Gallic acid ameliorates COPD-associated exacerbation in mice

Area of Science:

• Pulmonary Medicine
• Pharmacology
• Toxicology

Background:

• Chronic Obstructive Pulmonary Disease (COPD) involves lung inflammation, often worsened by microbial infections.
• Gallic acid (GA), a natural phenolic compound, exhibits known antioxidant and anti-inflammatory properties.
• Previous studies indicated GA protects against elastase-induced lung inflammation and emphysema.

Purpose of the Study:

• To investigate the protective effects of Gallic acid against COPD exacerbation-like conditions induced by elastase (ET) and lipopolysaccharide (LPS) in a mouse model.
• To elucidate the mechanisms underlying Gallic acid's beneficial effects on lung inflammation and redox balance.

Main Methods:

• A mouse model of COPD exacerbation was established using sequential instillation of elastase (ET) and lipopolysaccharide (LPS).
• Mice were treated daily with Gallic acid (200 mg/Kg body weight) starting before ET instillation.
• Evaluated inflammatory cell infiltration (neutrophils), pro-inflammatory cytokine levels (TNF-α, IL-1β, IL-6), myeloperoxidase activity, redox status, and key signaling pathway components (p65-NF-κB, Nrf2, HO-1, Prdx-1).

Main Results:

• ET+LPS instillation significantly increased inflammatory cell infiltration and pro-inflammatory cytokine levels in the lungs.
• Gallic acid administration significantly reduced neutrophil infiltration, myeloperoxidase activity, and pro-inflammatory cytokine production.
• GA treatment restored lung redox balance, reduced p65-NF-κB phosphorylation, and downregulated IL-1β and TNF-α gene expression.
• GA treatment increased Nrf2 protein levels and its downstream target genes HO-1 and Prdx-1.

Conclusions:

• Gallic acid effectively mitigates COPD exacerbation-like manifestations in a mouse model.
• GA's protective effects are mediated by suppressing inflammatory responses and restoring redox balance in the lungs.
• GA modulates key signaling pathways, including NF-κB and Nrf2, highlighting its therapeutic potential for COPD exacerbations.