title: Inhibition of syk activity and degranulation of human mast cells by flavonoids.
abstract: To investigate the effect of flavonoids on the activation of p72(syk) (Syk) protein tyrosine kinase which plays a pivotal role in the high affinity IgE receptor-mediated degranulation of mast cells, we picked out 10 flavonoids, classified them into 4 series, and examined their effects on the activation of Syk and on the degranulation of human mast cells. Flavones and flavonols showed clear inhibition, whereas flavanones and isoflavones had either weak or no effect on Syk enzymatic activity induced by amino acid peptide corresponding to the activation loop domain and on IgE-dependent degranulation of human cultured mast cells (HCMC). On the basis of calculated logP (ClogP) values as a prediction of compound lipophilicity, some flavonoids were speculated to have low lipophilicity, the reason for poor cell permeability. A significant relationship was observed between the inhibition of Syk activity and HCMC degranulation attributable to flavonoids when the ClogP values of the compounds were taken into account (r(2)=0.89). These results suggested that the impairment of mast cell degranulation by several flavonoids classified into flavones and flavonols might be mediated via inhibition of the intracellular activation of Syk.
authors.affiliation: Research Center Kyoto, Bayer Yakuhin, Ltd. Kyoto, Japan. michitaka.shichijo.ms@bayer.co.jp
authors.forename: Michitaka
authors.initials: M
authors.lastname: Shichijo
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hideki
authors.initials: H
authors.lastname: Tsujishita
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kimata
authors.forename: Hiroichi
authors.initials: H
authors.lastname: Nagai
authors.forename: Toshio
authors.initials: T
authors.lastname: Kokubo
mesh_terms: D015550:Cell Degranulation / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008407:Mast Cells / Q000166:cytology* / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D013329:Structure-Activity Relationship; D000072377:Syk Kinase; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D004792:Enzyme Precursors; D044950:Flavanones; D005419:Flavonoids; D047908:Intracellular Signaling Peptides and Proteins; C006680:baicalein; C040015:myricetin; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase