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Laxatives have shown potential in improving the cognitive function of AD, but the specific mechanism remains underexplored. Sennoside A (SA), a well-established laxative, is commonly used for treating constipation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      This work used SA as a probe to explore the therapeutic effects and potential mechanisms of laxatives on AD\n                      <jats:italic toggle=\"yes\">via<\/jats:italic>\n                      the gut-brain axis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Following a two-month treatment, behavioral experiments were used to assess the cognitive function. The central pathologies and neuroinflammation were evaluated by histopathology and ELISA. 16S rRNA sequencing, fecal microbiota transplantation and antibiotic treatment were conducted to verify whether SA exerts anti-AD effects via gut microbiota. Further, non-targeted metabolomics coupled with Spearman correlation analysis was employed to elucidate the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SA significantly countered cognitive dysfunction and central pathological damage in APP\/PS1 mice. Besides, SA ameliorated gut dysbiosis and affected the metabolic functions of the flora. Furthermore, the therapeutic effects of SA decrease with the depletion of gut microbes and could be transferred with the microbiota. Intriguingly, amino acid metabolism and aminoacyl-tRNA biosynthesis were the main metabolic pathways regulated by SA, consistent with the predicted functions of gut bacteria. Finally, correlation analysis revealed a strong correlation between gut microbes, fecal metabolites, and cognitive ability affected by SA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The study investigated the efficacy and mechanisms of laxatives represented by SA for AD from the perspective of the gut-brain axis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251389922","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T16:02:02Z","timestamp":1761580922000},"page":"1659-1676","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Sennoside A alleviating cognitive impairment in APP\/PS1 mice via balancing microbiome metabolism"],"prefix":"10.1177","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3163-5110","authenticated-orcid":false,"given":"Yulian","family":"Shi","sequence":"first","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4567-0600","authenticated-orcid":false,"given":"Huilin","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2432-1661","authenticated-orcid":false,"given":"Huajinzi","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 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