{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T15:07:37Z","timestamp":1788016057850,"version":"build-2784847793"},"reference-count":34,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T00:00:00Z","timestamp":1730332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Agriculture, Food, and Rural Affairs"},{"name":"Korea Food Research Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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\u2019s disease (AD) using a network pharmacology analysis, followed by experimental validation in an AD rat model. Methods: The biological activities of SCF\u2019s bioactive compounds were assessed through a network pharmacology analysis. An AD rat model was generated by infusing amyloid-\u03b2 peptide (A\u03b2) (25\u201335) into the hippocampus to induce A\u03b2 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 A\u03b2 (35\u201325) infusion (no A\u03b2 deposition) and were fed a control diet (Normal-C). A\u03b2 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-\u03b2 (25\u201335) into the hippocampus, the 0.5% SCF intake mitigated hippocampal amyloid-\u03b2 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.<\/jats:p>","DOI":"10.3390\/nu16213751","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T12:31:32Z","timestamp":1730377892000},"page":"3751","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Efficacy and Mechanism of Schisandra chinensis Fructus Water Extract in Alzheimer\u2019s Disease: Insights from Network Pharmacology and Validation in an Amyloid-\u03b2 Infused Animal Model"],"prefix":"10.3390","volume":"16","author":[{"given":"Hye-Jeong","family":"Yang","sequence":"first","affiliation":[{"name":"Food Functionality Research Division, Korea Food Research Institute, Wanju 55365, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Institute of Basic Science, Obesity\/Diabetes Research Center, Hoseo University, Asan 31499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Food Functionality Research Division, Korea Food Research Institute, Wanju 55365, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9469-010X","authenticated-orcid":false,"given":"Haeng-Jeon","family":"Hur","sequence":"additional","affiliation":[{"name":"Food Functionality Research Division, Korea Food Research Institute, Wanju 55365, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6293-7363","authenticated-orcid":false,"given":"Xuangao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Institute of Basic Science, Obesity\/Diabetes Research Center, Hoseo University, Asan 31499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4689-392X","authenticated-orcid":false,"given":"Dai-Ja","family":"Jang","sequence":"additional","affiliation":[{"name":"Food Functionality Research Division, Korea Food Research Institute, Wanju 55365, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6092-8340","authenticated-orcid":false,"given":"Sunmin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Institute of Basic Science, Obesity\/Diabetes Research Center, Hoseo University, Asan 31499, Republic of Korea"},{"name":"Department of Bioconvergence, Hoseo University, Asan 31499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41572-021-00269-y","article-title":"Alzheimer disease","volume":"7","author":"Knopman","year":"2021","journal-title":"Nat. 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