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This species is traditionally used to treat asthma, rheumatic pain, arthritis, and digestive problems. Recently, several studies have highlighted the significant anti\u2010inflammatory potential of <jats:italic>P. kadsura<\/jats:italic> extracts and secondary metabolites. Here, we report the isolation of kadsurenin F as an active component of <jats:italic>P. kadsura<\/jats:italic>. We found that kadsurenin F increases oxidative load and suppresses proteasome functionality in normal diploid human fibroblasts, and after administration in <jats:italic>Drosophila<\/jats:italic> flies. Moreover, kadsurenin F likely possesses anti\u2010inflammatory properties, as apart from suppressing proteasome activity, it reversed inflammatory phenotypes and inhibited NO production in RAW 264.7 macrophage cells when administered in parallel with LPS. Our findings suggest that the kadsurenin F scaffold can be used for the development of novel highly bioactive proteasome inhibitors and\/or anti\u2010inflammatory compounds.<\/jats:p>","DOI":"10.1002\/cbdv.202401848","type":"journal-article","created":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T08:54:12Z","timestamp":1732352052000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Neolignan Kadsurenin F Modulates Proteostatic Pathways and Possesses Potent Anti\u2010Inflammatory Properties"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3433-5960","authenticated-orcid":false,"given":"Zoi","family":"Evangelakou","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Biophysics Faculty of Biology National and Kapodistrian University of Athens  Athens 15784 Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3731-7349","authenticated-orcid":false,"given":"Stefan","family":"Schwaiger","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy\/Pharmacognosy University of Innsbruck  CCB, Innrain 80\u201382 6020 Innsbruck Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Despoina D.","family":"Gianniou","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Biophysics Faculty of Biology National and Kapodistrian University of Athens  Athens 15784 Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6179-2772","authenticated-orcid":false,"given":"Ioannis P.","family":"Trougakos","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Biophysics Faculty of Biology National and Kapodistrian University of Athens  Athens 15784 Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8862-0201","authenticated-orcid":false,"given":"Hermann","family":"Stuppner","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy\/Pharmacognosy University of Innsbruck  CCB, Innrain 80\u201382 6020 Innsbruck Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,23]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glu049"},{"key":"e_1_2_8_1_2","first-page":"38","journal-title":"S33"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18102036"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ircmb.2014.09.002"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2014.01.017"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2013.02.024"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2010.09.006"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a000034"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2010.177"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-015-0056-4"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-020-00708-5"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212389200"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2010.178"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/np200343t"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9422(97)00328-2"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2009.10.016"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phytochem.2022.113336"},{"key":"e_1_2_8_17_1","unstructured":"Z.\u2005N. 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