{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:53:58Z","timestamp":1789592038620,"version":"build-2803163510"},"reference-count":66,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"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":["82360479"],"award-info":[{"award-number":["82360479"]}],"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":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Paeoniflorin (PF), the primary bioactive component of Paeonia plants, exhibits neuroprotective and anti\u2010inflammatory activities. However, its potential role in alcohol\u2010induced depression (AID) through the microbiota\u2010metabolite\u2010brain axis remains unclear. This study aimed to investigate the antidepressant effect of PF and its underlying gut\u2010brain communication mechanisms. A mouse model of chronic alcohol exposure was established and treated with PF. Behavioral tests (SPT, FST, TST, OFT) and histopathological examinations were conducted. Network pharmacology and molecular docking were used to predict targets, followed by experimental validation of microglial activation and the NF\u2010\u03baB\/NLRP3 pathway. Multi\u2010omics approaches including 16S rRNA sequencing and untargeted metabolomics were applied to analyze gut microbiota and fecal metabolites. PF significantly alleviated depressive\u2010like behaviors, hippocampal damage, and oxidative stress, while restoring monoamine neurotransmitter levels. It suppressed microglial activation and the NF\u2010\u03baB\/NLRP3 inflammasome cascade. Furthermore, PF reshaped gut microbiota composition (reducing Rikenellaceae and Prevotellaceae) and modulated metabolite profiles and upregulated the neuroprotective metabolite niacin, along with other identified metabolites. These findings demonstrate that PF alleviates Alcohol\u2010Induced Depression (AID) by remodeling the microbiota\u2010metabolite\u2010brain axis and inhibiting neuroinflammation. The study highlights PF's therapeutic potential for alcohol\u2010related mood disorders and underscores the gut\u2010brain axis as a critical target for antidepressant therapy.<\/jats:p>","DOI":"10.1002\/ptr.70388","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T07:13:31Z","timestamp":1779779611000},"page":"5255-5276","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Paeoniflorin Ameliorates Alcohol\u2010Induced Depression via Modulating the Gut\u2013Brain Axis and Inhibiting the\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    \/\n                    <scp>NLRP3<\/scp>\n                    Inflammasome Pathway in Mice"],"prefix":"10.1002","volume":"40","author":[{"given":"Jingwei","family":"Yu","sequence":"first","affiliation":[{"name":"Key Laboratory of Cellular Function and Pharmacology of Jilin 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