Attenuation of Neutrophil Extracellular Trap Formation in Lipopolysaccharide-Induced Acute Lung Injury Associated with Cinnamaldehyde.

Abstract

Background: Excessive neutrophil activation and neutrophil extracellular trap (NET) formation play critical roles in the pathogenesis of acute lung injury (ALI). Cinnamaldehyde, a major bioactive component of cinnamon, has been reported to exert anti-inflammatory effects; however, its impact on NET formation in ALI remains unclear.

Methods: A lipopolysaccharide (LPS)-induced ALI rat model and a PMA-stimulated primary neutrophil model were employed to evaluate the effects of cinnamaldehyde in vivo and in vitro. Lung injury severity, pulmonary edema, inflammatory cell infiltration, cytokine production, and NET-associated markers were assessed using histopathology, wet-to-dry ratio analysis, BALF examination, immunofluorescence staining, and Western blotting.

Results: Cinnamaldehyde significantly alleviated LPS-induced lung injury, as evidenced by reduced lung wet-to-dry ratios and improved histopathological scores compared with the LPS group (p < .001). Treatment with cinnamaldehyde markedly decreased inflammatory cell and neutrophil infiltration in BALF and suppressed TNF-α, IL-6, and MCP-1 levels (p < .05-0.001). Furthermore, cinnamaldehyde significantly inhibited NET formation in lung tissues, as indicated by reduced levels of myeloperoxidase, cell-free DNA, citrullinated histone H3, and neutrophil elastase (p < .001). In vitro, cinnamaldehyde directly suppressed PMA-induced NET release from primary neutrophils without affecting cell viability (p < .001).

Conclusion: These findings demonstrate that cinnamaldehyde protects against LPS-induced acute lung injury by suppressing excessive NET formation, highlighting NET inhibition as a key mechanism underlying its pulmonary protective effects.