Eucalyptol suppresses matrix metalloproteinase-9 expression through an extracellular signal-regulated kinase-dependent nuclear factor-kappa B pathway to exert anti-inflammatory effects in an acute lung inflammation model

Abstract

Objectives The acute lung injury (ALI) model is characterised by a severe acute inflammatory response in the lungs that represents the pathogenesis of acute respiratory distress syndrome (ARDS). In this study, we sought to elucidate the anti-inflammatory mechanism of eucalyptol in relation to tissue remodelling in acute lung inflammation. Methods BALB/C mice were intraperitoneally injected with eucalyptol (100, 200 or 400mg/kg) or dexamethasone (1mg/kg) 1h before intratracheal challenge with lipopolysaccharide (LPS; 1.5mg/kg) and sacrificed after 4h. The anti-inflammatory effects of eucalyptol were assessed by determining cell counts, measuring cytokine and nitric oxide production and performing Western blotting and histological analyses. Key findings Eucalyptol attenuated inflammation-associated increases in cell numbers, matrix metalloproteinase-9 (MMP-9) expression, production of cytokines (tumour necrosis factor-α and interleukin-6) and nitric oxide, and nuclear factor-kappa B (NF-κB) and phosphorylated extracellular signal-regulated kinase protein levels induced by LPS in bronchoalveolar lavage fluid from ALI mice. Furthermore, pretreatment with 400mg/kg eucalyptol prevented LPS-induced histopathological changes. Collectively, these results indicate that eucalyptol acts through a mechanism involving decreased MMP-9 expression and an extracellular signal-regulated kinase-dependent NF-κB pathway to exert anti-inflammatory actions in acute lung inflammation. Conclusions Thus, eucalyptol may be a potentially important agent in the treatment of pulmonary inflammation.