{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T10:38:50Z","timestamp":1761129530240,"version":"3.41.2"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,3,14]],"date-time":"2018-03-14T00:00:00Z","timestamp":1520985600000},"content-version":"vor","delay-in-days":72,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1A6A1A03015642"],"award-info":[{"award-number":["2017R1A6A1A03015642"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Evidence-Based Complementary and Alternative Medicine"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p><jats:italic>Celtis choseniana<\/jats:italic> is the traditional plant used at Korea as a herbal medicine to ameliorate inflammatory responses. Although <jats:italic>Celtis choseniana<\/jats:italic> has been traditionally used as a herbal medicine at Korea, no systemic research has been conducted on its anti\u2010inflammatory activity. Therefore, the present study explored an anti\u2010inflammatory effect and its underlying molecular mechanism using <jats:italic>Celtis choseniana<\/jats:italic> methanol extract (Cc\u2010ME) in macrophage\u2010mediated inflammatory responses. <jats:italic>In vitro<\/jats:italic> anti\u2010inflammatory activity of Cc\u2010ME was evaluated using RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS), pam3CSK4 (Pam3), or poly(I:C). <jats:italic>In vivo<\/jats:italic> anti\u2010inflammatory activity of Cc\u2010ME was investigated using acute inflammatory disease mouse models, such as LPS\u2010induced peritonitis and HCl\/EtOH\u2010induced gastritis. The molecular mechanism of Cc\u2010ME\u2010mediated anti\u2010inflammatory activity was examined by Western blot analysis and immunoprecipitation using whole cell and nuclear fraction prepared from the LPS\u2010stimulated RAW264.7 cells and HEK293 cells. Cc\u2010ME inhibited NO production and mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX\u20102), and tumor necrosis factor\u2010alpha (TNF\u2010<jats:italic>\u03b1<\/jats:italic>) in the RAW264.7 cells and peritoneal macrophages induced by LPS, pam3, or poly(I:C) without cytotoxicity. High\u2010performance liquid chromatography (HPLC) analysis showed that Cc\u2010ME contained anti\u2010inflammatory flavonoids quercetin, luteolin, and kaempferol. Among those, the content of luteolin, which showed an inhibitory effect on NO production, was highest. Cc\u2010ME suppressed the NF\u2010<jats:italic>\u03ba<\/jats:italic>B signaling pathway by targeting Src and interrupting molecular interactions between Src and p85, its downstream kinase. Moreover, Cc\u2010ME ameliorated the morphological finding of peritonitis and gastritis in the mouse disease models. Therefore, these results suggest that Cc\u2010ME exerted <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> anti\u2010inflammatory activity in LPS\u2010stimulated macrophages and mouse models of acute inflammatory diseases. This anti\u2010inflammatory activity of Cc\u2010ME was dominantly mediated by targeting Src in NF\u2010<jats:italic>\u03ba<\/jats:italic>B signaling pathway during macrophage\u2010mediated inflammatory responses.<\/jats:p>","DOI":"10.1155\/2018\/3909038","type":"journal-article","created":{"date-parts":[[2018,3,14]],"date-time":"2018-03-14T23:31:15Z","timestamp":1521070275000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Src Is a Prime Target Inhibited by <i>Celtis choseniana<\/i> Methanol Extract in Its Anti\u2010Inflammatory Action"],"prefix":"10.1155","volume":"2018","author":[{"given":"Han 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