{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T05:24:18Z","timestamp":1787376258181,"version":"build-2736575974"},"reference-count":55,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development, and Innovation","award":["451-03-33\/2026-03\/200019"],"award-info":[{"award-number":["451-03-33\/2026-03\/200019"]}]},{"name":"Ministry of Science, Technological Development, and Innovation","award":["451-03-33\/2026-03\/200125"],"award-info":[{"award-number":["451-03-33\/2026-03\/200125"]}]},{"name":"Ministry of Science, Technological Development, and Innovation","award":["451-03-34\/2026-03\/200125"],"award-info":[{"award-number":["451-03-34\/2026-03\/200125"]}]},{"award":["451-03-33\/2026-03\/200019"],"award-info":[{"award-number":["451-03-33\/2026-03\/200019"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"publisher"}]},{"award":["451-03-33\/2026-03\/200125"],"award-info":[{"award-number":["451-03-33\/2026-03\/200125"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"publisher"}]},{"award":["451-03-34\/2026-03\/200125"],"award-info":[{"award-number":["451-03-34\/2026-03\/200125"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Vitis vinifera is a rich source of polyphenolic compounds that are known for their benefits on skin health, including antioxidant, anti-inflammatory, and photoprotective effects. Red wines have shown a positive impact on cardiovascular disease, diabetes, and cancer prevention; however, evidence regarding their effects on skin biology remains scarce. This study evaluated red wine concentrates obtained from Cabernet Sauvignon and Merlot varieties, selected based on their previously demonstrated biological activities, to identify the samples with the highest potential for skin health applications by assessing their inhibitory activity against skin-related enzymes (tyrosinase, elastase, and collagenase), along with their effects on HaCaT cells, including cytotoxic, antioxidant, anti-inflammatory, and wound healing activities. Methods: Enzyme inhibition studies were based on spectrophotometric methods; the MTT and CV assays were carried out to test the cytotoxicity, and the DCFH-DA assay was employed to evaluate the antioxidant activity of the wine concentrates; wound healing potential was examined by the cell scratch assay, and anti-inflammatory activity was investigated using ELISA and qPCR analyses. PCA of the samples and their biological activity was performed as well. Results: Examined red wine concentrates exhibited significant enzyme inhibitory activity and showed no cytotoxicity on HaCaT cells up to the concentration of 50 \u03bcg\/mL; the samples stimulated cell migration, inhibited intracellular ROS production in AAPH-stressed keratinocytes, and selectively modulated TNF-\u03b1-induced inflammatory responses, reducing IL-8 secretion while enhancing certain cytokine transcripts, underscoring the complexity of their bioactive effects. Conclusions: Red wine concentrates showed significant potential as skin-beneficial agents, demonstrating strong antiaging, marked cellular antioxidant effects and wound healing activity when applied at non-cytotoxic concentrations. Multivariate analysis revealed distinct bioactivity profiles among the wine concentrates.<\/jats:p>","DOI":"10.3390\/pharmaceutics18081034","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T12:57:53Z","timestamp":1787230673000},"page":"1034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Investigation of Red Wine Concentrates as Multifunctional Skin-Protective Agents"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3476-4642","authenticated-orcid":false,"given":"Gorana","family":"Ili\u0107","sequence":"first","affiliation":[{"name":"Institute for the Application of Nuclear Energy\u2014INEP, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7587-957X","authenticated-orcid":false,"given":"Ivana","family":"Beara","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3152-446X","authenticated-orcid":false,"given":"Ljiljana","family":"Milovanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5394-0125","authenticated-orcid":false,"given":"Aleksandra","family":"Jovanovi\u0107","sequence":"additional","affiliation":[{"name":"Institute for the Application of Nuclear Energy\u2014INEP, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8467-4165","authenticated-orcid":false,"given":"Dragana","family":"Dekanski","sequence":"additional","affiliation":[{"name":"Institute for the Application of Nuclear Energy\u2014INEP, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1182-4895","authenticated-orcid":false,"given":"Andrea","family":"Pirkovi\u0107","sequence":"additional","affiliation":[{"name":"Institute for the Application of Nuclear Energy\u2014INEP, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sharafan, M., Malinowska, M.A., Ekiert, H., Kwa\u015bniak, B., Sikora, E., and Szopa, A. 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