{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:17:13Z","timestamp":1788358633287,"version":"build-2803163510"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"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. Pharmacol."],"abstract":"<jats:p>\n                    Impaired intestinal epithelial barrier function is closely associated with the pathogenesis of ulcerative colitis (UC). Atractylenolide-I (AT-I), a major sesquiterpene derived from the herb\n                    <jats:italic>Atractylodes macrocephala<\/jats:italic>\n                    Koidz., has been reported to alleviate DSS-induced colitis in mice. This study aims to investigated the protective effects of AT-1 on intestinal epithelial barrier function and elucidate it\u2019s underlying mechanisms.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , an acute colitis model was established in mice, and transcriptomic analysis to identify differentially expressed genes.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , overexpression plasmids and recombinant protein were used to evaluate their effects on intestinal barrier function, and further analysis of its potential mechanisms.The study found that AT-1 ameliorate DSS-induced acute ulcerative colitis, exhibiting protective effects on the intestinal barrier. Transcriptomic analysis revealed that AT-1 significantly modulated the expression of S100A8 and S100A9. Further investigations indicated that S100A9, rather than S100A8, mediated the expression of tight junction proteins, meanwhile, AT-1 reduces neutrophil activation and subsequent release of S100A9. Mechanistically, recombinant human S100A9 protein was found to induce a decrease in intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    concentration, while AT-1 regulated the expression of tight junction proteins\n                    <jats:italic>via<\/jats:italic>\n                    modulation of the AMPK\/mTOR signaling pathway. AT-1 enhances the recovery of DSS-induced intestinal barrier dysfunction by regulating the recombinant human S100A9 protein-mediated AMPK\/mTOR signaling pathway. This study provides new insights into the pathogenesis of ulcerative colitis and suggests potential therapeutic strategies for its treatment.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2025.1530109","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T06:12:39Z","timestamp":1742796759000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Atractylenolide-I restore intestinal barrier function by targeting the S100A9\/AMPK\/mTOR signaling pathway"],"prefix":"10.3389","volume":"16","author":[{"given":"Chen","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingjie","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keming","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linhai","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaidi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengli","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yugen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/j.pop.2023.03.009","article-title":"Inflammatory Bowel disease","volume":"50","author":"Bruner","year":"2023","journal-title":"Prim. Care"},{"key":"B2","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/j.gtc.2020.07.005","article-title":"Epidemiology and pathogenesis of ulcerative colitis","volume":"49","author":"Du","year":"2020","journal-title":"Gastroenterol. Clin. North Am."},{"key":"B3","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1001\/jama.2023.15389","article-title":"Ulcerative colitis in Adults: A review","volume":"330","author":"Gros","year":"2023","journal-title":"JAMA"},{"key":"B4","doi-asserted-by":"publisher","first-page":"102836","DOI":"10.1016\/j.ceca.2023.102836","article-title":"The role of Ca(2+)-signaling in the regulation of epigenetic mechanisms","volume":"117","author":"Hern\u00e1ndez-Oliveras","year":"2024","journal-title":"Cell Calcium"},{"key":"B5","doi-asserted-by":"publisher","first-page":"3840","DOI":"10.1038\/srep03840","article-title":"Atractylenolide-I sensitizes human ovarian cancer cells to paclitaxel by blocking activation of TLR4\/MyD88-dependent pathway","volume":"4","author":"Huang","year":"2014","journal-title":"Sci. Rep."},{"key":"B6","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1186\/s13054-023-04652-x","article-title":"Therapeutic S100A8\/A9 blockade inhibits myocardial and systemic inflammation and mitigates sepsis-induced myocardial dysfunction","volume":"27","author":"Jakobsson","year":"2023","journal-title":"Crit. Care"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1161\/01.RES.0000171894.03801.03","article-title":"Angiopoietin-1 opposes VEGF-induced increase in endothelial permeability by inhibiting TRPC1-dependent Ca2 influx","volume":"96","author":"Jho","year":"2005","journal-title":"Circ. Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.cca.2020.08.025","article-title":"Calprotectin in inflammatory bowel disease","volume":"510","author":"Khaki-Khatibi","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"B9","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/S0140-6736(23)00966-2","article-title":"Ulcerative colitis","volume":"402","author":"Le Berre","year":"2023","journal-title":"Lancet"},{"key":"B10","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/nature11588","article-title":"The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMP","volume":"492","author":"Lee","year":"2012","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","first-page":"111308","DOI":"10.1016\/j.celrep.2022.111308","article-title":"Enterobacter ludwigii protects DSS-induced colitis through choline-mediated immune tolerance","volume":"40","author":"Li","year":"2022","journal-title":"Cell Rep."},{"key":"B12","doi-asserted-by":"publisher","first-page":"183","DOI":"10.3390\/biom14020183","article-title":"Calcium-associated proteins in neuroregeneration","volume":"14","author":"Lisek","year":"2024","journal-title":"Biomolecules"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e202401879","DOI":"10.1002\/cbdv.202401879","article-title":"The rhizome of Atractylodes macrocephala Koidz.: A comprehensive review on the traditional uses, phytochemistry and pharmacology","author":"Luo","year":"2024","journal-title":"Chem. Biodivers."},{"key":"B14","doi-asserted-by":"publisher","first-page":"107688","DOI":"10.1016\/j.intimp.2021.107688","article-title":"Costunolide ameliorates colitis via specific inhibition of HIF1\u03b1\/glycolysis-mediated Th17 differentiation","volume":"97","author":"Lv","year":"","journal-title":"Int. Immunopharmacol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2880","DOI":"10.1016\/j.apsb.2021.03.011","article-title":"Lonicerin targets EZH2 to alleviate ulcerative colitis by autophagy-mediated NLRP3 inflammasome inactivation","volume":"11","author":"Lv","year":"","journal-title":"Acta Pharm. Sin. B"},{"key":"B16","doi-asserted-by":"publisher","first-page":"105613","DOI":"10.1016\/j.phrs.2021.105613","article-title":"Didymin switches M1-like toward M2-like macrophage to ameliorate ulcerative colitis via fatty acid oxidation","volume":"169","author":"Lv","year":"","journal-title":"Pharmacol. Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/ncb3114","article-title":"Lysosomal calcium signalling regulates autophagy through calcineurin and \u200bTFEB","volume":"17","author":"Medina","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/s41575-020-00399-w","article-title":"The intestinal barrier, an arbitrator turned provocateur in IBD","volume":"18","author":"Mehandru","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1146\/annurev.physiol.68.040504.094707","article-title":"Signaling for contraction and relaxation in smooth muscle of the gut","volume":"68","author":"Murthy","year":"2006","journal-title":"Annu. Rev. Physiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1038\/s41467-021-22212-1","article-title":"Symbiotic polyamine metabolism regulates epithelial proliferation and macrophage differentiation in the colon","volume":"12","author":"Nakamura","year":"2021","journal-title":"Nat. Commun."},{"key":"B21","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/nrgastro.2016.169","article-title":"The intestinal epithelial barrier: a therapeutic target","volume":"14","author":"Odenwald","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/j.tcb.2020.08.004","article-title":"Tight junction structure and function revisited","volume":"30","author":"Otani","year":"2020","journal-title":"Trends Cell Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"eabj9954","DOI":"10.1126\/scitranslmed.abj9954","article-title":"Acute inflammatory response via neutrophil activation protects against the development of chronic pain","volume":"14","author":"Parisien","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"100577","DOI":"10.1016\/j.jbc.2021.100577","article-title":"Calmodulin influences MAPK signaling by binding KSR1","volume":"296","author":"Parvathaneni","year":"2021","journal-title":"J. Biol. Chem."},{"key":"B25","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1146\/annurev-pathmechdis-031621-025153","article-title":"The pathogenesis of African trypanosomiasis","volume":"18","author":"Pays","year":"2023","journal-title":"Annu. Rev. Pathol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e140966","DOI":"10.1172\/JCI140966","article-title":"Endothelial C3a receptor mediates vascular inflammation and blood-brain barrier permeability during aging","volume":"131","author":"Propson","year":"2021","journal-title":"J. Clin. Invest."},{"key":"B27","doi-asserted-by":"publisher","first-page":"2021","DOI":"10.1038\/s41590-023-01656-1","article-title":"E-selectin-mediated rapid NLRP3 inflammasome activation regulates S100A8\/S100A9 release from neutrophils via transient gasdermin D pore formation","volume":"24","author":"Pruenster","year":"2023","journal-title":"Nat. Immunol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.pharmthera.2016.07.015","article-title":"S100A8\/A9: From basic science to clinical application","volume":"167","author":"Pruenster","year":"2016","journal-title":"Pharmacol. Ther."},{"key":"B29","doi-asserted-by":"publisher","first-page":"153945","DOI":"10.1016\/j.phymed.2022.153945","article-title":"Atractylenolide-1 targets SPHK1 and B4GALT2 to regulate intestinal metabolism and flora composition to improve inflammation in mice with colitis","volume":"98","author":"Qu","year":"2022","journal-title":"Phytomedicine"},{"key":"B30","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1016\/j.it.2008.08.005","article-title":"Calcium\/calmodulin-dependent kinase IV in immune and inflammatory responses: novel routes for an ancient traveller","volume":"29","author":"Racioppi","year":"2008","journal-title":"Trends Immunol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1146\/annurev-pharmtox-051421-111814","article-title":"CaMKII as a therapeutic target in cardiovascular disease","volume":"63","author":"Reyes Gaido","year":"2023","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1080\/10408363.2019.1619159","article-title":"Clinical value of fecal calprotectin","volume":"56","author":"Ricciuto","year":"2019","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.exger.2014.09.015","article-title":"Skin aging, gene expression and calcium","volume":"68","author":"Rinnerthaler","year":"2015","journal-title":"Exp. Gerontol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1053\/j.gastro.2021.10.035","article-title":"Colorectal cancer in inflammatory bowel disease: mechanisms and management","volume":"162","author":"Shah","year":"2022","journal-title":"Gastroenterology"},{"key":"B35","doi-asserted-by":"publisher","first-page":"eabe5357","DOI":"10.1126\/sciadv.abe5357","article-title":"S100A8\/S100A9 cytokine acts as a transcriptional coactivator during breast cellular transformation","volume":"7","author":"Song","year":"2021","journal-title":"Sci. Adv."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2380","DOI":"10.1056\/NEJMicm1604333","article-title":"African trypanosomiasis","volume":"375","author":"Streit","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"2092","DOI":"10.1053\/j.gastro.2020.08.005","article-title":"Increased intestinal permeability is associated with later development of Crohn's disease","volume":"159","author":"Turpin","year":"2020","journal-title":"Gastroenterology"},{"key":"B38","doi-asserted-by":"publisher","first-page":"4107","DOI":"10.1038\/s41467-022-31803-5","article-title":"Hepatic non-parenchymal S100A9-TLR4-mTORC1 axis normalizes diabetic ketogenesis","volume":"13","author":"Ursino","year":"2022","journal-title":"Nat. Commun."},{"key":"B39","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1136\/gutjnl-2014-308323","article-title":"TLR-independent anti-inflammatory function of intestinal epithelial TRAF6 signalling prevents DSS-induced colitis in mice","volume":"65","author":"Vlantis","year":"2016","journal-title":"Gut"},{"key":"B40","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1001\/jama.2023.23814","article-title":"What is ulcerative colitis","volume":"331","author":"Voelker","year":"2024","journal-title":"JAMA"},{"key":"B41","doi-asserted-by":"publisher","first-page":"113006","DOI":"10.1016\/j.celrep.2023.113006","article-title":"S100A8\/A9-alarmin promotes local myeloid-derived suppressor cell activation restricting severe autoimmune arthritis","volume":"42","author":"von Wulffen","year":"2023","journal-title":"Cell Rep."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1038\/nprot.2017.044","article-title":"Chemically induced mouse models of acute and chronic intestinal inflammation","volume":"12","author":"Wirtz","year":"2017","journal-title":"Nat. Protoc."},{"key":"B43","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.cmet.2005.06.005","article-title":"Ca2+\/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells","volume":"2","author":"Woods","year":"2005","journal-title":"Cell Metab."},{"key":"B44","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1002\/cac2.12388","article-title":"Elevated neutrophil extracellular traps by HBV-mediated S100A9-TLR4\/RAGE-ROS cascade facilitate the growth and metastasis of hepatocellular carcinoma","volume":"43","author":"Zhan","year":"2023","journal-title":"Cancer Commun."},{"key":"B45","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.jep.2018.08.023","article-title":"The traditional uses, phytochemistry, and pharmacology of Atractylodes macrocephala Koidz.: a review","volume":"226","author":"Zhu","year":"2018","journal-title":"J. Ethnopharmacol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1530109\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T06:12:43Z","timestamp":1742796763000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1530109\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,24]]},"references-count":45,"alternative-id":["10.3389\/fphar.2025.1530109"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1530109","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,24]]},"article-number":"1530109"}}