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Fulltext Circulating Metabolites Associated with Alcohol Intake in the European Prospective Investigation into Cancer and Nutrition Cohort

van Roekel EH, Trijsburg L, Assi N, Carayol M, Achaintre D, Murphy N, et al.

Nutrients, 2018 May 22;10(5).
PMID: 29789452 DOI: 10.3390/nu10050654

Identifying the metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. We studied associations of alcohol consumption with circulating concentrations of 123 metabolites among 2974 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQTM p180 kit). Data were randomly divided into discovery (2/3) and replication (1/3) sets. Multivariable linear regression models were used to evaluate confounder-adjusted associations of alcohol consumption with metabolite concentrations. Metabolites significantly related to alcohol intake in the discovery set (FDR q-value < 0.05) were further tested in the replication set (Bonferroni-corrected p-value < 0.05). Of the 72 metabolites significantly related to alcohol intake in the discovery set, 34 were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Our results confirmed earlier findings that alcohol consumption was associated with several lipid metabolites, and possibly also with specific acylcarnitines and amino acids. This provides further leads for future research studies aiming at elucidating the mechanisms underlying the effects of alcohol in relation to morbid conditions.

Matched MeSH terms: Metabolomics/methods
Revealing metabolic and biochemical variations via 1H NMR metabolomics in streptozotocin-nicotinamide-induced diabetic rats treated with metformin

Zolkeflee NKZ, Wong PL, Maulidiani M, Ramli NS, Azlan A, Mediani A, et al.

Biochem Biophys Res Commun, 2024 May 14;708:149778.
PMID: 38507867 DOI: 10.1016/j.bbrc.2024.149778

The increasing prevalence of lean diabetes has prompted the generation of animal models that mimic metabolic disease in humans. This study aimed to determine the optimum streptozotocin-nicotinamide (STZ-NA) dosage ratio to elicit lean diabetic features in a rat model. It also used a proton nuclear magnetic resonance (1H NMR) urinary metabolomics approach to identify the metabolic effect of metformin treatment on this novel rat model. Three different STZ-NA dosage regimens (by body weight: Group A: 110 mg/kg NA and 45 mg/kg STZ; Group B: 180 mg/kg NA and 65 mg/kg STZ and Group C: 120 mg/kg NA and 60 mg/kg STZ) were administered to Sprague-Dawley rats along with oral metformin. Group A diabetic rats (A-DC) showed favorable serum biochemical analyses and a more positive response toward oral metformin administration relative to the other STZ-NA dosage ratio groups. Orthogonal partial least squares-discriminant analysis (OPLS-DA) revealed that glucose, citrate, pyruvate, hippurate, and methylnicotinamide differentiating the OPLS-DA of A-MTF rats (Group A diabetic rats treated with metformin) and A-DC model rats. Subsequent metabolic pathway analyses revealed that metformin treatment was associated with improvement in dysfunctions caused by STZ-NA induction, including carbohydrate metabolism, cofactor metabolism, and vitamin and amino acid metabolism. In conclusion, our results identify the best STZ-NA dosage ratio for a rat model to exhibit lean type 2 diabetic features with optimum sensitivity to metformin treatment. The data presented here could be informative to improve our understanding of non-obese diabetes in humans through the identification of possible activated metabolic pathways in the STZ-NA-induced diabetic rats model.

Matched MeSH terms: Metabolomics/methods
Acclimatisation-induced stress influenced host metabolic and gut microbial composition change

Yap IK, Kho MT, Lim SH, Ismail NH, Yam WK, Chong CW

Mol Biosyst, 2015 Jan;11(1):297-306.
PMID: 25382376 DOI: 10.1039/c4mb00463a

Understanding the basal gut bacterial community structure and the host metabolic composition is pivotal for the interpretation of laboratory treatments designed to answer questions pertinent to host-microbe interactions. In this study, we report for the first time the underlying gut microbiota and systemic metabolic composition in BALB/c mice during the acclimatisation period. Our results showed that stress levels were reduced in the first three days of the study when the animals were subjected to repetitive handling daily but the stress levels were increased when handling was carried out at lower frequencies (weekly). We also observed a strong influence of stress on the host metabolism and commensal compositional variability. In addition, temporal biological compartmental variations in the responses were observed. Based on these results, we suggest that consistency in the frequency and duration of laboratory handling is crucial in murine models to minimise the impact of stress levels on the commensal and host metabolism dynamics. Furthermore, caution is advised in consideration of the temporal delay effect when integrating metagenomics and metabonomics data across different biological matrices (i.e. faeces and urine).

Matched MeSH terms: Metabolomics/methods
Fulltext 1H NMR-based metabolomics investigation of copper-laden rat: a model of Wilson's disease

Xu J, Jiang H, Li J, Cheng KK, Dong J, Chen Z

PLoS One, 2015;10(4):e0119654.
PMID: 25849323 DOI: 10.1371/journal.pone.0119654

Wilson's disease (WD), also known as hepatoleticular degeneration (HLD), is a rare autosomal recessive genetic disorder of copper metabolism, which causes copper to accumulate in body tissues. In this study, rats fed with copper-laden diet are used to render the clinical manifestations of WD, and their copper toxicity-induced organ lesions are studied. To investigate metabolic behaviors of 'decoppering' process, penicillamine (PA) was used for treating copper-laden rats as this chelating agent could eliminate excess copper through the urine. To date, there has been limited metabolomics study on WD, while metabolic impacts of copper accumulation and PA administration have yet to be established.

Matched MeSH terms: Metabolomics/methods*
Fulltext NMF-Based Approach for Missing Values Imputation of Mass Spectrometry Metabolomics Data

Xu J, Wang Y, Xu X, Cheng KK, Raftery D, Dong J

Molecules, 2021 Sep 24;26(19).
PMID: 34641330 DOI: 10.3390/molecules26195787

In mass spectrometry (MS)-based metabolomics, missing values (NAs) may be due to different causes, including sample heterogeneity, ion suppression, spectral overlap, inappropriate data processing, and instrumental errors. Although a number of methodologies have been applied to handle NAs, NA imputation remains a challenging problem. Here, we propose a non-negative matrix factorization (NMF)-based method for NA imputation in MS-based metabolomics data, which makes use of both global and local information of the data. The proposed method was compared with three commonly used methods: k-nearest neighbors (kNN), random forest (RF), and outlier-robust (ORI) missing values imputation. These methods were evaluated from the perspectives of accuracy of imputation, retrieval of data structures, and rank of imputation superiority. The experimental results showed that the NMF-based method is well-adapted to various cases of data missingness and the presence of outliers in MS-based metabolic profiles. It outperformed kNN and ORI and showed results comparable with the RF method. Furthermore, the NMF method is more robust and less susceptible to outliers as compared with the RF method. The proposed NMF-based scheme may serve as an alternative NA imputation method which may facilitate biological interpretations of metabolomics data.

Matched MeSH terms: Metabolomics/methods*
Antidiabetic effect of Ardisia elliptica extract and its mechanisms of action in STZ-NA-induced diabetic rat model via 1H-NMR-based metabolomics

Wong PL, Zolkeflee NKZ, Ramli NS, Tan CP, Azlan A, Tham CL, et al.

J Ethnopharmacol, 2024 Jan 10;318(Pt B):117015.
PMID: 37572932 DOI: 10.1016/j.jep.2023.117015

ETHNOPHARMACOLOGICAL RELEVANCE: Ardisia elliptica Thunb. (AE) (Primulaceae) is a medicinal plant found in the Malay Peninsula and has been traditionally used to treat diabetes. However, limited studies to date in providing scientific evidence to support the antidiabetic efficacy of this plant by in-vitro and in-vivo models.
AIM OF THE STUDY: To investigate the anti-hyperglycemic potential of AE through in-vitro enzymatic activities and streptozotocin-nicotinamide (STZ-NA) induced diabetic rat models using proton-nuclear magnetic resonance (1H-NMR)-based metabolomics approach.
MATERIALS AND METHODS: Anti-α-amylase and anti-α-glucosidase activities of the hydroethanolic extracts of AE were evaluated. The absolute quantification of bioactive constituents, using ultra-high performance liquid chromatography (UHPLC) was performed for the most active extract. Three different dosage levels of the AE extract were orally administered for 4 weeks consecutively in STZ-NA induced diabetic rats. Physical assessments, biochemical analysis, and an untargeted 1H-NMR-based metabolomics analysis of the urine and serum were carried out on the animal model.
RESULTS: Type 2 diabetes mellitus (T2DM) rat model was successfully developed based on the clear separation observed between the STZ-NA induced diabetic and normal non-diabetic groups. Discriminating biomarkers included glucose, citrate, succinate, allantoin, hippurate, 2-oxoglutarate, and 3-hydroxybutyrate, as determined through an orthogonal partial least squares-discriminant analysis (OPLS-DA) model. A treatment dosage of 250 mg/kg body weight (BW) of standardized 70% ethanolic AE extract mitigated increase in serum glucose, creatinine, and urea levels, providing treatment levels comparable to that obtained using metformin, with flavonoids primarily contribute to the anti-hyperglycemic activities. Urinary metabolomics disclosed that the following disturbed metabolism pathways: the citrate cycle (TCA cycle), butanoate metabolism, glycolysis and gluconeogenesis, pyruvate metabolism, and synthesis and degradation of ketone bodies, were ameliorated after treatment with the standardized AE extract.
CONCLUSIONS: This study demonstrated the first attempt at revealing the therapeutic effect of oral treatment with 250 mg/kg BW of standardized AE extract on chemically induced T2DM rats. The present study provides scientific evidence supporting the ethnomedicinal use of Ardisia elliptica and further advances the understanding of the fundamental molecular mechanisms affected by this herbal antidote.

Matched MeSH terms: Metabolomics/methods
Fulltext Metabolomic analysis of low and high biofilm-forming Helicobacter pylori strains

Wong EHJ, Ng CG, Goh KL, Vadivelu J, Ho B, Loke MF

Sci Rep, 2018 01 23;8(1):1409.
PMID: 29362474 DOI: 10.1038/s41598-018-19697-0

The biofilm-forming-capability of Helicobacter pylori has been suggested to be among factors influencing treatment outcome. However, H. pylori exhibit strain-to-strain differences in biofilm-forming-capability. Metabolomics enables the inference of spatial and temporal changes of metabolic activities during biofilm formation. Our study seeks to examine the differences in metabolome of low and high biofilm-formers using the metabolomic approach. Eight H. pylori clinical strains with different biofilm-forming-capability were chosen for metabolomic analysis. Bacterial metabolites were extracted using Bligh and Dyer method and analyzed by Liquid Chromatography/Quadrupole Time-of-Flight mass spectrometry. The data was processed and analyzed using the MassHunter Qualitative Analysis and the Mass Profiler Professional programs. Based on global metabolomic profiles, low and high biofilm-formers presented as two distinctly different groups. Interestingly, low-biofilm-formers produced more metabolites than high-biofilm-formers. Further analysis was performed to identify metabolites that differed significantly (p-value

Matched MeSH terms: Metabolomics/methods*
iMSEA: A Novel Metabolite Set Enrichment Analysis Strategy to Decipher Drug Interactions

Wang Y, Liu X, Dong L, Cheng KK, Lin C, Wang X, et al.

Anal Chem, 2023 Apr 18;95(15):6203-6211.
PMID: 37023366 DOI: 10.1021/acs.analchem.2c04603

Drug combinations are commonly used to treat various diseases to achieve synergistic therapeutic effects or to alleviate drug resistance. Nevertheless, some drug combinations might lead to adverse effects, and thus, it is crucial to explore the mechanisms of drug interactions before clinical treatment. Generally, drug interactions have been studied using nonclinical pharmacokinetics, toxicology, and pharmacology. Here, we propose a complementary strategy based on metabolomics, which we call interaction metabolite set enrichment analysis, or iMSEA, to decipher drug interactions. First, a digraph-based heterogeneous network model was constructed to model the biological metabolic network based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Second, treatment-specific influences on all detected metabolites were calculated and propagated across the whole network model. Third, pathway activity was defined and enriched to quantify the influence of each treatment on the predefined functional metabolite sets, i.e., metabolic pathways. Finally, drug interactions were identified by comparing the pathway activity enriched by the drug combination treatments and the single drug treatments. A data set consisting of hepatocellular carcinoma (HCC) cells that were treated with oxaliplatin (OXA) and/or vitamin C (VC) was used to illustrate the effectiveness of the iMSEA strategy for evaluation of drug interactions. Performance evaluation using synthetic noise data was also performed to evaluate sensitivities and parameter settings for the iMSEA strategy. The iMSEA strategy highlighted synergistic effects of combined OXA and VC treatments including the alterations in the glycerophospholipid metabolism pathway and glycine, serine, and threonine metabolism pathway. This work provides an alternative method to reveal the mechanisms of drug combinations from the viewpoint of metabolomics.

Matched MeSH terms: Metabolomics/methods
Fulltext Differential metabolite profiles during fruit development in high-yielding oil palm mesocarp

Teh HF, Neoh BK, Hong MP, Low JY, Ng TL, Ithnin N, et al.

PLoS One, 2013;8(4):e61344.
PMID: 23593468 DOI: 10.1371/journal.pone.0061344

To better understand lipid biosynthesis in oil palm mesocarp, in particular the differences in gene regulation leading to and including de novo fatty acid biosynthesis, a multi-platform metabolomics technology was used to profile mesocarp metabolites during six critical stages of fruit development in comparatively high- and low-yielding oil palm populations. Significantly higher amino acid levels preceding lipid biosynthesis and nucleosides during lipid biosynthesis were observed in a higher yielding commercial palm population. Levels of metabolites involved in glycolysis revealed interesting divergence of flux towards glycerol-3-phosphate, while carbon utilization differences in the TCA cycle were proven by an increase in malic acid/citric acid ratio. Apart from insights into the regulation of enhanced lipid production in oil palm, these results provide potentially useful metabolite yield markers and genes of interest for use in breeding programmes.

Matched MeSH terms: Metabolomics/methods
Fulltext Metabolite profiling of Andrographis paniculata (Burm. f.) Nees. young and mature leaves at different harvest ages using 1H NMR-based metabolomics approach

Tajidin NE, Shaari K, Maulidiani M, Salleh NS, Ketaren BR, Mohamad M

Sci Rep, 2019 11 14;9(1):16766.
PMID: 31727911 DOI: 10.1038/s41598-019-52905-z

Andrographis paniculata (Burm. F.) Nees. is considered as the herb of the future due to its precious chemical compounds, andrographolide (ANDRO), neoandrographolide (NAG) and 14-deoxyandrographolide (DAG). This study aims to profile the metabolites in young and mature leaf at six different harvest ages using 1HNMR-based metabolomics combined with multivariate data analysis. Principal component analysis (PCA) indicated noticeable and clear discrimination between young and mature leaves. A comparison of the leaves stage indicated that young leaves were separated from mature leaves due to its larger quantity of ANDRO, NAG, DAG, glucose and sucrose. These similar metabolites are also responsible for the PCA separation into five clusters representing the harvest age at 14, 16, 18, 20, 22 weeks of leaves extract. Loading plots revealed that most of the ANDRO and NAG signals were present when the plant reached at the pre-flowering stage or 18 weeks after sowing (WAS). As a conclusion, A. paniculata young leaves at pre-flowering harvest age were found to be richer in ANDRO, NAG and DAG compared to mature leaves while glucose and choline increased with harvest age. Therefore, young leaves of A. paniculata should be harvested at 18 WAS in order to produce superior quality plant extracts for further applications by the herbal, nutraceutical and pharmaceutical industries.

Matched MeSH terms: Metabolomics/methods*
Fulltext Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study

Stepien M, Keski-Rahkonen P, Kiss A, Robinot N, Duarte-Salles T, Murphy N, et al.

Int J Cancer, 2021 Feb 01;148(3):609-625.
PMID: 32734650 DOI: 10.1002/ijc.33236

Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed for N1-acetylspermidine, isatin, p-hydroxyphenyllactic acid, tyrosine, sphingosine, l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, γ-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.

Matched MeSH terms: Metabolomics/methods*
Windows Scanning Multiomics: Integrated Metabolomics and Proteomics

Shi J, Zhao J, Zhang Y, Wang Y, Tan CP, Xu YJ, et al.

Anal Chem, 2023 Dec 26;95(51):18793-18802.
PMID: 38095040 DOI: 10.1021/acs.analchem.3c03785

Metabolomics and proteomics offer significant advantages in understanding biological mechanisms at two hierarchical levels. However, conventional single omics analysis faces challenges due to the high demand for specimens and the complexity of intrinsic associations. To obtain comprehensive and accurate system biological information, we developed a multiomics analytical method called Windows Scanning Multiomics (WSM). In this method, we performed simultaneous extraction of metabolites and proteins from the same sample, resulting in a 10% increase in the coverage of the identified biomolecules. Both metabolomics and proteomics analyses were conducted by using ultrahigh-performance liquid chromatography mass spectrometry (UPLC-MS), eliminating the need for instrument conversions. Additionally, we designed an R-based program (WSM.R) to integrate mathematical and biological correlations between metabolites and proteins into a correlation network. The network created from simultaneously extracted biomolecules was more focused and comprehensive compared to those from separate extractions. Notably, we excluded six pairs of false-positive relationships between metabolites and proteins in the network established using simultaneously extracted biomolecules. In conclusion, this study introduces a novel approach for multiomics analysis and data processing that greatly aids in bioinformation mining from multiomics results. This method is poised to play an indispensable role in systems biology research.

Matched MeSH terms: Metabolomics/methods
Metabolic Effect of Dietary Taurine Supplementation on Nile Tilapia (Oreochromis nilotictus) Evaluated by NMR-Based Metabolomics

Shen G, Huang Y, Dong J, Wang X, Cheng KK, Feng J, et al.

J Agric Food Chem, 2018 Jan 10;66(1):368-377.
PMID: 29215281 DOI: 10.1021/acs.jafc.7b03182

Taurine is indispensable in aquatic diets that are based solely on plant protein, and it promotes growth of many fish species. However, the physiological and metabolome effects of taurine on fish have not been well described. In this study, 1H NMR-based metabolomics approaches were applied to investigate the metabolite variations in Nile tilapia (Oreochromis nilotictus) muscle in order to visualize the metabolic trajectory and reveal the possible mechanisms of metabolic effects of dietary taurine supplementation on tilapia growth. After extraction using aqueous and organic solvents, 19 taurine-induced metabolic changes were evaluated in our study. The metabolic changes were characterized by differences in carbohydrate, amino acid, lipid, and nucleotide contents. The results indicate that taurine supplementation could significantly regulate the physiological state of fish and promote growth and development. These results provide a basis for understanding the mechanism of dietary taurine supplementation in fish feeding. 1H NMR spectroscopy, coupled with multivariate pattern recognition technologies, is an efficient and useful tool to map the fish metabolome and identify metabolic responses to different dietary nutrients in aquaculture.

Matched MeSH terms: Metabolomics/methods*
Prioritization of natural extracts by LC-MS-PCA for the identification of new photosensitizers for photodynamic therapy

Samat N, Tan PJ, Shaari K, Abas F, Lee HB

Anal Chem, 2014 Feb 4;86(3):1324-31.
PMID: 24405504 DOI: 10.1021/ac403709a

Photodynamic therapy (PDT) is an alternative treatment for cancer that involves administration of a photosensitive drug or photosensitizer that localizes at the tumor tissue followed by in situ excitation at an appropriate wavelength of light. Tumour tissues are then killed by cytotoxic reactive oxygen species generated by the photosensitizer. Targeted excitation and photokilling of affected tissues is achieved through focal light irradiation, thereby minimizing systemic side effects to the normal healthy tissues. Currently, there are only a small number of photosensitizers that are in the clinic and many of these share the same structural core based on cyclic tetrapyrroles. This paper describes how metabolic tools are utilized to prioritize natural extracts to search for structurally new photosensitizers from Malaysian biodiversity. As proof of concept, we analyzed 278 photocytotoxic extracts using a hyphenated technique of liquid chromatography-mass spectrometry coupled with principal component analysis (LC-MS-PCA) and prioritized 27 extracts that potentially contained new photosensitizers for chemical dereplication using an in-house UPLC-PDA-MS-Photocytotoxic assay platform. This led to the identification of 2 new photosensitizers with cyclic tetrapyrrolic structures, thereby demonstrating the feasibility of the metabolic approach.

Matched MeSH terms: Metabolomics/methods*
Analysis of Terpenoid Indole Alkaloids, Carotenoids, Phytosterols, and NMR-Based Metabolomics for Catharanthus roseus Cell Suspension Cultures

Saiman MZ, Mustafa NR, Verpoorte R

Methods Mol Biol, 2018;1815:437-455.
PMID: 29981141 DOI: 10.1007/978-1-4939-8594-4_31

The plant Catharanthus roseus is a rich source of terpenoid indole alkaloids (TIA). Some of the TIA are important as antihypertensive (ajmalicine) and anticancer (vinblastine and vincristine) drugs. However, production of the latter is very low in the plant. Therefore, in vitro plant cell cultures have been considered as a potential supply of these chemicals or their precursors. Some monomeric alkaloids can be produced by plant cell cultures, but not on a level feasible for commercialization, despite extensive studies on this plant that deepened the understanding of the TIA biosynthesis and its regulation. In order to analyze the metabolites in C. roseus cell cultures, this chapter presents the method of TIA, carotenoids, and phytosterols analyses. Furthermore, an NMR-based metabolomics approach to study C. roseus cell culture is described.

Matched MeSH terms: Metabolomics/methods*
Fulltext Serum Metabolomics Profiling of Commercially Mixed Functional Foods-Effects in Beta-Amyloid Induced Rats Measured Using 1H NMR Spectroscopy

Rosli NHM, Yahya HM, Ibrahim FW, Shahar S, Ismail IS, Azam AA, et al.

Nutrients, 2020 Dec 12;12(12).
PMID: 33322743 DOI: 10.3390/nu12123812

Functional foods such as pomegranate, dates and honey were shown by various previous studies to individually have a neuroprotective effect, especially in neurodegenerative disease such as Alzheimer's disease (AD). In this novel and original study, an 1H NMR spectroscopy tool was used to identify the metabolic neuroprotective mechanism of commercially mixed functional foods (MFF) consisting of pomegranate, dates and honey, in rats injected with amyloid-beta 1-42 (Aβ-42). Forty-five male albino Wistar rats were randomly divided into five groups: NC (0.9% normal saline treatment + phosphate buffer solution (PBS) solution injection), Abeta (0.9% normal saline treatment + 0.2 µg/µL Aβ-42 injection), MFF (4 mL/kg MFF treatment + PBS solution injection), Abeta-MFF (4 mL/kg MFF treatment + 0.2 µg/µL Aβ-42 injection) and Abeta-NAC (150 mg/kg N-acetylcysteine + 0.2 µg/µL Aβ-42 injection). Based on the results, the MFF and NAC treatment improved the spatial memory and learning using Y-maze. In the metabolic analysis, a total of 12 metabolites were identified, for which levels changed significantly among the treatment groups. Systematic metabolic pathway analysis found that the MFF and NAC treatments provided a neuroprotective effect in Aβ-42 injected rats by improving the acid amino and energy metabolisms. Overall, this finding showed that MFF might serve as a potential neuroprotective functional food for the prevention of AD.

Matched MeSH terms: Metabolomics/methods
Isolating the metabolic pathways involved in the hepatoprotective effect of Muntingia calabura against CCl4-induced liver injury using LC/MS Q-TOF

Rofiee MS, Yusof MI, Abdul Hisam EE, Bannur Z, Zakaria ZA, Somchit MN, et al.

J Ethnopharmacol, 2015 May 26;166:109-18.
PMID: 25792013 DOI: 10.1016/j.jep.2015.03.016

Muntingia calabura L. has been used in Southeast Asia and tropical America as antipyretic, antiseptic, analgesic, antispasmodic and liver tonic. This study aims to determine the acute toxicity and the metabolic pathways involved in the hepatoprotective mechanism of M. calabura.

Matched MeSH terms: Metabolomics/methods
Fulltext Review on a Traditional Herbal Medicine, Eurycoma longifolia Jack (Tongkat Ali): Its Traditional Uses, Chemistry, Evidence-Based Pharmacology and Toxicology

Rehman SU, Choe K, Yoo HH

Molecules, 2016 Mar 10;21(3):331.
PMID: 26978330 DOI: 10.3390/molecules21030331

Eurycoma longifolia Jack (known as tongkat ali), a popular traditional herbal medicine, is a flowering plant of the family Simaroubaceae, native to Indonesia, Malaysia, Vietnam and also Cambodia, Myanmar, Laos and Thailand. E. longifolia, is one of the well-known folk medicines for aphrodisiac effects as well as intermittent fever (malaria) in Asia. Decoctions of E. longifolia leaves are used for washing itches, while its fruits are used in curing dysentery. Its bark is mostly used as a vermifuge, while the taproots are used to treat high blood pressure, and the root bark is used for the treatment of diarrhea and fever. Mostly, the roots extract of E. longifolia are used as folk medicine for sexual dysfunction, aging, malaria, cancer, diabetes, anxiety, aches, constipation, exercise recovery, fever, increased energy, increased strength, leukemia, osteoporosis, stress, syphilis and glandular swelling. The roots are also used as an aphrodisiac, antibiotic, appetite stimulant and health supplement. The plant is reported to be rich in various classes of bioactive compounds such as quassinoids, canthin-6-one alkaloids, β-carboline alkaloids, triterpene tirucallane type, squalene derivatives and biphenyl neolignan, eurycolactone, laurycolactone, and eurycomalactone, and bioactive steroids. Among these phytoconstituents, quassinoids account for a major portion of the E. longifolia root phytochemicals. An acute toxicity study has found that the oral Lethal Dose 50 (LD50) of the alcoholic extract of E. longifolia in mice is between 1500-2000 mg/kg, while the oral LD50 of the aqueous extract form is more than 3000 mg/kg. Liver and renal function tests showed no adverse changes at normal daily dose and chronic use of E. longifolia. Based on established literature on health benefits of E. longifolia, it is important to focus attention on its more active constituents and the constituents' identification, determination, further development and most importantly, the standardization. Besides the available data, more evidence is required regarding its therapeutic efficacy and safety, so it can be considered a rich herbal source of new drug candidates. It is very important to conserve this valuable medicinal plant for the health benefit of future generations.

Matched MeSH terms: Metabolomics/methods
Cupriavidus malaysiensis sp. nov., a novel poly(3-hydroxybutyrate-co-4-hydroxybutyrate) accumulating bacterium isolated from the Malaysian environment

Ramachandran H, Shafie NAH, Sudesh K, Azizan MN, Majid MIA, Amirul AA

Antonie Van Leeuwenhoek, 2018 Mar;111(3):361-372.
PMID: 29022146 DOI: 10.1007/s10482-017-0958-8

Bacterial classification on the basis of a polyphasic approach was conducted on three poly(3 hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] accumulating bacterial strains that were isolated from samples collected from Malaysian environments; Kulim Lake, Sg. Pinang river and Sg. Manik paddy field. The Gram-negative, rod-shaped, motile, non-sporulating and non-fermenting bacteria were shown to belong to the genus Cupriavidus of the Betaproteobacteria on the basis of their 16S rRNA gene sequence analyses. The sequence similarity value with their near phylogenetic neighbour, Cupriavidus pauculus LMG3413T, was 98.5%. However, the DNA-DNA hybridization values (8-58%) and ribotyping analysis both enabled these strains to be differentiated from related Cupriavidus species with validly published names. The RiboPrint patterns of the three strains also revealed that the strains were genetically related even though they displayed a clonal diversity. The major cellular fatty acids detected in these strains included C15:0 ISO 2OH/C16:1 ω7c, hexadecanoic (16:0) and cis-11-octadecenoic (C18:1 ω7c). Their G+C contents ranged from 68.0 to 68.6 mol%, and their major isoprenoid quinone was Ubiquinone Q-8. Of these three strains, only strain USMAHM13 (= DSM 25816 = KCTC 32390) was discovered to exhibit yellow pigmentation that is characteristic of the carotenoid family. Their assembled genomes also showed that the three strains were not identical in terms of their genome sizes that were 7.82, 7.95 and 8.70 Mb for strains USMAHM13, USMAA1020 and USMAA2-4, respectively, which are slightly larger than that of Cupriavidus necator H16 (7.42 Mb). The average nucleotide identity (ANI) results indicated that the strains were genetically related and the genome pairs belong to the same species. On the basis of the results obtained in this study, the three strains are considered to represent a novel species for which the name Cupriavidus malaysiensis sp. nov. is proposed. The type strain of the species is USMAA1020T (= DSM 19416T = KCTC 32390T).

Matched MeSH terms: Metabolomics/methods
Urinary metabolic profiling of cisplatin nephrotoxicity and nephroprotective effects of Orthosiphon stamineus leaves elucidated by 1H NMR spectroscopy

Pariyani R, Ismail IS, Azam A, Khatib A, Abas F, Shaari K, et al.

J Pharm Biomed Anal, 2017 Feb 20;135:20-30.
PMID: 27987392 DOI: 10.1016/j.jpba.2016.12.010

Orthosiphon stamineus (OS) is a popular medicinal herb used in traditional Chinese medicine as a diuretic agent and for renal system disorders. This study employed 1H NMR based metabolomics approach to investigate the possible protective activity of OS in cisplatin induced nephrotoxicity owing to its diuretic and antioxidant activities. Aqueous (OSAE) and 50% aqueous ethanolic (OSFE) extracts of OS leaves were orally administered at 400mg/kg BW doses to rats which were then intraperitoneally injected with cisplatin at 5mg/kg BW dose. The 1H NMR profile of the urine samples collected on day 5 after cisplatin administration were analyzed by multivariate pattern recognition techniques, whereby 19 marker metabolites suggestive in the involvement of TCA cycle, disturbed energy metabolism, altered gut microflora and BCAA metabolism pathways were identified. It was observed that OSFE caused significant changes (p<0.05) in the levels of 8 markers namely leucine, acetate, hippurate, lysine, valine, 2-oxoglutarate, 3-HBT and acetoacetate resulting in a moderate ameliorative effect, however, it did not completely protect from nephrotoxicity. OSAE did not demonstrate significant down regulatory effects on any markers, albeit, it potentiated the cisplatin nephrotoxicity by inducing significant increase in glucose, glycine, creatinine, citrate, TMAO, acetate and creatine levels. A Principal Component Analysis (PCA) of the 1H NMR spectra of OS extracts identified that OSFE had higher concentrations of the secondary metabolites such as caffeic acid, chlorogenic acid, protocatechuic acid and orthosiphol, among others. Whereas, OSAE was characterized by higher concentrations of acetate, lactate, succinic acid, valine and phosphatidylcholine. This research denotes the first comprehensive analysis to identify the effects of OS extracts on cisplatin nephrotoxicity.

Matched MeSH terms: Metabolomics/methods*

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