Teadenol A in microbial fermented tea acts as a novel ligand on GPR120 to increase GLP-1 secretion.

Post-fermented teas, produced by microbial fermentation, are attracting attention due to their health benefits that reduce the risk of hyperlipidemia and atherosclerosis. Although several novel polyphenols have been identified from post-fermented teas, their biological activities have not yet been fully elucidated. In this study, we found that teadenol A, a polyphenol recently isolated from Japanese post-fermented tea, acts as a novel ligand on a long-chain fatty acid receptor, GPR120. Teadenol A activated GPR120 was over-expressed in 293T cells, and this activation was inhibited by the GPR120 antagonist AH7614. Additionally, teadenol A induced Erk1/2 phosphorylation and increased the intracellular Ca2+ concentration in 293T cells, and these effects were completely dependent on GPR120 expression. Our results suggest that teadenol A binds and activates GPR120 directly. Furthermore, teadenol A enhanced the secretion of GLP-1 from intestinal endocrine STC-1 cells. GLP-1 suppresses appetite and increases insulin secretion, exhibiting anti-diabetic effects. GPR120/GLP-1 signaling is attracting attention as a potential target for pharmaceuticals against type 2 diabetes. Our results suggest that teadenol A is a key molecule in post-fermented tea responsible for beneficial effects on metabolic syndrome.

Suppression of mast cell degranulation by a novel ceramide kinase inhibitor, the F-12509A olefin isomer K1.

Antigen-induced degranulation of mast cells plays a pivotal role in allergic and inflammatory responses. Recently, ceramide kinase (CERK) and its phosphorylated product ceramide 1-phosphate (C1P) have emerged as important players in mast cell degranulation. Here, we describe the synthesis of a novel F-12509A olefin isomer, K1, as an effective CERK inhibitor. In vitro kinase assays demonstrated that K1 effectively inhibits CERK without inhibiting sphingosine kinase and diacylglycerol kinase. Treating RBL-2H3 cells with K1 reduced cellular C1P levels to 40% yet had no effect on cell growth. Furthermore, treatment with K1 significantly suppressed both calcium ionophore- and IgE/antigen-induced degranulation, indicating that K1 interferes with signals that happen downstream of Ca(2+) mobilization. Finally, we show that K1 affects neither IgE/antigen-induced global tyrosine phosphorylation nor subsequent Ca(2+) elevation, suggesting a specificity for CERK-mediated signals. Our novel CERK inhibitor provides a useful tool for studying the biological functions of CERK and C1P. Moreover, to our knowledge, this is the first report demonstrating that inhibition of CERK suppresses IgE/antigen-induced mast cell degranulation. This finding suggests that CERK inhibitors might be a potential therapeutic tool in the treatment of allergic diseases.