title: C-kit binding properties of hesperidin (a major component of KMP6) as a potential anti-allergic agent.
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.
authors.affiliation: Biochip Research Center, Hoseo University, Asan, Republic of Korea.
authors.forename: Hyun-Ja
authors.initials: HJ
authors.lastname: Jeong
authors.forename: Youngjin
authors.initials: Y
authors.lastname: Choi
authors.forename: Kyu-Yeob
authors.initials: KY
authors.lastname: Kim
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Kim
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Kim
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002633:Chemotaxis; D006569:Hesperidin / Q000737:chemistry*; D006967:Hypersensitivity; D007249:Inflammation; D008297:Male; D010936:Plant Extracts / Q000737:chemistry*; D011485:Protein Binding; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012984:Software; D019089:Stem Cell Factor / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000199:Actins; D018926:Anti-Allergic Agents; D010936:Plant Extracts; D019089:Stem Cell Factor; C562348:pyeongwee-san extract; D006569:Hesperidin; D019009:Proto-Oncogene Proteins c-kit; D048051:p38 Mitogen-Activated Protein Kinases