{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:17:38Z","timestamp":1787962658252,"version":"build-2784847793"},"reference-count":39,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Psoriasis is a chronic immune-mediated inflammatory skin disorder characterized by excessive keratinocyte proliferation, oxidative stress, and dysregulated cytokine signaling. Although topical corticosteroids remain the first-line therapy, their long-term use is often limited by adverse effects, highlighting the need for safer non-steroidal therapeutic alternatives. This study investigated the therapeutic efficacy and underlying mechanisms of a topical astaxanthin (AST) formulation in an imiquimod (IMQ)-induced mouse model of psoriasiform dermatitis. Following IMQ induction, mice were randomly assigned to vehicle, clobetasol, or AST treatment groups (0.5\u20131.5%) for 14 days. Disease progression was evaluated through biochemical analysis of oxidative stress biomarkers, including NADPH oxidase (NOX), malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD), as well as ELISA-based quantification of inflammatory cytokines (TNF-\u03b1, IL-6, IL-17, and IL-23). Histopathological changes were assessed using hematoxylin and eosin staining, while molecular alterations were examined by RT-qPCR analysis of psoriasis-associated keratin genes (Krt16, Krt17, and Krt6a) and evaluation of JAK\u2013STAT signaling activity. AST treatment significantly suppressed the IL-23\/IL-17 inflammatory axis, reduced NOX activity and lipid peroxidation, restored endogenous antioxidant defenses, and inhibited JAK\u2013STAT signaling. These biochemical and molecular effects were accompanied by marked downregulation of keratin gene expression and substantial histological improvement, including normalization of epidermal thickness, reduced parakeratosis, and decreased inflammatory infiltration. Notably, high-dose AST demonstrated therapeutic efficacy comparable to, and in some parameters exceeding, that of clobetasol. Collectively, these findings indicate that topical astaxanthin exerts coordinated antioxidant, anti-inflammatory, and anti-proliferative effects, supporting its potential as a promising multi-target non-steroidal therapeutic candidate for psoriasis management.<\/jats:p>","DOI":"10.3390\/molecules31071191","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:19:32Z","timestamp":1775434772000},"page":"1191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Topical Astaxanthin Attenuates Imiquimod-Induced Psoriasiform Dermatitis by Downregulating Psoriasis-Associated Keratin Gene Expression (Krt16, Krt17, Krt6a) and Inhibiting the JAK-STAT Signaling Pathway"],"prefix":"10.3390","volume":"31","author":[{"given":"Waleed Khaled Younis","family":"Albahadly","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, University of Karbala, Karbala 56001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haider Falih Shamikh","family":"Al-Saedi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, University of Al-Ameed, Karbala 56001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4755-4049","authenticated-orcid":false,"given":"Jamal Ali","family":"Ashoor","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Karbala, Karbala 56001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0992-320X","authenticated-orcid":false,"given":"Mohammed Ibrahim","family":"Rasool","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, University of Karbala, Karbala 56001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samer Ali","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Kufa, Najaf 54001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meeqaat H.","family":"ALtrufi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Kufa, Najaf 54001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1152\/physrev.00009.2022","article-title":"Determinants, maintenance, and function of organellar pH","volume":"103","author":"Freeman","year":"2023","journal-title":"Physiol. 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