Aged garlic extract suppressed macrophage-mediated inflammation in acute respiratory distress syndrome

Abstract

Background: Acute respiratory distress syndrome (ARDS) is a severe lung disorder characterized by intense pulmonary inflammation. Although corticosteroids are the primary anti-inflammatory therapeutic option, increased susceptibility to infection remains a significant clinical concern. Aged garlic extract (AGE) is a natural agent demonstrating anti-inflammatory and antioxidant qualities, and a high safety profile. We investigated the combined effect of AGE and low-dose steroids as a therapeutic approach through AGE-induced anti-inflammatory effects. Methods: Differentiated M1 macrophages were established by stimulating THP-1 cells with lipopolysaccharide (LPS) and interferon-gamma. We assessed inflammatory cytokine release and related signaling to investigate the effects of AGE and/or low-dose dexamethasone (DEX). We also assessed nuclear factor-kappa B (NF-κB) pathway activation using immunoblotting. We evaluated the therapeutic efficacy of AGE by monitoring body weight, quantifying inflammatory cells in the bronchoalveolar lavage fluid (BALF), and histological scoring of lung injury in an ARDS mouse model by intratracheal LPS instillation. Results: AGE significantly inhibited cytokines like Interleukin (IL)-6 and Monocyte chemoattractant protein-1 and suppressed NF-κB phosphorylation. Combining AGE with DEX broadened and enhanced inhibition of inflammatory mediators compared to monotherapy, while further suppressing NF-κB expression. In an ARDS model, the combination of AGE and DEX significantly suppressed LPS-induced body weight loss, inflammatory cell infiltration in BALF, and lung injury. Conclusions: Co-administration of AGE and low-dose DEX effectively suppressed excessive pulmonary inflammation in ARDS. This suggests a novel therapeutic approach that could enhance anti-inflammatory function, simultaneously reducing the adverse outcomes associated with high-dose steroid monotherapy.