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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Effects of coadministration of natural polyphenols with doxycycline or calcium modulators on acute Chlamydia pneumoniae infection in vitro.
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Effects of coadministration of natural polyphenols with doxycycline or calcium modulators on acute Chlamydia pneumoniae infection in vitro.

机译：天然多酚与强力霉素或钙调节剂共同给药对急性肺炎衣原体感染的影响。

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摘要

Besides small molecules from medicinal chemistry, natural products are still major sources of innovative therapeutic agents for various conditions, including infectious diseases. Here we present the first attempt to design a combination treatment targeted against Chlamydia pneumoniae infection using coadministration of natural phenolics with calcium (Ca(2+)) modulators, and also the concomitant administration of these compounds with doxycycline. An in vitro acute C. pneumoniae model in human lung epithelial cells was used and Loewe additivity model was applied to evaluate the effects. In general, the phenolic compounds, quercetin, luteolin, rhamnetin and octyl gallate did not improve the antichlamydial effect of doxycycline, and, in some cases, resulted in antagonistic effects. The combination of doxycycline and Ca(2+) modulators (isradipine, verapamil and thapsigargin) was at most additive, and at subinhibitory concentrations of doxycycline, often even antagonistic. The Ca(2+) modulators showed no inhibitory effects on C. pneumoniae growth alone, whereas the coadminstration of Ca(2+) modulators with phenolic compounds resulted in potentiation of the antichlamydial effect of phenolic compounds. Verapamil (100 muM) was synergistic with low quercetin and luteolin concentrations (0.39 and 1.56 muM), whereas 10 muM isradipine was synergistic with high quercetin, rhamnetin and octyl gallate concentrations (12.5 muM and 100 muM). Use of thapsigargin with the phenolic compounds resulted in the most intense synergism. Interaction indices 0.12 and 0.14 were achieved with 0.39 muM luteolin and 10 and 100 nM thapsigargin, respectively. To conclude, the observed results indicate that the Ca(2+) modulators potentiate the antichlamydial effects of the phenolic compounds.
机译：除了药物化学中的小分子外，天然产物仍然是各种疾病（包括传染病）的创新治疗剂的主要来源。在这里，我们提出了使用天然酚类与钙（Ca（2+））调节剂共同给药设计针对肺炎衣原体感染的联合治疗的首次尝试，以及这些化合物与强力霉素的同时给药。使用在人肺上皮细胞中的体外急性肺炎衣原体模型，并使用Loewe可加性模型评估其效果。通常，酚类化合物槲皮素，木犀草素，鼠李素和没食子酸辛酯不能改善强力霉素的抗衣原体作用，在某些情况下会产生拮抗作用。强力霉素和Ca（2+）调节剂（伊沙地平，维拉帕米和毒胡萝卜素）的组合最多可加成，并且在强力霉素的亚抑制浓度下，甚至具有拮抗作用。 Ca（2+）调制器显示没有单独对肺炎衣原体生长的抑制作用，而Ca（2+）调制器与酚类化合物的共同给药导致酚类化合物的抗衣原体作用增强。维拉帕米（100μM）与低槲皮素和木犀草素浓度（0.39和1.56μM）协同作用，而10μM异拉地平与高槲皮素，鼠李素和没食子酸辛酯浓度（12.5μM和100μM）协同作用。 thapsigargin与酚类化合物的使用产生最强烈的协同作用。分别用0.39μM木犀草素和10和100 nM thapsigargin达到相互作用指数0.12和0.14。总而言之，观察到的结果表明Ca（2+）调节剂可增强酚类化合物的抗衣原体作用。

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