Nakano Nobuhiro, Nishiyama Chiharu, Tokura Tomoko, Nagasako-Akazome Yoko, Ohtake Yasuyuki, Okumura Ko, Ogawa Hideoki
Atopy Allergy Research Center, Juntendo University School of Medicine, Tokyo, Japan.
Int Arch Allergy Immunol. 2008;147(3):213-21. doi: 10.1159/000142044. Epub 2008 Jul 2.
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.
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.
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.
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.
从未成熟苹果(蔷薇科,苹果属)中提取的富含多酚的组分,主要由原花青素(儿茶素聚合物)组成,已知其对多种过敏性疾病患者具有抗过敏作用。尽管已有报道称苹果提取物可抑制肥大细胞释放组胺,但其抗过敏作用的分子机制尚不清楚。为阐明苹果提取物产生抗过敏作用的分子机制,研究了纯化的苹果提取物成分对IgE高亲和力受体(FcεRI)介导的肥大细胞活化的影响。
评估口服苹果原花青素提取物对BALB/c小鼠被动皮肤过敏反应的抗过敏作用。我们评估了原花青素组分的一种成分原花青素C1(PC1)[表儿茶素-(4β→8)-表儿茶素-(4β→8)-表儿茶素]对小鼠骨髓来源肥大细胞脱颗粒、细胞因子产生、蛋白酪氨酸磷酸化以及体外FcεRI交联刺激的细胞内活性氧(ROS)生成的影响。
在体内研究中,口服原花青素组分可抑制肥大细胞依赖性过敏反应。在体外研究中,PC1剂量依赖性地降低了FcεRI介导的肥大细胞脱颗粒和细胞因子产生。此外,PC1抑制Syk和T细胞活化连接蛋白的酪氨酸磷酸化以及刺激的肥大细胞中的ROS生成。
PC1通过抑制细胞内信号通路抑制FcεRI介导的肥大细胞活化。这些观察结果为富含原花青素的苹果提取物的抗过敏作用提供了证据。