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BACKGROUND: The present study focuses on the aroma and secondary metabolites profiling of three Pelargonium graveolens cultivars, baladi (GRB), sondos (GRS) and shish (GRSH), grown in Egypt. Utilizing a multiplex approach combining high resolution‐ultraperformance liquid chromatography (HR‐UPLC)/tandem mass spectrometry (MS/MS) and gas chromatography (GC)‐MS coupled with chemometrics, the study aims to identify and profile various secondary metabolites and aroma compounds in these cultivars. RESULTS: HR‐UPLC/MS/MS analysis led to the annotation of 111 secondary metabolites, including phenolics, flavonoids, terpenes and fatty acids, with several compounds being reported for the first time in geranium. Multivariate data analysis identified vinylanisole, dimethoxy‐flavonol, and eicosadienoic acid as discriminatory metabolites among the cultivars, particularly distinguishing the GRS cultivar in its phenolics profile. In total, 34 aroma compounds were detected using headspace solid‐phase microextraction coupled with GC‐MS, including alcohols, esters, ketones, ethers and monoterpene hydrocarbons. The major metabolites contributing to aroma discrimination among the cultivars were β‐citronellol in GRB, α‐farnesene in GRS and isomenthone in GRSH. CONCLUSION: The study provides a comprehensive profiling of the secondary metabolites and aroma compounds in the three Pelargonium graveolens cultivars. The GRS cultivar was identified as particularly distinct in both its phenolics and aroma profiles, suggesting its potential as a premium variety for cultivation and use. Future studies should focus on isolating and investigating the newly detected metabolites and exploring the biological effects of these compounds in food applications and other uses. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

A novel and simple strategy was proposed for the screening of secondary metabolites in Ginkgo biloba leaves. The information dependent acquisition (IDA) mass spectrometry mode was introduced for ginkgolides and flavonoids detection innovatively. The strategy consists of a one-step extraction and a simple ultra-performance liquid chromatography (UPLC) tandem with an IDA mode mass spectrometry (UPLC-(IDA)MS) process. The specificity of the target compounds was achieved with the retention difference, combining high resolution of MS1 as well as MS2 results. The extraction efficiency of three extractants was compared. With only one extraction step, secondary metabolites in Ginkgo biloba leaves, including four ginkgolides, six flavonoids, and four biflavonoids, were identified. The co-elution of ginkgolide A and ginkgolide B as well as bilobalide and ginkgolide C was eliminated with the optimized UPLC program. A quantification algorithm was proposed for ginkgolides. The strategy was applied to monitor the evolution of secondary metabolites in the extract solution successfully. The developed strategy is a powerful tool to facilitate the screening of secondary metabolites in Ginkgo biloba leaves and its related products. [ABSTRACT FROM AUTHOR]

This study utilized a colorimeter to determine the color values of 23 beauty tea (BT) samples, the color and the taste characteristics were also quantitatively described through ultraviolet–visible (UV–Vis) spectroscopy and taste equivalent quantification. Furthermore, metabolomic analysis was conducted by using ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS). Correlation analysis was employed to preliminarily identify the compounds that contribute to the color and taste of BT infusion. Finally, the contributing compounds were further determined through verification experiment. The results showed that within a certain range, as the color of BT infusion deepened, the taste became stronger, more bitter and astringent, while on the contrary, it became sweeter and mellower. Theaflavins, kaempferol, astragalin, and 5-p-coumaroylquinic acid influenced both the color and taste of the BT infusion. Gallic acid was also determined as a contributor to the color. This study provides new insights into research on tea quality in infusion color and taste aspects.

Choline and related metabolites are key factors in many metabolic processes, and insufficient supply can adversely affect reproduction and fetal development. Choline status is mainly regulated by intake, and human milk is the only choline source for exclusively breastfed infants. Further, maternal status, genotype, and phenotype, as well as infant outcomes, have been related to milk choline concentrations. In order to enable the rapid assessment of choline intake for exclusively breastfed infants and to further investigate the associations between milk choline and maternal and infant status and other outcomes, we have developed a simplified method for the simultaneous analysis of human milk choline, glycerophosphocholine, phosphocholine, and the less abundant related metabolites betaine, carnitine, creatinine, dimethylglycine (DMG), methionine, and trimethylamine N-oxide (TMAO) using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). These analytes have milk concentrations ranging over 3 orders of magnitude. Unlike other recently described LC-based methods, our approach does not require an ion-pairing reagent or high concentrations of solvent modifiers for successful analyte separation and thus avoid signal loss and potential permanent contamination. Milk samples (10 μl) were diluted (1:80) in water : methanol (1:4, v:v) and filtered prior to analysis with an optimized gradient of 0.1% propionic acidaq and acetonitrile, allowing efficient separation and removal of contaminants. Recovery rates ranged from 108.0 to 130.9% (inter-day variation: 3.3-9.6%), and matrix effects (MEs) from 54.1 to 114.3%. MEs were greater for carnitine, creatinine, and TMAO at lower dilution (1:40, p < 0.035 for all), indicating concentration-dependent ion suppression. Milk from Brazilian women (2-8, 28-50, and 88-119 days postpartum, n total = 53) revealed increasing concentration throughout lactation for glycerophosphocholine, DMG, and methionine, while carnitine decreased. Choline and phosphocholine were negatively correlated consistently at all three collection time intervals. The method is suitable for rapid analysis of human milk water-soluble forms of choline as well as previously not captured related metabolites with minimal sample volumes and preparation.

Summary: Plants are widely recognized as chemical factories, with each species producing dozens to hundreds of unique secondary metabolites. These compounds shape the interactions between plants and their natural enemies. We explore the evolutionary patterns and processes by which plants generate chemical diversity, from evolving novel compounds to unique chemical profiles.We characterized the chemical profile of one‐third of the species of tropical rainforest trees in the genus Inga (c. 100, Fabaceae) using ultraperformance liquid chromatography‐mass spectrometry‐based metabolomics and applied phylogenetic comparative methods to understand the mode of chemical evolution.We show: each Inga species contain structurally unrelated compounds and high levels of phytochemical diversity; closely related species have divergent chemical profiles, with individual compounds, compound classes, and chemical profiles showing little‐to‐no phylogenetic signal; at the evolutionary time scale, a species' chemical profile shows a signature of divergent adaptation. At the ecological time scale, sympatric species were the most divergent, implying it is also advantageous to maintain a unique chemical profile from community members; finally, we integrate these patterns with a model for how chemical diversity evolves.Taken together, these results show that phytochemical diversity and divergence are fundamental to the ecology and evolution of plants. [ABSTRACT FROM AUTHOR]

In order to understand the characteristics and changes of metabolites in the "flowering" process of Fu brick tea, the ultra-high phase liquid chromatography-mass spectrometry (UPLC-MS) combinedmethod was used to determine the abundance of the metabolites at Day 0 d, 7 and 14. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) of the metabolite data were performed. The results showed that there were large metabolic differences in samples of Fu brick tea at different flowering stages, and a total of 1 316 signal peaks were detected.Among which, 260, 229 and 506 differential metabolites were screened out between Day 0 and Day 7, between Day 7 and Day 14, and between Day 0 and Day 14, respectively. These substances belong to classes such as alkaloids, amino acids and their derivatives, flavonoids, tea polyphenols and catechins, organic acids and their derivatives, Further investigations on the main metabolites affecting the quality and function of Fu brick tea revealed that flowering changed the composition of main metabolites such as polyphenols, catechins, flavonoids and amino acids of Fu brick teat, reduced the bitterness and astringent sensation of Fu brick tea, and promoted the formation of mellow taste and red soup color. The up-regulation of carnitine, isoquinoline, abrine, catharanthine and other alkaloids in the process of flowering enhanced the lipid-lowering, blood pressure-lowering and anti-inflammatory effects of Fu brick tea. The flowering process is the critical process for changing the metabolic profile of Fu brick tea, and plays an important role in forming the unique quality and health-care functions of Fu brick tea, which provides a basis for revealing the formationmechanismof the flavor and health-care functions of Fu brick tea. [ABSTRACT FROM AUTHOR]

Aims: To evaluate abnormal metabolites related to treatment response and prognosis of multiple myeloma (MM) patients through ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS). Methods: Forty-six symptomatic MM patients were included in this study who had a prior high level of positive monoclonal proteins before receiving targeted therapy with bortezomib-based regimens. UPLC-MS along with traditional immunofixation was performed on MM diagnostic samples and effective serum samples, and UPLC-MS was used to target valuable metabolic markers related to M protein.MM patients were segregated into pre-therapy (pre-T) and post-therapy (post-T) groups according to the response after chemotherapy. A monoclonal protein could be detected at baseline in 33 newly diagnosed MM (NDMM), 13 refractory and relapsed MM (RRMM) patients and 20 healthy controls (HC) by immunofixation. Results: Between pre-T and post-T patients, the data showed that 32, 28 and 3 different metabolites were significantly correlated with M protein in IgG, IgA and light chain-type MM, respectively. These identified metabolites were significantly enriched in arginine and proline metabolism as well as glycerophospholipid metabolism pathways. Among them, PC (19:0/22:2) was displayed to increase significantly and consistently with M protein in each subtype of MM after treatment, which obviously indicated that it was related to the treatment response of MM. Further survival analysis of metabolic markers found that aspartic acid, LysoPE (16:0), SM (d18:1/17:0), PC (18:0/24:1), PC (16:0/16:0), TG (18:1/18:1/22:5) and LysoPE (18:2) reaching a certain cutoff value may be associated with shorter progression free survival (PFS). Finally, Cox multivariate regression analysis identified three factors were independent prognostic factors of MM. Moreover, there were significantly different in PC (19:0/22:2) and in aspartic acid between MM patients and healthy people. Conclusion: This work identified significant metabolic disorders in 46 pairs off pre- and post-therapy MM patients, specifically in arginine, proline and glycerophospholipid pathways. The abnormal metabolites have the potential to serve as new biomarkers for evaluating treatment response and prognosis, as well as early monitoring of disease activity. Therefore, these systematic studies on abnormal metabolites as biomarkers for diagnosis and treatment will provide the evidence for future precise treatment of MM. [ABSTRACT FROM AUTHOR]

Blueberries are rich in anthocyanins, which are plant-specific secondary metabolites that are a good source of plant nutrients. Although anthocyanins have been investigated, there is a lack of comprehensive detailed research that includes large numbers of blueberry cultivars, and the anthocyanin compositions of some cultivars are still unknown. Consequently, we determined the anthocyanin compositions of 62 cultivars using ultra-performance liquid chromatography–mass spectrometry (UPLC–MS). In total, we identified 30 anthocyanins derived from five kinds of anthocyanidin. We also identified four glycosides having three kinds of modifications. Among the tested cultivars, 'Rubel' contained the highest anthocyanin content, at 534.158 mg/100 g fresh weight (FW), whereas 'Puru' contained the lowest anthocyanin content at 71.734 mg/100 g FW. 'Malvidin-gal' had the highest average content among all the anthocyanin monomers, at 48.95 mg/100 g FW. 'HL9' had the greatest methylation degree, at 79.39%, and 'HL2' had the greatest acetylation degree, at 25.14%. This study provides detailed anthocyanin compositions and modifications of different blueberry cultivars. These data will aid in breeding high-quality blueberry cultivars and in developing related healthy functional foods. [ABSTRACT FROM AUTHOR]

Magnoflorine (Mag) has multiple pharmacological activities for the prevention and treatment of prostatitis. However, its molecular mechanisms andpharmacological targets are not clear. In this study, the ultra-performance liquid tandem mass spectrometry-based metabolomics method was used to clarify the intervention of Mag against prostatitis and the biological mechanism. A total of 25 biomarkers associated with the prostatitis model were identified by metabolomics, and a number of metabolic pathways closely related to the model were obtained by MetPA analysis. After given Mag treatment, the results of each indicator were shown that Mag alkaloid could inhibit the development of prostatitis effectively. We found that Mag had regulative effects on potential biomarkers of prostatitis model, which can regulate them to the control group. Our results indicated that alkaloids have an effective intervention therapy for prostatitis, and five types of metabolic pathways closely related to prostatitis model were obtained, including phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, tyrosine metabolism, arginine and proline metabolism, glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism. This study has provided the basic experimental data for the development of Mag in the prevention and treatment of prostatitis. [ABSTRACT FROM AUTHOR]

Magnoflorine (Mag) has multiple pharmacological activities for the prevention and treatment of prostatitis. However, its molecular mechanisms andpharmacological targets are not clear. In this study, the ultra-performance liquid tandem mass spectrometry-based metabolomics method was used to clarify the intervention of Mag against prostatitis and the biological mechanism. A total of 25 biomarkers associated with the prostatitis model were identified by metabolomics, and a number of metabolic pathways closely related to the model were obtained by MetPA analysis. After given Mag treatment, the results of each indicator were shown that Mag alkaloid could inhibit the development of prostatitis effectively. We found that Mag had regulative effects on potential biomarkers of prostatitis model, which can regulate them to the control group. Our results indicated that alkaloids have an effective intervention therapy for prostatitis, and five types of metabolic pathways closely related to prostatitis model were obtained, including phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, tyrosine metabolism, arginine and proline metabolism, glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism. This study has provided the basic experimental data for the development of Mag in the prevention and treatment of prostatitis.

Objective The pathogenesis of IgG4-related disease (IgG4-RD) remains unclear. Metabolomic profiling of IgG4-RD patients offers an opportunity to identify novel pathophysiological targets and biomarkers. This study aims to identify potential plasma biomarkers associated with IgG4-RD. Methods Thirty newly diagnosed IgG4-RD patients, age-matched healthy controls and post-treated IgG4-RD patients were enrolled. Patients' clinical data, laboratory parameters and plasma were collected. Plasma was measured for ultraperformance liquid chromatography-tandem mass spectrometry based metabolomics and lipidomics profiling. Multivariate and univariate statistical analyses were conducted to identify potential biomarkers. The receiver operating characteristic and the correlations between biomarkers and clinical parameters were investigated. Results The plasma metabolites are altered among healthy controls, newly diagnosed IgG4-RD and post-treated IgG4-RD groups. Of the identified features, eight metabolites were significantly perturbed in the IgG4-RD group, including glyceric acid 1,3-biphosphate (1,3-BPG), uridine triphosphate (UTP), uridine diphosphate glucose (UDP-Glc) or uridine diphosphate galactose (UDP-Gal), lysophospholipids, linoleic acid derivatives and ceramides. Receiver operating characteristic analysis indicated that UTP, UDP-Glc/UDP-Gal and LysoPC (18:1) had high sensitivity and specificity in diagnosis of IgG4-RD. A Pearson correlation analysis showed that 1,3-BPG and UTP were strongly correlated with clinical parameters. Conclusion IgG4-RD patients have a unique plasma metabolomic profile compared with healthy controls. Our study suggested that metabolomic profiling may provide important insights into pathophysiology and testable biomarkers for diagnosis of IgG4-RD. [ABSTRACT FROM AUTHOR]

Gut microbiota based metabolism of choline produces trimethylamine (TMA) which is further converted to a pro-atherosclerotic metabolite, trimethylamine-N-oxide (TMAO) by flavin monooxygenase (FMO 3 ). Trigonelline from the plant Trigonella foenum-graecum has been reported for the treatment of CVD. Aim of the present study was to check the effect of trigonelline on the gut microbiota based conversion of TMA to TMAO. Trigonelline was isolated from hydroalcoholic extract of seeds of Trigonella foenum-graecum . The isolated trigonelline was characterized through TLC and UPLC-MS. Anaerobic microbe responsible for the metabolism of choline to TMA was isolated by culturing the human gut microbiota in choline enriched medium. The isolated bacteria was identified at molecular level based on PCR amplification of 1500bp of 16S rRNA gene sequence. Isolated FMO 3 was used for ex vivo conversion of TMA to TMAO. Further, we investigated the effect of trigonelline in isolated gut microbe based metabolism of choline, lipid profile and TMAO levels in mice with or without suppression of gut microbiota with antibiotics. Liquid-liquid purification and chromatographic analysis confirmed the trigonelline purity (87.26%) and which was also confirmed by mass spectroscopy with m/z 137.4 in positive ionization mode. A total of 30 anaerobic microbes responsible for TMA production were isolated and Citrobacter freundii was the superior among others for the production of TMA. In vitro culture of C. freundii in choline enriched medium supplemented with trigonelline resulted in significantly reduction TMA and followed by TMAO production. In ex vivo , a maximum of 85.3% TMAO production was reduced by trigonelline at concentration of about 300 μg/mL. Serum level of lipids and TMAO were significantly altered in choline fed animals with or without suppression of gut microbiota and this phenomenon was reversed upon the oral administration of trigonelline in a dose-dependent manner. This study demonstrates the effect of trigonelline on gut microbiota responsible for choline metabolism and this can be used as a model for evaluation of herbal drugs and its effect in gut microbiota prompted cardiovascular disorders. [ABSTRACT FROM AUTHOR]

Key message: Gibberellic acid elicited synthesis of many phenols from different classes and enhanced production of sesquiterpenoids, polyterpenoids, steroids and monoterpenoids compared to control and 6-benzylaminopurine.Abstract: Little is known about the effects of 6-benzylaminopurine (BA) and gibberellic acid (GA3) on the synthesis of secondary metabolites in species of Lamiaceae. In this study, for the first time, the profile of secondary metabolites in plantlets of Cunila menthoides was characterized, using UPLC-ESI-Qq-oaTOF-MS. Ninety metabolites were identified, including polyphenols and terpenes. BA down-regulated most of the identified molecules in relation to GA3 and MS0 (control). The results showed that GA3 elicited synthesis of many phenols from different classes, and seemed to play a major role in the shikimate pathway in relation to BA. GA3 enhanced production of sesquiterpenoids, polyterpenoids, steroids and monoterpenoids compared to MS0 and BA, and also seemed to positively influence the MEP/DOXP and MVA pathways. These data show the most comprehensive metabolomic profile of Cunila menthoides to date, and the effects of BA and GA3 on the synthesis of secondary metabolites, modulating quantitative aspects of metabolism in Lamiaceae. [ABSTRACT FROM AUTHOR]

Endophytes are microorganisms living inside plant hosts and are known to be beneficial for the host plant vitality. In this study, we isolated three endophytic fungus species from the roots of Scots pine seedlings growing on Finnish drained peatland setting. The isolated fungi belonged to dark septate endophytes (DSE). The metabolic profiles of the hot water extracts of the fungi were investigated using Ultrahigh Performance Liquid Chromatography with Diode Array Detection and Electron Spray Ionization source Mass Spectrometry with Orbitrap analyzer (UPLC−DAD−ESI−MS−Orbitrap). Out of 318 metabolites, we were able to identify 220, of which a majority was amino acids and peptides. Additionally, opine amino acids, amino acid quinones, Amadori compounds, cholines, nucleobases, nucleosides, nucleotides, siderophores, sugars, sugar alcohols and disaccharides were found, as well as other previously reported metabolites from plants or endophytes. Some differences of the metabolic profiles, regarding the amount and identity of the found metabolites, were observed even though the fungi were isolated from the same host. Many of the discovered metabolites have been described possessing biological activities and properties, which may make a favorable contribution to the host plant nutrient availability or abiotic and biotic stress tolerance.

Flavour stability is vital to the brewing industry as beer is often stored for an extended time under variable conditions. Developing an accelerated model to evaluate brewing techniques that affect flavour stability is an important area of research. Here, we performed metabolomics on non-volatile compounds in beer stored at 37 °C between 1 and 14 days for two beer types: an amber ale and an India pale ale. The experiment determined high temperature to influence non-volatile metabolites, including the purine 5-methylthioadenosine (5-MTA). In a second experiment, three brewing techniques were evaluated for improved flavour stability: use of antioxidant crowns, chelation of pro-oxidants, and varying plant content in hops. Sensory analysis determined the hop method was associated with improved flavour stability, and this was consistent with reduced 5-MTA at both regular and high temperature storage. Future studies are warranted to understand the influence of 5-MTA on flavour and aging within different beer types. [ABSTRACT FROM AUTHOR]

Passiflora incarnata as well as some other Passiflora species are reported to possess anxiolytic and sedative activity and to treat various CNS disorders. The medicinal use of only a few Passiflora species has been scientifically verified. There are over 400 species in the Passiflora genus worldwide, most of which have been little characterized in terms of phytochemical or pharmacological properties. Herein, large-scale multi-targeted metabolic profiling and fingerprinting techniques were utilized to help gain a broader insight into Passiflora species leaves' chemical composition. Nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) spectra of extracted components derived from 17 Passiflora accessions and from different geographical origins were analyzed using multivariate data analyses. A total of 78 metabolites were tentatively identified, that is, 20 C-flavonoids, 8 O-flavonoids, 21 C, O-flavonoids, 2 cyanogenic glycosides, and 23 fatty acid conjugates, of which several flavonoid conjugates are for the first time to be reported in Passiflora spp. To the best of our knowledge, this study provides the most complete map for secondary metabolite distribution within that genus. Major signals in H-NMR and MS spectra contributing to species discrimination were assigned to those of C-flavonoids including isovitexin-2″- O-xyloside, luteolin- C-deoxyhexoside- O-hexoside, schaftoside, isovitexin, and isoorientin. P. incarnata was found most enriched in C-flavonoids, justifying its use as an official drug within that genus. Compared to NMR, LC-MS was found more effective in sample classification based on genetic and/ or geographical origin as revealed from derived multivariate data analyses. Novel insight on metabolite candidates to mediate for Passiflora CNS sedative effects is also presented. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Targeted metabolite profiling has aided in the understanding of a variety of biological processes in the malaria parasite as well as in drug discovery. A fast and sensitive analytical method, based on ion-pairing reversed phase ultra-high performance liquid chromatography tandem mass spectrometry (IP-RP–UPLC–MS/MS), was optimized for the simultaneous analysis of intracellular levels of 35 purine and pyrimidine nucleobases, nucleosides, and nucleotides. This analytical method allows for chromatographic separation of highly polar metabolites using reverse phase chemistry within 15 min. The analytical performance of the method was evaluated and successfully applied to the quantification of purines and pyrimidines in Plasmodium falciparum and its host cell, the human erythrocyte. In addition, this method can be customized to include other related metabolites such as NADPH and NADP, among others. [ABSTRACT FROM AUTHOR]

• Geographical origin of Argan kernels based on secondary-metabolite profiles. • 36 secondary metabolites (33 polyphenolic and 3 non-phenolic) were quantified. • Untargeted UPLC-MS fingerprints were decomposed by metabolomic data handling tools. • MCR–ALS and XCMS were compared to extract the features from UPLC-MS data. • PCA, PLS-DA, SIMCA and data fusion (low- and mid-) were used to handle the data. Argan (Argania spinosa L.) fruit kernels' composition has been poorly studied and received less research intensity than the resulting Argan oil. The Moroccan Argan kernels contain a wealth of metabolites and can be investigated for nutritional and health aspects as well as for economic benefits. Ultra-Performance Liquid Chromatography Mass Spectrometry (UPLC-MS) was employed to trace the geographical origin of Argan kernels based on secondary-metabolite profiles. One-hundred and twenty Argan fruit kernels from five regions ('Agadir', 'Ait-Baha' 'Essaouira', 'Tiznit' and 'Taroudant') were studied. Characterization and quantification of 36 secondary metabolites (33 polyphenolic and 3 non-phenolic) were achieved. Those metabolites are highly influenced by the geographic origin. Then, the untargeted UPLC-MS fingerprint was decomposed by metabolomic data handling tools, such as multivariate curve resolution alternating least squares (MCR–ALS) and XCMS. The two resulting data matrices were pretreated and prepared separately by chemometric tools and then two data fusion strategies (low- and mid-levels) were applied on them. The four data sets were comparatively investigated. Principal component analysis (PCA), Partial Least Squares Discriminant Analysis (PLS-DA), and Soft Independent Modeling of Class Analogies (SIMCA) were used to classify samples. The exploration or classification models demonstrated a good ability to discriminate and classify the samples in the geographical-origin based classes. Summarized, the developed fingerprints and their metabolomics-based data handling successfully allowed geographical traceability evaluation of Moroccan Argan kernels. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Rhizoma Smilacis Glabrae (RSG) has been used in the clinical treatment of gout and hyperuricemia in China for thousands of years. Modern pharmacological studies have shown that RSG exhibits hypouricemic effects because of its significant inhibitory effect on the activity of xanthine oxidase. Materials and methods: The Rhizoma Smilacis Glabrae extract (RSGE) at 1mL/100g oral administration was demonstrated to possess in vivo potent hypouricemic effects in hyperuricemic rats pretreated with oxonic acid potassium salt (200mg/kg, 2mL/kg). UPLC–MS was used to identify the constituents absorbed in the serum. In addition, a bivariate correlation analysis between the changes in the relative contents of the constituents from RSGE detected by HPLC and the serum uric acid levels in hyperuricemic rats at different points in time was used to calculate their correlation coefficients. Results: A total of 14 constituents were observed in the RSGE-treated rat serum, and 11 of these were inferred. An RSGE constituent was considered correlated with the hypouricemic effects if its correlation coefficient was above 0.5. The results suggested that only seven of the constituents absorbed in the serum of the hyperuricemic rats were correlated with hypouricemic effects, namely, palmitic acid, 3′-O-methyltaxifolin glucuronide, 3′-O-methyiastilbin glucuronide, astilbin glucuronide, 5-O-caffeoylshikimic acid glucuronide, resveratrol glucuronide, and dihydrokaempferol. Conclusion: These findings provide potent evidence for the study on RSG as a pharmacodynamic material basis and for developing RSG as a safe and promising natural drug to prevent hyperuricemia and gout instead of allopurinol. [Copyright &y& Elsevier]

The A21978C family of compounds includes precursors of daptomycin, an important antibiotic for the treatment of diseases infected by Gram-positive resistant bacteria. Focusing on these valuable compounds, the differences in metabolites obtained with or without pH control in their producing strainStreptomyces parvusHCCB10043 were investigated by comparative metabolomics analysis based on UPLC-TOF-MS technology. According to principal component analysis, there were fourteen biomarker compounds selected under the two pH culture conditions. The ten known compounds were divided into two types: a glycoside family participating in the primary metabolism (daidzein, glycitein, genistein, and soyasaponin Bb) and a peptide family of secondary metabolites (valistatin, bestatin, 3-amino-2-hydroxy-4-phenylbutanoylvalylisoleucine, and arylomycins A2, A4, and A5). Through orthogonal partial least squares-discriminant analysis, three compounds, soyasaponin Bb and arylomycins A2 and A4 were identified as the most relevant compounds to A21978C1-3 production, the glycolytic pathway, and the NRPS synthesis pathway. The competitive relationship between arylomycin and A21978C was verified. These results have demonstrated the usefulness of the metabolomic strategy based on UPLC-MS in studying significant metabolic changes in actinomycetes. Moreover, this metabolomic strategy can provide new ideas and guidance for the regulation and improvement of secondary metabolites production. [ABSTRACT FROM AUTHOR]

Metabolomics entails identification and quantification of all metabolites within a biological system with a given physiological status; as such, it should be unbiased. A variety of techniques are used to measure the metabolite content of living systems, and results differ with the mode of data acquisition and output generation. LC-MS is one of many techniques that has been used to study the metabolomes of different organisms but, although used extensively, it does not provide a complete metabolic picture. Recent developments in technology, for example the introduction of UPLC-ESI-MS, have, however, seen LC-MS become the preferred technique for metabolomics. Here, we show that when MS settings are varied in UPLC-ESI-MS, different metabolite profiles result from the same sample. During use of a Synapt UPLC-high definition MS instrument, the collision energy was continually altered (3, 10, 20, and 30 eV) during MS acquisition. PCA and OPLS-DA analysis of the generated UPLC-MS data of metabolites extracted from elicited tobacco cells revealed different clustering and different distribution patterns. As expected, ion abundance decreases with increasing collision energy, but, more importantly, results in unique multivariate data patterns from the same samples. Our findings suggest that different collision energy settings should be investigated during MS data acquisition because these can contribute to coverage of a wider range of the metabolome by UPLC-ESI-MS and prevent biased results. [ABSTRACT FROM AUTHOR]

Abstract: The effect of temperature on non-volatile compounds in beer has not been well characterised during storage. Here, a metabolomics approach was applied to characterise the effect of storage temperature on non-volatile metabolite variation after 16weeks of storage, using fresh beer as a control. The metabolite profile of room temperature stored (RT) and cold temperature stored (CT) beer differed significantly from fresh, with the most substantial variation observed between RT and fresh beer. Metabolites that changed during storage included prenylated flavonoids, purines, and peptides, and all showed reduced quantitative variation under the CT storage conditions. Corresponding sensory panel observations indicated significant beer oxidation after 12 and 16weeks of storage, with higher values reported for RT samples. These data support that temperature affected beer oxidation during short-term storage, and reveal 5-methylthioadenosine (5-MTA) as a candidate non-volatile metabolite marker for beer oxidation and staling. [Copyright &y& Elsevier]

Abstract: This study assessed the effects of long-term, low-dose dimethoate administration to rats by ultra-performance liquid chromatography–mass spectrometry (UPLC–MS). Dimethoate (0.04, 0.12, and 0.36mg/kg body weight/day) was administered daily to male Wistar rats through their drinking water for 24weeks. Significant changes in serum clinical chemistry were observed in the middle- and high-dose groups. UPLC–MS revealed evident separate clustering among the different dose groups using global metabolic profiling by supervised partial least squares-discriminant analysis. Metabonomic analysis showed alterations in a number of metabolites (12 from urine and 13 from plasma), such as l-tyrosine, dimethylthiophosphate (DMTP), dimethyldithiophosphate (DMDTP), citric acid, uric acid, suberic acid, glycylproline, allantoin, isovalerylglutamic acid and kinds of lipids. The results suggest that long-term, low-dose exposure to dimethoate can cause disturbances in liver function, antioxidant and nervous systems, as well as the metabolisms of lipids, glucose, fatty acids, amino acids, and collagen in rats. DMTP and DMDTP, which had the most significant changes among all other studied biomarkers, were considered as early, sensitive biomarkers of exposure to dimethoate. The other aforementioned proposed toxicity biomarkers in metabonomic analysis may be useful in the risk assessment of the toxic effects of dimethoate. Metabonomics as a systems toxicology approach was able to provide comprehensive information on the dynamic process of dimethoate induced toxicity. In addition, the results indicate that metabonomic approach could detect systemic toxic effects at an earlier stage compared to clinical chemistry. The combination of metabonomics and clinical chemistry made the toxicity of dimethoate on rats more comprehensive. [Copyright &y& Elsevier]

Abstract: To study the toxic effect of chronic exposure to acephate at low-dose levels, a metabolomics approach based on ultra-performance liquid chromatography/mass spectrometry (UPLC-MS) was applied. Three different doses of 0.5mg/kg/day, 1.5mg/kg/day, and 4.5mg/kg/day acephate were administered to Wistar rats for 24 weeks. Endogenous metabolite profiles were obtained with UPLC-MS for all rats at six time points after treatment. Some metabolites like dimethylthiophosphate and uric acid in urine were detected at week 4. Dimethylthiophosphate, which had the most significant elevations compared with other biomarkers, was considered as an early, sensitive biomarker of exposure to acephate. Moreover, there were some endogenous metabolite changes, which demonstrated that the doses of 1.5mg/kg/day and 4.5mg/kg/day of acephate led to renal injury and perturbed the normal metabolic processes of rats, including glucose, nucleic acid, and protein metabolism. A connection between exposure to acephate and the metabolic disturbance has been found and interpreted. Our study indicates that the metabolomics approach based on UPLC-MS of urine provides more information on toxicity than the conventional toxicological evaluation methods in measuring changes and can be considered as a promising technique for the study of the toxic effect of acephate. [Copyright &y& Elsevier]

Abstract: An extraction method for intracellular metabolite profiling should ideally be able to recover the broadest possible range of metabolites present in a sample. However, the development of such methods is hampered by the diversity of the physico-chemical properties of metabolites as well as by the specific characteristics of samples and cells. In this study, we report the optimization of an UPLC–MS method for the metabolite analysis of platelet samples. The optimal analytical protocol was determined by testing seven different extraction methods as well as by employing two different LC–MS methods, in which the metabolites were separated by using hydrophilic interaction liquid chromatography (HILIC) and reversed phase liquid chromatography (RPLC). The optimal conditions were selected using the coverage of the platelets’ metabolome, the response of the identified metabolites, the reproducibility of the analytical method, and the time of the analysis as main evaluation criteria. Our results show that methanol–water (7:3) extraction coupled with HILIC–MS method provides the best compromise, allowing identification of 107 metabolites in a platelet cell extract sample, 91% of them with a RSD% lower than 20. A higher number of metabolites could be detected when analyzing the platelet samples with two different LC–MS methods or when using complementary extraction methods in parallel. [Copyright &y& Elsevier]

Introduction: Early diagnosis and treatment for thermal injury with septic complications continue to be a serious clinical problem. In this study, plasma biomarkers of rats in the burn and/or septic models were investigated with a metabolomic method. Methods: Rat plasma samples were analyzed by ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC–Q-TOF-MS). Multivariate analysis, the principal components analysis (PCA), was used to validate metabolic changes. In addition, another multivariate method, the orthogonal partial least-squares analysis (OPLS), was used to profile potential biomarkers in models. Results: Nine characteristic metabolites, including hypoxanthine, indoxyl sufate, glucuronic acid, gluconic acid, proline, uracil, nitrotyrosine, uric acid, and trihydroxy cholanoic acid were identified in models of thermal injury and/or sepsis. Conclusion: These biomarkers were mainly involved in oxidative stress and tissue damage, and might supply evidence for distinguishing burned septic patients from non-septic ones. [Copyright &y& Elsevier]

1. A study of the rates and routes of excretion of 3-fluoro-[U-14C]aniline following intraperitoneal administration to male bile-cannulated rats by liquid scintillation counting (LSC) gave a total recovery of ~ 90% in the 48 h following dosing, with the majority of the dose being excreted in the urine during the first 24 h (~ 49%). 2. The total recovery as determined by 19F-nuclear magnetic resonance (19F-NMR) was ~ 49%, with the majority of the dose excreted in the first 24 h (~ 41%). The comparatively low recovery in comparison to that obtained from LSC was due to matrix effects in bile and a contribution from metabolic defluorination. 3. High-performance liquid chromatography with radiometric profiling of urine and bile revealed a complex pattern of metabolites with the bulk of the dose excreted as a single peak. 4. Ultra-performance liquid chromatography-orthogonal acceleration time of flight mass spectrometry profiling also showed a complex pattern of metabolites, detecting ~ 21 metabolites of 3-fluoroaniline (3-FA) with six of these detected only in urine and four solely in bile. 5. 19F-NMR revealed the presence of the parent compound and 15 metabolites in urine collected during the first 24 h after -dosing. The matrix effects of bile on 19F-NMR spectroscopy made metabolite profiling impractical for this biofluid. 6. The major metabolite of 3-FA was identified as 2-fluoro-4-acetamidophenol-sulfate. [ABSTRACT FROM AUTHOR]

Abstract: A sensitive and fast method was developed to quantitate the carcinogenic polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) and eight of its oxidized metabolites by ultra-performance liquid chromatography (UPLC) coupling with mass spectrometry (MS). The UPLC method, using an acetonitrile:water gradient as a mobile phase, provided baseline separation of the BaP metabolites including three BaP diones. Linearity of detection was in the range of 0.2–5.0ng/μL, and limits of detection (LOD) were lower than 0.01ng/μL for BaP and all of the metabolites except BaP tetrol. In order to test this method in environmentally relevant samples, we exposed the small fish Fundulus heteroclitus to BaP and quantitated biliary BaP metabolites. Extraction recovery of all compounds varied from 65.4±21.3% to 92.4±3.0%. In exposed fish bile, the BaP diones, BaP-7,8-dihydrodiol, and 3-hydroxy BaP metabolites predominated, existing mainly as glucuronic acid conjugates. This UPLC–MS method will be useful for further defining the roles of cytochrome P450s with both in vivo and in vitro models in the understanding of the mechanisms of metabolic activation and detoxification of BaP. [Copyright &y& Elsevier]

Cannabidiol (CBD) is a hydrophobic non-psychoactive compound with therapeutic characteristics. Animal and human studies have shown its poor oral bioavailability in vivo, and the impact of consuming lipid-soluble CBD with and without food on gut bioaccessibility has not been explored. The purpose of this research was to study the bioaccessibility of CBD after a three-phase upper digestion experiment with and without food, and to test lipase activity with different substrate concentrations. Our results showed that lipase enzyme activity and fatty acid absorption increased in the presence of bile salts, which may also contribute to an increase in CBD bioaccessibility. The food matrix used was a mixture of olive oil and baby food. Overall, the fed-state digestion revealed significantly higher micellarization efficiency for CBD (14.15 ± 0.6% for 10 mg and 22.67 ± 2.1% for 100 mg CBD ingested) than the fasted state digestion of CBD (0.65 ± 0.7% for 10 mg and 0.14 ± 0.1% for 100 mg CBD ingested). The increase in bioaccessibility of CBD with food could be explained by the fact that micelle formation from hydrolyzed lipids aid in bioaccessibility of hydrophobic molecules. In conclusion, the bioaccessibility of CBD depends on the food matrix and the presence of lipase and bile salts. [ABSTRACT FROM AUTHOR]

Metabolic profile is a key component of fruit quality, which is a challenge to study due to great compound diversity, especially in species with high nutritional value. This study presents optimized analytical methods for metabolic profiling in the fruits of three Solanaceae species: Lycium barbarum, Lycium chinense and Solanumlycopersicum. It includes the most important chemical classes involved in nutrition and taste, i.e., carotenoids, phenolic compounds and primary compounds. Emphasis has been placed on the systematic achievement of good extraction yields, sample stability, and high response linearity using common LC-ESI-TQ-MS and GC-EI-MS apparatuses. A set of 13 carotenoids, 46 phenolic compounds and 67 primary compounds were profiled in fruit samples. Chemometrics revealed metabolic markers discriminating Lycium and Solanum fruits but also Lycium barbarum and Lycium chinense fruits and the effect of the crop environment. Typical tomato markers were found to be lycopene, carotene, glutamate and GABA, while lycibarbarphenylpropanoids and zeaxanthin esters characterized goji (Lycium spp.) fruits. Among the compounds discriminating the Lycium species, reported here for the first time to our knowledge, chlorogenic acids, asparagine and quinic acid were more abundant in Lycium chinense, whereas Lycium barbarum accumulated more lycibarbarphenylpropanoids A-B, coumaric acid, fructose and glucose. [ABSTRACT FROM AUTHOR]

The metabolic requirements of metastatic non-small cell lung (mNSCLC) tumors from patients receiving first-line platinum-doublet chemotherapy are hypothesized to imprint a blood signature suitable for survival prediction. Pre-treatment samples prospectively collected at baseline from a randomized phase III trial were assayed using nuclear magnetic resonance (NMR) spectroscopy (n = 341) and ultra-high performance liquid chromatography – mass spectrometry (UPLC-MS) (n = 297). Distributions of time to event outcomes were estimated by Kaplan-Meier analysis, and baseline characteristics adjusted Cox regression modeling was used to correlate markers' levels to time to event outcomes. Sixteen polar metabolites were significantly correlated with overall survival (OS) by univariate analysis (p < 0.025). Formate, 2-hydroxybutyrate, glycine and myo-inositol were selected for a multivariate model. The median OS was 6.6 months in the high-risk group compared to 11.4 months in the low risk group HR (Hazard Ratio) = 1.99, 95% C.I. (Confidence Interval) 1.45–2.68; p < 0.0001). Modeling of lipids by class (sphingolipids, acylcarnitines and lysophosphatidylcholines) revealed a median OS = 5.7 months vs. 11. 9 months for the high vs. low risk group. (HR: 2.23, 95% C.I. 1.55–3.20; p < 0.0001). These results demonstrate that metabolic profiles from pre-treatment samples may be useful to stratify clinical outcomes for mNSCLC patients receiving chemotherapy. Genomic and longitudinal measurements pre- and post-treatment may yield addition information to personalize treatment decisions further. [ABSTRACT FROM AUTHOR]

Introduction: Phoenix dactylifera L. (date palm) is one of the most valued crops worldwide for its economical and nutraceutical applications of its date fruit (pericarp). Currently date pits, considered as a waste product, is employed as coffee substitute post roasting. Whereas, pollen represents another valuable by-product used as a dietary supplement. Objectives: In this study, a large-scale comparative metabolomics approach was performed for the first characterization and standardization of date palm by-products viz., date pits and pollen. Moreover, roasting impact on date pit metabolite composition was also assessed. Methods: Metabolites profiling of pits and pollen was determined via a multiplex approach of UPLC–MS and NMR, coupled to multivariate analysis, in relation to its antioxidant activities. Results: Chemical analyses led to the identification of 67 metabolites viz., phenolic acids, flavonols, fatty acids, sphingolipids, steroids and saponins of which 10 are first time to be reported. The enrichment of steroids in date pollen accounts for its fertility promoting properties, whereas date pit was found a rich source for antioxidant polyphenols using metabolomics. [ABSTRACT FROM AUTHOR]

Endophytes are microorganisms living inside plant hosts and are known to be beneficial for the host plant vitality. In this study, we isolated three endophytic fungus species from the roots of Scots pine seedlings growing on Finnish drained peatland setting. The isolated fungi belonged to dark septate endophytes (DSE). The metabolic profiles of the hot water extracts of the fungi were investigated using Ultrahigh Performance Liquid Chromatography with Diode Array Detection and Electron Spray Ionization source Mass Spectrometry with Orbitrap analyzer (UPLC–DAD–ESI–MS–Orbitrap). Out of 318 metabolites, we were able to identify 220, of which a majority was amino acids and peptides. Additionally, opine amino acids, amino acid quinones, Amadori compounds, cholines, nucleobases, nucleosides, nucleotides, siderophores, sugars, sugar alcohols and disaccharides were found, as well as other previously reported metabolites from plants or endophytes. Some differences of the metabolic profiles, regarding the amount and identity of the found metabolites, were observed even though the fungi were isolated from the same host. Many of the discovered metabolites have been described possessing biological activities and properties, which may make a favorable contribution to the host plant nutrient availability or abiotic and biotic stress tolerance. [ABSTRACT FROM AUTHOR]

Red pigment (RP) was extracted from the peels of Zanthoxylum bungeanum Maxim (PZB) by ultrasonic-assisted extraction (UAE) in this work. Box–Behnken design–response surface methodology (BBD-RSM) was employed to research the efficiency of the RP extraction. Based on the optimization of RSM, results showed that the optimal extraction conditions were as follows: liquid–solid ratio of 31 mL/g, extraction time of 41 min, and extraction temperature of 27 °C, and under these conditions, the actual absorbance value was 0.615 ± 0.13%, highly agreeing with the predicted value by the model. Furthermore, ultra-performance liquid chromatography–mass spectrometry (UPLC-MS) was used to separate and analyze RP. The compounds of RP were mainly flavonoids, and there were five compounds detected for the first time in PZB. In addition, RP showed significant antioxidant activities in vitro, which could be developed for anti-aging candidate drugs and functional foods. In conclusion, ultrasound-assisted extraction with BBD-RSM and chromatographic separation technology with UPLC-MS are efficient strategies for the isolation and identification of RP from PZB. [ABSTRACT FROM AUTHOR]

Metabolic profiling focuses on the analysis of a wide range of small endogenous molecules in order to understand the response of a living system to perturbations. Ultra high performance liquid chromatography–mass spectrometry is a widely employed profiling tool, but its application is limited by difficulties in identification of detected metabolites. Herein, we demonstrate how the prediction of retention time can help resolve this major issue. We describe a general approach that enables the generation of reliable quantitative structure retention relationship models tailored to specific chromatographic protocols. This methodology, applied to 442 experimentally characterised standards, employs a combination of random forest and support vector regression models with molecular interaction descriptors. In this unusual application, the Volsurf + molecular descriptors demonstrated a high ability to describe chromatographic retention. On external validation sets, and for a wide range of chemical classes, predicted values were in average within 13 % of the experimentally observed retention time. More importantly, the presented procedure reduced by more than 80 % the number of false putative identification, greatly improving metabolite identification. Furthermore, in 95 % of cases, the correct identification was promoted within the top three metabolite suggestions. This retention time prediction framework can be replicated by different laboratories to suit their profiling platforms and enhance the value of standard library by providing a new tool for compound identification. [ABSTRACT FROM AUTHOR]