A synthetic compound, 4-acetyl-3-methyl-6-(3,4,5-trimethoxyphenyl)pyrano[ 3,4-c]pyran-1,8-dione, ameliorates ovalbumin-induced asthma
A synthetic compound, 4-acetyl-3-methyl-6-(3,4,5-trimethoxyphenyl)pyrano[ 3,4-c]pyran-1,8-dione, ameliorates ovalbumin-induced asthma
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DOI：
10.1016/j.bmc.2013.08.045
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发表时间：
2013-11-01
影响因子：
3.5
通讯作者：
Bae, Hyunsu
中科院分区：
文献类型：
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作者：
Chung, Hwan-Suck;Kim, Youngeun;Bae, Hyunsu
嗜酸性粒细胞增多症是过敏性炎症的特征性体征之一。嗜酸性粒细胞向气道的大量迁移可导致上皮组织损伤、气道平滑肌收缩和支气管反应性增加。在此之前，我们从圆叶荆条果实中发现了一个新化合物1H，8H-吡喃并[3，4-c]吡喃-1，8-二酮（PPY）。并评价其抗炎和抗哮喘特性。本研究以4-乙酰基-3-甲基-6-（3，4，5-三甲氧基苯基）吡喃并[3，4-c]吡喃-1，8-二酮（PPY-345）为骨架，合成了一种新的修饰化合物，并对其抗哮喘作用进行了评价。为了评价PPY-345的体外抗哮喘作用，用TNF-α、IL-4和IL-1-β刺激A549肺上皮细胞以诱导CCL 11（嗜酸性粒细胞趋化因子）的表达，CCL 11是一种参与嗜酸性粒细胞趋化的趋化因子。为了表征PPY-345在体内的抗哮喘特性，我们检查了PPY-345在卵清蛋白（OVA）诱导的哮喘模型中的影响。PPY-345处理显著减少CCL 11分泌。PPY-345处理不抑制NF-κ B B易位入核，但抑制信号转导和转录激活因子6（STAT 6）的磷酸化。PPY-345治疗显著降低了通过全身体积描记法测量的气道高反应性。PPY-345进一步减少了BAL液中的总细胞，包括嗜酸性粒细胞、巨噬细胞和淋巴细胞，肺组织中的杯状细胞增生和肌球蛋白轻链2阳性平滑肌细胞面积。此外，PPY-345显著抑制血清中存在的OVA-IgE水平。这些结果表明，PPY-345可以改善OVA致敏小鼠的哮喘症状。(C)2013爱思唯尔有限公司保留所有权利。
Eosinophilia is one of the characteristic signs of allergic inflammation. Massive migration of eosinophils to the airways can cause epithelial tissue injury, contraction of airway smooth muscle and increased bronchial responsiveness. Previously, we discovered a new compound, 1H,8H-pyrano[3,4-c]pyran-1,8-dione (PPY), derived from the fruit of Vitex rotundifolia L. and evaluated its anti-inflammatory and anti-asthmatic properties. In this study, we synthesized a new modified compound, 4-acetyl-3-methyl-6-(3,4,5-trimethoxyphenyl)pyrano[3,4-c]pyran-1,8-dione (PPY-345), which was based on the PPY skeleton, and we evaluated its anti-asthmatic effects. To evaluate the anti-asthmatic effect of PPY-345 in vitro, A549 lung epithelial cells were stimulated with TNF-alpha, IL-4 and IL-1-beta to induce the expression of CCL11 (Eotaxin), a chemokine involved in eosinophil chemotaxis. To characterize the anti-asthmatic properties of PPY-345 in vivo, we examined the influence of PPY-345 in an ovalbumin (OVA)-induced asthma model. PPY-345 treatments significantly reduced CCL11 secretion. PPY-345 treatment did not inhibit the translocation of NF-kappa B into the nucleus but suppressed the phosphorylation of signal transducers and activators of transcription 6 (STAT6). PPY-345 treatment significantly reduced airway hyper-reactivity as measured by whole-body plethysmography. PPY-345 further reduced total cells, including eosinophil, macrophage and lymphocytes, in the BAL fluid, goblet cell hyperplasia and myosin light chain 2 positive smooth muscle cell area in the lung tissue. Additionally, PPY-345 significantly suppressed the levels of OVA-IgE present in the serum. These results suggested that PPY-345 could improve asthma symptoms in OVA-sensitized mice. (C) 2013 Elsevier Ltd. All rights reserved.