title: Analysis of serum metabolites for the discovery of amino acid biomarkers and the effect of galangin on cerebral ischemia.
abstract: Ischemic stroke, a devastating disease with a complex pathophysiology, is a leading cause of death and disability worldwide. In our previous study, we reported that galangin provided direct protection against ischemic injury and acted as a potential neuroprotective agent. However, its associated neuroprotective mechanism has not yet been clarified. In this paper, we explored the potential AA biomarkers in the acute phase of cerebral ischemia and the effect of galangin on those potential biomarkers. In our study, 12 AAs were quantified in rat serum and found to be impaired by middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia. Using partial least squares discriminate analysis (PLS-DA), we identified the following amino acids as potential biomarkers of cerebral ischemia: glutamic acid (Glu), homocysteine (Hcy), methionine (Met), tryptophan (Trp), aspartic acid (Asp), alanine (Ala) and tyrosine (Tyr). Moreover, four amino acids (Hcy, Met, Glu and Trp) showed significant change in galangin-treated (100 and 50 mg kg(-1)) groups compared to vehicle groups. Furthermore, we identified three pathway-related enzymes tyrosine aminotransferase (TAT), glutamine synthetase (GLUL) and monocarboxylate transporter (SLC16A10) by multiplex interactions with Glu and Hcy, which have been previously reported to be closely related to cerebral ischemia. Through an analysis of the metabolite-protein network analysis, we identified 16 proteins that were associated with two amino acids by multiple interactions with three enzymes; five of them may become potential biomarkers of galangin for acute ischemic stroke as the result of molecule docking. Our results may help develop novel strategies to explore the mechanism of cerebral ischemia, discover potential targets for drug candidates and elucidate the related regulatory signal network.
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.forename: Hongjun
authors.initials: H
authors.lastname: Yang
authors.forename: Jianxin
authors.initials: J
authors.lastname: Chen
authors.forename: Jiansong
authors.initials: J
authors.lastname: Fang
authors.forename: Chang
authors.initials: C
authors.lastname: Chen
authors.forename: Rixin
authors.initials: R
authors.lastname: Liang
authors.forename: Gengliang
authors.initials: G
authors.lastname: Yang
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wu
authors.forename: Chuanhong
authors.initials: C
authors.lastname: Wu
authors.forename: Shaojing
authors.initials: S
authors.lastname: Li
mesh_terms: D026905:Amino Acid Transport Systems / Q000378:metabolism; D000596:Amino Acids / Q000097:blood* / Q000737:chemistry; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood / Q000737:chemistry; D002545:Brain Ischemia / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008516:Medicine, Chinese Traditional; D055432:Metabolomics / Q000379:methods; D062105:Molecular Docking Simulation; D018377:Neurotransmitter Agents / Q000097:blood; D011485:Protein Binding; D060066:Protein Interaction Maps; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry
chemical_list: D026905:Amino Acid Transport Systems; D000596:Amino Acids; D000975:Antioxidants; D015415:Biomarkers; D005419:Flavonoids; D018377:Neurotransmitter Agents; C037032:galangin