Displaying publications 1 - 20 of 76 in total

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  1. Massello FL, Chan CS, Chan KG, Goh KM, Donati E, Urbieta MS
    Microorganisms, 2020 Jun 16;8(6).
    PMID: 32560103 DOI: 10.3390/microorganisms8060906
    The study of microbial communities from extreme environments is a fascinating topic. With every study, biologists and ecologists reveal interesting facts and questions that dispel the old belief that these are inhospitable environments. In this work, we assess the microbial diversity of three hot springs from Neuquén, Argentina, using high-throughput amplicon sequencing. We predicted a distinct metabolic profile in the acidic and the circumneutral samples, with the first ones being dominated by chemolithotrophs and the second ones by chemoheterotrophs. Then, we collected data of the microbial communities of hot springs around the world in an effort to comprehend the roles of pH and temperature as shaping factors. Interestingly, there was a covariation between both parameters and the phylogenetic distance between communities; however, neither of them could explain much of the microbial profile in an ordination model. Moreover, there was no correlation between alpha diversity and these parameters. Therefore, the microbial communities' profile seemed to have complex shaping factors beyond pH and temperature. Lastly, we looked for taxa associated with different environmental conditions. Several such taxa were found. For example, Hydrogenobaculum was frequently present in acidic springs, as was the Sulfolobaceae family; on the other hand, Candidatus Hydrothermae phylum was strongly associated with circumneutral conditions. Interestingly, some singularities related to sites featuring certain taxa were also observed.
    Matched MeSH terms: Metabolome
  2. Durani LW, Hamezah HS, Ibrahim NF, Yanagisawa D, Makpol S, Damanhuri HA, et al.
    Biochem Biophys Res Commun, 2017 11 25;493(3):1356-1363.
    PMID: 28970069 DOI: 10.1016/j.bbrc.2017.09.164
    We have recently shown that age-dependent regional brain atrophy and lateral ventricle expansion may be linked with impaired cognitive and locomotor functions. However, metabolic profile transformation in different brain regions during aging is unknown. This study examined metabolic changes in the hippocampus, medial prefrontal cortex (mPFC) and striatum of middle- and late-aged Sprague-Dawley rats using ultrahigh performance liquid chromatography coupled with high-resolution accurate mass-orbitrap tandem mass spectrometry. Thirty-eight potential metabolites were altered in hippocampus, 29 in mPFC, and 14 in striatum. These alterations indicated that regional metabolic mechanisms in lated-aged rats are related to multiple pathways including glutathione, sphingolipid, tyrosine, and purine metabolism. Thus, our findings might be useful for understanding the complexity of metabolic mechanisms in aging and provide insight for aging and health span.
    Matched MeSH terms: Metabolome
  3. Zhu W, Zhong Z, Liu S, Yang B, Komatsu S, Ge Z, et al.
    Int J Mol Sci, 2019 Jan 16;20(2).
    PMID: 30654535 DOI: 10.3390/ijms20020365
    Morus alba is an important medicinal plant that is used to treat human diseases. The leaf, branch, and root of Morus can be applied as antidiabetic, antioxidant, and anti-inflammatory medicines, respectively. To explore the molecular mechanisms underlying the various pharmacological functions within different parts of Morus, organ-specific proteomics were performed. Protein profiles of the Morus leaf, branch, and root were determined using a gel-free/label-free proteomic technique. In the Morus leaf, branch, and root, a total of 492, 414, and 355 proteins were identified, respectively, including 84 common proteins. In leaf, the main function was related to protein degradation, photosynthesis, and redox ascorbate/glutathione metabolism. In branch, the main function was related to protein synthesis/degradation, stress, and redox ascorbate/glutathione metabolism. In root, the main function was related to protein synthesis/degradation, stress, and cell wall. Additionally, organ-specific metabolites and antioxidant activities were analyzed. These results revealed that flavonoids were highly accumulated in Morus root compared with the branch and leaf. Accordingly, two root-specific proteins named chalcone flavanone isomerase and flavonoid 3,5-hydroxylase were accumulated in the flavonoid pathway. Consistent with this finding, the content of the total flavonoids was higher in root compared to those detected in branch and leaf. These results suggest that the flavonoids in Morus root might be responsible for its biological activity and the root is the main part for flavonoid biosynthesis in Morus.
    Matched MeSH terms: Metabolome
  4. Zhu W, Zheng W, Hu X, Xu X, Zhang L, Tian J
    Biochim Biophys Acta Proteins Proteom, 2017 Apr;1865(4):404-413.
    PMID: 28087425 DOI: 10.1016/j.bbapap.2017.01.004
    Lonicera japonica Thunb., also known as Jin Yin Hua and Japanese honeysuckle, is used as a herbal medicine in Asian countries. Its flowers have been used in folk medicine in the clinic and in making food or healthy beverages for over 1500years in China. To investigate the molecular processes involved in L. japonica development from buds to flowers exposed to UV radiation, a comparative proteomics analysis was performed. Fifty-four proteins were identified as differentially expressed, including 42 that had increased expression and 12 that had decreased expression. The levels of the proteins related to glycolysis, TCA/organic acid transformation, major carbohydrate metabolism, oxidative pentose phosphate, stress, secondary metabolism, hormone, and mitochondrial electron transport were increased during flower opening process after exposure to UV radiation. Six metabolites in L. japonica buds and flowers were identified and relatively quantified using LC-MS/MS. The antioxidant activity was performed using a 1,1-diphenyl-2-picrylhydrazyl assay, which revealed that L. japonica buds had more activity than the UV irradiated flowers. This suggests that UV-B radiation induces production of endogenous ethylene in L. japonica buds, thus facilitating blossoming of the buds and activating the antioxidant system. Additionally, the higher metabolite contents and antioxidant properties of L. japonica buds indicate that the L. japonica bud stage may be a more optimal time to harvest than the flower stage when using for medicinal properties.
    Matched MeSH terms: Metabolome/radiation effects*
  5. 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
  6. Tan SC, Chong CW, Yap IKS, Thong KL, Teh CSJ
    Sci Rep, 2020 Jun 02;10(1):8997.
    PMID: 32488118 DOI: 10.1038/s41598-020-65891-4
    The gastrointestinal tract of humans and swine consist of a wide range of bacteria which interact with hosts metabolism. Due to the differences in co-evolution and co-adaptation, a large fraction of the gut microbiome is host-specific. In this study, we evaluated the effect of close human-animal interaction to the faecal metagenome and metabonome of swine, farmer and human control. Three distinct clusters were observed based on T-RFLP-derived faecal microbial composition. However, 16S-inferred faecal microbiota and metabolic profiles showed that only human control was significantly different from the swine (P 
    Matched MeSH terms: Metabolome/physiology*
  7. 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
  8. Wang S, Liu F, Tan KS, Ser HL, Tan LT, Lee LH, et al.
    J Cell Mol Med, 2020 01;24(1):722-736.
    PMID: 31680470 DOI: 10.1111/jcmm.14780
    Evidence demonstrates that M1 macrophage polarization promotes inflammatory disease. Here, we discovered that (R)-salbutamol, a β2 receptor agonist, inhibits and reprograms the cellular metabolism of RAW264.7 macrophages. (R)-salbutamol significantly inhibited LPS-induced M1 macrophage polarization and downregulated expressions of typical M1 macrophage cytokines, including monocyte chemotactic protein-1 (MCP-1), interleukin-1β (IL-1β) and tumour necrosis factor α (TNF-α). Also, (R)-salbutamol significantly decreased the production of inducible nitric oxide synthase (iNOS), nitric oxide (NO) and reactive oxygen species (ROS), while increasing the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. In contrast, (S)-salbutamol increased the production of NO and ROS. Bioenergetic profiles showed that (R)-salbutamol significantly reduced aerobic glycolysis and enhanced mitochondrial respiration. Untargeted metabolomics analysis demonstrated that (R)-salbutamol modulated metabolic pathways, of which three metabolic pathways, namely, (a) phenylalanine metabolism, (b) the pentose phosphate pathway and (c) glycerophospholipid metabolism were the most noticeably impacted pathways. The effects of (R)-salbutamol on M1 polarization were inhibited by a specific β2 receptor antagonist, ICI-118551. These findings demonstrated that (R)-salbutamol inhibits the M1 phenotype by downregulating aerobic glycolysis and glycerophospholipid metabolism, which may propose (R)-salbutamol as the major pharmacologically active component of racemic salbutamol for the treatment of inflammatory diseases and highlight the medicinal value of (R)-salbutamol.
    Matched MeSH terms: Metabolome/drug effects*
  9. Daphne Teh AL, Jayapalan JJ, Loke MF, Wan Abdul Kadir AJ, Subrayan V
    Exp Eye Res, 2021 10;211:108734.
    PMID: 34428458 DOI: 10.1016/j.exer.2021.108734
    This study aimed to investigate the metabolite differences between patients with keratoconus and control subjects and identify potential serum biomarkers for keratoconus using a non-targeted metabolomics approach. Venous blood samples were obtained from patients with keratoconus (n = 20) as well as from age-, gender- and race-matched control subjects (n = 20). Metabolites extracted from serum were separated and analyzed by liquid chromatography/quadrupole time-of-flight mass spectrometer. Processing of raw data and analysis of the data files was performed using Agilent Mass Hunter Qualitative software. The identified metabolites were subjected to a principal component and hierarchical cluster analysis. Appropriate statistical tests were used to analyze the metabolomic profiling data. Together, the analysis revealed that the dehydroepiandrosterone sulfate from the steroidal hormone synthesis pathway was significantly upregulated in patients with keratoconus (p 
    Matched MeSH terms: Metabolome/physiology
  10. Loy, S.L., Hamid Jan, J.M., Sirajudeen, K.N.S.
    Malays J Nutr, 2013;19(3):383-399.
    MyJurnal
    Critical time windows exert profound influences on foetal physiological and metabolic profiles, which predispose an individual to later diseases via a 'programming' effect. Obesity has been suggested to be 'programmed' during early life. Foetuses and infants who experience adverse growth are subjected to a higher risk of obesity. However, the key factors that link adverse foetal growth and obesity risk remain obscure. To date, there is considerable evidence showing that the overall balance between free radical damage and the anti.oxidative process being challenged occurs throughout gestation. With the view that pregnancy is a pro-inflammatory state confronted with enhanced oxidative stress, which possesses similar characteristics to obesity (a chronic inflammatory state with increased oxidative stress), oxidative stress is thus biologically plausibly be proposed as the underlying mechanism between this causal-disease relationship. Oxidative stress could act as a programming cue for the development of obesity by inducing complex functional and metabolic deregulations as well as inducing the alteration of the adipogenesis process. Thereby, oxidative stress promotes adipose tissue deposition from early life onwards. The enhancement of fat accumulation further exaggerates oxidative derangement and perpetuates the cycle of adiposity. This review focuses on the oxidative stress pathways in prenatal and early postnatal stages, from the aspects of various endogenous and exogenous oxidative insults. Because oxidative stress is a modifiable pathway, this modifiability suggests a potential therapeutic target to fight the obesity epidemic by understanding the causal factors of oxidant induction.
    Matched MeSH terms: Metabolome
  11. Noorhisham Tan Kofli, Nagahisa K, Shioya S, Shimizu H
    Sains Malaysiana, 2006;35:9-15.
    During fermentation cells are subjected to various kinds of stress. One of the stresses concerned is high osmotic environment, which cells need to encounter in order to continue growing. To understand how cells adapt to this stress condition, information from genome, proteome and metabolome levels are crucial. In yeast cells, it was report that they produce glycerol to avoid depletion of water in the cell that could lead to cell shrinkage and eventually death. Thus, investigation of physiological responses were executed by shake flask method using three different Saccharomyces cerevisiae strains namely s288c, IFO2347 and FY834 which were grown in yeast potato dextrose (YPD) medium under the treatment of sodium chloride (NaCl) and sorbitol at 1M concentration to create the osmotic condition. These agents were added into the medium after 5 hours of fermentation when the cells reached exponential phase and carbon source is still available. The results proved that addition of both NaCl and sorbitol created the osmotic condition during growth resulted in higher accumulation of glycerol and trehalose when compared to the control in all strains. Among these strains, production of glycerol (g glycerol/g cell dry weight) was found highest in IFO2347, followed by s288c and FY834.
    Matched MeSH terms: Metabolome
  12. Goon DE, Ab-Rahim S, Mohd Sakri AH, Mazlan M, Tan JK, Abdul Aziz M, et al.
    Sci Rep, 2021 10 25;11(1):21001.
    PMID: 34697380 DOI: 10.1038/s41598-021-00454-9
    Excessive high fat dietary intake promotes risk of developing non-alcoholic fatty liver disease (NAFLD) and predisposed with oxidative stress. Palm based tocotrienol-rich fraction (TRF) has been reported able to ameliorate oxidative stress but exhibited poor bioavailability. Thus, we investigated whether an enhanced formulation of TRF in combination with palm kernel oil (medium-chain triglycerides) (ETRF) could ameliorate the effect of high-fat diet (HFD) on leptin-deficient male mice. All the animals were divided into HFD only (HFD group), HFD supplemented with ETRF (ETRF group) and HFD supplemented with TRF (TRF group) and HFD supplemented with PKO (PKO group). After 6 weeks, sera were collected for untargeted metabolite profiling using UHPLC-Orbitrap MS. Univariate analysis unveiled alternation in metabolites for bile acids, amino acids, fatty acids, sphingolipids, and alkaloids. Bile acids, lysine, arachidonic acid, and sphingolipids were downregulated while xanthine and hypoxanthine were upregulated in TRF and ETRF group. The regulation of these metabolites suggests that ETRF may promote better fatty acid oxidation, reduce oxidative stress and pro-inflammatory metabolites and acts as anti-inflammatory in fatty liver compared to TRF. Metabolites regulated by ETRF also provide insight of its role in fatty liver. However, further investigation is warranted to identify the mechanisms involved.
    Matched MeSH terms: Metabolome*
  13. 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*
  14. Saeed OA, Sazili AQ, Akit H, Alimon AR, Samsudin AA
    Animals (Basel), 2019 Oct 11;9(10).
    PMID: 31614434 DOI: 10.3390/ani9100781
    Twenty-seven Dorper lambs were used to determine the effect of supplementing corn as a source of energy into the palm kernel cake (PKC) urea-treated rice straw basal diet on the blood metabolic profile and metals in lambs. The lambs were randomly allotted to three experimental treatments according to their initial body weight for a 120 day trial. Dietary treatments were: T1 (control diet) = 75.3% of PKC + 0% corn, T2 = 70.3% of PKC + 5% corn, and T3 = 65.3% of PKC + 10% corn. The results of this study indicated that copper (Cu), selenium (Se), zinc (Zn), and iron (Fe) concentration intake, retention, and its absorption from the gut and apparent mineral digestibility were highly significant for the levels of corn supplementation. The biochemical and hematological parameters remained within normal levels with the treatments, but the white blood cell, eosinophil count, cholesterol, and low-density lipoprotein cholesterol (LDL) were significantly higher in T3. Treatment 3 significantly increased the concentration of Se and Fe, while Zn was reduced in the blood serum of lambs on day 120. The result shows that the inclusion of corn has no effect on the hematological and biochemical parameters of lambs after incorporating corn into the PKC-based diet at 5% and 10%.
    Matched MeSH terms: Metabolome
  15. 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*
  16. 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
  17. Sari E, Mahira KF, Patel DN, Chua LS, Pratami DK, Sahlan M
    Heliyon, 2021 May;7(5):e06912.
    PMID: 34013079 DOI: 10.1016/j.heliyon.2021.e06912
    Royal jellies (RJs) possess moisturizing, emulsifying, and stabilizing properties, and several pharmacological activities have also been found to be present, which make them an ideal component for cosmetic and skin care products. However, despite the abundant efficacies, there is a lack of studies that explore the chemical composition of RJ using metabolome analysis. Furthermore, an evaluation of the chemical composition of Indonesian RJs collected from different regions has yet to be carried out. Therefore, the main objective of this study was to identify any differences in the chemical composition of such RJs. Chemical profiling was also carried out to enable more targeted utilization based on the actual compositions. Chemical profiling is also important given the rich Indonesian biodiversity and the high dependence of the RJ compositions on the botanical source. In this research, ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used as part of an untargeted metabolomics approach. From the chemical profiling, >30 compounds were identified across four RJ samples. The major constituents of the samples were found to be oligosaccharides, fatty acids, and adenosine monophosphate derivatives. Meanwhile, sucrose and planteose were found to be highest in the samples from Banjarnegara and Kediri, whereas dimethyloctanoic acid was found to be unique to the sample from Banjarnegara. It was also discovered that the RJs from Demak and Tuban contained more organic fatty acids and oligosaccharides than the other samples. Although the sample from Demak demonstrated good potential for use in the cosmetic, skin care, and bio-supplement industries, the higher abundance of fatty acids and oligosaccharides in the sample from Tuban indicated that it is perhaps the most suitable RJ for use in this field.
    Matched MeSH terms: Metabolome
  18. 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*
  19. Ibrahim MH, Jaafar HZ, Rahmat A, Rahman ZA
    Int J Mol Sci, 2011;12(8):5238-54.
    PMID: 21954355 DOI: 10.3390/ijms12085238
    A split plot 3 by 4 experiment was designed to examine the impact of 15-week variable levels of nitrogen fertilization (0, 90, 180 and 270 kg N/ha) on the characteristics of total flavonoids (TF), total phenolics (TP), total non structurable carbohydrate (TNC), net assimilation rate, leaf chlorophyll content, carbon to nitrogen ratio (C/N), phenyl alanine lyase activity (PAL) and protein content, and their relationships, in three varieties of Labisia pumila Blume (alata, pumila and lanceolata). The treatment effects were solely contributed by nitrogen application; there was neither varietal nor interaction effect observed. As nitrogen levels increased from 0 to 270 kg N/ha, the production of TNC was found to decrease steadily. Production of TF and TP reached their peaks under 0 followed by 90, 180 and 270 kg N/ha treatment. However, net assimilation rate was enhanced as nitrogen fertilization increased from 0 to 270 kg N/ha. The increase in production of TP and TF under low nitrogen levels (0 and 90 kg N/ha) was found to be correlated with enhanced PAL activity. The enhancement in PAL activity was followed by reduction in production of soluble protein under low nitrogen fertilization indicating more availability of amino acid phenyl alanine (phe) under low nitrogen content that stimulate the production of carbon based secondary metabolites (CBSM). The latter was manifested by high C/N ratio in L. pumila plants.
    Matched MeSH terms: Metabolomics*; Metabolome*
  20. Kandasamy M, Mak KK, Devadoss T, Thanikachalam PV, Sakirolla R, Choudhury H, et al.
    BMC Chem, 2019 Dec;13(1):117.
    PMID: 31572984 DOI: 10.1186/s13065-019-0633-4
    Background: The transcription factor Nuclear factor erythroid-2-related factor 2 (NRF2) and its principal repressive regulator, Kelch-like ECH-associated protein 1 (KEAP1), are perilous in the regulation of inflammation, as well as maintenance of homeostasis. Thus, NRF2 activation is involved in cytoprotection against many inflammatory disorders. N'-Nicotinoylquinoxaline-2-carbohdyrazide (NQC) was structurally designed by the combination of important pharmacophoric features of bioactive compounds reported in the literature.

    Methods: NQC was synthesised and characterised using spectroscopic techniques. The compound was tested for its anti-inflammatory effect using Lipopolysaccharide from Escherichia coli (LPSEc) induced inflammation in mouse macrophages (RAW 264.7 cells). The effect of NQC on inflammatory cytokines was measured using enzyme-linked immune sorbent assay (ELISA). The Nrf2 activity of the compound NQC was determined using 'Keap1:Nrf2 Inhibitor Screening Assay Kit'. To obtain the insights on NQC's activity on Nrf2, molecular docking studies were performed using Schrödinger suite. The metabolic stability of NQC was determined using mouse, rat and human microsomes.

    Results: NQC was found to be non-toxic at the dose of 50 µM on RAW 264.7 cells. NQC showed potent anti-inflammatory effect in an in vitro model of LPSEc stimulated murine macrophages (RAW 264.7 cells) with an IC50 value 26.13 ± 1.17 µM. NQC dose-dependently down-regulated the pro-inflammatory cytokines [interleukin (IL)-1β (13.27 ± 2.37 μM), IL-6 (10.13 ± 0.58 μM) and tumor necrosis factor (TNF)-α] (14.41 ± 1.83 μM); and inflammatory mediator, prostaglandin E2 (PGE2) with IC50 values, 15.23 ± 0.91 µM. Molecular docking studies confirmed the favourable binding of NQC at Kelch domain of Keap-1. It disrupts the Nrf2 interaction with kelch domain of keap 1 and its IC50 value was 4.21 ± 0.89 µM. The metabolic stability studies of NQC in human, rat and mouse liver microsomes revealed that it is quite stable with half-life values; 63.30 ± 1.73, 52.23 ± 0.81, 24.55 ± 1.13 min; microsomal intrinsic clearance values; 1.14 ± 0.31, 1.39 ± 0.87 and 2.96 ± 0.34 µL/min/g liver; respectively. It is observed that rat has comparable metabolic profile with human, thus, rat could be used as an in vivo model for prediction of pharmacokinetics and metabolism profiles of NQC in human.

    Conclusion: NQC is a new class of NRF2 activator with potent in vitro anti-inflammatory activity and good metabolic stability.

    Matched MeSH terms: Metabolome
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