{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T23:29:29Z","timestamp":1787873369381,"version":"build-2784847793"},"reference-count":38,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82160756"],"award-info":[{"award-number":["82160756"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Obesity can lead to depression via the microbiota\u2010gut\u2010brain axis. Icariside II (ICS II), a flavonoid compound derived from the traditional Chinese medicine\n                    <jats:italic>Herbal Epimedium,<\/jats:italic>\n                    exerts excellent neuroprotective effects. However, the pharmacological effects and underlying mechanisms of ICS II in obesity\u2010induced depression remain unexplored. The present study aims to investigate whether ICS II can mitigate depression induced by a high\u2010fat diet (HFD) in mice through modulating the microbiota\u2010gut\u2010brain axis. Metabolic parameters were reflected through changes in body weight and blood lipids, while depressive phenotypes were evaluated through behavioral tests and neurotransmitter analysis. The microbiota composition was analyzed by 16S ribosomal\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    gene sequencing, and short chain fatty acids (SCFAs) were detected by liquid chromatography\u2013tandem mass spectrometry. The gut barrier and brain blood barrier (BBB) functions were observed by pathological methods. Fecal microbiota transplantation was used to demonstrate the causality of microbiota\u2010mediated effects. The results showed that ICS II alleviated obesity status and depressive\u2010like behaviors. ICS II reshaped gut microbiota and increased SCFAs. Meanwhile, ICS II relieved gut barrier impairment and systemic inflammation. In the brain, ICS II alleviated neuroinflammation and BBB injury. Intriguingly, fecal microbiota from ICS II\u2010treated HFD mice improved depressive\u2010like behaviors, intestinal barrier dysfunction, and BBB damage compared with those receiving microbiota from HFD mice. Our findings reveal for the first time that ICS II improves the obesity\u2010related metabolic dysregulation and alleviates HFD\u2010induced depression via the microbiota\u2010gut\u2010brain axis. Overall, this study indicates that ICS II is a potential candidate compound for treating obesity\u2010related mental diseases.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70103","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T15:01:45Z","timestamp":1758812505000},"page":"5159-5173","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Icariside\n                    <scp>II<\/scp>\n                    Ameliorates Depression Induced by High\u2010Fat Diet via the Microbiota\u2010Gut\u2010Brain Axis in Mice"],"prefix":"10.1002","volume":"39","author":[{"given":"Yun\u2010mei","family":"Luo","sequence":"first","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine Macau University of Science and Technology  Macau China"},{"name":"Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of 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