An Integrated Metabolomic Screening Platform Discovers the Potential Biomarkers of Ischemic Stroke and Reveals the Protective Effect and Mechanism of Folic Acid

Abstract

Folic acid has a protective effect 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 in metabolites and pathways were characterized. We found that the metabolic alteration involved a total of 37 metabolites, of which 26 biomarkers such as γ-aminobutyric 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 middle cerebral artery occlusion-induced rat ischemic stroke model by delaying pathological development, reversing the metabolic biomarkers, and mainly regulating the perturbation in 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 a better understanding of the therapeutic effect and mechanism of drugs.

Neuroprotective Effects and Metabolomics Study of Protopanaxatriol (PPT) on Cerebral Ischemia/Reperfusion Injury In Vitro and In Vivo

“…When present at very high levels, phenylalanine acts as a neurotoxin and can damage nerve cells and tissues [ 34 ]. According to studies, brain ischemia damage can result in a rise in the phenylalanine [ 35 ]. According to our findings, phenylalanine levels in the model group were considerably higher than in the sham one, which is in line with other studies [ 36 ].…”

Metabolomic discoveries for early diagnosis and traditional Chinese medicine efficacy in ischemic stroke

“…Yang et al used metabolomics to study the protective effects of folic acid on IS [ 150 ]. They identified 26 differential metabolites, including γ-aminobutyric acid (GABA), lysine, and glutamate, which are involved in various processes such as inhibiting oxidative stress (Fig.…”