Subject(s)
Antioxidants , Carbon Tetrachloride , Chemical and Drug Induced Liver Injury , Liver , Plant Oils , Rosa , Seeds , Animals , Antioxidants/pharmacology , Mice , Rosa/chemistry , Chemical and Drug Induced Liver Injury/prevention & control , Seeds/chemistry , Carbon Tetrachloride/adverse effects , Male , Plant Oils/pharmacology , Plant Oils/chemistry , Liver/drug effects , Liver/metabolism , Protective Agents/pharmacology , Humans , Plant Extracts/pharmacologyABSTRACT
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 Aß25-35-induced cognitive impairment, improved hippocampal neuron morphology, decreased Aß 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.
Subject(s)
Alzheimer Disease , Metabolome , Metabolomics , Rats, Sprague-Dawley , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Animals , Metabolomics/methods , Rats , Chromatography, High Pressure Liquid/methods , Male , Metabolome/drug effects , Metabolome/physiology , Tandem Mass Spectrometry/methods , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/administration & dosage , Biomarkers/blood , Biomarkers/urine , Hippocampus/metabolism , Hippocampus/drug effects , Amyloid beta-Peptides/metabolismABSTRACT
Schisandra chinensis and Evodia rutaecarpa are traditional Chinese herbs used to treat neurodegenerative diseases. This study investigates the combined effects of SC and ER on learning and memory in an Alzheimer's disease rat model and their underlying mechanisms. Methods: High-performance liquid chromatography was employed to analyze the primary active constituents of Schisandra and Evodia. The effects of the combined treatment of Schisandra and Evodia on learning and memory in an Alzheimer's disease rat model were evaluated through Morris water maze and Hematoxylin-Eosin staining experiments. Immunohistochemical analysis was conducted to investigate the impact of S-E on Aß1-42 and P-tau proteins. Western blotting and real-time quantitative polymerase chain reaction were utilized to quantify the expression of pivotal proteins and genes within the BDNF/TRKB/CREB and GSK-3ß/Tau pathways. Results: The treatment group exhibited significant neuroprotective effects, ameliorating learning and memory impairments in the Alzheimer's disease rat model. The treatment regimen modulated the activity of the BDNF/TRKB/CREB and GSK-3ß/Tau pathways by influencing the expression of relevant genes, thereby reducing the generation of Aß1-42 and P-Tau proteins and inhibiting the deposition of senile plaques. Furthermore, among the three treatment groups, the combined treatment demonstrated notably superior therapeutic effects on Alzheimer's disease compared to the single-drug treatment groups.
