15, 16-Dihydrotanshinone I suppresses IgE-Ag stimulated mouse bone marrow-derived mast cell activation by inhibiting Syk kinase. (1st July 2015)

• Record Type: Journal Article
• Authors: Li, Xian; Yang, Ju Hye; Jin, Ye; Jin, Fansi; Kim, Dong-Young; Chang, Jae-Hoon; Kim, Jung-Ae; Son, Jong-Keun; Moon, Tae Chul; Son, Kun Ho; Chang, Hyeun Wook
• Is Part Of: Journal of ethnopharmacology. Volume 169(2015)
• Page Start: 138
• Page End: 144
• Publication Date: 2015-07-01
• Subjects: AA arachidonic acid -- BMMCs bone marrow-derived mast cells -- COX-1, -2 cyclooxygenase-1, -2 -- cPLA2 cytosolic phospholipase A2 -- DMSO dimethyl sulfoxide -- DNP dinitrophenol -- DTT dithiothreitol -- EIA enzyme immunoassay -- ERK1/2 extracellular signal regulated kinase1/2 -- FBS fetal bovine serum -- Gab2 Grb2-associated binder 2 -- HSA human serum albumin -- β-Hex β-hexosaminidase -- IKK IκB kinase -- JNK c-Jun N-terminal kinase -- LAT linker for activation of T cells -- LTC4 leukotriene C4 -- 5-LO 5-lipoxygenase -- MAPK mitogen-activated protein kinase -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide -- NF-κB nuclear factor-κB -- PI3K phosphatidylinositol 3-kinase -- PGD2 prostaglandin D2 -- PLCγ1 phospholipase Cγ1 -- PMSF phenylmethanesulfonylfluoride -- SLP-76 SH2 domain-containing leukocyte protein of 76 kDa -- Syk spleen tyrosine kinase; 15, 16-Dihydrotanshinone I -- Allergic inflammation -- Prostaglandin D2 -- Leukotriene C4 -- Spleen tyrosine kinase -- Bone marrow-derived mast cells; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2015.04.022
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: 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 D2 (PGD2 ) and leukotriene C4 (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 μM markedly inhibited degranulation and the generation of PGD2 and LTC4 in IgE/Ag-stimulated BMMCs (about 90% inhibitions, respectively). Analyses of FcεRI-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 [Ca 2+ ]i mobilization induced by the phosphorylation of phospholipase Cγ1 (PLCγ1), and the activations of mitogen-activated protein kinases (MAPKs) and the Akt-nuclear factor-κB (NF-κB) pathway. Conclusions: DHT-1 inhibits the release of allergic inflammatory mediators from IgE/Ag-stimulated mast cells by suppressing a FcεRI-mediated Syk-dependent signal pathway. This result suggests DHT-I offers a novel developmental basis for drugs targeting allergic inflammatory diseases. Graphical abstract: