{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T10:41:50Z","timestamp":1786444910965,"version":"build-2736575974"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T00:00:00Z","timestamp":1766793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007065","name":"UNIVERSITY OF SALERNO","doi-asserted-by":"publisher","award":["FARB 2022\/ORSA220292; FARB 2023\/ORSA232311; FARB 2024\/ORSA240994 granted to Prof. Stefania Marzocco"],"award-info":[{"award-number":["FARB 2022\/ORSA220292; FARB 2023\/ORSA232311; FARB 2024\/ORSA240994 granted to Prof. Stefania Marzocco"]}],"id":[{"id":"10.13039\/501100007065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Intestinal impairment plays a pivotal role in many chronic conditions, including chronic kidney disease (CKD), a progressive disorder affecting over 800 million people worldwide. CKD does not only affect the kidney, but it is recognized as a systemic condition characterized by chronic low-grade inflammation, that contributes to disease progression and associated complications. The intestine is one of the major sources of CKD-associated inflammation, also due to the production and accumulation of some uremic toxins, normally excreted by healthy kidneys, such as indoxyl sulfate (IS). IS is a pro-inflammatory and pro-oxidant protein-bound uremic toxin that increases intestinal epithelial permeability, promotes microbial translocation, and enhances inflammatory and oxidative responses. Although IS-induced intestinal damage has been documented, the underlying molecular mechanisms and effective therapeutic strategies to counteract its effects remain to be elucidated. Against this backdrop in the present study, we investigated the impact of plumericin, an iridoid spironolactone, on IS-induced intestinal impairment using IEC-6, an intestinal epithelial cells model. In IS-treated IEC-6, plumericin reduces apoptosis, inhibits inflammation and oxidative stress, and restores epithelial wound repair. In these conditions plumericin also promotes Nrf-2 and inhibits NF-kB and AhR activation induced by IS. Moreover, the same inhibitory effect of plumericin on inflammation and oxidative stress and in promoting wound repair is also observed in the presence of IS and pro-inflammatory stimuli, as occurs in CKD considering the associated systemic low-grade inflammation. These findings suggest that plumericin may represent a promising therapeutic candidate for intestinal impairment in CKD acting with an integrated mechanism.<\/jats:p>","DOI":"10.3390\/ijms27010293","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T05:28:19Z","timestamp":1766986099000},"page":"293","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Plumericin Modulates the AhR\u2013NF\u03baB\u2013Nrf2 Signaling Network to Counteract Indoxyl Sulfate-Induced Intestinal Epithelial Cells Impairment"],"prefix":"10.3390","volume":"27","author":[{"given":"Rosaria Margherita","family":"Rispoli","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy"},{"name":"PhD Program in Drug Discovery and Development, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3731-7349","authenticated-orcid":false,"given":"Stefan","family":"Schwaiger","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy\/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9843-8443","authenticated-orcid":false,"given":"Ada","family":"Popolo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8423-9489","authenticated-orcid":false,"given":"Giuseppina","family":"Autore","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0645-9800","authenticated-orcid":false,"given":"Marco","family":"Gargaro","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8862-0201","authenticated-orcid":false,"given":"Hermann","family":"Stuppner","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy\/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2333-1630","authenticated-orcid":false,"given":"Stefania","family":"Marzocco","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via Giovanni Paolo II 132, 84084 Fisciano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Barbara, G., Barbaro, M.R., Fuschi, D., Palombo, M., Falangone, F., Cremon, C., Marasco, G., and Stanghellini, V. 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