Low molecular weight sulfated galactan attenuates imiquimod‑induced psoriasis via suppression of proinflammatory cytokines and keratinocyte hyperproliferation

Psoriasis is a chronic immune-mediated inflammatory skin disorder characterized by keratinocyte hyperproliferation and immune cell infiltration. Low molecular weight sulfated galactan (LSG), derived from the red seaweed <i>Gracilaria fisheri</i>, has immunomodulatory potential relevant to psoriasis pathogenesis. The present study investigated the therapeutic potential of LSG using an imiquimod (IMQ)-induced murine model of psoriasis. BALB/c mice received intraperitoneal administration of LSG once daily, 2 h prior to IMQ application, for 7 consecutive days. Clinical severity was assessed using the Psoriasis Area and Severity Index (PASI). Histopathological and immunohistochemical analyses were performed to evaluate epidermal architecture, vascular change and immune cell infiltration. Expression of keratinocyte proliferation and differentiation markers, proinflammatory cytokines and JAK/STAT pathway components was analyzed using reverse transcription-quantitative PCR, ELISA and western blotting. Systemic inflammation was assessed by spleen and lymph node size. LSG significantly decreased PASI scores, neovascularization, epidermal thickness and dermal inflammation. LSG downregulated keratinocyte proliferation and differentiation markers (Ki67, keratin 6, 16 and 17, involucrin) and decreased proinflammatory cytokine expression (TNF-α, IL-1β, IL-17A, IL-23, IL-6), accompanied by decreased CD4⁺ T and mast cell infiltration. LSG downregulated JAK2/STAT2/STAT3 signaling and downstream genes (BCL2, CCND1). Furthermore, LSG alleviated systemic inflammation without inducing hepatic or renal toxicity. These findings indicated that LSG effectively ameliorates IMQ-induced psoriatic inflammation via coordinated reduction of keratinocyte hyperproliferation, cytokine production and immune cell activity. LSG represents a promising marine-derived therapeutic candidate for psoriasis management.