Suppression of MAPK and NF-κB Pathways by Limonene Contributes to Attenuation of Lipopolysaccharide-Induced Inflammatory Responses in Acute Lung Injury

Abstract-The present study aimed to investigate the protective role of limonene in lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS (0.5 mg/kg), and limonene (25, 50, and 75 mg/kg) was injected intraperitoneally 1 h prior to LPS administration. After 12 h, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. Limonene pretreatment at doses of 25, 50, and 75 mg/kg decreased LPS-induced evident lung histopathological changes, lung wet-to-dry weight ratio, and lung myeloperoxidase activity. In addition, pretreatment with limonene inhibited inflammatory cells and proinflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in BALF. Furthermore, we demonstrated that limonene blocked the phosphorylation of IκBα, nuclear factor-κB (NF-κB) p65, p38 mitogen-activated protein kinase (MAPK), c-Jun NH2-terminal kinase, and extracellular signalregulated kinase in LPS-induced ALI. The results presented here suggest that the protective mechanism of limonene may be attributed partly to decreased production of proinflammatory cytokines through the inhibition of NF-κB and MAPK activation. KEY WORDS: limonene; lipopolysaccharide (LPS); nuclear factor-κB (NF-κB); mitogen-activated protein kinase (MAPK)