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

Abstract

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.