Efficacy and Mechanism of Schisandra chinensis Fructus Water Extract in Alzheimer's Disease: Insights from Network Pharmacology and Validation in an Amyloid-β Infused Animal Model.

Publisher: MDPI Publishing Country of Publication: Switzerland NLM ID: 101521595 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6643 (Electronic) Linking ISSN: 20726643 NLM ISO Abbreviation: Nutrients Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI Publishing

Schisandra*/chemistry ; Alzheimer Disease*/drug therapy ; Amyloid beta-Peptides*/metabolism ; Disease Models, Animal* ; Hippocampus*/metabolism ; Hippocampus*/drug effects ; Plant Extracts*/pharmacology ; Network Pharmacology* ; Rats, Sprague-Dawley*; Animals ; Male ; Rats ; Lignans/pharmacology ; Cyclooxygenase 2/metabolism ; Peptide Fragments ; Fruit/chemistry ; Cyclooctanes/pharmacology ; Lipid Metabolism/drug effects ; Memory/drug effects ; Polycyclic Compounds/pharmacology

Background/objectives: Schisandra chinensis Fructus (SCF) is a traditional medicinal herb containing lignans that improves glucose metabolism by mitigating insulin resistance. We aimed to investigate the therapeutic potential and action mechanism of SCF for Alzheimer's disease (AD) using a network pharmacology analysis, followed by experimental validation in an AD rat model.
Methods: The biological activities of SCF's bioactive compounds were assessed through a network pharmacology analysis. An AD rat model was generated by infusing amyloid-β peptide (Aβ) (25-35) into the hippocampus to induce Aβ accumulation. The AD rats were fed either 0.5% dextrin (AD-Con) or 0.5% SCF (AD-SCF group) in a high-fat diet for seven weeks. The rats in the normal/control group received an Aβ (35-25) infusion (no Aβ deposition) and were fed a control diet (Normal-C). Aβ deposition, memory function, inflammation, and glucose/lipid metabolism were evaluated.
Results: The network analysis revealed significant intersections between AD-related targets and bioactive SCF compounds, like gomisin A, schisandrin, and longikaurin A. Key AD genes prostaglandin-endoperoxide synthase-2 ( PTGS2 , cyclooxygenase-2) and acetylcholinesterase ( AChE ) were linked to SCF compounds. In the rats with AD induced by bilaterally infusing amyloid-β (25-35) into the hippocampus, the 0.5% SCF intake mitigated hippocampal amyloid-β deposition, neuroinflammation, memory deficits, and dysregulated glucose and lipid metabolism versus the AD controls. SCF reduced hippocampal AChE activity, inflammatory cytokine expression related to PTGS2 , and malondialdehyde contents and preserved neuronal cell survival-related factors such as brain-derived neurotrophic factor and ciliary neurotrophic factor similar to normal rats. The neuroprotective effects validated the network analysis findings.
Conclusions: SCF could be a potential AD therapeutic agent by activating the parasympathetic nervous system to reduce hippocampal oxidative stress and inflammation, warranting further clinical investigations of its efficacy.

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2023-2 "Food Functionality Evaluation program" under the Ministry of Agriculture, Food and Rural Affairs and partly the Korea Food Research Institute.

Keywords: Alzheimer’s disease; Schisandra chinensis Fructus; acetylcholinesterase; network pharmacology; prostaglandin-endoperoxide synthase 2

0 (Amyloid beta-Peptides)
0 (Plant Extracts)
0 (Lignans)
EC 1.14.99.1 (Cyclooxygenase 2)
0 (Peptide Fragments)
0 (Cyclooctanes)
0 (amyloid beta-protein (25-35))
G01BQC0879 (schizandrin)
EC 1.14.99.1 (Ptgs2 protein, rat)
0 (Polycyclic Compounds)

Date Created: 20241109 Date Completed: 20241109 Latest Revision: 20241116

20250114

PMC11547720

10.3390/nu16213751

39519586