{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:10:31Z","timestamp":1790017831222,"version":"4.0.1"},"reference-count":59,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82160924"],"award-info":[{"award-number":["82160924"]}],"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":["82071364"],"award-info":[{"award-number":["82071364"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005329","name":"Natural Science Foundation of Guizhou Province","doi-asserted-by":"publisher","award":["ZK[2024]\u2010478"],"award-info":[{"award-number":["ZK[2024]\u2010478"]}],"id":[{"id":"10.13039\/501100005329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>Rhynchophylline (RHY) can alleviate some cognitive flexibility impairment and stereotyped behavior for attention\u2010deficit hyperactivity disorder (ADHD) and Tourette syndrome (TS) patients as one of a key\u00a0extract and an active ingredient in Ningdong granule (NDG), which is a Traditional Chinese medicine (TCM) preparation widely used in the treatment of ADHD and TS children in China; however, the underlying mechanism is not well understood. Therefore, this study aimed to evaluate how RHY alleviates hyperactivity and cognitive flexibility impairment while inhibiting inflammatory responses in mice that partly lack dopamine transporter protein (DAT\u2212 mice).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male DAT\u2212 mice were randomly divided into the RHY group (\n                      <jats:italic>n<\/jats:italic>\n                      = 8) and administered RHY (30\u00a0mg\/kg) in the DAT\u2212 group (\n                      <jats:italic>n<\/jats:italic>\n                      = 8) and administered saline (i.p., 10\u00a0mL\/kg) in wild\u2010type (WT) mice as the WT control group (\n                      <jats:italic>n<\/jats:italic>\n                      = 8). Hyperactivity and cognitive flexibility impairment were evaluated by the open field test (OFT) and the Morris water maze (MWM) test. The levels of the inflammatory factors of tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) and interleukin\u20101\u03b2 (IL\u20101\u03b2) in cortical homogenates were tested by enzyme\u2010linked immunosorbent assays (ELISA) after 8 weeks of treatment with RHY. In vitro, primary microglia and astrocytes extracted from the cortices of DAT\u2212 neonatal mice and WT neonatal mice were treated with lipopolysaccharide (LPS) (1\u00a0mg\/mL) to induce neuroinflammatory responses and with RHY (20\u00a0mM) for 48\u00a0h. The levels of the inflammatory factors TNF\u2010\u03b1, IL\u20101\u03b2, inducible nitric oxide synthase (iNOS), and cyclooxygenase\u20102 (COX2) in the culture medium were measured at 6\u00a0h, 24\u00a0h, and 48\u00a0h after treatment with LPS and RHY.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>RHY ameliorated hyperactivity and cognitive flexibility impairment in DAT\u2212 mice and inhibited the expression of the inflammatory factors TNF\u2010\u03b1, IL\u20101\u03b2, iNOS, and COX\u20102 in microglia and astrocytes in vitro, and also inhibited the expression of TNF\u2010\u03b1 and IL\u20101\u03b2 in cortical homogenates after 8 weeks of treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>RHY improved hyperactivity and cognitive flexibility impairment through inhibiting inflammatory responses in DAT\u2212 mice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70121","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:39:16Z","timestamp":1731371956000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Rhynchophylline Alleviates Hyperactivity and Cognitive Flexibility Impairment Associated With Inhibition of Inflammatory Responses in Mice That Partly Lack the Dopamine Transporter Protein"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2819-6557","authenticated-orcid":false,"given":"Jijun","family":"Li","sequence":"first","affiliation":[{"name":"Department of Integrative Medicine on Pediatrics, Shanghai Children's Medical Center Shanghai Jiao Tong University School of Medicine  Shanghai P.R. 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