{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:18:26Z","timestamp":1780503506117,"version":"3.54.1"},"reference-count":41,"publisher":"S. Karger AG","issue":"8","license":[{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int Arch Allergy Immunol"],"abstract":"<jats:p>Introduction: Osthole, a naturally occurring coumarin derivative, has been isolated from the traditional Chinese medicinal herb Cnidium monnieri. This compound exhibits a range of pharmacological properties, including anticancer, antioxidant, anti-inflammatory, and immunomodulatory effects. The objective of this study was to investigate the role of osthole in tissue remodeling in chronic rhinosinusitis with nasal polyp (CRSwNP). Methods: The effects of osthole on nasal polyp (NP) formation were examined within a mouse model of NPs induced by cigarette smoke (CS). The detection of polypoid changes and goblet cell metaplasia was achieved through the use of hematoxylin-eosin and periodic acid-Schiff staining, respectively. The levels of TGF-\u03b21, matrix metalloproteinases 2, 7, 9, and 12 (MMP2, MMP7, MMP9, MMP12), as well as tissue inhibitor of metalloproteinase-1 (TIMP-1) in nasal lavage fluid were determined by enzyme-linked immunosorbent assay (ELISA). Western blotting was employed to ascertain the expression of epithelial-to-mesenchymal transition (EMT) markers (E-cadherin, ZO-1, \u03b1-SMA, and vimentin), as well as the activity of the PI3K\/AKT\/NF-\u03baB pathway. The expression of E-cadherin in nasal epithelium was determined through immunohistochemistry. Results: In the OVA+SEB or CS-exposed NP mouse model, osthole was observed to reduce the incidence of polypoid changes and goblet cells, while simultaneously increasing the expression of E-cadherin in the epithelium when compared to the CS-treated group. After treatment with osthole, the levels of TGF-\u03b21, MMP2, MMP7, MMP9, and MMP12 in nasal lavage fluid were observed to decrease, while the levels of TIMP-1 were found to increase. In vitro, cigarette smoke extract was observed to downregulate the expression of E-cadherin and ZO-1, while simultaneously upregulating the expression of \u03b1-SMA and vimentin. Moreover, osthole upregulated the expression of E-cadherin and ZO-1 while downregulating the expression of \u03b1-SMA and vimentin. This effect of osthole was reversed by PI3K\/AKT\/NF-\u03baB pathway agonists. Conclusion: Osthole attenuates CS exposure-induced EMT via the PI3K\/AKT\/NF-\u03baB pathway, providing a theoretical and experimental basis for its clinical application in the treatment of CRSwNP. <\/jats:p>","DOI":"10.1159\/000543408","type":"journal-article","created":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T12:00:33Z","timestamp":1735905633000},"page":"747-757","source":"Crossref","is-referenced-by-count":4,"title":["Osthole Ameliorates Cigarette Smoke-Induced Epithelial-To-Mesenchymal Transition via PI3K\/Akt\/NF-\u03baB Pathway in Chronic Rhinosinusitis with Nasal Polyps"],"prefix":"10.1159","volume":"186","author":[{"given":"Peiqiang","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2025,1,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200307000-00016"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1002\/lary.20223"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.04.024"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-14-67"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1080\/19336918.2015.1016686"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v17.i5.625"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21626"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/S1875-9572(08)60028-5"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.941608"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.117547"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2016.02.001"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-022-00702-1"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1002\/lary.26548"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1111\/all.14287"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2012-201761"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1002\/tox.22271"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2020.12.001"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2012.03.020"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2011.02646.x"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2017.01.011"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2020.4682"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1111\/all.15446"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2012.1044"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-021-00677-3"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1002\/lary.20930"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.2174\/1389557522666220214101231"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2017.71"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.07.009"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1021\/jf2021489"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1211-8"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2023.2232113"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2018.05.019"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01650"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/7099097"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015700"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21695"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1080\/19336918.2016.1259058"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1021\/jf501047g"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30759"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)81698-0"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.175909"}],"container-title":["International 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