Methoxyeugenol Protects Against Lung Inflammation and Suppresses Neutrophil Extracellular Trap Formation in an LPS-Induced Acute Lung Injury Model.

ABSTRACT

Acute lung injury (ALI) is a life-threatening acute inflammatory disease with high rates of morbidity and mortality worldwide. 4-Allyl-2,6-dimethoxyphenol (methoxyeugenol), a phenylpropanoid from a synthetic source, exhibits strong anti-inflammatory activity, but its effects on the inflammation of ALI have not yet been reported. In our study, the anti-inflammatory effects of methoxyeugenol were investigated on RAW 264.7 cells and a mice model of ALI. Our results showed that methoxyeugenol (7.5 and 30 µM) attenuated the proliferation and gene expression of interleukin (IL)-6 in LPS-stimulated RAW 264.7 cells. In a mice model of ALI induced with LPS, methoxyeugenol exhibited a significant protective effect, based on influx reduction of macrophages and neutrophils into the lungs; reduction in release of the cytokines IL-6, TNF-α, and IL-10; and in reactive oxygen species (ROS) formation. We show that the anti-inflammatory effects of methoxyeugenol are associated with the suppression of the NFκB signaling pathway. Moreover, we demonstrated for the first time that a phenolic compound, from a synthetic source, protects against lung tissue inflammation and promotes a reduction of NET formation. These findings provided evidence for the use of methoxyeugenol as a new strategy to control inflammation in ALI disease.