Hagenlocher Yvonne, Kiessling Kristina, Schäffer Michael, Bischoff Stephan C, Lorentz Axel
Department of Nutritional Medicine, University of Hohenheim, Fruwirthstraße 12, 70593, Stuttgart, Germany.
Department of General, Visceral, and Thorax Surgery, Marienhospital Stuttgart, Böheimstraße 37, 70199, Stuttgart, Germany.
Eur J Nutr. 2015 Dec;54(8):1297-309. doi: 10.1007/s00394-014-0810-0. Epub 2014 Dec 11.
In terms of their involvement in allergic and inflammatory conditions, mast cells (MC) can be promising targets for medical agents in therapy. Because of their good compliance and effectiveness, phytochemicals are of great interest as new therapeutic tools in form of nutraceuticals. We found recently that cinnamon extract (CE) inhibits mast cell activation. Here, we analysed the effects of a major compound of CE, cinnamaldehyde (CA), on mast cell activation.
Release of prestored and de novo synthesised mediators as well as expression of pro-inflammatory cytokines and mast cell-specific proteases were analysed in RBL-2H3 cells or in human mast cells isolated from intestinal tissue (hiMC) treated with CA prior to stimulation by FcεRI crosslinking or IONO/PMA. The results were compared with the corresponding effects of CE.
Following treatment with CA, release of β-hexosaminidase in IgE-dependent or IgE-independent activated RBL-2H3 cells was down-regulated in a dose-dependent manner to about 10%. In hiMC, release of β-hexosaminidase was also significantly reduced, and release of LTC4 and CXCL8 was almost completely inhibited by CA. Moreover, IgE-mediated expression of CXCL8, CCL2, CCL3 and CCL4 in hiMC was significantly down-regulated by CA. With the exception of the expression of the mast cell proteases tryptase and chymase, the inhibitory effects of CA were very similar to the effects shown for CE treatment. The reducing effect of CA on mast cell mediators-seen for long- and for short-term incubations-could be related to particular signalling pathways as CA caused a down-regulation in ERK as well as PLCγ1 phosphorylation.
CA decreases release and expression of pro-inflammatory mast cell mediators. This inhibitory action is similar to the effects observed for CE indicating CA as the main active compound in CE leading to its anti-allergic properties.
鉴于肥大细胞（MC）参与过敏和炎症反应，它们有望成为治疗用药物的靶点。由于植物化学物质具有良好的耐受性和有效性，作为营养保健品形式的新型治疗工具备受关注。我们最近发现肉桂提取物（CE）可抑制肥大细胞活化。在此，我们分析了CE的主要成分肉桂醛（CA）对肥大细胞活化的影响。
在通过FcεRI交联或离子霉素/佛波酯刺激之前，用CA处理RBL-2H3细胞或从肠道组织分离的人肥大细胞（hiMC），分析预先储存和新合成介质的释放以及促炎细胞因子和肥大细胞特异性蛋白酶的表达。将结果与CE的相应作用进行比较。
用CA处理后，IgE依赖性或IgE非依赖性活化的RBL-2H3细胞中β-己糖胺酶的释放以剂量依赖性方式下调至约10%。在hiMC中，β-己糖胺酶的释放也显著降低，CA几乎完全抑制了白三烯C4（LTC4）和趋化因子CXCL8的释放。此外，CA显著下调了hiMC中IgE介导的CXCL8、CCL2、CCL3和CCL4的表达。除肥大细胞蛋白酶类胰蛋白酶和糜蛋白酶的表达外，CA的抑制作用与CE处理的效果非常相似。CA对肥大细胞介质的减少作用——无论是长期还是短期孵育——可能与特定的信号通路有关，因为CA导致细胞外信号调节激酶（ERK）以及磷脂酶Cγ1（PLCγ1）磷酸化下调。
CA可减少促炎性肥大细胞介质的释放和表达。这种抑制作用与CE观察到的效果相似，表明CA是CE中导致其抗过敏特性的主要活性化合物。
