Journal Article

Topical Astaxanthin Attenuates Imiquimod-Induced Psoriasiform Dermatitis by Downregulating Psoriasis-Associated Keratin Gene Expression (Krt16, Krt17, Krt6a) and Inhibiting the JAK-STAT Signaling Pathway

Rasool, Mohammed Ibrahim, ALtrufi, Meeqaat H., Ashoor, Jamal Ali, Al-Saedi, Haider Falih Shamikh, Hasan, Samer Ali, Albahadly, Waleed Khaled Younis

2026

Overview

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 (0.5–1.5%) 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-α, 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–STAT 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–STAT 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.

• Publisher: MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
• Subject: Administration, Topical / Animals / Antioxidants / astaxanthin / Carotenoids / Cytokines / Cytokines - metabolism / Dermatitis / Development and progression / Disease / Disease Models, Animal / Down-Regulation - drug effects / Drug dosages / Enzyme-linked immunosorbent assay / Gene expression / Gene Expression Regulation - drug effects / Genes / Health aspects / Hyperplasia / IL-23/IL-17 axis / Imiquimod / Imiquimod - adverse effects / Inflammation / JAK–STAT signaling / Janus Kinases - metabolism / Keratin / Keratins - genetics / Keratins - metabolism / Lipid peroxidation / Lipids / Mice / Morphology / Nitric oxide / Oxidases / Oxidative stress / Oxidative Stress - drug effects / Psoriasis / Psoriasis - chemically induced / Psoriasis - drug therapy / Psoriasis - genetics / Psoriasis - metabolism / Psoriasis - pathology / Reactive oxygen species / Signal Transduction - drug effects / Skin / STAT Transcription Factors - metabolism / Superoxide / Xanthophylls - administration & dosage / Xanthophylls - pharmacology