Mast Cell Stabilizing Effect of (-)-Elema-1,3,11(13)-trien-12-ol and Thujopsene from Thujopsis dolabrata Is Mediated by Down-Regulation of Interleukin-4 Secretion in Antigen-Induced RBL-2H3 Cells

Abstract

Several isolated compounds from the wood part of Thujopsis dolabrata were evaluated for their inhibitory effects against antigen-induced mast cell degranulation and interleukin-4 (IL-4) secretion, as well as IL-4 mRNA and protein expression in immunoglobulin E (IgE)-sensitized RBL-2H3 cells. Among the five isolated compounds, (-)-elema-1,3,11(13)-trien-12-ol (1) and thujopsene (2) exhibited the potent inhibitory activity against mast cell degranulation measured by beta-hexosaminidase release with IC50 values of 27.4 mu m and 25.1 mu m, respectively. These compounds also inhibited the release of IL-4 (IC50 values of 7.0, 6.7 mu m, respectively), IL-4 mRNA expression (IC50 values of 16.5, 7.2 mu m, respectively) and IL-4 protein expression (IC50 values of 17.0, 9.6 mu m, respectively) in antigen-induced IgE-sensitized RBL-2H3 cells. These results suggested that (-)-elema-1,3,11(13)-trien-12-ol (1) and thujopsene (2) effectively inhibits mast cell degranulation as well as IL-4 production, suggesting that these compounds from Thujopsis dolabrata can be used as candidates for IgE-mediated allergic disorders.