{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:40:56Z","timestamp":1782970856691,"version":"3.54.5"},"reference-count":50,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Henan Provincial Science and Technology Key Project","award":["262102310255"],"award-info":[{"award-number":["262102310255"]}]},{"name":"Key Scientific Research Foundation of Henan Colleges and Universities","award":["26A180030"],"award-info":[{"award-number":["26A180030"]}]},{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan","doi-asserted-by":"crossref","award":["252300423668"],"award-info":[{"award-number":["252300423668"]}],"id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Zhoukou Normal University High-level Talent Start-up Foundation","award":["ZKNUC2024030"],"award-info":[{"award-number":["ZKNUC2024030"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Mulberroside A (MsA) possesses neuroprotective effects, but whether it alleviates Alzheimer\u2019s disease (AD)-like cognitive impairment through the microbiota\u2013gut\u2013brain axis remains unclear. Using a scopolamine-induced mouse model of acute cognitive impairment (male ICR mice, n = 10\/group), we demonstrated that daily administration of MsA (10, 20, and 30 mg\/kg\/day) for 5 weeks significantly ameliorated cognitive performance in novel object recognition and Morris water maze tests. At the optimal dose (30 mg\/kg\/day), MsA suppressed hippocampal microglial activation, reduced pro-inflammatory cytokines (IL-6, IL-1\u03b2, TNF-\u03b1), and attenuated oxidative stress by decreasing malondialdehyde (MDA) while restoring superoxide dismutase (SOD) and glutathione (GSH) levels. MsA also strengthened intestinal barrier integrity (ZO-1, occludin) and significantly altered the gut microbiota, notably increasing the beneficial genus Dubosiella. Brain metabolomics indicated that MsA reversed scopolamine-induced metabolic disturbances, mainly restoring phospholipid balance. Correlation analysis demonstrated a strong gut\u2013brain connection, with Dubosiella abundance positively associated with neuroprotective phospholipids and negatively with stress markers. Furthermore, fecal microbiota transplantation from MsA-treated donors successfully replicated these behavioral improvements in recipient mice, underscoring the functional involvement of the reshaped microbiome rather than a simple autonomous recovery. These results suggest that MsA alleviates AD-like cognitive impairment by reducing neuroinflammation and oxidative stress through microbiota remodeling, enhancing the intestinal barrier, and modulating the Dubosiella-associated gut\u2013metabolite\u2013brain axis, making MsA a promising multi-target nutraceutical for ameliorating AD-like cognitive deficits.<\/jats:p>","DOI":"10.3390\/biology15131030","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:54:42Z","timestamp":1782694482000},"page":"1030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mulberroside A Alleviates Scopolamine-Induced Cognitive Deficits by Suppressing Neuroinflammation and Oxidative Stress via the Dubosiella-Associated Microbiota\u2013Gut\u2013Brain Axis"],"prefix":"10.3390","volume":"15","author":[{"given":"Jin","family":"Li","sequence":"first","affiliation":[{"name":"College of Life Sciences and Agronomy, Zhoukou Normal University, Zhoukou 466001, China"},{"name":"Fuxi Laboratory, Zhoukou Normal University, Zhoukou 466001, China"},{"name":"Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology & College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirui","family":"Cheng","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agronomy, Zhoukou Normal University, Zhoukou 466001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agronomy, Zhoukou Normal University, Zhoukou 466001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shourong","family":"Qiao","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agronomy, Zhoukou Normal University, Zhoukou 466001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luzhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agronomy, Zhoukou Normal University, Zhoukou 466001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxu","family":"Yao","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agronomy, Zhoukou Normal University, Zhoukou 466001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6680-5632","authenticated-orcid":false,"given":"Yunxia","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agronomy, Zhoukou Normal University, Zhoukou 466001, China"},{"name":"Fuxi Laboratory, Zhoukou Normal University, Zhoukou 466001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agronomy, Zhoukou Normal University, Zhoukou 466001, China"},{"name":"Fuxi Laboratory, Zhoukou Normal University, Zhoukou 466001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9196-8532","authenticated-orcid":false,"given":"Changjing","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Agronomy, Zhoukou Normal University, Zhoukou 466001, China"},{"name":"Fuxi Laboratory, Zhoukou Normal University, Zhoukou 466001, China"},{"name":"Field Observation and Research Station of Green Agriculture in Dancheng County, Zhoukou 466001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e105","DOI":"10.1016\/S2468-2667(21)00249-8","article-title":"Estimation of the Global Prevalence of Dementia in 2019 and Forecasted Prevalence in 2050: An Analysis for the Global Burden of Disease Study 2019","volume":"7","author":"Nichols","year":"2022","journal-title":"Lancet Public Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/s41746-025-01640-z","article-title":"Alzheimer\u2019s Disease Digital Biomarkers Multidimensional Landscape and AI Model Scoping Review","volume":"8","author":"Qi","year":"2025","journal-title":"npj Digit. 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