Abstract
Objective and design
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.
Materials
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.
Results
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.
Conclusion
Overall, our data show that GA effectively modulates pulmonary inflammation and emphysema associated with COPD pathogenesis in mice.
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Acknowledgement
The present work was supported by funds from Department of Biotechnology, Government of India (BT/PR17968/MED/122/33/2016 and BT/RLF/Re-entry/36/2012), DST-PURSE and UGC-SAP to ASN. We also acknowledge the Senior Research Fellowship to ES from ICMR, New Delhi, India.
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Singla, E., Dharwal, V. & Naura, A.S. Gallic acid protects against the COPD-linked lung inflammation and emphysema in mice. Inflamm. Res. 69, 423–434 (2020). https://doi.org/10.1007/s00011-020-01333-1
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DOI: https://doi.org/10.1007/s00011-020-01333-1