Department of Clinical Analysis, Faculty of Pharmaceutical Sciences, UNESP - São Paulo State University, 14800-903, Araraquara, São Paulo, Brazil.
Food Funct. 2017 Jul 19;8(7):2500-2511. doi: 10.1039/c7fo00707h.
Helicobacter pylori infection is marked by intense production of reactive oxygen species (ROS) through the activation of neutrophils that are constantly attracted to the infected gastric mucosa. Here, gallic acid and its alkyl esters were evaluated as compounds able to act as antimicrobial agents and inhibitors of ROS released by H. pylori-activated neutrophils simultaneously. We found that the higher hydrophobicity caused by esterification of gallic acid led to a significant increase in its ability as a cytotoxic agent against H. pylori, a scavenger of ROS and an inhibitor of NADPH oxidase in neutrophils. Octyl gallate, a widely used food additive, showed the highest antimicrobial activity against H. pylori, with a minimum inhibitory concentration (MIC) value of 125 μg mL, whereas gallic acid had a MIC value higher than 1000 μg mL. The production of superoxide anion radicals was almost 100% abolished by the addition of 10 μM (2.82 μg mL) octyl gallate, whereas gallic acid inhibited around 20%. A similar tendency was also found when measuring the production of hypochlorous acid. The protective effect of the esters was cytochemically confirmed. In conclusion, this study showed that hydrophobicity is a crucial factor to obtain a significant anti-ROS and anti-H. pylori activity. Finally, it highlights octyl gallate, a food additive widely used in the food industry, as a promising molecule in the treatment of H. pylori infection.
幽门螺杆菌感染通过不断吸引到感染的胃黏膜的中性粒细胞的激活,导致活性氧(ROS)的大量产生。在这里,没食子酸及其烷基酯被评估为能够同时作为抗微生物剂和幽门螺杆菌激活的中性粒细胞释放的 ROS 的抑制剂的化合物。我们发现,没食子酸酯化导致的更高疏水性使其对幽门螺杆菌的细胞毒性作用显著增强,对 ROS 的清除作用和对中性粒细胞 NADPH 氧化酶的抑制作用也显著增强。辛基没食子酸酯是一种广泛使用的食品添加剂,对幽门螺杆菌表现出最高的抗菌活性,最小抑菌浓度(MIC)值为 125 μg mL,而没食子酸的 MIC 值高于 1000 μg mL。添加 10 μM(2.82 μg mL)辛基没食子酸几乎可完全消除超氧阴离子自由基的产生,而没食子酸抑制率约为 20%。在测量次氯酸生成时也发现了类似的趋势。酯的保护作用通过细胞化学得到证实。总之,本研究表明疏水性是获得显著抗 ROS 和抗幽门螺杆菌活性的关键因素。最后,它突出了辛基没食子酸酯作为一种有前途的分子,可用于治疗幽门螺杆菌感染,辛基没食子酸酯是一种广泛应用于食品工业的食品添加剂。