Anti-degranulating activity in rat basophil leukemia RBL-2H3 cells of flavanone glycosides and their aglycones in citrus fruits.
The anti-degranulating activity of flavonoids present in Citrus fruits was comprehensively evaluated. Among these, hesperetin and naringenin, respectively aglycones of hesperidin and narirutin, showed significant activity. The targets of hesperetin and naringenin were found: hesperetin inhibited phosphorylation of Syk and Akt, while naringenin suppressed the expression of Lyn and inhibited the phosphorylation of Akt. These results suggest that hesperetin and naringenin inhibit degranulation by suppression of pathway signals and reduce the symptoms of allergy by inhibiting phosphorylation of Akt, which leads to the suppression of cytokines. In addition, hesperetin showed inhibitory activity against the degranulation induced by calcium ionophores, indicating that hesperetin exerts its inhibitory activity by stabilizing the membrane structure.
Faculty of Pharmacy, Kinki University, 3-4-1 Kowakae, Higashiosaka, Osaka, 577-8502, Japan.
Kazuya
K
Murata
Seiya
S
Takano
Megumi
M
Masuda
Munekazu
M
Iinuma
Hideaki
H
Matsuda
D000818:Animals; D018926:Anti-Allergic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D015549:Basophil Degranulation Test; D001491:Basophils / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D061207:Calcium Ionophores / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects*; D045744:Cell Line, Tumor; D002957:Citrus / Q000737:chemistry*; D004187:Disaccharides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000302:isolation & purification / Q000494:pharmacology*; D006027:Glycosides / Q000302:isolation & purification / Q000494:pharmacology*; D006569:Hesperidin / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007938:Leukemia; D010766:Phosphorylation; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D000072377:Syk Kinase; D019061:src-Family Kinases / Q000378:metabolism
D018926:Anti-Allergic Agents; D061207:Calcium Ionophores; D004187:Disaccharides; D044950:Flavanones; D006027:Glycosides; D047908:Intracellular Signaling Peptides and Proteins; D010936:Plant Extracts; C500601:narirutin; D006569:Hesperidin; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606898:Syk protein, rat; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; C005273:naringenin; C013015:hesperetin; D002118:Calcium