15,16-Dihydrotanshinone I suppresses IgE-Ag stimulated mouse bone marrow-derived mast cell activation by inhibiting Syk kinase

Ethnopharmacological relevance: 15,16-Dihydrotanshinone I (DHT-I), isolated from the dried root of Salvia miltiorrhiza Bung, which is traditionally used to treat cardiovascular and inflammatory diseases agent in Chinese medicine. DHT-I has been reported to have a broad range of biological activities, including antibacterial activity, and has been used to treat circulatory disorders, hepatitis, inflammation, cancer, and neurodegenerative diseases. Aim of the study: The aim of this study was to evaluate the anti-allergic inflammatory effects of DHT-I on degranulation and on the generation of eicosanoids, such as, prostaglandin D-2 (PGD(2)) and leukotriene C-4 (LTC4), in IgE/Ag-stimulated bone marrow-derived mast cells (BMMCs). Materials and methods: The anti-allergic inflammatory activity of DHT-I was evaluated using BMMCs. The effects of DHT-I on mast cell activation were investigated by following degranulation and eicosanoid generation using ELISA and immunoblotting and immunoprecipitation techniques. Results: DHT-I at a concentration of 20 mu M markedly inhibited degranulation and the generation of PGD2 and LTC4 in IgE/Ag-stimulated BMMCs (about 90% inhibitions, respectively). Analyses of Fc epsilon RI-mediated signaling pathways demonstrated that DHT-I inhibited the phosphorylations of spleen tyrosine kinase (Syk) and linker for activation of T cells (LAT), and inhibited downstream signaling process, including [Ca2+](i) mobilization induced by the phosphorylation of phospholipase C gamma 1 (PLC gamma 1), and the activations of mitogen-activated protein kinases (MAPKs) and the Akt-nuclear factor-kappa B (NF-kappa B) pathway. Conclusions: DHT-1 inhibits the release of allergic inflammatory mediators from IgE/Ag-stimulated mast cells by suppressing a Fc epsilon RI-mediated Syk-dependent signal pathway. This result suggests DHT-I offers a novel developmental basis for drugs targeting allergic inflammatory diseases. (C) 2015 Elsevier Ireland Ltd. All rights reserved.