{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T14:00:05Z","timestamp":1766066405337,"version":"3.48.0"},"reference-count":69,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2022YFD1600404-04"],"award-info":[{"award-number":["2022YFD1600404-04"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32201951"],"award-info":[{"award-number":["32201951"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Center of Technology Innovation for Dairy","award":["2024-QNJJ-014"],"award-info":[{"award-number":["2024-QNJJ-014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Emerging evidence suggests that hippocampal neuroinflammation (HNF) drives cognitive decline via dysregulation of the microbiota-gut-brain axis. Corylus heterophylla Fisch. male flower extract (CFE), a flavonoid-rich by-product of hazelnut processing, presents a promising yet unexplored neuroprotective candidate. This study investigated the preventive effects and mechanisms of CFE against HNF-induced cognitive decline. Methods: In the present study, mice were pretreated with CFE (200 mg\/kg) before the Lipopolysaccharide (LPS) administration. Cognitive function, inflammation, core pathology, neuroplasticity, gut microbiota and serum metabolites were assessed. The chemical composition of CFE was analyzed by UHPLC-MS and its direct immunomodulatory effects were investigated in BV2 cells. Results: Behavioral assessments demonstrated significant therapeutic efficacy. This was evidenced by the recovery from hippocampal damage, accompanied by reduced levels of core pathological markers (A\u03b21\u201342, Tau, p-Tau (Ser404), GSK-3\u03b2), decreased expression of pro-inflammatory mediators including IL-33, elevated levels of neurotrophic factors (BDNF and MAP2), and attenuated abnormal activation of astrocytes and microglia. The 16S rRNA analysis confirmed that CFE ameliorated gut microbial dysbiosis. Notably, CFE significantly increased the relative abundance of Muribaculaceae and Lachnospiraceae, while significantly decreased Staphylococcus and Helicobacter. Metabolomics revealed enhanced levels of \u03b1-linolenic acid (ALA), serotonin (5-HT) and acetic acid, which correlated positively with Muribaculaceae and Lachnospiraceae. Phytochemical analysis identified luteolin and kaempferol as the predominant flavonoids in CFE. In BV2 cells, CFE, luteolin and kaempferol shifted microglial polarization from the M1 phenotype toward the M2 phenotype. Conclusions: CFE alleviated HNF-induced cognitive decline by regulating microbiota-gut-brain axis and microglial M1\/M2 polarization.<\/jats:p>","DOI":"10.3390\/nu17243958","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T13:45:07Z","timestamp":1766065507000},"page":"3958","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Microbiota to Metabolomics: How Corylus heterophylla Fisch. Male Flower Extract Shields Mice from Cognitive Decline"],"prefix":"10.3390","volume":"17","author":[{"given":"Wei","family":"Lu","sequence":"first","affiliation":[{"name":"School of Food and Health, Beijing Technology and Business University, Beijing 100048, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6783-3677","authenticated-orcid":false,"given":"Yujie","family":"Li","sequence":"additional","affiliation":[{"name":"School of Food and Health, Beijing Technology and Business University, Beijing 100048, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyuan","family":"Liao","sequence":"additional","affiliation":[{"name":"School of Food and Health, Beijing Technology and Business University, Beijing 100048, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Hu","sequence":"additional","affiliation":[{"name":"Bee Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100093, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6746-493X","authenticated-orcid":false,"given":"Bolin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Forest Food Processing and Safety, Department of Food Science and Engineering, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisong","family":"Liang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Silviculture of State Forestry Administration, Research Institute of Forestry Chinese Academy of Forestry, Beijing 100091, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haina","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Food and Health, Beijing Technology and Business University, Beijing 100048, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101044","DOI":"10.1016\/j.eclinm.2021.101044","article-title":"Cognitive deficits in people who have recovered from COVID-19","volume":"39","author":"Hampshire","year":"2021","journal-title":"eClinicalMedicine"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Tran, N.B., Lee, H., Ji, M.G., Ngo Hoang, L., and Lee, S.J. 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