Intervention effect of adenosine on Alzheimer's disease based upon non-targeted metabolomics
OBJECTIVE To employ metabolomics to explore the intervention effect of adenosine on metabolic disorders in murine model of Aβ25-35 peptide-induced Alzheimer's disease(AD).METHODS Mice were divided into four groups of con-trol,model,positive drug and adenosine.Intracerebroventricular injection(ICV)of Aβ 25-35 peptide simulated the physiological and pathological state of AD.The urinary samples of each group were collected at 12 hours after the last oral administration.UHPLC-Q/TOF-MS was utilized for detecting all metabolites from urinary samples.The pre-processed data were imported into SIMCA-P software for principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)and screening out potential biomarkers.The biomarkers were further identified by online datasets of HMDB and MassBank.Mev software was adopted for hierarchical cluster analysis of relative content of biomarkers in each group.Finally pathway enrich-ment analysis and metabolic network construction were carried out by combining the online databases of MBRole,KEGG and MetaboAnalyst 5.0.RESULTS The metabolic profiles of mice in model group became significantly altered by intervention of adenosine group and reversed towards control group.Fifty-night biomarkers were identified between model and adenosine groups(38 in positive ion mode,21 in negative ion mode).The biomarkers were enriched to obtain the markedly altered metabolic path-ways of nicotinate/nicotinamide metabolism,arginine/proline metabolism,arginine biosynthesis,phenylalanine metabolism and cysteine/methionine metabolism.CONCLUSION Adenosine may repair nervous damage in AD mice through regulating amino acid and vitamin metabolisms.It provides theoretical rationales for clinical dosing of adenosine for AD.
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