Abstract:
Veronica persica is a flowering plant belonging to the family Scrophulariaceae. Here, we aimed to evaluate the pharmacological activity of the ethanol extract of Veronica persica (EEVP) in an airway inflammation model. We examined airway responsiveness to aerosolized methacholine, serum immunoglobulin (Ig)E levels, and total cell numbers in the lung and bronchoalveolar lavage fluid (BALF). Histological analysis of the lung tissue was performed using hematoxylin-eosin, Masson trichrome, or periodic acid-Schiff staining. Fluorescence-activated cell sorting analysis in the lung and BALF was applied to clarify the changes in immune cell types. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction were applied to investigate cytokine levels and gene expression related to airway inflammation. STAT-3/6 phosphorylation was examined in primary bronchial/tracheal epithelial cells using western blot analysis. EEVP significantly suppressed total IgE levels and methacholine-induced increase of Penh value in the HDM-challenged mouse model. EEVP also attenuated the severity of airway remodeling in lung tissues and decreased eosinophil and neutrophil infiltration in the lungs and BALF. EEVP significantly reduced the production of cytokines in BAL and splenocyte culture medium, and the expression of mRNAs related to airway inflammation in the lung tissue. EEVP suppressed IL-4/13-induced STAT-3/6 phosphorylation in the epithelial cells. We showed for the first time that EEVP effectively inhibits eosinophilic airway inflammation by suppressing the expression of inflammatory factors for T cell activation and polarization, and inhibits MCP-1 production of bronchial/tracheal epithelial cells by suppressing STAT-3/6 activation. EEVP may be a potential pharmacological agent to prevent inflammatory airway diseases.
摘要:
维罗妮卡是一种开花植物,属于玄参科。这里,我们旨在评估维罗妮卡乙醇提取物(EEVP)在气道炎症模型中的药理活性。我们检查了气道对雾化乙酰甲胆碱的反应,血清免疫球蛋白(Ig)E水平,肺和支气管肺泡灌洗液(BALF)中的总细胞数。使用苏木精-伊红对肺组织进行组织学分析,Masson三色,或高碘酸希夫染色。肺和BALF中的荧光激活细胞分选分析用于阐明免疫细胞类型的变化。应用酶联免疫吸附试验和实时定量聚合酶链反应研究与气道炎症相关的细胞因子水平和基因表达。使用蛋白质印迹分析在原发性支气管/气管上皮细胞中检查STAT-3/6磷酸化。在HDM攻击的小鼠模型中,EEVP显着抑制了总IgE水平和乙酰甲胆碱诱导的Penh值增加。EEVP还减轻了肺组织中气道重塑的严重程度,并减少了肺和BALF中的嗜酸性粒细胞和中性粒细胞浸润。EEVP显著降低BAL和脾细胞培养基中细胞因子的产生,与气道炎症相关的mRNA在肺组织中的表达。EEVP抑制IL-4/13诱导的上皮细胞STAT-3/6磷酸化。我们首次显示EEVP通过抑制T细胞活化和极化的炎症因子的表达,有效抑制嗜酸性粒细胞气道炎症,并通过抑制STAT-3/6激活来抑制支气管/气管上皮细胞的MCP-1产生。EEVP可能是预防炎症性气道疾病的潜在药物。