{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T13:27:07Z","timestamp":1768829227194,"version":"3.49.0"},"reference-count":69,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T00:00:00Z","timestamp":1748044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Urbino Carlo Bo"},{"name":"Centre for Nutraceuticals research reserve at the University of Westminster"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Ferroptosis, a regulated form of cell death driven by iron accumulation and lipid peroxidation, contributes to oxidative stress-related skin damage. This study evaluates the antioxidant and anti-inflammatory effects of a nanoformulation derived from an Annurca apple callus extract in an in vitro model of ferroptosis using human keratinocytes (HaCaT cells). A hydroalcoholic extract from light Annurca apple callus (LCE) was nanoformulated with Pluronic\u00ae F127 and Soluplus\u00ae to enhance stability and bioavailability. The resulting nanoformulation (NF-LCE) exhibited optimal particle size (103.17 \u00b1 0.87 nm), polydispersity index (0.21 \u00b1 0.00), and zeta potential (\u22121.88 \u00b1 0.64 mV). Iron overload (100 \u00b5M) was employed to induce oxidative stress and inflammation in HaCaT cells, resulting in elevated levels of inflammatory markers (COX2, IL-6, TNF-\u03b1) and a diminished antioxidant response, as indicated by decreased expression of GPX4 and Nrf2. NF-LCE treatment restored GPX4 and Nrf2 levels (~0.8-fold increase, p &lt; 0.05) while significantly reducing COX2 (36.6%, p &lt; 0.01), IL-6 (79.6%, p &lt; 0.0001), and TNF-\u03b1 (30.9%, p &lt; 0.1). These results suggest NF-LCE as a promising therapeutic strategy for mitigating ferroptosis-induced skin damage, warranting further investigation in advanced skin models and clinical applications.<\/jats:p>","DOI":"10.3390\/antiox14060631","type":"journal-article","created":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T20:39:36Z","timestamp":1748205576000},"page":"631","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of Antioxidant and Anti-Inflammatory Effects of a Nanoformulation Derived from Annurca Apple Callus Extract in an In Vitro Model of Iron Overload-Induced Inflammation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3692-6118","authenticated-orcid":false,"given":"Federica","family":"Gubitosa","sequence":"first","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy"},{"name":"Centre for Nutraceuticals, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3803-7351","authenticated-orcid":false,"given":"Laura","family":"Taramova","sequence":"additional","affiliation":[{"name":"Centre for Nutraceuticals, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1912-3081","authenticated-orcid":false,"given":"Stefanie Ho Yi","family":"Chan","sequence":"additional","affiliation":[{"name":"Centre for Nutraceuticals, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK"},{"name":"Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0777-5189","authenticated-orcid":false,"given":"Joan","family":"Liu","sequence":"additional","affiliation":[{"name":"Centre for Nutraceuticals, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8489-4747","authenticated-orcid":false,"given":"Daniele","family":"Fraternale","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9334-2525","authenticated-orcid":false,"given":"Vinood B.","family":"Patel","sequence":"additional","affiliation":[{"name":"Centre for Nutraceuticals, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5361-4610","authenticated-orcid":false,"given":"Satyanarayana","family":"Somavarapu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3619-9413","authenticated-orcid":false,"given":"Lucia","family":"Potenza","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9944-8451","authenticated-orcid":false,"given":"Mohammed Gulrez","family":"Zariwala","sequence":"additional","affiliation":[{"name":"Centre for Nutraceuticals, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1046\/j.1523-1747.2003.12359.x","article-title":"Barrier function of the skin: \u201cla raison d\u2019\u00eatre\u201d of the epidermis","volume":"121","author":"Madison","year":"2003","journal-title":"J. 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