Yang Yan-Hui, Lei Lei, Bao Yin-Ping, Zhang Lu
Department of Clinical Nutrition, The Second Affiliated Hospital, Harbin Medical University, Harbin, China.
Department of Nutrition, Harbin First Hospital, Harbin, China.
Front Mol Biosci. 2022 May 18;9:783793. doi: 10.3389/fmolb.2022.783793. eCollection 2022.
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 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.
叶酸对缺血性中风具有保护作用。然而，其保护作用的药理机制仍不清楚。本研究旨在通过一个综合代谢组学生物标志物筛选平台，探索叶酸对缺血性中风动物的保护作用。基于超高效液相色谱-串联质谱（UPLC/MS）结合多变量数据分析，对代谢物和代谢途径的变化进行了表征。我们发现，代谢改变共涉及37种代谢物，其中26种生物标志物，如γ-氨基丁酸、赖氨酸、谷氨酸、核糖和缬氨酸，可被叶酸调节，涉及氨基酸代谢、碳水化合物代谢、脂肪酸代谢、柠檬酸循环和丙酮酸代谢等代谢途径，这些可能是叶酸抗缺血性中风的潜在治疗靶点。叶酸作为一种新兴的潜在天然抗纤维化剂，通过延缓病理发展、逆转代谢生物标志物以及主要调节氨基酸代谢、碳水化合物代谢、脂肪酸代谢、柠檬酸循环和丙酮酸代谢的紊乱，在保护大脑中动脉闭塞诱导的大鼠缺血性中风模型方面具有显著活性。研究还表明，综合代谢组学生物标志物筛选平台能够更好地理解药物的治疗效果和机制。
