Integrated metabolomics and mass spectrometry imaging reveal the Anti-Alzheimer's mechanisms of turmeric and curcumin.

INTRODUCTION

Turmeric and its major bioactive component, curcumin, have shown promising potential in the prevention and management of Alzheimer's disease (AD). However, the underlying molecular mechanisms and the contribution of turmeric residues remain incompletely understood. This study aimed to investigate the protective effects of curcumin and turmeric residue in an Aβ1-42-induced AD mouse model and to elucidate their metabolic regulatory mechanisms.

METHODS

The phytochemical profiles of turmeric and turmeric residue were characterized using UPLC-MS/MS combined with bioinformatics analysis. An Aβ1-42-induced AD mouse model was established, and mass spectrometry imaging (AFAI-MSI) was applied to determine the optimal modeling time point. The therapeutic effects of curcumin and turmeric residue were evaluated through behavioral assessments, including the Morris water maze test, as well as histopathological and molecular analyses involving H&E staining, Nissl staining, immunofluorescence, and immunohistochemistry. Furthermore, non-targeted metabolomics was performed to identify metabolic alterations associated with treatment.

RESULTS

UPLC -MS/MS analysis identified 132 and 104 compounds in turmeric and turmeric residue, respectively, with 10 compounds showing significant differences in abundance between the two materials. AFAI-MSI analysis indicated that three weeks after Aβ1-42 injection represented an optimal time point for AD model establishment. Behavioral experiments demonstrated that both curcumin and turmeric residue significantly improved spatial learning and memory impairment in AD mice. Histological and molecular analyses revealed reduced neuronal damage and modulation of Aβ1-42 and Iba-1 expression in brain tissues. Metabolomic profiling identified 25 differential plasma metabolites and 38 differential brain metabolites following treatment. Pathway enrichment analysis suggested that these metabolic alterations were mainly associated with ether lipid, sphingolipid, glycerophospholipid, glutamate, purine, and arachidonic acid metabolism.

DISCUSSION: These findings demonstrate that curcumin and turmeric residue exert neuroprotective effects against AD-related pathological alterations by regulating metabolic disturbances and restoring metabolite homeostasis. The integration of chemical profiling, AFAI-MSI, and metabolomics provides new insights into the therapeutic potential and metabolic mechanisms of turmeric-derived resources in Alzheimer's disease.