AUTHOR=Yang Yan-hui , Lei Lei , Bao Yin-ping , Zhang Lu TITLE=An Integrated Metabolomic Screening Platform Discovers the Potential Biomarkers of Ischemic Stroke and Reveals the Protective Effect and Mechanism of Folic Acid JOURNAL=Frontiers in Molecular Biosciences VOLUME=Volume 9 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2022.783793 DOI=10.3389/fmolb.2022.783793 ISSN=2296-889X ABSTRACT=Folic acid has an effect on the protecting against ischemic stroke. However, the protective pharmacological mechanism remains unclear. The aim of this study is to explore the protective effect of folic acid on ischemic stroke animals by an integrated metabolomic biomarker screening platform. Based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MS) coupled with multivariate data analysis, the changes of metabolites and pathways were characterized. We found the metabolic alteration involved in a total of 37 metabolites, of which 26 biomarkers such as γ-amino butyric acid, lysine, glutamate, ribose and valine can be regulated by folic acid via metabolic pathways of amino acid metabolism, carbohydrate metabolism, fatty acid metabolism, citrate cycle and pyruvate metabolism, which may be the potential therapeutic targets of folic acid against ischemic stroke. Folic acid as an emerging potential natural anti-fibrosis agent has significant activity in protecting against in middle cerebral artery occlusion-induced rat ischemic stroke model by delaying pathological development, reversing the metabolic biomarkers and mainly regulating the perturbation amino acid metabolism, carbohydrate metabolism, fatty acid metabolism, citrate cycle and pyruvate metabolism. It also showed that the integrated metabolic biomarker screening platform could provide better understanding of therapeutic effect and mechanism for drug.