A metabolomic study based on accurate mass and isotopic fine structures by dual mode combined-FT-ICR-MS to explore the effects of Rhodiola crenulata extract on Alzheimer disease in rats

Abstract

A metabolomic strategy based on accurate mass and isotopic fine structures (IFSs) by dual mode combined-Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) was established to explore the effects of Rhodiola crenulata extract (RCE) on Alzheimer disease (AD) in rats. Experimental AD model was induced in rats by bilateral hippocampal injection of Aβ1-42, and Morris water maze task (MWM) was used to evaluate the effects of RCE on AD. Subsequently, the metabolomic study was performed using HPLC-FT-ICR-MS, fraction collector and direct infusion (DI)-FT-ICR-MS to screen and identify the potential biomarkers. A total of 20 metabolites contributing to AD progress were identified, and 17 metabolites of them were restored to the control-like levels after RCE treatment (daily dose: 2.24 g/kg). The metabolic pathway analysis revealed that the disturbed pathways including tryptophan metabolism, sphingolipid metabolism and glycerophospholipid metabolism in AD model rats were regulated after high dose RCE application. It is the first time that the dual mode combined-FT-ICR-MS based metabolomic strategy was applied to biochemically profile the serum metabolic pathways of AD rats affected by RCE. These outcomes provide reliable evidence to illuminate the biochemical mechanisms of AD and facilitate investigation of the therapeutic benefits of RCE in AD treatment. Notably, it indicated that the developed method based on accurate mass and IFSs has sufficient performance for identification of biomarkers in metabolomic studies.