Ultraperformance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Mass Spectrometry-Based Metabolomics and Lipidomics Identify Biomarkers for Efficacy Evaluation of Mesalazine in a Dextran Sulfate Sodium-Induced Ulcerative Colitis Mouse Model

Abstract

This study aims to identify biomarkers for evaluating the therapeutic efficacy of mesalazine on ulcerative colitis by metabolomics and lipidomics. A dextran sulfate sodium-induced mouse model was used. The disease status was assessed by a disease activity index, the TNF-α level of colon was measured by an enzyme-linked immunosorbent assay, and the pathological changes of colon tissue was examined by hematoxylin−eosin staining. Serum metabolomics and lipidomics analysis based on ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry were applied to decipher the metabolic profile changes. Multivariate analysis was applied to differentiate the metabolites of controls, models, and mesalazine-treated mice. By the receiver operating characteristic (ROC) analysis, 40 differential metabolites with an area under curve (AUC) >0.80 were screened out between control and model groups. Among them, four potential biomarkers (palmitoyl glucuronide, isobutyrylglycine, PC (20:3 (5Z, 8Z, 11Z)/15:0) and L-arginine) had a signficantly reversed level of peak areas in the mesalazine group, and three of them were closely correlated with mesalazine efficacy by linear regression analysis. Furthermore, metabolic pathway analysis revealed several dysregulated pathways in colitis mice, including glycerophospholipid metabolism, pyrimidine metabolism, linoleic acid metabolism, arginine biosynthesis, etc. This study indicates that serum metabolomics is a useful approach that can noninvasively evaluate the therapeutic effect and provide unique insights into the underlying mechanism of mesalazine.

The development and validation of a sensitive HPLC-MS/MS method for the quantitative and pharmacokinetic study of the seven components of Buddleja lindleyana Fort.

“…Four sample-solvent ratios (1 : 15, 1 : 25, 1 : 35 and 1 : 60, w/v) were compared, and the sample-solvent ratio of 1 : 25 was chosen. Different ultrasonication times (15,30,40,45 and 60 min) were also compared. The results displayed that the extraction efficiency would no longer increase when the time of extraction was higher than 40 min.…”

“…15,16 Moreover, it has been used to study drug metabolism, [17][18][19][20][21][22] toxicokinetics, 23,24 lipidomics, 25,26 proteomics 27,28 and metabolomics. 29,30 The main advantage of mass spectrometry (MS/MS) is the ability to detect a broad range of drugs with high sensitivity and specicity in a single analytical run. [31][32][33][34] Chemical compounds are recognized by comparing their retention times and parent-daughter ions with those of reference substances.…”

Gancao Xiexin Decoction Ameliorates Ulcerative Colitis in Mice via Modulating Gut Microbiota and Metabolites

“… 27–29 Then mice in the GCXX group received 8.55 g/kg GCXX once daily, the Mes group received 200 mg/kg mesalazine, and the GMes group received 8.55 g/kg GCXX and 200 mg/kg mesalazine. 33 , 34 The mice of the NC and UC groups received an equal volume of distilled water. All mice were treated for 7 days by gastric gavage once a day.…”

Ion Mobility Coupled to a Time-of-Flight Mass Analyzer Combined With Fragment Intensity Predictions Improves Identification of Classical Bioactive Peptides and Small Open Reading Frame-Encoded Peptides

“…In this study, we introduce a two-step methodology combining firstly a trapped ion mobility spectrometry coupled to a time-of-flight mass analyzer (timsTOF) to generate the highest quality MSMS spectra, secondly the MS 2 ReScore (Silva et al, 2019) application leading to an improved identification of potential bioactive peptides in different regions of the mouse brain. timsTOF offers an enhanced peptide coverage and reduction in chemical noise (Lubeck et al, 2018) because of its extra dimension of separation (Meier et al, 2018), previously described in different applications in the field of clinical proteomics (Azkargorta et al, 2020;Macron et al, 2020;Hamada et al, 2021;Liu et al, 2021). The MS 2 ReScore tool, including MS 2 PIP that predicts the fragment ion intensity as an additional feature, DeepLC predicting retention times (Bouwmeester et al, 2021) and the post-processing tool Percolator, further boost the yield of identified peptides.…”