Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells

  • Hyo-Hyun Park
  • Soyoung Lee
  • Hee-Young Son
  • Seung-Bin Park
  • Mi-Sun Kim
  • Eun-Ju Choi
  • Thoudam S. K. Singh
  • Jeoung-Hee Ha
  • Maan-Gee Lee
  • Jung-Eun Kim
  • Myung Chul Hyun
  • Taeg Kyu Kwon
  • Yeo Hyang Kim
  • Sang-Hyun Kim
Research Article Drug Efficacy and Safety

Abstract

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-α (TNF-α), interleukin (IL)-1β, 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-α and IL-6 but not IL-1β and IL-8. Fisetin, myricetin, and rutin suppressed activation of NF-κB indicated by inhibition of nuclear translocation of NF-κB, NF-κB/DNA binding, and NF-κB-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.

Key words

Flavonoids Mast cells Histamine Inflammatory cytokines Nuclear factor-κB 

Abbreviations

HMC-1

human mast cell

TNF

tumor necrosis factor

IL

interleukin

NF

nuclear factor

PMA

phorbol 12-myristate 13-acetate

PMACI

PMA and calcium ionophore A23187

EMSA

electrophoretic mobility shift assay

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Copyright information

© The Pharmaceutical Society of Korea 2008

Authors and Affiliations

  • Hyo-Hyun Park
    • 1
    • 2
  • Soyoung Lee
    • 1
  • Hee-Young Son
    • 1
  • Seung-Bin Park
    • 1
  • Mi-Sun Kim
    • 1
  • Eun-Ju Choi
    • 1
  • Thoudam S. K. Singh
    • 1
  • Jeoung-Hee Ha
    • 1
  • Maan-Gee Lee
    • 1
  • Jung-Eun Kim
    • 3
  • Myung Chul Hyun
    • 4
  • Taeg Kyu Kwon
    • 5
  • Yeo Hyang Kim
    • 6
  • Sang-Hyun Kim
    • 1
  1. 1.CMRI, Department of PharmacologyKyungpook National UniversityDaeguKorea
  2. 2.Department of Neurobiology BK21 Project for Medical Science, School of MedicineKorea UniversitySeoulKorea
  3. 3.Department of Molecular MedicineKyungpook National UniversityDaeguKorea
  4. 4.Department of PediatricsKyungpook National UniversityDaeguKorea
  5. 5.Department of ImmunologyKeimyung UniversityDaeguKorea
  6. 6.Department of PediatricsKeimyung UniversityDaeguKorea

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