{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T03:42:52Z","timestamp":1791776572976,"version":"4.3.4"},"reference-count":35,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T00:00:00Z","timestamp":1714176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2014Next Generation EU","award":["2022Z3RN9X"],"award-info":[{"award-number":["2022Z3RN9X"]}]},{"name":"European Union\u2014Next Generation EU","award":["Progetto Eccellenza 2023\u20132027"],"award-info":[{"award-number":["Progetto Eccellenza 2023\u20132027"]}]},{"DOI":"10.13039\/501100003407","name":"MIUR","doi-asserted-by":"publisher","award":["2022Z3RN9X"],"award-info":[{"award-number":["2022Z3RN9X"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"MIUR","doi-asserted-by":"publisher","award":["Progetto Eccellenza 2023\u20132027"],"award-info":[{"award-number":["Progetto Eccellenza 2023\u20132027"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acne vulgaris is a prevalent skin disorder affecting many young individuals, marked by keratinization, inflammation, seborrhea, and colonization by Cutibacterium acnes (C. acnes). Ellagitannins, known for their antibacterial and anti-inflammatory properties, have not been widely studied for their anti-acne effects. Chestnut (Castanea sativa Mill., C. sativa), a rich ellagitannin source, including castalagin whose acne-related bioactivity was previously unexplored, was investigated in this study. The research assessed the effect of C. sativa leaf extract and castalagin on human keratinocytes (HaCaT) infected with C. acnes, finding that both inhibited IL-8 and IL-6 release at concentrations below 25 \u03bcg\/mL. The action mechanism was linked to NF-\u03baB inhibition, without AP-1 involvement. Furthermore, the extract displayed anti-biofilm properties and reduced CK-10 expression, indicating a potential role in mitigating inflammation, bacterial colonization, and keratosis. Castalagin\u2019s bioactivity mirrored the extract\u2019s effects, notably in IL-8 inhibition, NF-\u03baB inhibition, and biofilm formation at low \u03bcM levels. Other polyphenols, such as flavonol glycosides identified via LC-MS, might also contribute to the extract\u2019s biological activities. This study is the first to explore ellagitannins\u2019 potential in treating acne, offering insights for developing chestnut-based anti-acne treatments pending future in vivo studies.<\/jats:p>","DOI":"10.3390\/ijms25094764","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T08:02:22Z","timestamp":1714723342000},"page":"4764","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Investigation into the Anti-Acne Effects of Castanea sativa Mill Leaf and Its Pure Ellagitannin Castalagin in HaCaT Cells Infected with Cutibacterium acnes"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2470-6038","authenticated-orcid":false,"given":"Stefano","family":"Piazza","sequence":"first","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti\u201d, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0742-0521","authenticated-orcid":false,"given":"Giulia","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti\u201d, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8416-1307","authenticated-orcid":false,"given":"Nicole","family":"Maranta","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti\u201d, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2107-3033","authenticated-orcid":false,"given":"Carola","family":"Pozzoli","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti\u201d, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Fumagalli","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti\u201d, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5752-1758","authenticated-orcid":false,"given":"Vincenzo","family":"Nicolaci","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti\u201d, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Sonzogni","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti\u201d, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4133-7202","authenticated-orcid":false,"given":"Luca","family":"Colombo","sequence":"additional","affiliation":[{"name":"Consorzio Castanicoltori di Brinzio, Orino e Castello Cabiaglio, Societ\u00e0 Cooperativa Agricola-Varese, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2811-8628","authenticated-orcid":false,"given":"Enrico","family":"Sangiovanni","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti\u201d, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5378-402X","authenticated-orcid":false,"given":"Mario","family":"Dell\u2019Agli","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti\u201d, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S0140-6736(11)60321-8","article-title":"Acne vulgaris","volume":"379","author":"Williams","year":"2012","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1111\/bjd.12149","article-title":"Epidemiology of acne vulgaris","volume":"168","author":"Bhate","year":"2013","journal-title":"Br. 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