Allergy is an immunological disorder that develops in response to exposure to an allergen, and histamines mediate these effects via histidine decarboxylase (HDC) activity at the intracellular level. In the present study, we developed a 3D model of Klebsiella pneumoniae histidine decarboxylase (HDC) and analyzed the HDC inhibitory potential of cinnamaldehyde (CA) and subsequent anti-allergic potential using a bacterial and mammalian mast cell model. A computational and in vitro study using K. pneumonia revealed that CA binds to HDC nearby the pyridoxal-5′-phosphate (PLP) binding site and inhibited histamine synthesis in a bacterial model. Further study using a mammalian mast cell model also showed that CA decreased the levels of histamine in the stimulated RBL-2H3 cell line and attenuated the release of β-hexoseaminidase and cell degranulation. In addition, CA treatment also significantly suppressed the levels of pro-inflammatory cytokines TNF-α and IL-6 and the nitric oxide (NO) level in the stimulated mast cells. A gene expression and Western blotting study revealed that CA significantly downregulated the expressions of MAPKp38/ERK and its downstream pro-allergic mediators that are involved in the signaling pathway in mast cell cytokine synthesis. This study further confirms that CA has the potential to attenuate mast cell activation by inhibiting HDC and modifying the process of allergic disorders.

中文翻译：

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肉桂醛通过组氨酸脱羧酶 (HDC) 产生肺炎克雷伯菌的抑制作用的抗过敏潜力

过敏是一种免疫性疾病，它是在暴露于过敏原后发生的，组胺通过细胞内水平的组氨酸脱羧酶 (HDC) 活性介导这些作用。在本研究中，我们开发了肺炎克雷伯菌组氨酸脱羧酶 (HDC) 的 3D 模型，并使用细菌和哺乳动物肥大细胞模型分析了肉桂醛 (CA) 的 HDC 抑制潜力和随后的抗过敏潜力。一项使用肺炎克雷伯菌的计算和体外研究表明，CA 在 5'-磷酸吡哆醛 (PLP) 结合位点附近与 HDC 结合并抑制细菌模型中的组胺合成。使用哺乳动物肥大细胞模型的进一步研究还表明，CA 降低了受刺激的 RBL-2H3 细胞系中组胺的水平，并减弱了 β-己糖胺酶的释放和细胞脱颗粒。此外，CA 治疗还显着抑制了受刺激的肥大细胞中促炎细胞因子 TNF-α 和 IL-6 的水平以及一氧化氮 (NO) 的水平。基因表达和蛋白质印迹研究表明，CA 显着下调 MAPKp38/ERK 及其下游促过敏介质的表达，这些介质参与肥大细胞细胞因子合成的信号通路。该研究进一步证实，CA 具有通过抑制 HDC 和改变过敏性疾病过程来减弱肥大细胞活化的潜力。基因表达和蛋白质印迹研究表明，CA 显着下调 MAPKp38/ERK 及其下游促过敏介质的表达，这些介质参与肥大细胞细胞因子合成的信号通路。该研究进一步证实，CA 具有通过抑制 HDC 和改变过敏性疾病过程来减弱肥大细胞活化的潜力。基因表达和蛋白质印迹研究表明，CA 显着下调 MAPKp38/ERK 及其下游促过敏介质的表达，这些介质参与肥大细胞细胞因子合成的信号通路。该研究进一步证实，CA 具有通过抑制 HDC 和改变过敏性疾病过程来减弱肥大细胞活化的潜力。