a mechanistic experiment showed that circ_0002538 promotes PLLP expression by sponging miR-138-5p,while a lack of circ_0002538 led to a PLLP deficiency that further suppressed Schwann cell migration.These findings suggest that the circ_0002538/miR-138-5p/PLLP axis can promote the migration of Schwann cells in diabetic peripheral neuropathy patients,improving myelin sheath structure and nerve function.Thus,this axis is a potential target for therapeutic treatment of diabetic peripheral neuropathy.
基金supported by National Natural Science Foundation of China(Nos.81373967 and 81402887)Traditional Chinese Medicine Administration Bureau of Traditional Chinese Medicine Standardization project(No.ZYBZH-Y-SH-38)
文摘The raw and processed roots of Plygonum multiflorum Thunb(PM) are used to treat different diseases in clinical practice. In order to clarify the influence of processing, a comparative study of chemical substance analysis was carried out. As the xenobiotics with a high enough exposure in target organs being considered as the potential effective or toxicity components, an in vivo study was also implemented to characterize the constitutes and metabolites, and meanwhile, the factor of compatibility with black bean were also considered. As a result, a total of 148 compounds were detected in PM extracts and more than 40 compounds were only detected in the processed products, which were probably new components produced during the steaming process. In in vivo study, 7 prototype components and 66 metabolites were detected or tentatively identified, 24 of which were reported for the first time. Our results indicated that processing greatly changed the chemical composition of PM and influenced the disposition of the compounds in vivo. To the best of our knowledge, this was the first global comparative study of raw and processed PM. These results expanded our knowledge about the influence of processing of PM and provided the essential data for further efficacy or toxicity studies.
基金supported by National Key Research and Development Program of China(No.2017ZX 09301005).
文摘Chang-Kang-Fang(CKF)formula,a Traditional Chinese Medicine(TCM)prescription,has been widely used for the treatment of irritable bowel syndrome(IBS).However,its potential material basis and underlying mechanism remain elusive.Therefore,this study employed an integrated approach that combined ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS)with network pharmacology to systematically characterize the phytochemical components and metabolites of CKF,as well as elucidating its underlying mechanism.Through this comprehensive analysis,a total of 150 components were identified or tentatively characterized within the CKF formula.Notably,six N-acetyldopamine oligomers from Cicadae Periostracum and eight resin glycosides from Cuscutae Semen were characterized in this formula for the first time.Meanwhile,149 xenobiotics(58 prototypes and 91 metabolites)were detected in plasma,urine,feces,brain,and intestinal contents,and the in vivo metabolic pathways of resin glycosides were elaborated for the first time.Furthermore,network pharmacology and molecular docking analyses revealed that alkaloids,flavonoids,chromones,monoterpenes,N-acetyldopamine dimers,p-hydroxycinnamic acid,and Cus-3/isomer might be responsible for the beneficial effects of CKF in treating IBS,and CASP8,MARK14,PIK3C,PIK3R1,TLR4,and TNF may be its potential targets.These discoveries offer a comprehensive understanding of the potential material basis and clarify the underlying mechanism of the CKF formula in treating IBS,facilitating the broader application of CKF in the field of medicine.
基金Supported by the National Natural Science Foundation of China(No.81001686) and the Project Funded by the Priority Aca- demic Program Development of Jiangsu Higher Education Institutions, China.