{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T06:24:12Z","timestamp":1786947852532,"version":"build-2736575974"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["No.2022J01849"],"award-info":[{"award-number":["No.2022J01849"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2025J01073"],"award-info":[{"award-number":["2025J01073"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Emerging evidence indicates that the neuroprotective effects of\n                      <jats:italic>Astragalus polysaccharides<\/jats:italic>\n                      (APS), an extract compound and bioactive constituent derived from traditional Chinese herbs, may be relevant to an effective prescription for delaying progression of Alzheimer\u2019s disease (AD), yet the underlying mechanisms remain to be fully elucidated. This study aimed to investigate the therapeutic efficacy of APS in alleviating cognitive impairment and neuropathology in 5\u00d7FAD transgenic mice, with a specific focus on the regulatory role of the gut-brain axis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male 5\u00d7FAD mice were orally administered APS (200\u00a0mg\/kg\/day) for 60 days. General observations were conducted to assess the\n                      <jats:italic>in vivo<\/jats:italic>\n                      tolerance of APS. Cognitive function was evaluated using the Morris water maze (MWM). Neuropathological assessments included immunofluorescence and Western blotting for amyloid-\u03b2 (A\u03b2) deposition, synaptic proteins, and neuroinflammatory markers. Gut microbiota composition and metabolic profiles were analyzed via 16S rRNA gene sequencing and targeted metabolomics. Furthermore, fecal microbiota transplantation (FMT) was performed to verify the causal contribution of gut microbiota to the observed therapeutic effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      APS administration was well-tolerated throughout the study period, with no overt toxic effects observed. Moreover, APS administration significantly ameliorated spatial learning and memory deficits in 5\u00d7FAD mice. Mechanistically, APS treatment reduced A\u03b2 plaque burden, restored synaptic protein expression (PSD-95 and Syntaxin), and attenuated microglia-mediated neuroinflammation by suppressing pro-inflammatory cytokines (IL-6, TNF-\u03b1) and upregulating TREM2. Microbiome analysis revealed that APS reshaped gut microbial diversity and composition, enriching beneficial taxa such as\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      . Metabolomics indicated a partial restoration of amino acid metabolism. Notably, FMT from APS-treated donors successfully reproduced the cognitive improvements and anti-inflammatory effects in recipient mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings demonstrate that APS alleviates cognitive deficits and AD-like pathology, partially through remodeling gut microbiota and modulating the gut-brain axis. APS represents a promising natural compound-based therapeutic candidate for managing cognitive decline associated with Alzheimer\u2019s disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1830927","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T05:25:30Z","timestamp":1786944330000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Astragalus polysaccharide alleviates neuropathology and cognitive deficits by modulating gut microbiota and neuroinflammation in an Alzheimer\u2019s disease model"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaoli","family":"Cui","sequence":"first","affiliation":[{"name":"Department of Geriatric, The People\u2019s Hospital Affiliated to Fujian University of Traditional Chinese Medicine","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fuzhou University Affiliated Provincial Hospital, Fujian Provincial Hospital,Shengli Clinical Medical College of Fujian Medical University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingshui","family":"Wang","sequence":"additional","affiliation":[{"name":"The Affiliated People\u2019s Hospital, College of Integrative Medicine, Fujian-Hong Kong-Macau-Taiwan Collaborative Laboratory for the Inheritance and Innovation of Traditional Chinese Medicine, Fujian University of Traditional Chinese Medicine","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sizhe","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Geriatric, The People\u2019s Hospital Affiliated to Fujian University of Traditional Chinese Medicine","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Geriatric, The People\u2019s Hospital Affiliated to Fujian University of Traditional Chinese Medicine","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zibo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Geriatric, The People\u2019s Hospital Affiliated to Fujian University of Traditional Chinese Medicine","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Geriatric, The People\u2019s Hospital Affiliated to Fujian University of Traditional Chinese Medicine","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Geriatric, The People\u2019s Hospital Affiliated to Fujian University of Traditional Chinese Medicine","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanfang","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Geriatric, The People\u2019s Hospital Affiliated to Fujian University of Traditional Chinese Medicine","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoman","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Neurology and Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital","place":["Fuzhou, China"]},{"name":"Fujian Key Laboratory of Molecular Neurology, Fujian Key Laboratory of Vascular Aging, School of Basic Medical Sciences, Fujian Medical University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"He","sequence":"additional","affiliation":[{"name":"Department of Geriatric, The People\u2019s Hospital Affiliated to Fujian University of Traditional Chinese Medicine","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"8905","DOI":"10.3390\/ijms26188905","article-title":"The interplay of inflammation and Gut-Microbiota dysbiosis in Alzheimer's Disease: mechanisms and therapeutic potential","volume":"26","author":"Abdol Samat","year":"2025","journal-title":"Int. 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