Cho Mi Suk, Park Won Sun, Jung Won-Kyo, Qian Zhong-Ji, Lee Dae-Sung, Choi Jung-Sik, Lee Da-Young, Park Sae-Gwang, Seo Su-Kil, Kim Hak-Ju, Won Jun Yeon, Yu Byeng Chul, Choi Il-Whan
Department of Dental Hygiene, Choonhae College of Health Sciences , Ulsan , Republic of Korea .
Pharm Biol. 2014 Jul;52(7):926-32. doi: 10.3109/13880209.2013.865243.
Caffeic acid phenethyl ester (CAPE), an active component of honeybee propolis, is known to have antioxidant, anti-inflammatory, and other beneficial medicinal properties. However, the molecular mechanisms underlying its anti-allergic effects in mast cells are unknown.
The purpose of the present study was to examine whether CAPE modulates the immunoglobulin E (IgE)-mediated local allergic reaction in animals, as well as to elucidate the effects of CAPE on mast cells in vitro.
To investigate the bioactive potential of CAPE (10 or 20 µM), HMC-1 cells were stimulated with phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI) for 24 h in the presence or absence of CAPE. To study the pharmacological effects of CAPE, enzyme-linked immunosorbent assays (ELISAs), RT-PCR, Western blot analysis, electrophoretic mobility shift assays (EMSAs), and fluorescence assays were used.
CAPE (10 mg/kg) inhibited local IgE-mediated allergic reactions (0.164 versus 0.065 O.D.) in a mouse model. Additionally, CAPE (20 µM) attenuated PMACI-stimulated histamine release (3146.42 versus 2564.83 pg/ml) and the production of inflammatory cytokines, such as interleukin (IL)-1β (4.775 versus 0.713 pg/ml, IC50 = 6.67 µM), IL-6 (4771.5 versus 449.1 pg/ml, IC50 = 5.25 µM), and IL-8 (5991.7 versus 2213.1 pg/ml, IC50 = 9.95 µM) in HMC-1 cells. In activated HMC-1 cells, pretreatment with CAPE decreased the phosphorylation of c-Jun N-terminal kinase. In addition, CAPE inhibited PMACI-induced nuclear factor (NF)-κB activation by suppressing IκBα phosphorylation and its degradation.
Our results indicated that CAPE can modulate mast cell-mediated allergic disease.
咖啡酸苯乙酯（CAPE）是蜜蜂蜂胶的一种活性成分，已知具有抗氧化、抗炎及其他有益的药用特性。然而，其在肥大细胞中抗过敏作用的分子机制尚不清楚。
本研究旨在探讨CAPE是否能调节动物体内免疫球蛋白E（IgE）介导的局部过敏反应，以及阐明CAPE在体外对肥大细胞的影响。
为研究CAPE（10或20µM）的生物活性潜力，在存在或不存在CAPE的情况下，用佛波醇12-肉豆蔻酸酯13-乙酸酯加钙离子载体A23187（PMACI）刺激人肥大细胞系HMC-1细胞24小时。为研究CAPE的药理作用，采用酶联免疫吸附测定（ELISA）、逆转录聚合酶链反应（RT-PCR）、蛋白质免疫印迹分析、电泳迁移率变动分析（EMSA）和荧光测定。
在小鼠模型中，CAPE（10mg/kg）抑制了局部IgE介导的过敏反应（光密度为0.164对0.065）。此外，CAPE（20µM）减弱了PMACI刺激的组胺释放（3146.42对2564.83pg/ml）以及炎性细胞因子如白细胞介素（IL）-1β（4.775对0.713pg/ml，半数抑制浓度[IC50]=6.67µM）、IL-6（4771.5对449.1pg/ml，IC50=5.25µM）和IL-8（5991.7对2213.1pg/ml，IC50=9.95µM）在HMC-1细胞中的产生。在活化的HMC-1细胞中，用CAPE预处理可降低c-Jun氨基末端激酶的磷酸化。此外，CAPE通过抑制IκBα磷酸化及其降解来抑制PMACI诱导的核因子（NF）-κB活化。
我们的结果表明，CAPE可调节肥大细胞介导的过敏性疾病。
