Procyanidin C1 from apple extracts inhibits Fc epsilon RI-mediated mast cell activation.
BACKGROUND
Polyphenol-enriched fractions, which are extracted from unripe apples (Rosaceae, Malus spp.), consisting of procyanidins (polymers of catechins) are known to have an anti-allergenic effect on patients with various allergic diseases. Although it has been reported that apple extracts inhibit histamine release from mast cells, the molecular mechanisms for this anti-allergenic effect are not well understood. To elucidate the molecular mechanisms by which apple extracts induce their anti-allergenic effects, the effects of purified apple extract components on high-affinity receptors for IgE (Fc epsilon RI)-mediated mast cell activation were investigated.


METHODS
The anti-allergic effect of oral administration of apple procyanidin extracts on passive cutaneous anaphylactic responses of BALB/c mice was assessed. We evaluated the effects of procyanidin C1 (PC1) [epicatechin-(4beta-->8)-epicatechin-(4beta-->8)-epicatechin], a component of the procyanidin fraction, on mouse bone-marrow-derived mast cell degranulation, cytokine production, protein tyrosine phosphorylation and on the generation of intracellular reactive oxygen species (ROS) of cells stimulated by Fc epsilon RI cross-linking in vitro.


RESULTS
In an in vivo study, oral administration of the procyanidin fraction suppressed the mast-cell-dependent allergic reaction. In in vitro studies, PC1 dose-dependently decreased Fc epsilon RI-mediated degranulation and cytokine production of mast cells. Furthermore, PC1 inhibited tyrosine phosphorylation of Syk and linker for activation of T cells, and the ROS generation in stimulated mast cells.


CONCLUSIONS
PC1 suppresses Fc epsilon RI-mediated mast cell activation by inhibiting intracellular signaling pathways. These observations provide evidence for the anti-allergenic effects of the procyanidin-enriched apple extract.
Nakano
Nobuhiro
N
Atopy Allergy Research Center, Juntendo University School of Medicine, Tokyo, Japan. nbnakano@med.juntendo.ac.jp
Nishiyama
Chiharu
C
Tokura
Tomoko
T
Nagasako-Akazome
Yoko
Y
Ohtake
Yasuyuki
Y
Okumura
Ko
K
Ogawa
Hideoki
H
D000818:Animals; D044946:Biflavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D002392:Catechin / Q000008:administration & dosage / Q000494:pharmacology*; D015550:Cell Degranulation; D016207:Cytokines / Q000378:metabolism; D007073:Immunoglobulin E / Q000378:metabolism; D027845:Malus / Q000737:chemistry*; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D010766:Phosphorylation; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D044945:Proanthocyanidins / Q000008:administration & dosage / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D044946:Biflavonoids; D016207:Cytokines; D010936:Plant Extracts; D044945:Proanthocyanidins; D017382:Reactive Oxygen Species; D017455:Receptors, IgE; C479583:procyanidin C; D007073:Immunoglobulin E; D014443:Tyrosine; D002392:Catechin