{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:39:36Z","timestamp":1791916776579,"version":"4.3.4"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,5,18]],"date-time":"2025-05-18T00:00:00Z","timestamp":1747526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,5,18]],"date-time":"2025-05-18T00:00:00Z","timestamp":1747526400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the effect of hypericin on ameliorating depressive behaviour in post\u2010stroke depression (PSD) rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Rats underwent a middle cerebral artery occlusion and chronic mild stress for 28 days to create a PSD model. Behavioural tests included the open field test (OFT) and the elevated plus maze test. Hypericin at a low (100\u2009mg\/kg) and a high (400\u2009mg\/kg) dose was administered via gavage. Lipopolysaccharide (LPS) was used to establish a microglia\u2010injury model, with hypericin treatment at 0.25, 0.5, 1, and 2 \u03bcmol\/L, and ELISA was used to measure serotonin (5\u2010HT), interleukin (IL)\u20106 and IL\u201010 levels. Additionally, Western blot analysis and immunohistochemistry analysed protein levels and the expression of iNOS and Arg\u20101 in the hippocampus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Following the PSD model preparation, the rats showed substantially reduced movement in the OFT and spent less time in the open arms of the elevated plus maze, whereas treatment with hypericin and fluoxetine improved depressive behaviour in these tests. In addition, hypericin decreased IL\u20106, increased IL\u201010 and 5\u2010HT and enhanced p\u2010MEK\/MEK, p\u2010ERK\/ERK and p\u2010CREB\/CREB expression in the serum of the PSD rats and the LPS cell model. Hypericin also reduced iNOS but increased Arg\u20101 expression in the PSD rat hippocampus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Hypericin promotes M2 microglial polarisation, reduces inflammation and improves depressive behaviour in PSD rats by activating the MEK\/ERK\/CREB pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbt.70295","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T02:51:49Z","timestamp":1747623109000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hypericin Regulates Inflammation Levels and Improves Depressive Symptoms in Rats With Post\u2010Stroke Depression Through the MEK\/ERK\/CREB Pathway"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7134-6219","authenticated-orcid":false,"given":"Kui","family":"Jia","sequence":"first","affiliation":[{"name":"The Second Ward of the Department of Integrative Chinese and Western Medicine The First Affiliated Hospital of Xinxiang Medical University  Xinxiang China"},{"name":"Henan University of Chinese Medicine  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlong","family":"Li","sequence":"additional","affiliation":[{"name":"The Second Ward of the Department of Integrative Chinese and Western Medicine The First Affiliated Hospital of Xinxiang Medical University  Xinxiang China"},{"name":"Henan University of Chinese Medicine  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Li","sequence":"additional","affiliation":[{"name":"The Second Ward of the Department of Integrative Chinese and Western Medicine The First Affiliated Hospital of Xinxiang Medical University  Xinxiang China"},{"name":"Henan University of Chinese Medicine  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Qian","sequence":"additional","affiliation":[{"name":"The Second Ward of the Department of Integrative Chinese and Western Medicine The First Affiliated Hospital of Xinxiang Medical University  Xinxiang China"},{"name":"Henan University of Chinese Medicine  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,18]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1506214"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2019.01.013"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2018.04.005"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31269-8"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-021-10597-4"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16380"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2021.9850"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.18m12106"},{"issue":"8","key":"e_1_2_12_10_1","article-title":"Evaluation and Treatment of Depression in Stroke Patients: A Systematic Review","volume":"14","author":"Lavu V. 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