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

  • Authors:
    • Kamonwan Jongsomchai
    • Arnon Pudgerd
    • Laorrat Phuapittayalert
    • Sataporn Jamsuwan
    • Teera Chanmanee
    • Kanokpan Wongprasert
    • Phennapa Promthale
    • Tawut Rudtanatip
  • View Affiliations / Copyright

    Affiliations: Division of Anatomy, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand, Department of Anatomy, Faculty of Science, Mahidol University, Bangkok 10400, Thailand, Anatomy Unit, Department of Medical Sciences, Faculty of Science, Rangsit University, Pathum Thani 12000, Thailand, Electron Microscopy Unit, Department of Anatomy, Faculty of Medicine, Khon Kaen University, Mueang, Khon Kaen 40002, Thailand
    Copyright: © Jongsomchai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 190
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    Published online on: October 8, 2025
       https://doi.org/10.3892/br.2025.2068
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Abstract

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 Gracilaria fisheri, 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.
View Figures

Figure 1

LSG ameliorates psoriasis-like skin
lesions in IMQ-induced psoriatic mice. Mice were treated daily with
IMQ, MTX or LSG for 7 consecutive days and sacrificed on day 8 for
macroscopic and microscopic evaluation of the skin (n=8). (A) Gross
morphology showing the macroscopic appearance of mouse skin. (B)
Microscopic appearance of psoriatic lesions, highlighting visible
blood vessels. (C) PAS-stained skin sections with blood vessels
(arrow). (D) Psoriasis Area and Severity Index scores assessing
erythema, scaling, thickness and cumulative disease severity.
*P<0.05 and ***P<0.001. LSG, Low
molecular weight sulfated galactan; IMQ, imiquimod; MTX,
Methotrexate; PAS, Periodic Acid-Schiff; NC, Normal control.

Figure 2

Effect of LSG on keratinocyte
proliferation and differentiation. (A) Representative
H&E-stained sections and Ki67 immunostaining of dorsal skin.
Arrows indicate Ki67-positive cells. Magnification, x10 (scale bar,
200 µm) and x40 (scale bar, 50 µm). Quantification of (B) epidermal
and (C) dermal thickness and (D) Ki67-positive cells (n=8). (E)
Ki67 protein expression assessed by western blot and quantified
relative to β-actin (n=3). Reverse transcription-quantitative PCR
analysis of keratinocyte differentiation markers keratin (F) 6, (G)
16 and (H) 17 and (I) involucrin (n=4). *P<0.05,
**P<0.01 and ***P<0.001. LSG, low
molecular weight sulfated galactan; H&E, Hematoxylin and Eosin;
NC, Normal control; MTX, Methotrexate; IMQ, Imiquimod.

Figure 3

Effect of LSG on cutaneous
inflammation in IMQ-induced psoriatic mice. Cytokine levels in skin
tissue and blood serum were evaluated by ELISA and western blotting
(n=5). ELISA quantification of (A) TNF-α, (B) IL-1β, (C) IL-17A and
(D) IL-23 in skin tissue. Serum levels of (E) TNF-α, (F) IL-1β, (G)
IL-17A and (H) IL-23. (I) Protein expression of (J) TNF-α, (K) IL-6
and (L) IL-10 in skin tissue, normalized to β-actin.
*P<0.05, **P<0.01 and
***P<0.001. LSG, Low molecular weight sulfated
galactan; NC, Normal control; MTX, methotrexate; IMQ,
Imiquimod.

Figure 4

Effect of LSG on CD4+ cell
infiltration in IMQ-induced psoriatic mice. (A) Representative
immunohistochemical images of CD4+ cells (arrow) in
dorsal skin. Magnification, x10 (scale bar, 100 µm) and x40 (scale
bar, 50 µm). (B) Quantification of CD4+ cells.
*P<0.05. LSG, Low molecular weight sulfated galactan;
NC, Normal control; MTX, Methotrexate; IMQ, Imiquimod.

Figure 5

Effect of LSG on mast cell
infiltration in IMQ-induced psoriatic mice. (A) Representative
Giemsa-stained dorsal skin showing mast cells (arrow).
Magnification, x10 (scale bar, 100 µm) and x40 (scale bar, 50 µm).
(B) Quantification of mast cells in each group.
***P<0.001. LSG, Low molecular weight sulfated
galactan; NC, Normal control; MTX, Methotrexate; IMQ,
Imiquimod.

Figure 6

Effect of LSG on JAK/STAT pathway
activation in IMQ-induced psoriatic mice. Reverse
transcription-quantitative PCR analysis was used to measure mRNA
expression levels of (A) STAT1, (B) STAT2, (C) STAT3, (D) JAK1, (E)
JAK2 and (F) JAK3 and JAK/STAT target genes (G) BCL2 and (H) CCND1
(n=4). *P<0.05, **P<0.01 and
***P<0.001. LSG, Low molecular weight sulfated
galactan; NC, normal control; MTX, Methotrexate; IMQ,
Imiquimod.

Figure 7

Effect of LSG on IMQ-induced
organomegaly in psoriatic mice. (A) Representative right axillary
lymph node. (B) Relative weights of right axillary lymph node. (C)
Representative spleen. (D) Relative spleen weight. n=8.
*P<0.05, **P<0.01 and
***P<0.001. LSG, Low molecular weight sulfated
galactan; NC, Normal control; MTX, Methotrexate; IMQ,
Imiquimod.

Figure 8

Histological evaluation of kidney and
liver tissues following LSG treatment in IMQ-induced psoriatic
mice. (A) Kidney and (B) liver sections stained with hematoxylin
and eosin. Scale bar, 50 µm. LSG, Low molecular weight sulfated
galactan; NC, Normal control; MTX, Methotrexate; IMQ,
Imiquimod.
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Copy and paste a formatted citation
Spandidos Publications style
Jongsomchai K, Pudgerd A, Phuapittayalert L, Jamsuwan S, Chanmanee T, Wongprasert K, Promthale P and Rudtanatip T: Low molecular weight sulfated galactan attenuates imiquimod‑induced psoriasis via suppression of proinflammatory cytokines and keratinocyte hyperproliferation. Biomed Rep 23: 190, 2025.
APA
Jongsomchai, K., Pudgerd, A., Phuapittayalert, L., Jamsuwan, S., Chanmanee, T., Wongprasert, K. ... Rudtanatip, T. (2025). Low molecular weight sulfated galactan attenuates imiquimod‑induced psoriasis via suppression of proinflammatory cytokines and keratinocyte hyperproliferation. Biomedical Reports, 23, 190. https://doi.org/10.3892/br.2025.2068
MLA
Jongsomchai, K., Pudgerd, A., Phuapittayalert, L., Jamsuwan, S., Chanmanee, T., Wongprasert, K., Promthale, P., Rudtanatip, T."Low molecular weight sulfated galactan attenuates imiquimod‑induced psoriasis via suppression of proinflammatory cytokines and keratinocyte hyperproliferation". Biomedical Reports 23.6 (2025): 190.
Chicago
Jongsomchai, K., Pudgerd, A., Phuapittayalert, L., Jamsuwan, S., Chanmanee, T., Wongprasert, K., Promthale, P., Rudtanatip, T."Low molecular weight sulfated galactan attenuates imiquimod‑induced psoriasis via suppression of proinflammatory cytokines and keratinocyte hyperproliferation". Biomedical Reports 23, no. 6 (2025): 190. https://doi.org/10.3892/br.2025.2068
Copy and paste a formatted citation
x
Spandidos Publications style
Jongsomchai K, Pudgerd A, Phuapittayalert L, Jamsuwan S, Chanmanee T, Wongprasert K, Promthale P and Rudtanatip T: Low molecular weight sulfated galactan attenuates imiquimod‑induced psoriasis via suppression of proinflammatory cytokines and keratinocyte hyperproliferation. Biomed Rep 23: 190, 2025.
APA
Jongsomchai, K., Pudgerd, A., Phuapittayalert, L., Jamsuwan, S., Chanmanee, T., Wongprasert, K. ... Rudtanatip, T. (2025). Low molecular weight sulfated galactan attenuates imiquimod‑induced psoriasis via suppression of proinflammatory cytokines and keratinocyte hyperproliferation. Biomedical Reports, 23, 190. https://doi.org/10.3892/br.2025.2068
MLA
Jongsomchai, K., Pudgerd, A., Phuapittayalert, L., Jamsuwan, S., Chanmanee, T., Wongprasert, K., Promthale, P., Rudtanatip, T."Low molecular weight sulfated galactan attenuates imiquimod‑induced psoriasis via suppression of proinflammatory cytokines and keratinocyte hyperproliferation". Biomedical Reports 23.6 (2025): 190.
Chicago
Jongsomchai, K., Pudgerd, A., Phuapittayalert, L., Jamsuwan, S., Chanmanee, T., Wongprasert, K., Promthale, P., Rudtanatip, T."Low molecular weight sulfated galactan attenuates imiquimod‑induced psoriasis via suppression of proinflammatory cytokines and keratinocyte hyperproliferation". Biomedical Reports 23, no. 6 (2025): 190. https://doi.org/10.3892/br.2025.2068
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