{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:09:39Z","timestamp":1793138979167,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"unspecified","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82305144"],"award-info":[{"award-number":["82305144"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jiangsu Provincial Natural Science Foundation Project for Universities","award":["23KJB360004"],"award-info":[{"award-number":["23KJB360004"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82305144"],"award-info":[{"award-number":["82305144"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Natural Science Foundation Supporting Project of Nanjing University of Chinese Medicine","award":["XPT82305144"],"award-info":[{"award-number":["XPT82305144"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Gen. Psychiatry"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Major depressive disorder (MDD), characterised by persistent anhedonia and elevated suicide risk, represents a global mental health challenge. Recent studies suggest a link between gut\u2013brain axis dysfunction and depression. The natural compound paeoniflorin demonstrates clinically relevant antidepressant effects, yet its underlying neurobiological mechanisms remain elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This study aims to examine how paeoniflorin alleviates depression\u2010like behaviours in rats subjected to chronic unpredictable mild stress (CUMS) by modulating the function of gut\u2013brain axis, and explore the connections between gut microbiota, metabolites and MDD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Depression\u2010like behaviours in rats were induced by CUMS, and the antidepressant effect of paeoniflorin was assessed using behavioural tests. The composition and function of the intestinal microbiota were analysed using 16S rRNA sequencing, and metabolomic analysis was performed on serum, hippocampus, jejunum and faecal samples. Enzyme\u2010linked immunosorbent assay and hematoxylin and eosin staining were used to detect the levels of inflammatory factors and cortisol, as well as the infiltration of inflammatory cells in the jejunum of rats after cohousing. Long\u2010term potentiation assays and Golgi staining were used to detect dendritic spine density and synaptic plasticity, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Paeoniflorin significantly alleviated depression\u2010like behaviours and cognitive deficits in CUMS rats. 16S rRNA sequencing revealed that paeoniflorin improved the abundance and diversity of the gut microbiota in CUMS rats. Enrichment of differential metabolites in the brain, intestine, faeces and serum revealed a primary accumulation in the amino acid metabolism pathway. We further observed a correlation between the relative abundance of microbial communities and metabolites. Cohousing experiments verified that microbial metabolites of paeoniflorin can reduce neuroinflammation and improve synaptic plasticity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Disruptions in gut microbiota and its metabolites impair gut\u2013brain interactions. Paeoniflorin's neuroprotective and antidepressant effects are mediated through the modulation of the function of the gut\u2013brain axis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/gpsych-2024-101979","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T02:12:40Z","timestamp":1756174360000},"update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["Paeoniflorin ameliorates depressive behaviours by modulating microbiota\u2013gut\u2013brain axis functions"],"prefix":"10.1002","volume":"38","author":[{"given":"Sha","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Nursing Nanjing University of Chinese Medicine Nanjing Jiangsu China"},{"name":"Department of Pediatrics Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing Jiangsu 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Changchun Jilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason H","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Baylor Scott &amp; White Health Temple Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingchen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2010-6254","authenticated-orcid":false,"given":"Fushun","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Brain and Psychological Science Sichuan 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