Anti-allergic Effects and Immunomodulatory Activity of Sacran, a Bioactive Compound from River alga Aphanothece sacrum

Abstract

Sacran is a newly discovered sulfated glycosaminoglycan-like compound extracted from river alga Aphanothece sacrum (Suizenji-nori in Japanese). The present study evaluated the clinical effects and immunomodulatory activity of topical sacran in a murine model of contact allergy and in vitro . Two experiments were conducted to evaluate sacran’s effect on cell degranulation and the release of b -hexosaminidase release by RBL-2H3 basophilic cells in a model of IgE-mediated allergic reaction in vitro, and the curative effects and immunomodulatory activity of topical application of sacran on hapten-induced eczematous skin lesions in mice. In the in vitro experiment, RBL-2H3 basophilic cells were sensitized with DNP-specific IgE, and b -hexosaminidase release activity was evaluated by ELISA. In the in vivo experiment, 24 NC/Nga male mice, including six normal and three treatment groups of six mice with hapten-induced contact allergy were used. Diseased mice were topically treated either with 20 mL of 2% sacran, 10 mg/ml hydrocortisone (HCT) or phosphate buffered saline (Control). Clinical severity of skin lesions was evaluated, and blood samples were collected to determine the serum levels of the following biomarkers: eotaxin, MCP-1, IgE, IFN-g, IL-4 and IL-5. Skin specimens were taken to determine gene expression levels of IFN-gmRNA, TNF-amRNA, and IL-4 mRNA by RT-PCR. Results of the in vitro experiment showed that sacran solutions inhibited RBL-2H3 cell degranulation and the release of b -hexosaminidase, as significantly low levels of this enzyme were found for sacran-treated cells (vs. control solution; p<0.05). In the in vivo experiment, topical application of sacran markedly reduced serum IL-4, IL-5, total IgE, eotaxin, MCP-1 in allergic mice. In addition, TNF-amRNA gene expression level in lesional mouse skin was also reduced in sacran group as compared with buffer-treated controls (p<0.05). Furthermore, topical sacran, and hydrocortisone as well , alleviated skin symptoms (scaling/dryness, erythema/hemorrhage and erosion/excoriation) and reduced ear thickness (vs. controls). This study showed that sacran inhibited the release of b -hexosaminidase by allergen-challenged RBL-2H3 basophilic cells, exerted anti-inflammatory activity on eczematous skin lesions and downregulated TNF-amRNA expression in mice. These findings suggest that sacran has a potential to serve as an alternative remedy for skin allergic disorders.