# A λ-Carrageenan-Enriched Sulfated Galactan from Gigartina radula Attenuates Atopic Dermatitis via Coordinated Anti-Inflammatory and Immunomodulatory Mechanisms

**Authors:** Kexin Du, Shuo Liang, Zijing Wu, Yujing Wang, Pengcheng Gao, Wei Han, Youjing Lv, Guangli Yu, Guoyun Li

PMC · DOI: 10.3390/md24030119 · Marine Drugs · 2026-03-22

## TL;DR

A sulfated galactan from a red alga reduces atopic dermatitis symptoms through anti-inflammatory and immune-modulating effects.

## Contribution

GRB-H, a λ-carrageenan-enriched galactan from Gigartina radula, is newly shown to alleviate AD via both local and systemic mechanisms.

## Key findings

- GRB-H reduced inflammation markers in macrophages and keratinocytes in vitro.
- Topical GRB-H improved skin inflammation and immune cell infiltration in a murine AD model.
- GRB-H lowered IgE levels and restored Th1/Th2 balance while downregulating inflammatory cytokines.

## Abstract

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease driven by immune dysregulation and epidermal barrier dysfunction. Current therapeutic options are often limited by safety concerns or suboptimal tolerability. In this study, we isolated and structurally characterized GRB-H—a λ-carrageenan-enriched sulfated hybrid galactan from the marine red alga Gigartina radula—as a complex polysaccharide containing κ-, ι-, μ-, ν-, and λ-carrageenan structural units, and systematically evaluated its anti-AD potential using both in vitro and in vivo models. In vitro, GRB-H significantly suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in RAW 264.7 macrophages, and reduced 2,4-dinitrochlorobenzene (DNCB)-evoked TNF-α and IL-1β expression in HaCaT keratinocytes. In a DNCB-induced murine model of AD, topical application of GRB-H markedly ameliorated skin inflammation, epidermal hyperplasia, and dermal immune cell infiltration. GRB-H treatment lowered total serum immunoglobulin E (IgE) levels, restored the imbalanced Th1/Th2 cell ratio in the spleen, and downregulated the mRNA expression of key inflammatory cytokines—including TNF-α, IL-4, IL-5, IL-31, and interferon-γ (IFN-γ)—in lesional skin. Collectively, these findings demonstrate that GRB-H alleviates AD symptoms through coordinated local anti-inflammatory and systemic immunomodulatory actions, highlighting its promise as a marine-derived candidate for the topical management of AD.

## Linked entities

- **Proteins:** TNF (tumor necrosis factor), IL6 (interleukin 6), IL1B (interleukin 1 beta), IL4 (interleukin 4), IL5 (interleukin 5), IL31 (interleukin 31), IFNG (interferon gamma)
- **Chemicals:** nitric oxide (PubChem CID 145068), 2,4-dinitrochlorobenzene (PubChem CID 6)
- **Diseases:** atopic dermatitis (MONDO:0004980)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 14433] {aka Gapd}, Nos2 (nitric oxide synthase 2, inducible) [NCBI Gene 18126] {aka MAC-NOS, NOS-II, Nos-2, Nos2a, i-NOS, iNOS}, Ptprc (protein tyrosine phosphatase receptor type C) [NCBI Gene 19264] {aka B220, CD45R, Cd45, L-CA, Ly-5, Lyt-4}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, IL31 (interleukin 31) [NCBI Gene 386653] {aka IL-31}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56717] {aka 2610315D21Rik, FRAP, FRAP2, Frap1, RAFT1, RAPT1}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Il1a (interleukin 1 alpha) [NCBI Gene 16175] {aka Il-1a}, Cd3e (CD3 antigen, epsilon polypeptide) [NCBI Gene 12501] {aka CD3, CD3epsilon, T3e}, Flg (filaggrin) [NCBI Gene 14246] {aka ft}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Myd88 (myeloid differentiation primary response gene 88) [NCBI Gene 17874], Mpo (myeloperoxidase) [NCBI Gene 17523] {aka mKIAA4033}, Il33 (interleukin 33) [NCBI Gene 77125] {aka 9230117N10Rik, Il-33, Il1f11, NF-HEV}, Cxcl1 (C-X-C motif chemokine ligand 1) [NCBI Gene 14825] {aka Fsp, Gro1, KC, Mgsa, N51, Scyb1}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 17709], Smad3 (SMAD family member 3) [NCBI Gene 17127] {aka Madh3}, Il5 (interleukin 5) [NCBI Gene 16191] {aka Il-5}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, FLG (filaggrin) [NCBI Gene 2312] {aka ATOD2, FLG-1, FLG1}, Prkca (protein kinase C, alpha) [NCBI Gene 18750] {aka Pkca}, Il31 (interleukin 31) [NCBI Gene 76399] {aka 1700013B14Rik}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 20296] {aka HC11, JE, MCAF, MCP-1, MCP1, SMC-CF}, Tslp (thymic stromal lymphopoietin) [NCBI Gene 53603], Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Ptgs2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 19225] {aka COX2, Cox-2, PES-2, PGHS-2, PHS II, PHS-2}, Blnk (B cell linker) [NCBI Gene 17060] {aka BASH, Bca, Ly-57, Ly57, Lyw-57, SLP-65}, Apc (APC, WNT signaling pathway regulator) [NCBI Gene 11789] {aka CC1, Min, mAPC}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, IGHE (immunoglobulin heavy constant epsilon) [NCBI Gene 3497] {aka IgE}
- **Diseases:** eczematous lesions (MESH:D017443), epidermal hyperplasia (MESH:D006965), edema (MESH:D004487), Skin (MESH:D012871), acanthosis (MESH:D000052), allergic (MESH:D004342), Inflammation (MESH:D007249), immune dysregulation (OMIM:614878), hepatorenal toxicity (MESH:D006530), chronic (MESH:D002908), AD (MESH:D003876), inflammatory skin disorder (MESH:D012868), erythema (MESH:D004890), inflammatory hyperalgesia (MESH:D006930), Cytotoxicity (MESH:D064420), hyperkeratosis (MESH:D017488), atrophy (MESH:D001284), peritonitis (MESH:D010538), lymphoid hyperplasia (MESH:D019310), dryness (MESH:D014987), telangiectasia (MESH:D013684), Lesional (MESH:D009059), pruritus (MESH:D011537), injury to (MESH:D014947), Dermatitis (MESH:D003872)
- **Chemicals:** water (MESH:D014867), KBr (MESH:C039004), 4,4-dimethyl-4-silapentane-1-sulfonic acid (MESH:C009580), dextran (MESH:D003911), sugar (MESH:D000073893), cyclosporine (MESH:D016572), glucose (MESH:D005947), carrageenan (MESH:D002351), 3,6-anhydro-galactose (MESH:C117625), LPS (MESH:D008070), CO2 (MESH:D002245), methanol (MESH:D000432), Sacran (MESH:C571099), clobetasol propionate (MESH:D002990), H&amp;E (MESH:D006371), histamine (MESH:D006632), olive oil (MESH:D000069463), phenol (MESH:D019800), resorcinol (MESH:C031389), Fucoidan (MESH:C007789), acetonitrile (MESH:C032159), ROS (MESH:D017382), paraffin (MESH:D010232), barium chloride (MESH:C024986), phosphate (MESH:D010710), A23187 (MESH:D000001), 2,4-Dinitrochlorobenzene (MESH:D004137), Trizol (MESH:C411644), lipid (MESH:D008055), D-galactose (MESH:D005690), polysaccharide (MESH:D011134), H2SO4 (MESH:C033158), dupilumab (MESH:C582203), paraformaldehyde (MESH:C003043), Monosaccharide (MESH:D009005), galactan (MESH:D005685), 1-phenyl-3-methyl-5-pyrazolone (MESH:D000077553), carbon (MESH:D002244), acetone (MESH:D000096), ethanol (MESH:D000431), TB (MESH:D014048), SYBR Green (MESH:C098022), 13C (MESH:C000615229), TFA (MESH:D014269), calcium (MESH:D002118), D2O (MESH:D017666), DMEM (-), agarose (MESH:D012685), NO (MESH:D009569), Sulfate (MESH:D013431), polymers (MESH:D011108)
- **Species:** Sarcothalia crispata (species) [taxon 29243], Rhodophyta (red algae, phylum) [taxon 2763], Cladosiphon okamuranus (species) [taxon 309737], Gracilaria intermedia (species) [taxon 172956], Sarcothalia radula (species) [taxon 33671], Gracilaria caudata (species) [taxon 2572395], Sargassum fusiforme (species) [taxon 590727], Gelidium crinale (species) [taxon 143013], Chondrus verrucosus (species) [taxon 29223], Homo sapiens (human, species) [taxon 9606], Aphanothece (genus) [taxon 1121], Chondracanthus chamissoi (species) [taxon 38341], Mus musculus (house mouse, species) [taxon 10090], Sargassum horneri (species) [taxon 74089]
- **Cell lines:** RAW 264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), GRB-H. — Oryctolagus cuniculus (Rabbit), Hybridoma (CVCL_C2N1), HaCaT — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0038)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13028040/full.md

## References

55 references — full list in the complete paper: https://tomesphere.com/paper/PMC13028040/full.md

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Source: https://tomesphere.com/paper/PMC13028040