20(S)-Protopanaxatriol inhibits release of inflammatory mediators in immunoglobulin E-mediated mast cell activation

Background: Antiallergic effect of 20(S)-protopanaxatriol (PPT), an intestinal metabolite of ginseng sa-ponins, was investigated in guinea pig lung mast cells and mouse bone marrow-derived mast cells activated by a specific antigen/antibody reaction. Methods: Increasing concentrations of PPT were pretreated 5 min prior to antigen stimulation, and various inflammatory mediator releases and their relevant cellular signaling events were measured in those cells. Results: PPT dose-dependently reduced the release of histamine and leukotrienes in both types of mast cells. Especially, in activated bone marrow-derived mast cells, PPT inhibited the expression of Syk protein, cytokine mRNA, cyclooxygenase-1/2, and phospholipase A(2) (PLA(2)), as well as the activities of various protein kinase C isoforms, mitogen-activated protein kinases, PLA(2), and transcription factors (nuclear factor-kappa B and activator protein-1). Conclusion: PPT reduces the release of inflammatory mediators via inhibiting multiple cellular signaling pathways comprising the Ca2+ influx, protein kinase C, and PLA(2), which are propagated by Syk activation upon allergic stimulation of mast cells. Copyright (C) 2014, The Korean Society of Ginseng, Published by Elsevier. All rights reserved.