{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T19:11:02Z","timestamp":1788462662096,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"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":["32471014"],"award-info":[{"award-number":["32471014"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32200778"],"award-info":[{"award-number":["32200778"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20220494"],"award-info":[{"award-number":["BK20220494"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011198","name":"State Key Laboratory of Drug Research, Chinese Academy of Sciences","doi-asserted-by":"publisher","award":["SKLDR\u20102023\u2010KF\u201005"],"award-info":[{"award-number":["SKLDR\u20102023\u2010KF\u201005"]}],"id":[{"id":"10.13039\/501100011198","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">Panax quinquefolius<\/jats:styled-content>\n                        Radix\n                      <\/jats:italic>\n                      (American ginseng) is a medicinal herb used for its neuroprotective and tonic effects. However, the antidepressant potential of its polysaccharide components is not well studied. This research aimed to investigate the antidepressant effects of XYS1, a polysaccharide from American ginseng, focusing on mechanisms related to the complement system and the gut\u2010brain axis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A chronic unpredictable mild stress (CUMS) mouse model was used to induce depressive behaviors. Mice were treated with XYS1 via oral gavage, followed by assessments of behavior, molecular changes, and gut microbiota.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>XYS1 treatment significantly alleviated depression\u2010like behaviors in CUMS mice, as demonstrated by reduced immobility time in the TST and FST, and increased sucrose preference and body weight. Mechanistically, XYS1 attenuated complement system activation by downregulating C1Q expression in microglia and C3 expression in astrocytes, not only in the hippocampal CA1 region but also in the mPFC and PVN, as well as in the colon. Furthermore, XYS1 inhibited microglial activation and associated synaptic phagocytosis, preserved glutamatergic neuron density, restored excitatory synapse density, and reversed CUMS\u2010induced gut microbiota dysbiosis by enriching Bacillota and reducing Bacteroidota abundance. Additionally, XYS1 effectively mitigated both colonic and systemic inflammation, reducing pro\u2010inflammatory cytokines TNF\u2010\u03b1 and IL\u20101\u03b2 and complement components C1Q and C3, while restoring anti\u2010inflammatory IL\u201010 levels, thereby modulating the gut\u2010brain axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>XYS1 exerts antidepressant effects by modulating the C1Q\/C3 complement pathway, inhibiting microglial\u2010mediated synaptic pruning, and restoring gut microbiota homeostasis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70859","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T08:15:25Z","timestamp":1774944925000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<i>Panacis Quinquefolii Radix<\/i>\n                    Polysaccharides Alleviate Depressive\u2010Like Behaviors in Chronic Unpredictable Mild Stress\u2010Induced Mice by Suppressing Complement\n                    <scp>C1Q<\/scp>\n                    \/\n                    <scp>C3<\/scp>\n                    \u2010Mediated Microglial Synaptic Pruning and Modulating Gut Microbiota"],"prefix":"10.1002","volume":"32","author":[{"given":"Mengjun","family":"Xie","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, Institute of Neuroscience Soochow University  Suzhou China"},{"name":"Department of Nephrology the Second Affiliated Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Feng","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, Institute of Neuroscience Soochow University  Suzhou 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