Modulation of Chloride Channel Functions by the Plant Lignan Compounds Kobusin and Eudesmin.
Modulation of Chloride Channel Functions by the Plant Lignan Compounds Kobusin and Eudesmin.
复制标题
植物木酚素化合物科布辛和尤地斯明对氯离子通道功能的调节。
DOI：
10.3389/fpls.2015.01041
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发表时间：
2015
影响因子：
5.6
通讯作者：
Yang H
中科院分区：
文献类型：
--
作者：
Jiang Y;Yu B;Fang F;Cao H;Ma T;Yang H
植物木脂素是广泛存在于蔬菜、水果和谷物中的双酚类化合物。这些化合物已被证明对癌症、高血压和糖尿病具有保护作用。在本研究中，我们发现两个木脂素化合物，kobusin和桉叶素，从木兰花中分离，可以调节肠氯离子转运介导的囊性纤维化跨膜传导调节因子（CFTR）和钙激活的氯离子通道（CaCCs）。化合物在FRT细胞和HT-29细胞中激活CFTR通道功能。研究了Kobusin和Eudesmin对CaCCgie（表达于胃肠道上皮细胞的CaCC）活性的调节作用，结果表明两种化合物均能刺激CaCCgie介导的短路电流，且这种刺激作用与ATP具有协同作用。在离体研究中，两种化合物均激活小鼠结肠上皮中的CFTR和CaCCgie氯离子通道活性。值得注意的是，这些化合物对表达ANO 1/CaCC的FRT细胞中ANO 1/CaCC介导的短路电流显示出抑制作用，其中Kobusin的IC 50值为100 μM，Eudesmin为200 μM。在活性炭转运研究中，两种化合物均轻度降低小鼠的胃肠动力。总之，这些结果揭示了木脂素化合物显示的一种新的活性，其与氯离子通道功能的调节有关。
Plant lignans are diphenolic compounds widely present in vegetables, fruits, and grains. These compounds have been demonstrated to have protective effect against cancer, hypertension and diabetes. In the present study, we showed that two lignan compounds, kobusin and eudesmin, isolated from Magnoliae Flos, could modulate intestinal chloride transport mediated by cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated chloride channels (CaCCs). The compounds activated CFTR channel function in both FRT cells and in HT-29 cells. The modulating effects of kobusin and eudesmin on the activity of CaCCgie (CaCC expressed in gastrointestinal epithelial cells) were also investigated, and the result showed that both compounds could stimulate CaCCgie-mediated short-circuit currents and the stimulation was synergistic with ATP. In ex vivo studies, both compounds activated CFTR and CaCCgie chloride channel activities in mouse colonic epithelia. Remarkably, the compounds showed inhibitory effects toward ANO1/CaCC-mediated short-circuit currents in ANO1/CaCC-expressing FRT cells, with IC50 values of 100 μM for kobusin and 200 μM for eudesmin. In charcoal transit study, both compounds mildly reduced gastrointestinal motility in mice. Taken together, these results revealed a new kind of activity displayed by the lignan compounds, one that is concerned with the modulation of chloride channel function.