Phenolic constituents isolated from Fragaria ananassa Duch. inhibit antigen-stimulated degranulation through direct inhibition of spleen tyrosine kinase activation.
We isolated eight phenolic constituents from Fragaria ananassa Duch. (strawberry) and determined their structures using 1D, 2D-NMR. Among the isolated compounds, linocinnamarin (LN), 1-O-trans-cinnamoyl-beta-d-glucopyranose (CG), and cinnamic acid (CA) exhibited antigen (Ag)-stimulated degranulation in rat basophilic leukemia RBL-2H3 cells. In order to reveal the underlying mechanisms, we examined the effects of LN and CA on cellular responses induced by antigen stimulation. Treatment with both LN and CA markedly inhibited antigen-stimulated elevation of intracellular free Ca(2+) concentration and reactive oxygen species (ROS). Both LN and CA suppressed Ag-stimulated spleen tyrosine kinase (Syk) activation. These results indicate that inhibition of antigen-stimulated degranulation by LN and CA is mainly due to inactivation of Syk/phospholipase Cgamma (PLCgamma) pathways. Our findings suggest that LN and CA isolated from F. ananassa Duch. (strawberry) could be beneficial agents for alleviating symptoms of type I allergy.
Ninomiya
Masayuki
M
Department of Materials Science and Technology, Faculty of Engineering, Gifu University, Gifu, Japan.
Itoh
Tomohiro
T
Ishikawa
Suguru
S
Saiki
Miho
M
Narumiya
Kenji
K
Yasuda
Masaharu
M
Koshikawa
Kaneyuki
K
Nozawa
Yoshinori
Y
Koketsu
Mamoru
M
D000818:Animals; D018926:Anti-Allergic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000941:Antigens / Q000276:immunology; D001491:Basophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D015550:Cell Degranulation / Q000187:drug effects* / Q000276:immunology; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D031985:Fragaria / Q000737:chemistry*; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology*; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000276:immunology*; D051381:Rats; D000072377:Syk Kinase
D018926:Anti-Allergic Agents; D000941:Antigens; D047908:Intracellular Signaling Peptides and Proteins; D010636:Phenols; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606898:Syk protein, rat