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

Abstract

Psoriasis is a chronic immune‑mediated inflam‑ matory skin disorder characterized by keratinocyte hyperproliferation and immune cell infiltration. Low molec‑ ular weight sulfated galactan (LSG), derived from the red seaweed Gracilaria fisheri, has immunomodulatory potential relevant to psoriasis pathogenesis. The present study investi‑ gated 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, proin‑ flammatory 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 proinflamma‑ tory cytokine expression (TNF‑α, IL‑1β, IL‑17A, IL‑23, IL‑6), accompanied by decreased CD4⁺ T and mast cell infiltra‑ tion. 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 coordi‑ nated reduction of keratinocyte hyperproliferation, cytokine production and immune cell activity. LSG represents a promising marine‑derived therapeutic candidate for psoriasis management.