Abstract
Allergic diseases such as atopic dermatitis, rhinitis, asthma, and anaphylaxis are attractive research areas. Tyrosol (2-(4-hydroxyphenyl)ethanol) is a polyphenolic compound with diverse biological activities. In this study, we investigated whether tyrosol has anti-allergic inflammatory effects. Ovalbumin-induced active systemic anaphylaxis and immunoglobulin E-mediated passive cutaneous anaphylaxis models were used for the immediate-type allergic responses. Oral administration of tyrosol reduced the allergic symptoms of hypothermia and pigmentation in both animal models. Mast cells that secrete allergic mediators are key regulators on allergic inflammation. Tyrosol dose-dependently decreased mast cell degranulation and expression of inflammatory cytokines. Intracellular calcium levels and activation of inhibitor of κB kinase (IKK) regulate cytokine expression and degranulation. Tyrosol blocked calcium influx and phosphorylation of the IKK complex. To define the molecular target for tyrosol, various signaling proteins involved in mast cell activation such as Lyn, Syk, phosphoinositide 3-kinase (PI3K), and Akt were examined. Our results showed that PI3K could be a molecular target for tyrosol in mast cells. Taken together, these findings indicated that tyrosol has anti-allergic inflammatory effects by inhibiting the degranulation of mast cells and expression of inflammatory cytokines; these effects are mediated via PI3K. Therefore, we expect tyrosol become a potential therapeutic candidate for allergic inflammatory disorders.
Highlights
There are a range of allergic disorders including atopic dermatitis, allergic rhinitis, asthma, food allergy, and anaphylaxis
The OVA-induced systemic anaphylaxis model is appropriate for the investigation of the antiallergic inflammatory effects of drug candidates [9]
The rectal temperature of the mice decreased over 40–50 min; administration of tyrosol alleviated this hypothermia, which was associated with the serum histamine level (Fig 1A)
Summary
There are a range of allergic disorders including atopic dermatitis, allergic rhinitis, asthma, food allergy, and anaphylaxis. Anti-Allergic Inflammatory Effects of Tyrosol the production and secretion of allergic mediators; histamine, chemokines, cytokines, and growth factors [1]. Type 2 helper T (Th2) cells differentiated by stimulation of antigenpresenting cells activate B cells to produce immunoglobulin E (IgE), which binds to high affinity IgE receptor (FcεRI) on the surface of mast cells [2]. FcεRI-mediated mast cell activation is triggered by antigen-IgE cross-linking and leads to the degranulation and expression of inflammatory cytokines [3]. PLCγ catalyzes the production of inositol 1,4,5-trisphosphate (IP3), which binds to IP3 receptors on the surface of the endoplasmic reticulum (ER). It causes release of calcium stored in the ER into the cytoplasm. The expression and release of allergic molecules are enhanced by NF-κB, SNAP23, and increased intracellular calcium
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