{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T06:15:42Z","timestamp":1788156942110,"version":"build-2803163510"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Aquaporin-4 (AQP4), predominantly expressed in astrocytes, has been implicated in neuroinflammation through the amplification of cytokine and chemokine production. Goreisan (GRS), a traditional Japanese herbal medicine, modulates AQP4-related water homeostasis. However, its effects on AQP4-associated inflammatory processes remain unclear. This study aimed to elucidate the anti-inflammatory effects of GRS, with particular emphasis on inflammatory responses observed under AQP4-expressing conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vitro<\/jats:italic>\n                      experiments were conducted using primary cultured astrocytes and AQP4-overexpressing NIH-3T3 fibroblasts stimulated with lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-\u03b1), with or without GRS. Cytokine and chemokine expression levels were assessed by quantitative reverse transcription polymerase chain reaction, whereas ERK phosphorylation was evaluated by Western blotting. An\n                      <jats:italic>in vivo<\/jats:italic>\n                      mouse model of LPS-induced neuroinflammation was employed to assess the effects of orally administered GRS on inflammatory markers and glial activation. The contributions of individual herbal components were also examined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      GRS suppressed LPS- and TNF-\u03b1-induced cytokine and chemokine mRNA expression in primary astrocytes and AQP4-expressing NIH-3T3 cells.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , GRS administration reduced inflammatory cytokine expression and attenuated glial activation in the brain. GRS attenuated ERK phosphorylation under AQP4-expressing conditions, in parallel with reduced chemokine mRNA expression. Furthermore,\n                      <jats:italic>Cinnamomi cortex<\/jats:italic>\n                      , a component of GRS, was identified as a major contributor to these anti-inflammatory effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings indicate that the effects of GRS on inflammatory gene expression and ERK activation are associated with AQP4-expressing conditions. However, the present data do not establish AQP4 as a direct or primary molecular target of GRS. Therefore, GRS may provide a potential pharmacological approach for modulating inflammatory responses observed under AQP4-expressing conditions, although further studies are required to confirm its therapeutic relevance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1860290","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:40:35Z","timestamp":1788154835000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Goreisan-mediated suppression of chemokine and cytokine production in astrocytes under AQP4-expressing conditions"],"prefix":"10.3389","volume":"20","author":[{"given":"Kazuhito","family":"Murakami","sequence":"first","affiliation":[{"name":"Laboratory of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science","place":["Tokyo, Japan"]},{"name":"TSUMURA Kampo Research Laboratories, Research & Development Division, TSUMURA & CO.","place":["Ibaraki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomofumi","family":"Shimizu","sequence":"additional","affiliation":[{"name":"TSUMURA Kampo Research Laboratories, Research & Development Division, TSUMURA & CO.","place":["Ibaraki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshitaka","family":"Kido","sequence":"additional","affiliation":[{"name":"TSUMURA Kampo Research Laboratories, Research & Development Division, TSUMURA & CO.","place":["Ibaraki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Isohama","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2266","DOI":"10.1212\/01.wnl.0000286385.59836.e2","article-title":"Aquaporin-4, homeostasis, and neurologic disease.","volume":"69","author":"Benarroch","year":"2007","journal-title":"Neurology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.3892\/ijmm.2018.3749","article-title":"AQP4-knockout alleviates the lipopolysaccharide-induced inflammatory response in astrocytes via SPHK1\/MAPK\/AKT signaling.","volume":"42","author":"Dai","year":"2018","journal-title":"Int. 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