{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T21:48:31Z","timestamp":1792619311712,"version":"4.5.0"},"reference-count":118,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Heilongjiang Province Joint Fund Cultivation Project","award":["PL2025T010"],"award-info":[{"award-number":["PL2025T010"]}]},{"name":"Heilongjiang Provincial Postdoctoral Scientific Research Foundation","award":["LBH-Q18115"],"award-info":[{"award-number":["LBH-Q18115"]}]},{"name":"Heilongjiang Province Traditional Chinese Medicine Scientific Research Project","award":["ZHY2024-012"],"award-info":[{"award-number":["ZHY2024-012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a neurodegenerative disorder characterized by A\u03b2 deposition, tau hyperphosphorylation, and neuroinflammation. No effective drugs can slow disease progression. Polysaccharides from traditional Chinese medicine (TCM) exhibit neuroprotective activities (e.g., antioxidant, anti-inflammatory) with good safety. However, their clinical application is limited by low oral bioavailability, poor blood\u2013brain barrier (BBB) permeability, and a pharmacokinetic\u2013pharmacodynamic paradox. The emerging role of the microbiota\u2013gut\u2013brain axis in AD offers a strategy to overcome this paradox. This review summarizes the structural features and classification of TCM polysaccharides (from plants, fungi, and roots\/rhizomes) and highlights their anti-AD mechanisms via the gut\u2013brain axis. Acting as prebiotics, these polysaccharides escape upper digestion and are fermented by gut microbiota into short-chain fatty acids (SCFAs) and other metabolites, which enter circulation, cross the BBB, and alleviate AD pathology through metabolic, immune, and neuronal pathways. Outcomes include reduced A\u03b2 deposition and tau phosphorylation, suppressed neuroinflammation, restored synaptic function, and improved cognition. This review provides a theoretical framework for TCM polysaccharide intervention in AD via the gut\u2013brain axis and a pharmacological basis for developing natural product-based AD therapies.<\/jats:p>","DOI":"10.3390\/molecules31152622","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:55:41Z","timestamp":1785225341000},"page":"2622","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Plant Polysaccharides in Alzheimer\u2019s Disease: From Phytochemistry to Microbiota-Gut\u2013Brain Axis Mechanisms\u2014Resolving the Pharmacokinetic-Pharmacodynamic Paradox"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0641-7954","authenticated-orcid":false,"given":"Jie","family":"Gao","sequence":"first","affiliation":[{"name":"Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liheng","family":"Li","sequence":"additional","affiliation":[{"name":"Heilongjiang University of Chinese Medicine, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Medicine Informatics of Heilongjiang Province, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Medicine Informatics of Heilongjiang Province, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Medicine Informatics of Heilongjiang Province, Harbin 150040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5541","DOI":"10.2147\/IJN.S200490","article-title":"Alzheimer\u2019s disease: Pathogenesis, diagnostics, and therapeutics","volume":"14","author":"Tiwari","year":"2019","journal-title":"Int. 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