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Mast cells are primary cells initiating allergic inflammation by the release of various allergic mediators, such as histamine and pro-inflammatory cytokines. Aspalathin (ASP) is the predominant flavonoid found exclusively in rooibos, an herb that has been traditionally used in allergy relief therapy. In the present study, we investigated the beneficial effects of ASP on mast cell-mediated allergic inflammation. For in vivo study, two well-known mast cell-mediated local and systemic allergic inflammation mouse models were used: passive cutaneous anaphylaxis (PCA) and active systemic anaphylaxis mouse models (ASA). Oral administration of ASP dose-dependently suppressed immunoglobulin (Ig)E-mediated PCA responses evidenced by Evans blue extravasation, ear thickening, and mast cell degranulation. ASP also significantly mitigated ovalbumin-induced ASA responses, including hypothermia, histamine secretion, and the production of IgE and interleukin-4. Notably, ASP was more effective in suppressing allergic inflammation than nothofagin, another prominent flavonoid known as an anti-allergic component of rooibos. The regulatory mechanism of mast cell activation by ASP was clarified using mast cell line and primary cultured mast cells (RBL-2H3 and mouse bone marrow-derived mast cells). ASP reduced IgE-stimulated mast cells degranulation and intracellular calcium influx by the inhibition of FcεRI signaling pathway (Lyn, Fyn, and Syk). Moreover, ASP reduced pro-inflammatory cytokine expressions by inhibiting two major transcription factors, nuclear factor of activated T cells and nuclear factor-κB. Collectively, we proposed that ASP could be a potential therapeutic candidate for the treatment of mast cell-mediated allergic inflammatory diseases. [ABSTRACT FROM AUTHOR]

Backgrounds: Mast cells play a major role in allergic inflammation by the release of histamine, an important mediator of type I hypersensitivity. Cencerns regarding potential harmful effects of perfluorooctane sulfonate (PFOS) have been raised. Previous studies reported that PFOS causes various adverse effects such as immunotoxicity and neurotoxicity. This report studied whether PFOS affects mast cells-mediated allergic inflammation.Methods: Ovalbumin-induced active systemic anaphylaxis model was used to assess for the type I hypersensitivity. After sensitization, mice were orally administered with PFOS and then allergic symptoms such as hypothermia and increase of serum allergic mediator were measured. In additional, this study investigated whether PFOS deteriorate allergic inflammation in immunoglobulin E-stimulated mast cells.Results: PFOS aggravated the allergic symptoms such as hypothermia, and increase of serum histamine, tumor necrosis factor-α and immunoglobulin (Ig) E/ G1. PFOS increased the release of histamine and β-hexosaminidase through the up-regulation of intracellular calcium in IgE-stimulated mast cells. PFOS also enhanced the gene expression of pro-inflammatory cytokines by activating nuclear factor-κB.Conclusion: This study demonstrated that PFOS more intensifies the mast cell-mediated allergic inflammation. [ABSTRACT FROM AUTHOR]