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Aging Neurosci."],"abstract":"<jats:p>\n                    Alzheimer\u2019s disease (AD), with the most prominent pathological feature of the accumulation of amyloid-beta (A\u03b2) plaques and neurofibrillary tangles of hyperphosphorylated tau proteins (P-tau), is the foremost cause of dementia. Ershiwuwei Shanhu Pill (ESP) is commonly used in clinical practice in Tibetan areas to treat AD, and has been shown to alleviate cognitive impairment. However, whether ESP exerts its therapeutic effects by modulating the gut microbiota and serum metabolites remains unclear. In this study, APPswe\/PSEN1dE9 transgenic (APP\/PS1) mice (\n                    <jats:italic>n<\/jats:italic>\n                    = 11 per group) were treated with ESP (200 mg\/kg, oral gavage) daily for 2 months and evaluated using the Morris Water Maze (MWM), brain histopathology, immunofluorescence, 16S rRNA sequencing, and untargeted serum metabolomics. ESP improved cognitive performance, reduced A\u03b2 deposition and P-tau levels, and attenuated neuroinflammation. Concurrently, ESP significantly reshaped the gut microbiota (e.g., increasing\n                    <jats:italic>Dubosiella<\/jats:italic>\n                    and decreasing\n                    <jats:italic>Bacteroides<\/jats:italic>\n                    ) and altered serum metabolites involved in tryptophan metabolism and glycolysis pathways (e.g., elevating Fructose 1,6-bisphosphate and reducing N-Acetylserotonin). In conclusion, these neuroprotective effects of ESP are associated with a remodeling of the gut microbiota and metabolic profile, providing a pharmacological basis for its clinical application and novel insights into AD intervention via the gut microbiota-metabolite-brain axis.\n                  <\/jats:p>","DOI":"10.3389\/fnagi.2026.1820691","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T05:48:49Z","timestamp":1781848129000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Ershiwuwei Shanhu Pill ameliorates cognitive impairment in Alzheimer\u2019s disease mice by remodeling gut microbiota and host serum metabolites"],"prefix":"10.3389","volume":"18","author":[{"given":"Ning","family":"Li","sequence":"first","affiliation":[{"name":"Chongqing Three Gorges Medical College","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunxia","family":"Jiang","sequence":"additional","affiliation":[{"name":"Chongqing Three Gorges Medical College","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyuan","family":"Peng","sequence":"additional","affiliation":[{"name":"Chongqing Three Gorges Medical College","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ce","family":"Yang","sequence":"additional","affiliation":[{"name":"Chongqing Three Gorges Medical College","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xiong","sequence":"additional","affiliation":[{"name":"Chongqing Three Gorges Medical College","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Chongqing Three Gorges Medical College","place":["Chongqing, China"]},{"name":"Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e14856","DOI":"10.1111\/cns.14856","article-title":"The neuroinflammatory role of microglia in Alzheimer\u2019s disease and their associated therapeutic targets.","volume":"30","author":"AmeliMojarad","year":"2024","journal-title":"CNS Neurosci. 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