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

• Published in: Inflammation Vol. 45; no. 4; pp. 1534 - 1547
• Main Authors: Antunes, Géssica Luana, Matzenbacher, Lucas Strassburger, Costa, Bruna Pasqualotto, de Sousa Basso, Bruno, Levorse, Vitor Giancarlo Schneider, Antunes, Krist Helen, Costa-Ferro, Zaquer Suzana Munhoz, de Oliveira, Jarbas Rodrigues
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-08-2022; Springer Nature B.V
• Subjects: Acute Lung Injury - chemically induced; Acute Lung Injury - drug therapy; Acute Lung Injury - prevention & control; Animals; Anti-inflammatory agents; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Biomedical and Life Sciences; Biomedicine; Disease Models, Animal; Extracellular Traps - metabolism; Gene expression; Immunology; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - prevention & control; Inflammatory diseases; Interleukin 10; Interleukin 6; Interleukin-6 - metabolism; Internal Medicine; Leukocytes (neutrophilic); Lipopolysaccharides; Lipopolysaccharides - pharmacology; Lung - metabolism; Lungs; Macrophages; Mice; Mice, Inbred C57BL; Morbidity; NF-κB protein; Original Article; Pathology; Pharmacology/Toxicology; Phenolic compounds; Pneumonia - metabolism; Reactive oxygen species; Rheumatology; Signal transduction; Tumor necrosis factor-α; methoxyeugenol; inflammation; acute lung injury; neutrophil extracellular trap
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-022-01639-8

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.