{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T16:40:16Z","timestamp":1783960816065,"version":"3.55.0"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T00:00:00Z","timestamp":1730764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dong-A Pharmaceutical Co. Ltd"},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["NRF- 2022R1A5A2027161"],"award-info":[{"award-number":["NRF- 2022R1A5A2027161"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Eupatilin, a flavone isolated from <jats:italic>Artemisia<\/jats:italic> species, exerts anti-inflammatory, anti-oxidative, and anti-neoplastic activities. However, the effects of eupatilin on <jats:italic>H<\/jats:italic>. <jats:italic>pylori<\/jats:italic>-associated gastritis remain unclear. Thus, this study aimed to investigate the anti-inflammatory effects of eupatilin on gastric epithelial cells infected with cytotoxin-associated gene A (CagA)-positive <jats:italic>Helicobacter pylori<\/jats:italic>.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Materials and methods<\/jats:title>\n<jats:p>AGS human gastric carcinoma cells were infected with a CagA-positive <jats:italic>H<\/jats:italic>. <jats:italic>pylori<\/jats:italic> strain and then treated with 10, 50, or 100 ng of eupatilin. After 24 h, the expression levels of CagA, phosphoinositide 3-kinase 1 (PI3K), nuclear factor (NF)-\u03baB, interleukin (IL)-1\u03b2, and tumor necrosis factor (TNF)-\u03b1 in the cell lysates were measured using western blotting, and the mRNA levels of IL-6, IL-8, and monocyte chemoattractant protein (MCP)-1 were measured using real-time polymerase chain reaction.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>CagA translocation into AGS cells resulted in an elongated cell morphology, which was significantly suppressed by eupatilin treatment in a dose-dependent manner. Immunofluorescence staining for anti-CagA showed that eupatilin treatment dose-dependently inhibited CagA expression in the <jats:italic>H<\/jats:italic>. <jats:italic>pylori<\/jats:italic>-infected AGS cells. <jats:italic>H<\/jats:italic>. <jats:italic>pylori<\/jats:italic> infection increased the levels of pro-inflammatory cytokines including IL-1\u03b2, TNF-\u03b1, IL-6, IL-8, and MCP-1, and eupatilin treatment significantly reduced the levels of these cytokines in a dose-dependent manner. Additionally, eupatilin treatment dose-dependently suppressed the expression of PI3K and NF-\u03baB.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Eupatilin treatment demonstrated anti-inflammatory effects on CagA-positive <jats:italic>H<\/jats:italic>. <jats:italic>pylori<\/jats:italic>-infected gastric epithelial cells by inhibiting CagA translocation, thereby suppressing the NF-\u03baB signaling pathway. These results suggest that eupatilin plays a protective role against CagA-positive <jats:italic>H<\/jats:italic>. <jats:italic>pylori<\/jats:italic>-induced gastritis.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0313251","type":"journal-article","created":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T18:23:36Z","timestamp":1730831016000},"page":"e0313251","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Anti-inflammatory effects of eupatilin on Helicobacter pylori CagA-induced gastric inflammation"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2734-2134","authenticated-orcid":true,"given":"Bong Eun","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Jin","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9721-5734","authenticated-orcid":true,"given":"Gwang Ha","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Chan","family":"Joo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moon Won","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,11,5]]},"reference":[{"key":"pone.0313251.ref001","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1159\/000538079","article-title":"H. pylori infection: A 40-year journey through shifting the paradigm to transforming the management","volume":"42","author":"P Malfertheiner","year":"2024","journal-title":"Dig Dis"},{"key":"pone.0313251.ref002","doi-asserted-by":"crossref","first-page":"16339","DOI":"10.1073\/pnas.0502598102","article-title":"Helicobacter pylori CagA induces a transition from polarized to invasive phenotypes in MDCK cells","volume":"102","author":"F Bagnoli","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0313251.ref003","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1172\/JCI11830","article-title":"NF-\u03baB: a key role in inflammatory diseases","volume":"107","author":"PP Tak","year":"2001","journal-title":"J Clin Invest"},{"key":"pone.0313251.ref004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10286020.2018.1492565","article-title":"Eupatilin: a natural pharmacologically active flavone compound with its wide range applications","volume":"22","author":"B Nageen","year":"2020","journal-title":"J Asian Nat Prod Res"},{"key":"pone.0313251.ref005","doi-asserted-by":"crossref","first-page":"16","DOI":"10.5230\/jgc.2011.11.1.16","article-title":"Eupatilin inhibits gastric cancer cell growth by blocking STAT3-mediated VEGF expression","volume":"11","author":"J-H Cheong","year":"2011","journal-title":"J Gastric Cancer"},{"key":"pone.0313251.ref006","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1097\/MCO.0b013e3282f0cef2","article-title":"Polyphenols and inflammation: basic interactions","volume":"10","author":"HK Biesalski","year":"2007","journal-title":"Curr Opin Clin Nutr Metab Care"},{"key":"pone.0313251.ref007","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1007\/BF02975366","article-title":"Studies on protective effect of DA-9601, Artemisia asiatica extract, on acetaminophen-and CCI 4-induced liver damage in rats","volume":"21","author":"BK Ryu","year":"1998","journal-title":"Arch Pharm Res"},{"key":"pone.0313251.ref008","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S1383-5718(01)00234-0","article-title":"Eupatilin, a pharmacologically active flavone derived from Artemisia plants, induces apoptosis in human promyelocytic leukemia cells","volume":"496","author":"H-J Seo","year":"2001","journal-title":"Mutat Res"},{"key":"pone.0313251.ref009","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.phymed.2015.04.003","article-title":"Protective effect of Artemisia asiatica (Pamp.) 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