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Protective effects of Gallic acid against COPD linked inflammation and emphysema
Author(s) -
Singla Esha,
Naura Amarjit Singh
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.03890
Subject(s) - copd , gallic acid , myeloperoxidase , inflammation , oxidative stress , lung , elastase , medicine , proinflammatory cytokine , immunology , bronchoalveolar lavage , pharmacology , tumor necrosis factor alpha , chemistry , antioxidant , biochemistry , enzyme
Chronic Obstructive Pulmonary Disorder (COPD) is a chronic inflammatory disease, currently affecting around 328 million people worldwide. Gallic acid (GA), a naturally occurring phenolic compound is known to possess anti‐oxidant and anti‐inflammatory activities. The aim of the present work was to investigate the beneficial effects of Gallic acid against COPD linked inflammation and emphysema by utilizing Elastase (ET) and Cigarette smoke (CS) based mouse model(s) of the disease. 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 induction of injury with ET or CS exposure. Broncho‐alveolar lavage was analysed for inflammatory cells and pro‐inflammatory cytokines. Lung homogenate was assessed for oxidative stress related biochemical parameters. Further, lung tissue was subjected to semi‐quantitative RT‐PCR, Immunoblotting and histological analysis. Our data showed that GA treatment suppressed the ET induced recruitment of inflammatory cells particularly neutrophils as well as myeloperoxidase activity in lungs at 24 hrs post injury. Reduction in the inflammatory cells was associated with subdued production of pro‐inflammatory cytokines namely IL‐1β, TNF‐α and IL‐6. Additionally, GA normalized the ET induced redox imbalance in the lungs towards normal as reflected by levels of ROS, MDA, GSH and protein carbonyls. Further, GA treatment blunted the ET induced phosphorylation of p65NF‐kB and its inhibitor IκBα along with down‐regulation of mRNA expression of NF‐kB dependent pro‐inflammatory factors including IL‐1β, TNF‐α, MIP‐2, KC and GCSF. Moreover, GA suppressed the CS induced influx of neutrophils and macrophages along with blunted gene expression of pro‐inflammatory cytokines TNF‐α, MIP‐2 and KC. Finally, histological analysis of lungs at 21 days after elastase administration showed that the phytochemical blocks the development of emphysema by restoring the balance between matrix metallo‐proteinases and their inhibitor(s). Overall, our data shows that GA effectively modulates pulmonary inflammation and emphysema associated with COPD pathogenesis in mice and thus may offer a new/alternative treatment strategies in the area. Support or Funding Information Financial support from Department of Biotechnology, Government of India (BT/PR17968/MED/122/33/2016 and BT/RLF/Re‐entry/36/2012), UGC‐SAP and Senior Research Fellowship from Indian Council of Medical Research (ICMR), India