Salvinorin A inhibits ovalbumin-stimulated allergic rhinitis and RBL-2H3 cells degranulation.

Abstract

Allergic rhinitis (AR) is a long‐term noncommunicable inflammatory disease of the nasal mucosa mediated by immunoglobulin E and is mainly caused by exposure of genetically susceptible individuals to environmental allergens. Mast cells contribute to the pathogenesis of allergic and nonallergic inflammatory diseases. Salvinorin A has been previously shown to inhibit leukotriene production and mast cell degranulation to suppress airway hyperresponsiveness caused by sensitization; thus, we hypothesized that salvinorin A has an anti‐AR effect. We tested this hypothesis using monoclonal anti‐2,4,6‐dinitrophenyl immunoglobulin E/human serum albumin‐induced rat basophilic leukemia cells (RBL‐2H3 cells) and ovalbumin (OVA)‐induced AR in mice as in vivo and in vitro AR models, respectively. The expression levels of histamine, β‐hexosaminidase, interleukin‐4 and tumor necrosis factor‐α were decreased by salvinorin A in vitro. Granule release and F‐actin organization were also suppressed by salvinorin A. Furthermore, salvinorin A inhibited OVA‐induced features of AR in mice, including nasal rubbing and sneezing, as well as increased OVA‐specific immunoglobulin E, histamine, tumor necrosis factor‐α and interleukin‐4 levels. In addition, salvinorin A decreased the phosphorylation of phosphoinositide 3‐kinase/Akt in vitro and in vivo. Our work suggests that salvinorin A suppresses AR caused by sensitization by inhibiting the inflammatory responses of mast cells; thus, salvinorin A may have potential for treatment of AR.