Serum and urine metabolomics based on UPLC–QTOF/MS reveal the effect and potential mechanism of “schisandra–evodia” herb pair in the treatment of Alzheimer's disease

The “schisandra–evodia” herb pair (S–E) is a herbal preparation to treat Alzheimer's disease (AD). This study aims to investigate the therapeutic efficacy and potential mechanism of S–E in AD rats, utilizing pharmacodynamic assessments and serum‐ and urine‐based metabolomic analyses. Pharmacodynamic assessments included Morris water maze test, hematoxylin–eosin staining and immunohistochemistry experiments. The results of the study showed that the AD model was successful; the S–E significantly enhanced long‐term memory and spatial learning in AD rats. Meanwhile, S–E notably ameliorated Aβ25–35‐induced cognitive impairment, improved hippocampal neuron morphology, decreased Aβ deposition in the hippocampus and mitigated inflammatory damage. We then analyzed serum and urine samples using UPLC–MS/MS to identify potential biomarkers and metabolic pathways. Metabolomic analysis revealed alterations in 40 serum metabolites and 38 urine metabolites following S–E treatment, predominantly affecting pathways related to taurine and hypotaurine metabolism, linoleic acid metabolism, α‐linolenic acid metabolism, glycerophospholipid metabolism and arachidonic acid metabolism. This study elucidates the biochemical mechanism underlying AD and the metabolic pathway influenced by S–E, laying the groundwork for future clinical applications.