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  1. Urine NMR Metabolomic Study on Biochemical Activities to Investigate the Effect of P. betle Extract on Obese Rats
    Abdul Ghani ZDF, Ab Rashid AH, Shaari K, Chik Z
    Appl Biochem Biotechnol, 2019 Oct;189(2):690-708.
    PMID: 31111377 DOI: 10.1007/s12010-019-03042-w
    The present studies are to evaluate the ability of PB to induce weight loss and urine metabolite profile of Piper betle L. (PB) leaf extracts using metabolomics approach. Dried PB leaves were extracted with ethanol 70% and the studies were performed in different groups of rats fed with high fat (HFD) and normal diet (ND). Then, fed with the PB extract with 100, 300, and 500 mg/kg and two negative control groups given water (WTR). The body weights were monitored and evaluated. Urine was collected and 1H NMR-based metabolomics approach was used to detect the metabolite changes. Results showed that PB-treated group demonstrated inhibition of body weight gain. The trajectory of urine metabolites showed that PB-treated group gave the different distribution from week 12 to 16 compared with the control groups. In 1H NMR metabolomic approach analysis, the urine metabolites gave the best separation in principle component 1 and 3, with 40.0% and 9.56% of the total variation. Shared and unique structures (SUS) plot model showed that higher concentration PB-treated group was characterized by high level of indole-3-acetate, aspartate, methanol, histidine, and creatine, thus caused an increased the metabolic function and maintaining the body weight of the animals treated.
    Matched MeSH terms: Metabolome/drug effects
  2. Fulltext Metabolite characterization of different palm date varieties and the correlation with their NO inhibitory activity, texture and sweetness
    Abdul-Hamid NA, Mediani A, Maulidiani M, Shadid K, Ismail IS, Abas F, et al.
    J Food Sci Technol, 2018 Apr;55(4):1541-1551.
    PMID: 29606769 DOI: 10.1007/s13197-018-3073-6
    The aim of this study was to examine the variation in metabolite constituents of five commercial varieties of date fruits; Ajwa, Safawi and Ambar which originated from Madinah, the Iranian Bam and Tunisian Deglet Noor. The differences of metabolome were investigated using proton nuclear magnetic resonance (1H NMR) spectroscopy combined with multivariate data analysis (MVDA). Principal Component Analysis (PCA) revealed clear separation between the date varieties. The Tunisian Deglet Noor demonstrated distinct cluster from the rest of the palm date samples based on the metabolite composition as shown by the pattern observed in Hierarchical Clustering Analysis (HCA) and PCA. Deglet Noor exhibited a significant higher level of sucrose (δ 5.40) and fructose (δ 4.16) in comparison with the other four varieties which can be associated with the distinctive sweet taste of this variety. Dates originated from Madinah and Tunisia exhibited a contrast manner in the amount of xylose and moisture content. These two aspects may contribute towards the soft texture of Tunisian dates. All Madinah dates were found to contain phenolic compounds which were well established as great antioxidant and anti-inflammatory agent. Ajwa dates exerted greater effect in inhibiting the generation of nitric oxide (NO) from the stimulated RAW264.7 cells at 95.37% inhibition. Succinic acid was suggested to have the most significant correlation with the trend of NO inhibitory shown by the selected date palm varieties.
    Matched MeSH terms: Metabolome
  3. Metabolite Variation in Lean and Obese Streptozotocin (STZ)-Induced Diabetic Rats via (1)H NMR-Based Metabolomics Approach
    Abu Bakar Sajak A, Mediani A, Maulidiani, Ismail A, Abas F
    Appl Biochem Biotechnol, 2017 Jun;182(2):653-668.
    PMID: 27995574 DOI: 10.1007/s12010-016-2352-9
    Diabetes mellitus (DM) is considered as a complex metabolic disease because it affects the metabolism of glucose and other metabolites. Although many diabetes studies have been conducted in animal models throughout the years, the pathogenesis of this disease, especially between lean diabetes (ND + STZ) and obese diabetes (OB + STZ), is still not fully understood. In this study, the urine from ND + STZ, OB + STZ, lean/control (ND), and OB + STZ rats were collected and compared by using (1)H NMR metabolomics. The results from multivariate data analysis (MVDA) showed that the diabetic groups (ND + STZ and OB + STZ) have similarities and dissimilarities for a certain level of metabolites. Differences between ND + STZ and OB + STZ were particularly noticeable in the synthesis of ketone bodies, branched-chain amino acid (BCAA), and sensitivity towards the oral T2DM diabetes drug metformin. This finding suggests that the ND + STZ group was more similar to the T1DM model and OB + STZ to the T2DM model. In addition, we also managed to identify several pathways and metabolism aspects shared by obese (OB) and OB + STZ. The results from this study are useful in developing drug target-based research as they can increase understanding regarding the cause and effect of DM.
    Matched MeSH terms: Metabolome*
  4. Fulltext The Changes in Endogenous Metabolites in Hyperlipidemic Rats Treated with Herbal Mixture Containing Lemon, Apple Cider, Garlic, Ginger, and Honey
    Abu Bakar Sajak A, Azlan A, Abas F, Hamzah H
    Nutrients, 2021 Oct 12;13(10).
    PMID: 34684574 DOI: 10.3390/nu13103573
    An herbal mixture composed of lemon, apple cider, garlic, ginger and honey as a polyphenol-rich mixture (PRM) has been reported to contain hypolipidemic activity on human subjects and hyperlipidemic rats. However, the therapeutic effects of PRM on metabolites are not clearly understood. Therefore, this study aimed to provide new information on the causal impact of PRM on the endogenous metabolites, pathways and serum biochemistry. Serum samples of hyperlipidemic rats treated with PRM were subjected to biochemistry (lipid and liver profile) and hydroxymethylglutaryl-CoA enzyme reductase (HMG-CoA reductase) analyses. In contrast, the urine samples were subjected to urine metabolomics using 1H NMR. The serum biochemistry revealed that PRM at 500 mg/kg (PRM-H) managed to lower the total cholesterol level and low-density lipoprotein (LDL-C) (p < 0.05) and reduce the HMG-CoA reductase activity. The pathway analysis from urine metabolomics reveals that PRM-H altered 17 pathways, with the TCA cycle having the highest impact (0.26). Results also showed the relationship between the serum biochemistry of LDL-C and HMG-CoA reductase and urine metabolites (trimethylamine-N-oxide, dimethylglycine, allantoin and succinate). The study's findings demonstrated the potential of PRM at 500 mg/kg as an anti-hyperlipidemic by altering the TCA cycle, inhibiting HMG-CoA reductase and lowering the LDL-C in high cholesterol rats.
    Matched MeSH terms: Metabolome*
  5. Fulltext Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study
    Adams CD, Richmond R, Ferreira DLS, Spiller W, Tan V, Zheng J, et al.
    Cancer Epidemiol Biomarkers Prev, 2019 Jan;28(1):208-216.
    PMID: 30352818 DOI: 10.1158/1055-9965.EPI-18-0079
    BACKGROUND: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR).

    METHODS: The case-control portion of the study was conducted in nine UK centers with men ages 50-69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.

    RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (P < 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.

    CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.

    IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.

    Matched MeSH terms: Metabolome*
  6. Fulltext 1H-NMR-Based Metabolomics: An Integrated Approach for the Detection of the Adulteration in Chicken, Chevon, Beef and Donkey Meat
    Akhtar MT, Samar M, Shami AA, Mumtaz MW, Mukhtar H, Tahir A, et al.
    Molecules, 2021 Jul 30;26(15).
    PMID: 34361796 DOI: 10.3390/molecules26154643
    Meat is a rich source of energy that provides high-value animal protein, fats, vitamins, minerals and trace amounts of carbohydrates. Globally, different types of meats are consumed to fulfill nutritional requirements. However, the increasing burden on the livestock industry has triggered the mixing of high-price meat species with low-quality/-price meat. This work aimed to differentiate different meat samples on the basis of metabolites. The metabolic difference between various meat samples was investigated through Nuclear Magnetic Resonance spectroscopy coupled with multivariate data analysis approaches like principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA). In total, 37 metabolites were identified in the gluteal muscle tissues of cow, goat, donkey and chicken using 1H-NMR spectroscopy. PCA was found unable to completely differentiate between meat types, whereas OPLS-DA showed an apparent separation and successfully differentiated samples from all four types of meat. Lactate, creatine, choline, acetate, leucine, isoleucine, valine, formate, carnitine, glutamate, 3-hydroxybutyrate and α-mannose were found as the major discriminating metabolites between white (chicken) and red meat (chevon, beef and donkey). However, inosine, lactate, uracil, carnosine, format, pyruvate, carnitine, creatine and acetate were found responsible for differentiating chevon, beef and donkey meat. The relative quantification of differentiating metabolites was performed using one-way ANOVA and Tukey test. Our results showed that NMR-based metabolomics is a powerful tool for the identification of novel signatures (potential biomarkers) to characterize meats from different sources and could potentially be used for quality control purposes in order to differentiate different meat types.
    Matched MeSH terms: Metabolomics/methods*; Metabolome*
  7. Fulltext Integration of proteomics and metabolomics to elucidate metabolic adaptation in Leishmania
    Akpunarlieva S, Weidt S, Lamasudin D, Naula C, Henderson D, Barrett M, et al.
    J Proteomics, 2017 02 23;155:85-98.
    PMID: 28040509 DOI: 10.1016/j.jprot.2016.12.009
    Leishmania parasites multiply and develop in the gut of a sand fly vector in order to be transmitted to a vertebrate host. During this process they encounter and exploit various nutrients, including sugars, and amino and fatty acids. We have previously generated a mutant Leishmania line that is deficient in glucose transport and which displays some biologically important phenotypic changes such as reduced growth in axenic culture, reduced biosynthesis of hexose-containing virulence factors, increased sensitivity to oxidative stress, and dramatically reduced parasite burden in both insect vector and macrophage host cells. Here we report the generation and integration of proteomic and metabolomic approaches to identify molecular changes that may explain these phenotypes. Our data suggest changes in pathways of glycoconjugate production and redox homeostasis, which likely represent adaptations to the loss of sugar uptake capacity and explain the reduced virulence of this mutant in sand flies and mammals. Our data contribute to understanding the mechanisms of metabolic adaptation in Leishmania and illustrate the power of integrated proteomic and metabolomic approaches to relate biochemistry to phenotype.

    BIOLOGICAL SIGNIFICANCE: This paper reports the application of comparative proteomic and metabolomic approaches to reveal the molecular basis for important phenotypic changes Leishmania parasites that are deficient in glucose uptake. Leishmania cause a very significant disease burden across the world and there are few effective drugs available for control. This work shows that proteomics and metabolomics can produce complementary data that advance understanding of parasite metabolism and highlight potential new targets for chemotherapy.

    Matched MeSH terms: Metabolome/physiology*
  8. Fulltext Metabolic profiling of Lactococcus lactis under different culture conditions
    Azizan KA, Baharum SN, Mohd Noor N
    Molecules, 2012 Jul 03;17(7):8022-36.
    PMID: 22759915 DOI: 10.3390/molecules17078022
    Gas chromatography mass spectrometry (GC-MS) and headspace gas chromatography mass spectrometry (HS/GC-MS) were used to study metabolites produced by Lactococcus lactis subsp. cremoris MG1363 grown at a temperature of 30 °C with and without agitation at 150 rpm, and at 37 °C without agitation. It was observed that L. lactis produced more organic acids under agitation. Primary alcohols, aldehydes, ketones and polyols were identified as the corresponding trimethylsilyl (TMS) derivatives, whereas amino acids and organic acids, including fatty acids, were detected through methyl chloroformate derivatization. HS analysis indicated that branched-chain methyl aldehydes, including 2-methylbutanal, 3-methylbutanal, and 2-methylpropanal are degdradation products of isoleucine, leucine or valine. Multivariate analysis (MVA) using partial least squares discriminant analysis (PLS-DA) revealed the major differences between treatments were due to changes of amino acids and fermentation products.
    Matched MeSH terms: Metabolome/drug effects*
  9. Metabolomics in Systems Biology
    Baharum SN, Azizan KA
    Adv Exp Med Biol, 2018 11 2;1102:51-68.
    PMID: 30382568 DOI: 10.1007/978-3-319-98758-3_4
    Over the last decade, metabolomics has continued to grow rapidly and is considered a dynamic technology in envisaging and elucidating complex phenotypes in systems biology area. The advantage of metabolomics compared to other omics technologies such as transcriptomics and proteomics is that these later omics only consider the intermediate steps in the central dogma pathway (mRNA and protein expression). Meanwhile, metabolomics reveals the downstream products of gene and expression of proteins. The most frequently used tools are nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). Some of the common MS-based analyses are gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). These high-throughput instruments play an extremely crucial role in discovery metabolomics to generate data needed for further analysis. In this chapter, the concept of metabolomics in the context of systems biology is discussed and provides examples of its application in human disease studies, plant responses towards stress and abiotic resistance and also microbial metabolomics for biotechnology applications. Lastly, a few case studies of metabolomics analysis are also presented, for example, investigation of an aromatic herbal plant, Persicaria minor metabolome and microbial metabolomics for metabolic engineering applications.
    Matched MeSH terms: Metabolome
  10. The differential metabolite profiles of acute lymphoblastic leukaemic patients treated with 6-mercaptopurine using untargeted metabolomics approach
    Bannur Z, Teh LK, Hennesy T, Rosli WR, Mohamad N, Nasir A, et al.
    Clin Biochem, 2014 Apr;47(6):427-31.
    PMID: 24582698 DOI: 10.1016/j.clinbiochem.2014.02.013
    Acute lymphoblastic leukaemia (ALL) has posed challenges to the clinician due to variable patients' responses and late diagnosis. With the advance in metabolomics, early detection and personalised treatment are possible.
    Matched MeSH terms: Metabolomics/methods*; Metabolome*
  11. Pharmacometabonomics Technique to Identify Warfarin Response Using Nuclear Magnetic Resonance Spectroscopy
    Bawadikji AA, Teh CH, Kader MABSA, Sulaiman SAS, Ibrahim B
    Curr Pharm Biotechnol, 2017;18(9):740-747.
    PMID: 29110602 DOI: 10.2174/1389201018666171103141828
    BACKGROUND: Warfarin, an anticoagulant medication, is prescribed regularly despite of its bleeding tendency for the prevention and/or treatment of various thromboembolic conditions, such as deep vein thrombosis, and complications associated with atrial fibrillation, and myocardial infarction, but because of its narrow therapeutic window, it has a lot of interactions with drugs and diet.

    METHODS: Warfarin relies on regular monitoring of International Normalized Ratio which is a standardized test to measure prothrombin time and appropriate dose adjustment. Pharmacometabonomics is a novel scientific field which deals with identification and quantification of the metabolites present in the metabolome using spectroscopic techniques such as Nuclear Magnetic Resonance (NMR). Pharmacometabonomics helps to indicate perturbation in the levels of metabolites in the cells and tissues due to drug or ingestion of any substance. NMR is one of the most widely-used spectroscopic techniques in metabolomics because of its reproducibility and speed.

    RESULTS: There are many factors that influence the metabolism of warfarin, making changes in drug dosage common, and clinical factors like drug-drug interactions, dietary interactions and age explain for the most part the variability in warfarin dosing. Some studies have showed that pharmacogenetic testing for warfarin dosing does not improve health outcomes, and around 26% of the variation in warfarin dose requirements remains unexplained yet.

    CONCLUSION: Many recent pharmacometabonomics studies have been conducted to identify novel biomarkers of drug therapies such as paracetamol, aspirin and simvastatin. Thus, a technique such as NMR based pharmacometabonomics to find novel biomarkers in plasma and urine might be useful to predict warfarin outcome.

    Matched MeSH terms: Metabolome/drug effects; Metabolome/genetics
  12. Fulltext Blood Metabolic Signatures of Body Mass Index: A Targeted Metabolomics Study in the EPIC Cohort
    Carayol M, Leitzmann MF, Ferrari P, Zamora-Ros R, Achaintre D, Stepien M, et al.
    J Proteome Res, 2017 Sep 01;16(9):3137-3146.
    PMID: 28758405 DOI: 10.1021/acs.jproteome.6b01062
    Metabolomics is now widely used to characterize metabolic phenotypes associated with lifestyle risk factors such as obesity. The objective of the present study was to explore the associations of body mass index (BMI) with 145 metabolites measured in blood samples in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolites were measured in blood from 392 men from the Oxford (UK) cohort (EPIC-Oxford) and in 327 control subjects who were part of a nested case-control study on hepatobiliary carcinomas (EPIC-Hepatobiliary). Measured metabolites included amino acids, acylcarnitines, hexoses, biogenic amines, phosphatidylcholines, and sphingomyelins. Linear regression models controlled for potential confounders and multiple testing were run to evaluate the associations of metabolite concentrations with BMI. 40 and 45 individual metabolites showed significant differences according to BMI variations, in the EPIC-Oxford and EPIC-Hepatobiliary subcohorts, respectively. Twenty two individual metabolites (kynurenine, one sphingomyelin, glutamate and 19 phosphatidylcholines) were associated with BMI in both subcohorts. The present findings provide additional knowledge on blood metabolic signatures of BMI in European adults, which may help identify mechanisms mediating the relationship of BMI with obesity-related diseases.
    Matched MeSH terms: Metabolome*
  13. Fulltext Physical fitness in community-dwelling older adults is linked to dietary intake, gut microbiota, and metabolomic signatures
    Castro-Mejía JL, Khakimov B, Krych Ł, Bülow J, Bechshøft RL, Højfeldt G, et al.
    Aging Cell, 2020 03;19(3):e13105.
    PMID: 31967716 DOI: 10.1111/acel.13105
    When humans age, changes in body composition arise along with lifestyle-associated disorders influencing fitness and physical decline. Here we provide a comprehensive view of dietary intake, physical activity, gut microbiota (GM), and host metabolome in relation to physical fitness of 207 community-dwelling subjects aged +65 years. Stratification on anthropometric/body composition/physical performance measurements (ABPm) variables identified two phenotypes (high/low-fitness) clearly linked to dietary intake, physical activity, GM, and host metabolome patterns. Strikingly, despite a higher energy intake high-fitness subjects were characterized by leaner bodies and lower fasting proinsulin-C-peptide/blood glucose levels in a mechanism likely driven by higher dietary fiber intake, physical activity and increased abundance of Bifidobacteriales and Clostridiales species in GM and associated metabolites (i.e., enterolactone). These factors explained 50.1% of the individual variation in physical fitness. We propose that targeting dietary strategies for modulation of GM and host metabolome interactions may allow establishing therapeutic approaches to delay and possibly revert comorbidities of aging.
    Matched MeSH terms: Metabolomics/methods; Metabolome*
  14. Fulltext Variable carbon catabolism among Salmonella enterica serovar Typhi isolates
    Chai LC, Kong BH, Elemfareji OI, Thong KL
    PLoS One, 2012;7(5):e36201.
    PMID: 22662115 DOI: 10.1371/journal.pone.0036201
    Salmonella enterica serovar Typhi (S. Typhi) is strictly a human intracellular pathogen. It causes acute systemic (typhoid fever) and chronic infections that result in long-term asymptomatic human carriage. S. Typhi displays diverse disease manifestations in human infection and exhibits high clonality. The principal factors underlying the unique lifestyle of S. Typhi in its human host during acute and chronic infections remain largely unknown and are therefore the main objective of this study.
    Matched MeSH terms: Metabolome
  15. Fulltext Metabolite Characterization and Correlations with Antioxidant and Wound Healing Properties of Oil Palm (Elaeis guineensis Jacq.) Leaflets via 1H-NMR-Based Metabolomics Approach
    Che Zain MS, Lee SY, Nasir NM, Fakurazi S, Shaari K
    Molecules, 2020 Nov 30;25(23).
    PMID: 33265992 DOI: 10.3390/molecules25235636
    Oil palm (Elaeis guineensis Jacq.) leaflets (OPLs) are one of the major agricultural by-products generated from the massive cultivation of Malaysian palm oil. This biomass is also reported to be of potential value based on its health-improving effects. By employing proton nuclear magnetic resonance (1H-NMR) spectroscopy combined with multivariate data analysis (MVDA), the metabolite profile of OPLs was characterized and correlated with their antioxidant and wound healing properties. Principal component analysis (PCA) classified four varieties of extracts, prepared using solvents ranging from polar to medium polarity, into three distinct clusters. Cumulatively, six flavonoids, eight organic acids, four carbohydrates, and an amine were identified from the solvent extracts. The more polar extracts, such as, the ethyl acetate-methanol, absolute methanol, and methanol-water, were richer in phytochemicals. Based on partial least square (PLS) analysis, the constituents in these extracts, such as (+)-catechin, (-)-epicatechin, orientin, isoorientin, vitexin, and isovitexin, were strongly correlated with the measured antioxidant activities, comprising ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and nitric oxide (NO) free radical scavenging activities, as well as with cell proliferation and migration activities. This study has provided crucial evidence on the importance of these natural antioxidant compounds on the wound healing properties of OPL.
    Matched MeSH terms: Metabolome/drug effects*
  16. Wheat mitochondrial respiration shifts from the tricarboxylic acid cycle to the GABA shunt under salt stress
    Che-Othman MH, Jacoby RP, Millar AH, Taylor NL
    New Phytol, 2020 02;225(3):1166-1180.
    PMID: 30688365 DOI: 10.1111/nph.15713
    Mitochondrial respiration and tricarboxylic acid (TCA) cycle activity are required during salt stress in plants to provide ATP and reductants for adaptive processes such as ion exclusion, compatible solute synthesis and reactive oxygen species (ROS) detoxification. However, there is a poor mechanistic understanding of how salinity affects mitochondrial metabolism, particularly respiratory substrate source. To determine the mechanism of respiratory changes under salt stress in wheat leaves, we conducted an integrated analysis of metabolite content, respiratory rate and targeted protein abundance measurements. Also, we investigated the direct effect of salt on mitochondrial enzyme activities. Salt-treated wheat leaves exhibit higher respiration rate and extensive metabolite changes. The activity of the TCA cycle enzymes pyruvate dehydrogenase complex and the 2-oxoglutarate dehydrogenase complex were shown to be directly salt-sensitive. Multiple lines of evidence showed that the γ-aminobutyric acid (GABA) shunt was activated under salt treatment. During salt exposure, key metabolic enzymes required for the cyclic operation of the TCA cycle are physiochemically inhibited by salt. This inhibition is overcome by increased GABA shunt activity, which provides an alternative carbon source for mitochondria that bypasses salt-sensitive enzymes, to facilitate the increased respiration of wheat leaves.
    Matched MeSH terms: Metabolome/drug effects
  17. Fulltext Different altered stage correlative expression of high abundance acute-phase proteins in sera of patients with epithelial ovarian carcinoma
    Chen Y, Lim BK, Hashim OH
    J Hematol Oncol, 2009;2:37.
    PMID: 19709441 DOI: 10.1186/1756-8722-2-37
    The general enhanced expression of alpha1-antichymotrypsin (ACT), clusterin (CLU), alpha1-antitrypsin (AAT), haptoglobin beta-chain (HAP), and leucine rich glycoprotein (LRG) in the sera of patients with epithelial ovarian carcinoma (EOCa) was recently reported. In the present study, we compared the expression of the serum acute-phase proteins (APPs) in the patients according to their stages of cancer.
    Matched MeSH terms: Metabolome
  18. Untargeted MS-based small metabolite identification from the plant leaves and stems of Impatiens balsamina
    Chua LS
    Plant Physiol Biochem, 2016 Sep;106:16-22.
    PMID: 27135814 DOI: 10.1016/j.plaphy.2016.04.040
    The identification of plant metabolites is very important for the understanding of plant physiology including plant growth, development and defense mechanism, particularly for herbal medicinal plants. The metabolite profile could possibly be used for future drug discovery since the pharmacological activities of the indigenous herbs have been proven for centuries. An untargeted mass spectrometric approach was used to identify metabolites from the leaves and stems of Impatiens balsamina using LC-DAD-MS/MS. The putative compounds are mostly from the groups of phenolic, organic and amino acids which are essential for plant growth and as intermediates for other compounds. Alanine appeared to be the main amino acid in the plant because many alanine derived metabolites were detected. There are also several secondary metabolites from the groups of benzopyrones, benzofuranones, naphthoquinones, alkaloids and flavonoids. The widely reported bioactive components such as kaempferol, quercetin and their glycosylated, lawsone and its derivatives were detected in this study. The results also revealed that aqueous methanol could extract flavonoids better than water, and mostly, flavonoids were detected from the leaf samples. The score plots of component analysis show that there is a minor variance in the metabolite profiles of water and aqueous methanolic extracts with 21.5 and 30.5% of the total variance for the first principal component at the positive and negative ion modes, respectively.
    Matched MeSH terms: Metabolome*
  19. Fulltext Heat stress modifies the lactational performances and the urinary metabolomic profile related to gastrointestinal microbiota of dairy goats
    Contreras-Jodar A, Nayan NH, Hamzaoui S, Caja G, Salama AAK
    PLoS One, 2019;14(2):e0202457.
    PMID: 30735497 DOI: 10.1371/journal.pone.0202457
    The aim of the study is to identify the candidate biomarkers of heat stress (HS) in the urine of lactating dairy goats through the application of proton Nuclear Magnetic Resonance (1H NMR)-based metabolomic analysis. Dairy does (n = 16) in mid-lactation were submitted to thermal neutral (TN; indoors; 15 to 20°C; 40 to 45% humidity) or HS (climatic chamber; 37°C day, 30°C night; 40% humidity) conditions according to a crossover design (2 periods of 21 days). Thermophysiological traits and lactational performances were recorded and milk composition analyzed during each period. Urine samples were collected at day 15 of each period for 1H NMR spectroscopy analysis. Principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA) assessment with cross validation were used to identify the goat urinary metabolome from the Human Metabolome Data Base. HS increased rectal temperature (1.2°C), respiratory rate (3.5-fold) and water intake (74%), but decreased feed intake (35%) and body weight (5%) of the lactating does. No differences were detected in milk yield, but HS decreased the milk contents of fat (9%), protein (16%) and lactose (5%). Metabolomics allowed separating TN and HS urinary clusters by PLS-DA. Most discriminating metabolites were hippurate and other phenylalanine (Phe) derivative compounds, which increased in HS vs. TN does. The greater excretion of these gut-derived toxic compounds indicated that HS induced a harmful gastrointestinal microbiota overgrowth, which should have sequestered aromatic amino acids for their metabolism and decreased the synthesis of neurotransmitters and thyroid hormones, with a negative impact on milk yield and composition. In conclusion, HS markedly changed the thermophysiological traits and lactational performances of dairy goats, which were translated into their urinary metabolomic profile through the presence of gut-derived toxic compounds. Hippurate and other Phe-derivative compounds are suggested as urinary biomarkers to detect heat-stressed dairy animals in practice.
    Matched MeSH terms: Metabolome
  20. Evaluation of metabolomics behavior of human colon cancer HT29 cell lines treated with ionic liquid graviola fruit pulp extract
    Daddiouaissa D, Amid A, Abdullah Sani MS, Elnour AAM
    J Ethnopharmacol, 2021 Apr 24;270:113813.
    PMID: 33444719 DOI: 10.1016/j.jep.2021.113813
    ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants have been used by indigenous people across the world for centuries to help individuals preserve their wellbeing and cure diseases. Annona muricata L. (Graviola) which is belonging to the Annonaceae family has been traditionally used due to its medicinal abilities including antimicrobial, anti-inflammatory, antioxidant and cancer cell growth inhibition. Graviola is claimed to be a potential antitumor due to its selective cytotoxicity against several cancer cell lines. However, the metabolic mechanism information underlying the anticancer activity remains limited.

    AIM OF THE STUDY: This study aimed to investigate the effect of ionic liquid-Graviola fruit pulp extract (IL-GPE) on the metabolomics behavior of colon cancer (HT29) by using an untargeted GC-TOFMS-based metabolic profiling.

    MATERIALS AND METHODS: Multivariate data analysis was used to determine the metabolic profiling, and the ingenuity pathway analysis (IPA) was used to predict the altered canonical pathways after treating the HT29 cells with crude IL-GPE and Taxol (positive control).

    RESULTS: The principal components analysis (PCA) identified 44 metabolites with the most reliable factor loading, and the cluster analysis (CA) separated three groups of metabolites: metabolites specific to the non-treated HT29 cells, metabolites specific to the treated HT29 cells with the crude IL-GPE and metabolites specific to Taxol treatment. Pathway analysis of metabolomic profiles revealed an alteration of many metabolic pathways, including amino acid metabolism, aerobic glycolysis, urea cycle and ketone bodies metabolism that contribute to energy metabolism and cancer cell proliferation.

    CONCLUSION: The crude IL-GPE can be one of the promising anticancer agents due to its selective inhibition of energy metabolism and cancer cell proliferation.

    Matched MeSH terms: Metabolome/drug effects*
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