MetaboLightsapplication/xmlftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/m_MTBLS867_metabolite_profiling_mass_spectrometry-3_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/m_MTBLS867_metabolite_profiling_mass_spectrometry-1_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/m_MTBLS867_metabolite_profiling_mass_spectrometry_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/m_MTBLS867_metabolite_profiling_mass_spectrometry-2_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/a_MTBLS867_LC-MS_metabolite_profiling_mass_spectrometry.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/a_MTBLS867_LC-MS_metabolite_profiling_mass_spectrometry-2.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/a_MTBLS867_LC-MS_metabolite_profiling_mass_spectrometry-3.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/s_MTBLS867.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/a_MTBLS867_LC-MS_metabolite_profiling_mass_spectrometry-1.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/i_Investigation.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180824_12549HL.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180824_12550T.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180824_11481H.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180927_11479B.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180921_13418T.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180927_QC_14.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180927_11481H.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180824_11479B.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180824_QC_12.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180921_QC_11.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180927_12550T.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180927_11170HB.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180927_QC_12.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180927_11468H.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180911_13418BT.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180911_QC_14.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180911_QC_11.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180921_11170HB.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180824_13418HB.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180911_11481HB.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180824_11471CL.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180921_QC_16.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180824_11468H.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180927_11468BT.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180824_13415HBT.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180927_13418T.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180921_11468BT.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180921_11479B.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180911_13418HB.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180824_11481HB.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180921_QC_14.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180921_12549HL.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180921_13418HB.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180911_13415HBT.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180824_11170HB.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180921_13415HBT.raw.zipftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS867/FILES/20180911_13418T.raw.zipftp://ftp.ebi.ac.uk/pub/databa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QI (Waters, Nonlinear Dynamics, and the USA) was used for the identification of metabolite features. Metabolites identification search was performed using the Human Metabolome Database (HMDB2016) within a mass error of 10 ppm. Identifications matched with fragmentation database were labeled as MSI level 2 and remaining annotations were labeled as MSI level 3 as described earlier.MetaboLightsPublicRP_Neg_MSHILIC_Pos_MSHILIC_Neg_MSRP_Pos_MSAn ultra-performance liquid chromatography system (ACQUITY UPLC, Waters) attached to a mass spectrometer was used for the analysis. The Hydrophilic Interaction Chromatography (HILIC) method was performed with a BEH column (ACQUITY BEH HILIC column, 130 A°, 1.7 μm, 2.1mm X 150mm, Waters). For the HILIC mobile phase, A was 95% Acetonitrile in 10mM ammonium acetate and B was 50% Acetonitrile in 10mM ammonium acetate. Both A and B contained 0.1% formic acid and 0.1% acetic acid in positive ion mode and negative ion mode respectively. The HILIC positive ion gradient was 0 min, 1% B; 5 min, 20% B; 10 min, 50% B; 14 min, 95% B; 16 min, 95% B; 17 min, 1% B; and 20 min, 1% B. Reversed-Phase Liquid Chromatography (RPLC) technique was employed with a C18 column (ACQUITY UPLC HSS T3 C18 column, 100 A°, 1.8 μm, 2.1mm X 100mm, Waters). In the RPLC Method, mobile phase consisted of aqueous (A) and organic (B) solvent components, where A was 0.1% formic acid in water and B was 0.1% formic acid in methanol. The gradient was 0 min, 0% B; 1 min, 0% B; 16 min, 100% B; 20 min, 100% B, and 22 min, 0% B. The injection volume was 5 µl with a flow rate of 0.4 ml/min and the column temperature of 40°C.Untargeted metabolomics reveals alterations in metabolites of lipid metabolism and immune pathways in the serum of rats after long-term oral administration of Amalaki rasayana. 10.1007/s11010-019-03637-1.Aneesh KumarRGCBblood plasmamass spectrometrySerum samples of rats were stored at -80 °C until analysis. Frozen cryovials were thawed, vortexed and centrifuged for 10 mins at 2000 rpm, 4 °C. Quality control samples were prepared by pooling equal volume of aliquots from all the samples (10 μl) to a fresh Eppendorf tube and mixing with methanol (4 times the volume of total sample in Eppendorf tube). For sample preparation, 100 μl of sample was added to a fresh Eppendorf tube and mixed with 400 μl methanol. Samples and quality control samples were then incubated for 1 hr at -20 °C, vortexed and then centrifuged for 20 mins at 14000 rpm, 4 °C. Supernatant was collected in fresh Eppendorf tubes and vacuum dried. Dried samples were stored at -80 °C until analysis. Samples were dissolved in 100 µl of solvent containing 50% methanol and 0.1% formic acid.Rattus norvegicushttps://www.ebi.ac.uk/metabolights/MTBLS867Aneesh A.. Rajiv Gandhi Centre for Biotechnology. Cardiovascular Diseases and Diabetes Biology. aneeshkumar@rgcb.res.in. 0471 252 9624.MassLynx4.1 SCN781 (Waters) was used for data acquisition. Progenesis QI (Non-linear dynamics, Waters) was used for raw data analysis. Progenesis produced a feature matrix that contained accurate mass (m/z), retention time (RT), and chromatographic peak area. The features detected in <70% of the QC samples were removed with a relative standard deviation of < 30% in the QC samples were used for further statistical analysis. The quality of the data was evaluated by principal component analysis (PCA) of QC samples and study samples as described earlier.GroupTreatmentSample typeDoseaneeshkumar@rgcb.res.inAnimal experiments were conducted after approval from the Institutional Animal Ethics Committee (IAEC) of Rajiv Gandhi Center for Biotechnology (RGCB). During all the animal experiments, we strictly followed the rules and regulations of the Committee for the purpose of Control and Supervision of Experiments on Animals (CPCSEA), Government of India. Three months old male Wistar rats were procured from the animal house and kept at 12 hrs day/night cycle at controlled humidity and temperature with food and water ad libitum. Animals were then divided into three groups, each group having 8 animals. Amalaki rasayana or GH (500 mg/kg, orally) was administered for 18 months to two groups of rats. One group of rats was left untreated. Body weights were monitored on a weekly basis until the sacrifice of the animals. Body weights were recoded for all the rats on a weekly basis. At 21 months of age (after 18 months of AR administration), all the animals were sacrificed and blood samples were collected.Metabolomicsultra-performance liquid chromatography-mass spectrometryinflammationAmalakirasayanauntargeted metabolitesultra-performance liquid chromatography-mass spectrometryinflammationAmalakirasayanauntargeted metabolitesThe Quadrupole - Time of Flight (Q-TOF) mass spectrometer (MS/MS, SYNAPT-G2, Waters) was operated in resolution mode (MSE) with electrospray ionization (ESI). The selected mass range was from 50 to 1200 m/z in full scan mode with a scan time of 0.25 secs and an inter-scan delay of 0.024 secs. Ion source and desolvation gas (nitrogen) temperatures were kept at 112 °C and 350 °C respectively. The sampling cone and desolvation gas flow rates were 60 l/h and 875 l/h respectively. Capillary voltage was set at 2.85 kV. Sampling cone voltage was set at 40 V. The lock mass acquisition was made every 10 secs by Leucine enkephalin (MW= 555.62) for accurate on-line mass calibration. Initially 10 QC sample runs were used for the stabilisation of the system. QC samples were then acquired after every 5th sample run.S-AdenosylmethioninamineCorchorifatty acid F1H-Indole-3-carboxaldehydeMollicellin F9,10-DHOMENilvadipineGlycerylphosphorylethanolamineGentamicinp-Cresol sulfateAmisulprideUrsocholic acidLysoPC(22:6(4Z,7Z,10Z,13Z,16Z,19Z))Tauroursodeoxycholic acidBilirubinLysoPC(17:0)CortolD-XyloseLysoPC(P-18:0)Alpha-dimorphecolic acidOleoyl-CoA12(13)Ep-9-KODE3b,12a-Dihydroxy-5a-cholanoic acidLactosamineHarmalolNetilmicinTaurocholic acidHexadecanedioic acidL-RibuloseBortezomibLuteolinidin3a,7a,12b-Trihydroxy-5b-cholanoic acid9,12,13-TriHOMEBiotin amideQuininePyrocatechol sulfateLysoPC(14:0)Ethyl 3-hydroxytridecanoate11-Dehydro-thromboxane B2Muricholic acid4-HydroxydebrisoquineBerberrubineFluphenazineCandoxatrilLysoPC(20:4(5Z,8Z,11Z,14Z))L-LysineOrnithineLamotrigineLysoPE(0:0/16:0)Procainamide2,4-Diamino-6-nitrotolueneN-DesmethylcitalopramProstaglandin E1Indole-3-carboxilic acid-O-sulphateGlutamyl-GlutamateTaurodeoxycholic acidLysoPC(15:0)Perfluorooctanoic acidGestrinoneO-methoxycatechol-O-sulphateL-Tryptophan(R)-3-Hydroxy-hexadecanoic acidbeta-D-3-Ribofuranosyluric acidSulfacytineLysoPE(0:0/20:4(5Z,8Z,11Z,14Z))LysoPC(18:2(9Z,12Z))AvocadeneMiglitol1-ArachidonoylglycerophosphoinositolTofisopamXanthineTetrabenazine8-iso-PGA1Gamma-TocotrienolLysoPC(16:0)LysoPC(18:3(6Z,9Z,12Z))1-[(5-Amino-5-carboxypentyl)amino]-1-deoxyfructose19,20-DiHDPACis-stilbene oxideLysoPE(0:0/18:2(9Z,12Z))DeoxycytidineArachidyl carnitineHeptadecanoic acidDoxapramPhenol sulphateLysoPC(16:1(9Z))MepyramineRat, Other diseases of pericardium (disorder), 9alpha, Immune Systems, Cardiovascular disease, determination, Laboratory, Other pericardial disease NOS (disorder), Blood, Other heart disease NOS (disorder), Cardiovascular disorder, Metabonomic, metazoans, PAPILLARY MUSCLE DIS NEC, Norway Rat, Metabonomics, protein, Cardiac Event, Tumor, Serum, [X]Other specified diseases of pericardium (disorder), Norway Rats, extracted material, prevention, rat, unspecified, Anhydrous Butterfats, Disease of cardiovascular system (disorder), Other heart disease NOS, gamma-L-Glutamyl-L-cysteinyl-glycine, CVD, 13-dien-1-oic acid, Norway rat, Wistar, protein aggregate, 9, prevention and control, Animalia, treatment, Group, Cardiovascular Diseases, Thromboxa-5, reference sample, Glycine, long, Reduced, [X]Other forms of heart disease (disorder), 5-L-Glutamyl-L-cysteinylglycine, Other ill-defined heart disease (disorder), Other diseases of endocardium, Groups, circulatory system disease, SURGICAL AND MEDICAL PROCEDURES, Laboratory Rat, Glutathione, Reduced glutathione, preventive measures, 13E, Disorder of cardiovascular system, Immune, malignant neoplasm, arachidonic acid metabolism, disease management, Therapies, Malignancies, Event, Tumors, Therapy, Circulatory system disease NOS (disorder), preventive therapy, Disorder of circulatory system, gamma-L-Glu-L-Cys-Gly, Rattus, Procedure, Blood Serum, disease of subdivision of hemolymphoid system, Menstruation, Mus norvegicus, Benign, Rattus norwegicus, Lipid, Period., Adverse Cardiac Event, NOS, Other pericardial disease NOS, CIRCULATORY DISEASE NOS, CARDIOVASC DIS, System, Adverse Cardiac Events, Disorder of the circulatory system, Control, Benign Neoplasms, [X]Other ill-defined heart diseases (disorder), 15S)-, rats, Anhydrous Butterfat, Treatments, GSH, Malignant Neoplasms, Physician, phospholipid metabolism, ILL-DEFINED HRT DIS NEC, (5Z, Butter Oil, Clarified, Disease affecting entire cardiovascular system, Elderly, Cardiovascular Disorders, ASCVD, Cardiovascular system disease, norvegicus, Neoplasms, Other heart disease (disorder), Benign Neoplasm, Amalaki Rasayana, 7-hydroxy-3-(4-hydroxyphenyl)-6-methoxy-4H-1-benzopyran-4-one, Gene, gamma-L-Glutamyl-L-Cysteinylglycine, Other diseases of pericardium, Other disorders of papillary muscle, Adverse, protein-containing complex, Malignant, animals, unspecified (disorder), Intervention or Procedure, N-(N-L-gamma-glutamyl-L-cysteinyl)-, Disorder of cardiovascular system (disorder), [X]Cardiovascular disease, Rattus sp. strain Wistar, Oils, Cardiac, Wistar Rats, Rats, Clarified Butters, Ghees, Metabolism, Gene Products, Rattus rattiscus, Animal, Metabolomic, Other ill-defined heart disease NOS (disorder), Unspecified circulatory system disorder, brown rat, study, Other diseases of endocardium (disorder), Rattus norvegicus, lipid metabolism, [X]Other specified diseases of pericardium, Malignancy, interventionDescription, Other heart disease, Interventional, Other forms of heart disease, N-(N-gamma-L-Glutamyl-L-cysteinyl)glycine, 11-keto-thromboxane B2, Other specified pericardial disease NOS, 15-dihydroxy-11-oxo-, gamma L Glutamyl L Cysteinylglycine, cardiovascular disease, Neoplasias, Butter, Butterfat, gamma L Glu L Cys Gly, Control Group, arachidonic acid metabolic process, Disease of cardiovascular system, Wistar Rat, Circulatory system disease NOS, Anhydrous, Controlled, OTHER SEQUELAE OF MI NEC, Cancer, Rattus norvegicus8, Intervention Strategies, Disease, Controlling, Other ill-defined heart diseases, Malignant Neoplasm, protein complex, not elsewhere classified, Proteins, Honeys, Disease affecting entire cardiovascular system (disorder), Other ill-defined heart disease, Cardiac Events, MT, native protein, Laboratory Rats, Metazoa, chemical analysis, Protein, Systems, Neoplasm, Oil, Other forms of heart disease (disorder), Other ill-defined heart disease NOS, Reduced Glutathione, PERICARDIAL DISEASE NEC, Intervention, Other specified diseases of pericardium, 11-dehydrothromboxane B2, Cardiovascular, primary cancer, Butters, [X]Other ill-defined heart diseases, prophylaxis, [X]Other forms of heart disease, Butter Oils, Cancers, Other sequelae of myocardial infarction, malignant tumor, Cardiovascular Disease, CVS disease, Protein Gene Products, multicellular animals, Gene Proteins, Other specified pericardial disease NOS (disorder), fatty acid metabolism, Therapeutic, control, 11-dehydro-TXB2, Clarified Butter, Treatment, leukotriene metabolism, Glutathione-SH, Major Adverse Cardiac Events, Norway, assay, Butterfats, Neoplasia, Serums, Gunn ratsbrown rat, Rat, Oral Administrations, lipid metabolism, Rattus norvegicus, Amalaki Rasayana., norvegicus, Drug Administration, Laboratory, Oral, Blood, long, Oral Administration, Metabonomic, Oral Drug Administrations, Norway Rat, Metabonomics, Rattus, Blood Serum, Serum, rats, Norway Rats, Laboratory Rat, Administration, rat, Rattus sp. strain Wistar, Mus norvegicus, Rattus norwegicus, Rats, Metabolism, Laboratory Rats, Lipid, Drug Administrations, Norway rat, Norway, Rattus rattiscus, Metabolomic, Oral Drug Administration, Serums, Oral Drug, Rattus norvegicus8, Gunn rats, AdministrationsfalseUntargeted metabolomics reveals alterations in metabolites of lipid metabolism and immune pathways in serum of rats after long term oral administration of Amalaki rasayanaAmalaki rasayana (AR), a traditional preparation is widely used by Ayurvedic physicians for the treatment of inflammatory conditions, cardiovascular diseases, cancer and for rejuvenating aged people. Metabolic alterations induced by Amalaki rasayana intervention are unknown. We aimed to investigate modulations in serum metabolomic profiles following long term oral Amalaki rasayana administration in Wistar rats. A global metabolic profiling was performed of the serum of rats administered with Amalaki rasayana or ghee+honey (GH) for 18 months and control animals which were left untreated. Amalaki rasayana components were identified from AR extract using HR-LCMS analysis. Significant reductions in prostaglandin J2, 11-dehydrothromboxane B2 and higher levels of reduced glutathione and glycitein metabolites were observed in serum of AR administered rats compared to the control groups. Pathway analysis suggest that altered metabolites in AR administered rats are those associated with different biochemical pathways of arachidonic acid metabolism, fatty acid metabolism, leukotriene metabolism, G-protein mediated events, phospholipid metabolism and the immune system. Our study identifies the AR components that induce alterations in lipid metabolism and immune pathways in animals which consume AR for a long period.2019-05-242019-02-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