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This study aimed to investigate the neuroprotective effects and underlying mechanisms of XSBO in AD. A scopolamine\u2010induced AD rat model was established to evaluate the effects of XSBO on cognitive function, pathological changes, and neuroinflammation. Gut microbiota alterations were analyzed by 16S rDNA sequencing. Fecal microbiota transplantation (FMT) and short\u2010chain fatty acid (SCFA) supplementation experiments were performed to explore the role of gut microbiota\u2010derived metabolites. The TLR4\/MyD88\/MAPK signaling pathway was further examined. XSBO treatment improved cognitive deficits, reduced neuronal damage and neuroinflammation, and enhanced intestinal barrier integrity in AD rats. XSBO restored gut microbiota dysbiosis and increased SCFA\u2010producing bacteria. FMT and SCFA supplementation confirmed that microbiota\u2010derived metabolites contributed to XSBO\u2010mediated cognitive improvement and neuroprotection. Mechanistically, XSBO inhibited lipopolysaccharide\u2010induced neuroinflammation by suppressing TLR4\/MyD88\/MAPK signaling activation. XSBO alleviates AD\u2010related cognitive impairment and neuroinflammation by modulating the gut microbiota\u2013SCFA axis and inhibiting TLR4\/MyD88\/MAPK\u2010mediated inflammatory responses. These findings suggest that XSBO may serve as a promising dietary intervention for neurodegenerative disease management.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70432","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:09:51Z","timestamp":1787562591000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Breaking Alzheimer's Disease Barrier: The Role of\n                    <i>Xanthoceras sorbifolia<\/i>\n                    Bunge Oil in Gut\u2010Brain Axis and\n                    <scp>TLR4<\/scp>\n                    \/Myd88\/\n                    <scp>MAPK<\/scp>\n                    Pathway Inhibition"],"prefix":"10.1002","author":[{"given":"Lijing","family":"Du","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs School of Pharmacy, Shanghai Jiao Tong University  Shanghai China"},{"name":"The Second Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shikai","family":"Yan","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs School of Pharmacy, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopeng","family":"Ren","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Institute of Traditional Chinese Medicine Guangdong Pharmaceutical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Shams ul","family":"Hassan","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs School of Pharmacy, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanfang","family":"Sun","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs School of Pharmacy, Shanghai Jiao Tong University  Shanghai China"},{"name":"The Second Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Gan","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0683-5028","authenticated-orcid":false,"given":"Xue","family":"Xiao","sequence":"additional","affiliation":[{"name":"Institute of Traditional Chinese Medicine Guangdong Pharmaceutical University  Guangzhou China"},{"name":"Jiyuan Neurohealth Industry Research Institute of Guangdong Pharmaceutical University  Jiyuan Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1170-4591","authenticated-orcid":false,"given":"Shasha","family":"Li","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6901-5898","authenticated-orcid":false,"given":"Huizi","family":"Jin","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs School of Pharmacy, Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms10030522"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10339\u2010011\u20100430\u2010z"},{"issue":"3","key":"e_1_2_13_4_1","first-page":"199","article-title":"The p38 MAP Kinase Family as Regulators of Proinflammatory Cytokine Production in Degenerative Diseases of the CNS","volume":"1","author":"Bachstetter A. 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