Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells.
Mast cells participate in allergy and inflammation by secreting inflammatory mediators such as histamine and proinflammatory cytokines. Flavonoids are naturally occurring molecules with antioxidant, cytoprotective, and antiinflammatory actions. However, effect of flavonoids on the release of histamine and proinflammatory mediator, and their comparative mechanism of action in mast cells were not well defined. Here, we compared the effect of six flavonoids (astragalin, fisetin, kaempferol, myricetin, quercetin, and rutin) on the mast cell-mediated allergic inflammation. Fisetin, kaempferol, myricetin, quercetin, and rutin inhibited IgE or phorbol-12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-mediated histamine release in RBL-2H3 cells. These five flavonoids also inhibited elevation of intracellular calcium. Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-8 were assessed in PMACI-stimulated human mast cells (HMC-1). Fisetin, quercetin, and rutin decreased gene expression and production of all the proinflammatory cytokines after PMACI stimulation. Myricetin attenuated TNF-alpha and IL-6 but not IL-1beta and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-kappaB indicated by inhibition of nuclear translocation of NF-kappaB, NF-kappaB/DNA binding, and NF-kappaB-dependent gene reporter assay. The pharmacological actions of these flavonoids suggest their potential activity for treatment of allergic inflammatory diseases through the down-regulation of mast cell activation.
Park
Hyo-Hyun
HH
CMRI, Department of Pharmacology, Kyungpook National University, Daegu 700-422, Korea.
Lee
Soyoung
S
Son
Hee-Young
HY
Park
Seung-Bin
SB
Kim
Mi-Sun
MS
Choi
Eun-Ju
EJ
Singh
Thoudam S K
TS
Ha
Jeoung-Hee
JH
Lee
Maan-Gee
MG
Kim
Jung-Eun
JE
Hyun
Myung Chul
MC
Kwon
Taeg Kyu
TK
Kim
Yeo Hyang
YH
Kim
Sang-Hyun
SH
D000893:Anti-Inflammatory Agents; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D017931:DNA Primers / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005419:Flavonoids / Q000494:pharmacology*; D006633:Histamine Antagonists; D006636:Histamine Release / Q000187:drug effects*; D008156:Luciferases / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D017931:DNA Primers; D005419:Flavonoids; D006633:Histamine Antagonists; D016328:NF-kappa B; D008156:Luciferases; D002118:Calcium