UHPLC-QTOF/MS-based metabolomics investigation for the protective mechanism of Danshen in Alzheimer's disease cell model induced by Aβ1-42.

Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disorder with neither definitive pathogenesis nor effective therapy so far. Danshen, the dried root and rhizome of Salvia miltiorrhiza Bunge, is used extensively in Alzheimer's disease treatment to ameliorate the symptoms, but the underlying mechanism remains to be clarified. To investigate potential biomarkers for AD and elucidate the protective mechanism of Danshen on AD cell model. An ultra high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-QTOF/MS)-based approach combined with partial least squares discriminant analysis (PLS-DA) has been developed to discriminate the metabolic modifications between human brain microvascular endothelial cell (hBMEC) and AD cell model induced by amyloid-β protein (Aβ1-42). To further elucidate the pathophysiology of AD, related metabolic pathways have been studied. Thirty-three distinct potential biomarkers were screened out and considered as potential biomarkers corresponding to AD, which were mostly improved and partially restored back to normalcy in Danshen pre-protection group. It was found that AD was closely related to disturbed arginine and proline metabolism, glutathione metabolism, alanine aspartate and glutamate metabolism, histidine metabolism, pantothenate and CoA biosynthesis, phenylalanine tyrosine and tryptophan biosynthesis, citrate cycle and glycerophospholipid metabolism, and the protective mechanism of Danshen in AD cell model may be related to partially regulating the perturbed pathways. These outcomes provide valuable evidences for therapeutic mechanism investigation of Danshen in AD treatment, and such an approach could be transferred to unravel the mechanism of other traditional Chinese medicine (TCM) and diseases.