C-kit binding properties of hesperidin (a major component of KMP6) as a potential anti-allergic agent

PLoS One. 2011 Apr 29;6(4):e19528. doi: 10.1371/journal.pone.0019528.

Abstract

Accumulation of mast cells can be causally related to several allergic inflammations. Stem cell factor (SCF) as a mast cell chemotaxin induces mast cell migration. To clarify a new effect of Pyeongwee-San extract (KMP6, a drug for indigestion) for the treatment of allergy, we investigated the effects of KMP6 on SCF-induced migration of rat peritoneal mast cells (RPMCs). A molecular docking simulation showed that hesperidin, a major component of KMP6, controls the SCF and c-kit binding by interaction with the active site of the c-kit. KMP6 and hesperidin significantly inhibited SCF-induced migration of RPMCs (P<0.05). The ability of the SCF to enhance morphological alteration and F-actin formation was also abolished by treatment with KMP6 or hesperidin. KMP6 and hesperidin inhibited SCF-induced p38 MAPK activation. In addition, SCF-induced inflammatory cytokine production was significantly inhibited by treatment with KMP6 or hesperidin (P<0.05). Our results show for the first time that KMP6 potently regulates SCF-induced migration, p38 MAPK activation and inflammatory cytokines production through hindrance of SCF and c-kit binding in RPMCs. Such modulation may have functional consequences during KMP6 treatment, especially mast cell-mediated allergic inflammation disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Anti-Allergic Agents / pharmacology*
  • Cells, Cultured
  • Chemotaxis
  • Hesperidin / chemistry*
  • Hypersensitivity
  • Inflammation
  • Male
  • Plant Extracts / chemistry*
  • Protein Binding
  • Proto-Oncogene Proteins c-kit / metabolism*
  • Rats
  • Rats, Wistar
  • Software
  • Stem Cell Factor / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Actins
  • Anti-Allergic Agents
  • Plant Extracts
  • Stem Cell Factor
  • pyeongwee-san extract
  • Hesperidin
  • Proto-Oncogene Proteins c-kit
  • p38 Mitogen-Activated Protein Kinases