Department of Biochemistry, Panjab University, Chandigarh, 160014, India.
Inflamm Res. 2020 Apr;69(4):423-434. doi: 10.1007/s00011-020-01333-1. Epub 2020 Mar 6.
Gallic acid (GA) a naturally occurring phenolic compound, known to possess antioxidant/anti-inflammatory activities. The aim of the present work was to investigate the beneficial effects of GA against COPD-linked lung inflammation/emphysema by utilizing elastase (ET) and cigarette smoke (CS)-induced mice model.
Male BALB/c mice were treated with ET (1U/mouse) or exposed to CS (9 cigarettes/day for 4 days). GA administration was started 7 days (daily) prior to ET/CS exposure. Broncho-alveolar lavage was analyzed for inflammatory cells and pro-inflammatory cytokines. Lung homogenate was assessed for MPO activity/GSH/MDA/protein carbonyls. Further, Lung tissue was subjected to semi-quantitative RT-PCR, immunoblotting, and histological analysis.
GA suppressed the ET-induced neutrophil infiltration, elevated MPO activity and production of pro-inflammatory cytokines (IL-6/TNF-α/IL-1β) at 24 h. Reduced inflammation was accompanied with normalization of redox balance as reflected by ROS/GSH/MDA/protein carbonyl levels. Further, GA suppressed phosphorylation of p65NF-κB and IκBα along with down-regulation of IL-1β/TNF-α/KC/MIP-2/GCSF genes. Furthermore, GA offered protection against ET-induced airspace enlargement and ameliorated MMP-2/MMP-9. Finally, GA suppressed the CS-induced influx of neutrophils and macrophages and blunted gene expression of TNF-α/MIP-2/KC.
Overall, our data show that GA effectively modulates pulmonary inflammation and emphysema associated with COPD pathogenesis in mice.
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。本工作的目的是利用弹性蛋白酶（ET）和香烟烟雾（CS）诱导的小鼠模型研究 GA 对 COPD 相关肺炎症/肺气肿的有益作用。
雄性 BALB/c 小鼠用 ET（1U/只）处理或暴露于 CS（每天 9 支，持续 4 天）。GA 给药在 ET/CS 暴露前 7 天（每天）开始。分析支气管肺泡灌洗液中的炎症细胞和促炎细胞因子。评估肺匀浆中的 MPO 活性/GSH/MDA/蛋白质羰基。此外，对肺组织进行半定量 RT-PCR、免疫印迹和组织学分析。
GA 抑制了 ET 诱导的中性粒细胞浸润，在 24 小时内升高了 MPO 活性和促炎细胞因子（IL-6/TNF-α/IL-1β）的产生。减少炎症伴随着 ROS/GSH/MDA/蛋白质羰基水平的氧化还原平衡正常化。此外，GA 抑制了 p65NF-κB 和 IκBα的磷酸化以及 IL-1β/TNF-α/KC/MIP-2/GCSF 基因的下调。此外，GA 对 ET 诱导的气腔扩大提供了保护，并改善了 MMP-2/MMP-9。最后，GA 抑制了 CS 诱导的中性粒细胞和巨噬细胞流入，并减弱了 TNF-α/MIP-2/KC 的基因表达。
总的来说，我们的数据表明，GA 可有效调节与 COPD 发病机制相关的小鼠肺部炎症和肺气肿。
