Inhibitory effects of flavonoids isolated from Fragaria ananassa Duch on IgE-mediated degranulation in rat basophilic leukemia RBL-2H3.
We isolated the 4 kinds of flavonoids from strawberry 'Nohime' and examined the effect of these flavonoids on the degranulation in RBL-2H3 cells. The flavonoids were found to suppress the degranulation from Ag-stimulated RBL-2H3 cells to different extents. To disclose the inhibitory mechanism of degranulation by flavonoids, we examined their effects on the intracellular free Ca(2+) concentration ([Ca(2+)]i) and the intracellular signaling pathway such as Lyn, Syk, and PLCgammas. The intracellular free Ca(2+) concentration ([Ca(2+)]i) was elevated by Fc epsilonRI activation, but these flavonoid treatments reduced the elevation of [Ca(2+)]i by suppressing Ca(2+) influx. Kaempferol strongly suppressed the activation of Syk and PLCgammas. It was thus suggested that suppression of Ag-stimulated degranulation by the flavonoids is mainly due to suppression of [Ca(2+)]i elevation and Syk activation. These results suggested that strawberry would be of some ameliorative benefit for the allergic symptoms.
Itoh
Tomohiro
T
Gifu International Institute of Biotechnology, 1-1 Naka-Fudogaoka, Kakamigahara, Gifu 504-0838, Japan. titoh@giib.or.jp
Ninomiya
Masayuki
M
Yasuda
Masaharu
M
Koshikawa
Kaneyuki
K
Deyashiki
Yoshihiro
Y
Nozawa
Yoshinori
Y
Akao
Yukihiro
Y
Koketsu
Mamoru
M
D000818:Animals; D018926:Anti-Allergic Agents / Q000032:analysis / Q000302:isolation & purification* / Q000494:pharmacology*; D015549:Basophil Degranulation Test; D001491:Basophils / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects*; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000032:analysis / Q000302:isolation & purification* / Q000494:pharmacology*; D031985:Fragaria / Q000737:chemistry*; D005638:Fruit / Q000737:chemistry*; D007073:Immunoglobulin E / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007938:Leukemia / Q000201:enzymology / Q000276:immunology; D015394:Molecular Structure; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D017455:Receptors, IgE / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D000072377:Syk Kinase; D001619:beta-N-Acetylhexosaminidases / Q000037:antagonists & inhibitors / Q000378:metabolism
D018926:Anti-Allergic Agents; D005419:Flavonoids; D047908:Intracellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; D017455:Receptors, IgE; D007073:Immunoglobulin E; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606898:Syk protein, rat; D001619:beta-N-Acetylhexosaminidases; D002118:Calcium