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Bunge (AS) has antioxidative, gut microbiota\u2010regulating, and cognitive\u2010improving effects.\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      (\n                      <jats:italic>E. coli<\/jats:italic>\n                      ) abundance is associated with cognitive dysfunction. This study explored the mechanism by which AS improves VD by regulating\n                      <jats:italic>E. coli<\/jats:italic>\n                      along the gut\u2013brain axis, providing a basis for VD drug research and development.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>VD models were established by permanent ligation of the common carotid artery. Morris water maze, Doppler cerebral blood flow measurement, blood lipid assays, pathological staining, Western blot, and ELISA were used to evaluate AS's protective effects on the brain. 16S rRNA sequencing analyzed gut microbiota to screen differential strains. Metabolomics screened endogenous differential metabolites. Oxygen\u2013glucose deprivation (OGD) was established to evaluate 5\u2010aminovaleric acid effects on neuronal mitochondrial function and oxidative stress.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      AS significantly improved cognitive dysfunction, restored cerebral blood flow, and attenuated abnormal protein accumulation and oxidative stress in VD rat brains. Microbiota analysis revealed that AS inhibited\n                      <jats:italic>E. coli<\/jats:italic>\n                      proliferation and mitigated associated pathological damage. Furthermore, endogenous metabolite 5\u2010aminovaleric acid alleviated OGD\u2010induced neuronal damage and oxidative stress.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>\n                      AS can treat cognitive dysfunction and brain injury in rodents, regulate gut microbiota balance, and reduce the contribution of\n                      <jats:italic>E. coli<\/jats:italic>\n                      . Meanwhile, AS\u2010regulated endogenous metabolite 5\u2010aminovaleric acid can also treat OGD\u2010induced nerve cell injury. These findings suggest that AS may be a promising candidate for VD treatment and provide mechanistic insight into gut\u2013brain axis regulation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70645","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T04:37:11Z","timestamp":1792557431000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Saponin extract from\n                    <scp>\n                      <i>Astragalus membranaceus<\/i>\n                    <\/scp>\n                    (Fisch.) Bunge regulates gut\u2013brain axis through intestinal\n                    <scp>\n                      <i>Escherichia coli<\/i>\n                    <\/scp>\n                    to reduce cerebral oxidative stress to treat vascular dementia in rodents"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1387-4048","authenticated-orcid":false,"given":"Wei","family":"Yin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology, College of Pharmacy Harbin Medical University  Harbin China"},{"name":"Department of Medicinal Chemistry and Natural Medicinal Chemistry, College of Pharmacy Harbin Medical University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6616-5951","authenticated-orcid":false,"given":"Chengbing","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Frigid Zone 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