{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T16:04:18Z","timestamp":1785773058658,"version":"3.56.0"},"reference-count":55,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation, FAPESP","doi-asserted-by":"publisher","award":["2016\/20600-0"],"award-info":[{"award-number":["2016\/20600-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chemotherapy with irinotecan (CPT-11) induces intestinal mucositis via oxidative stress and NF-\u03baB-driven cytokine amplification. We investigated the protective effects of the anthocyanidins cyanidin and malvidin (5 mg\/kg) in a murine CPT-11 mucositis model. Both compounds increased duodenal glutathione level (GSH) and reduced lipid peroxidation (MDA), with distinct antioxidant profiles: malvidin enhanced catalase (CAT) activity, while cyanidin elevated superoxide dismutase (SOD). In the colon, cyanidin lowered MDA, whereas other oxidative and inflammatory markers remained largely unchanged. Malvidin significantly reduced IL-1\u03b2 and IL-17 in both intestinal segments; cyanidin selectively decreased IL-6 in the colon, and this reduction was also observed for malvidin treatment. Gene expression analysis revealed broad transcriptional suppression in the duodenum for both compounds (Nrf2, NF-\u03baB, TNF-\u03b1, IL-1\u03b2, IL-6, IL-17, IL-10), while colonic effects were more limited (suppression in IL-6 for both compounds). Despite these biochemical and transcriptional improvements\u2014which were more pronounced with malvidin\u2014neither compound prevented CPT-11-induced weight loss or colonic histopathology, indicating that redox and cytokine modulation alone are insufficient to restore mucosal integrity. Overall, malvidin demonstrated a more significant modulation in the antioxidant response in the duodenum, with anti-inflammatory activity in both segments, while cyanidin showed targeted modulation of oxidative stress. These findings position both anthocyanidins as complementary agents with distinct mechanistic profiles, warranting further investigation into dose\u2013response, pharmacokinetics, NRF2 protein dynamics, and barrier-repair strategies. Early-phase clinical evaluation is recommended to assess their potential as adjunctive therapies for chemotherapy-induced intestinal mucositis.<\/jats:p>","DOI":"10.3390\/ijms262110747","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T13:19:29Z","timestamp":1762348769000},"page":"10747","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Anthocyanidins Malvidin and Cyanidin Alleviate Irinotecan-Triggered Intestinal Mucositis by Modulating Oxidative Stress and Cytokine Release"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4075-2288","authenticated-orcid":false,"given":"Giovana Fil\u00f3como","family":"Machado","sequence":"first","affiliation":[{"name":"Post Graduate Program in Health Sciences, Laboratory of Natural Products, S\u00e3o Francisco University, Bragan\u00e7a Paulista 12916-900, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3442-7224","authenticated-orcid":false,"given":"Qu\u00e9lita Cristina","family":"Pereira","sequence":"additional","affiliation":[{"name":"Post Graduate Program in Health Sciences, Laboratory of Natural Products, S\u00e3o Francisco University, Bragan\u00e7a Paulista 12916-900, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3629-0316","authenticated-orcid":false,"given":"Felipe Leonardo","family":"Fagundes","sequence":"additional","affiliation":[{"name":"Post Graduate Program in Health Sciences, Laboratory of Natural Products, S\u00e3o Francisco University, Bragan\u00e7a Paulista 12916-900, S\u00e3o Paulo, Brazil"},{"name":"Department of Structural and Functional Biology, Physiology Sector, Institute of Bioscience, S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5466-3414","authenticated-orcid":false,"given":"Maycon Tavares","family":"Em\u00edlio-Silva","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Physiology Sector, Institute of Bioscience, S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9312-2431","authenticated-orcid":false,"given":"Vin\u00edcius Peixoto","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology, Physiology Sector, Institute of Bioscience, S\u00e3o Paulo State University (UNESP), Botucatu 18618-689, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1610-2728","authenticated-orcid":false,"given":"Mariana de Almeida","family":"Pati\u00f1o","sequence":"additional","affiliation":[{"name":"Post Graduate Program in Health Sciences, Laboratory of Medical Investigation, S\u00e3o Francisco Medical School, Bragan\u00e7a Paulista 12916-900, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4463-9483","authenticated-orcid":false,"given":"Giulia Izzo","family":"Jorge","sequence":"additional","affiliation":[{"name":"Post Graduate Program in Health Sciences, Laboratory of Medical Investigation, S\u00e3o Francisco Medical School, Bragan\u00e7a Paulista 12916-900, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Aires","family":"Pereira","sequence":"additional","affiliation":[{"name":"Post Graduate Program in Health Sciences, Laboratory of Medical Investigation, S\u00e3o Francisco Medical School, Bragan\u00e7a Paulista 12916-900, S\u00e3o Paulo, 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