Title : The repurposing of nitazoxanide for psoriasis treatment exerts therapeutic effects through skin metabolic reprogramming

Background: Psoriasis is a chronic inflammatory skin disease characterized by excessive keratinocyte proliferation and immune dysregulation. Increasing evidence suggests that metabolic reprogramming contributes to disease pathogenesis, making metabolic pathways attractive therapeutic targets. Nitazoxanide (NTZ), an FDA-approved antiparasitic drug, has recently been recognized for its immunometabolic regulatory properties.

Methods: The therapeutic effects of NTZ were investigated using IL-17A-stimulated human keratinocytes and imiquimod-induced psoriasis-like mouse models. Cellular metabolism was evaluated using extracellular flux analysis, glucose uptake assays, and mitochondrial function analyses. Immune cell populations were analyzed by flow cytometry, while inflammatory mediators and signaling pathways were assessed using quantitative PCR and Western blotting.

Results: NTZ significantly reduced the expression of psoriasis-associated inflammatory mediators and antimicrobial peptides in keratinocytes. Treatment suppressed glycolytic metabolism and restored mitochondrial function through activation of AMPK and inhibition of mTORC1 signaling. In vivo, NTZ markedly alleviated psoriasis-like skin inflammation, reduced epidermal hyperplasia, and decreased inflammatory cell infiltration. Furthermore, NTZ suppressed Th17 cell responses while promoting regulatory immune homeostasis, accompanied by normalization of metabolic pathways within psoriatic skin lesions.

Conclusion: NTZ ameliorates psoriasis by regulating skin metabolic reprogramming through the AMPK/mTORC1 pathway and by suppressing pathogenic inflammatory responses. These findings support drug repurposing of NTZ as a promising therapeutic strategy for psoriasis and highlight immunometabolic modulation as a potential target for inflammatory skin diseases.

Ha Eun Kim is a PhD student in the Department of Immunology at Jeonbuk National University Medical School, Republic of Korea. Her research focuses on immunometabolism and immune regulation in inflammatory diseases, including psoriasis, atopic dermatitis, osteoarthritis, and regulatory B cell (Breg)-mediated immune responses. She also investigates exercise-induced immune modulation and metabolic signaling pathways to identify novel therapeutic targets and drug repurposing strategies. She has authored multiple SCI publications in the fields of immunology and inflammatory diseases, including studies published in the Journal of Investigative Dermatology and Antioxidants.