{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:47:04Z","timestamp":1792511224816,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["CSTB2022NSCQ\u2010MSX1640"],"award-info":[{"award-number":["CSTB2022NSCQ\u2010MSX1640"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["CSTB2022NSCQ\u2010MSX1562"],"award-info":[{"award-number":["CSTB2022NSCQ\u2010MSX1562"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Food Science &amp; Nutrition"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Chaihu Shugan San (CHSGS) is a traditional Chinese formula widely used in the treatment of depression, but its antidepressant\u2010like effects remain incompletely understood. This study investigated the effects of CHSGS on stress\u2010induced behavioral abnormalities with a focus on hippocampal glutamate homeostasis. Ultra\u2010performance liquid chromatography\u2013tandem mass spectrometry (UPLC\u2010MS\/MS) was used to identify the chemical constituents of CHSGS, and network pharmacology combined with molecular docking was applied to predict potential targets and signaling pathways. A chronic restraint stress (CRS)\u2010induced mouse model was established to evaluate the antidepressant\u2010like effects of CHSGS through behavioral tests and molecular analyses. UPLC\u2010MS\/MS identified flavonoids as the major constituents of CHSGS. Network pharmacology analysis suggested that the AGE\u2013RAGE signaling pathway may be involved in the effects of CHSGS, with several flavonoids, including kaempferol, hesperetin, isorhamnetin, naringenin, and nobiletin, showing potential interactions with key targets. In CRS mice, CHSGS treatment improved behavioral abnormalities, reduced hippocampal glutamate levels, alleviated neuronal Nissl body damage, restored hippocampal GFAP and GLT\u20101 expression, and inhibited RAGE\/NF\u2010\u03baB signaling activation. These findings suggest that CHSGS effectively alleviated CRS\u2010induced behavioral abnormalities and improved hippocampal glutamate homeostasis in mice, which may be associated with the regulation of GLT\u20101 expression and involvement of the RAGE\/NF\u2010\u03baB signaling pathway.<\/jats:p>","DOI":"10.1002\/fsn3.72384","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:58:22Z","timestamp":1789966702000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Network Pharmacology and Experimental Validation Reveal the Potential Antidepressant\u2010Like Effects of Chaihu Shugan San Associated With Glutamate Homeostasis"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7426-6712","authenticated-orcid":false,"given":"Yu","family":"Xu","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine Chongqing University of Chinese Medicine  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian","family":"Xia","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4784-4970","authenticated-orcid":false,"given":"Keyun","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0749-3279","authenticated-orcid":false,"given":"Chuanxin","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoting","family":"Tian","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Chongqing Medical and Pharmaceutical College  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7399-1720","authenticated-orcid":false,"given":"Zongchun","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Chongqing University of Chinese Medicine  Chongqing China"},{"name":"College of Traditional Chinese Medicine Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2021.10.041"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010025\u201005244\u20102"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.896268"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2023.1155175"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2025.03.016"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyab052"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.03.013"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0302\u201011.2011"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1337876"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215\u20100366(17)30015\u20109"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14061123"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2022.2057914"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.483826"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010020\u20100843\u20100"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13727"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.157338"},{"key":"e_1_2_10_18_1","unstructured":"Li W.2021.\u201cUsing Bioinformatics Analysis to Explore the Modern Biological Implications of the Formula\u2010Syndrome Association of Chaihu Shugan San (Master's Thesis). 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