COPD is an inflammatory lung disease, which is often exacerbated with microbial infections resulting in worsening of respiratory symptoms. Gallic acid (GA), a naturally occurring phenolic compound is known to possess anti-oxidant/anti-inflammatory activity. We have recently reported that GA protects against the elastase (ET) induced lung inflammation and emphysema and the present work was designed to investigate the beneficial effects of Gallic acid against ET + Lipopolysachharide (LPS) induced COPD exacerbation like condition in mice model. Our data showed that i.t. administration of LPS at 21 days after ET instillation resulted in significant infiltration of inflammatory cells particularly neutrophils (p < 0.0001) into the lungs along with elevated levels of pro-inflammatory cytokines like TNF-α, IL-1β and IL-6 (p < 0.0001). Interestingly, daily administration of GA (200 mg/Kg b. wt.) starting 7 days before ET instillation, significantly blunted the ET + LPS induced inflammation as indicated by reduced number of inflammatory cells particularly neutrophils (p < 0.0001) in BALF along with suppression of myeloperoxidase activity (p = 0.0009) and production of pro-inflammatory cytokines (p < 0.0001). Further, GA also restored the redox imbalance in the lungs towards normal. Additionally, phosphorylation of p65-NF-κB was found to be reduced (p = 0.015), which was associated with downregulation in the gene expression of IL-1β (p = 0.022) and TNF-α (p = 0.04). Conversely, GA treatment resulted in increased protein levels of Nrf2 (p = 0.021) with concomitant increase in transcription of its downstream target genes HO-1 (p = 0.033) and Prdx-1 (p = 0.006). Overall, our data show that GA effectively modulates COPD exacerbation manifestations in mice potentially by restoring redox imbalance in lungs.

中文翻译：

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没食子酸可改善小鼠的 COPD 相关恶化。

COPD 是一种炎症性肺病，常因微生物感染而加剧，导致呼吸道症状恶化。没食子酸 (GA) 是一种天然存在的酚类化合物，已知具有抗氧化/抗炎活性。我们最近报道了 GA 可防止弹性蛋白酶 (ET) 诱导的肺部炎症和肺气肿，目前的工作旨在研究没食子酸对 ET + 脂多糖 (LPS) 诱导的 COPD 急性加重样病症在小鼠模型中的有益作用。我们的数据显示，在 ET 滴注后 21 天施用 LPS 导致炎症细胞，尤其是中性粒细胞（p < 0.0001）显着浸润到肺部，同时促炎细胞因子（如 TNF-α、IL-1β 和 IL）水平升高-6 (p < 0.0001)。有趣的是，在 ET 滴注前 7 天开始每天施用 GA（200 mg/Kg b. wt.），显着减弱了 ET + LPS 诱导的炎症，如 BALF 中炎症细胞数量的减少，特别是中性粒细胞（p < 0.0001）以及抑制髓过氧化物酶活性 (p = 0.0009) 和促炎细胞因子的产生 (p < 0.0001)。此外，GA 还使肺中的氧化还原失衡恢复正常。此外，发现 p65-NF-κB 的磷酸化降低（p = 0.015），这与 IL-1β（p = 0.022）和 TNF-α（p = 0.04）基因表达的下调有关。相反，GA 处理导致 Nrf2（p = 0.021）的蛋白质水平增加，同时其下游靶基因 HO-1（p = 0.033）和 Prdx-1（p = 0.006）的转录增加。全面的，