3, 4-dihydroxybenzalacetone attenuates lipopolysaccharide-induced inflammation in acute lung injury via down-regulation of MMP-2 and MMP-9 activities through suppressing ROS-mediated MAPK and PI3K/AKT signaling pathways

Abstract

3, 4-Dihydroxybenzalacetone (DBL) is a constituent of Phellinus linteus. This study demonstrated the protective effect of DBL on lipopolysaccharide (LPS)–induced acute lung injuries in mice.Pretreatment with DBL significantly improved LPS–induced histological alterations in lung tissues. In addition, DBL markedly reduced the total cell number, the leukocytes, the protein concentrations, and decreased the release of nitrite, tumor necrosis factor (TNF)–α, interleukin (IL)–1β, IL–6 and the activities of matrix metalloproteinase (MMP)–2 and –9 in the bronchoalveolar lavage fluid. DBL also inhibited the W/D ratio and myeloperoxidase activity in the lung tissues. Western blot analysis indicated DBL efficiently blocked the protein expressions of inducible nitric oxide synthase, cyclooxygenase–2, MMP–2, MMP–9, and the phosphorylation of mitogen–activated protein kinase (MAPK), phosphoinositide–3–kinase (PI3K), AKT, Toll–like receptor 4 (TLR4) and nuclear factor (NF)–κB. Moreover, DBL enhanced the expression of anti–oxidant proteins, such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx). Based on our results, DBL might be a potential target for attenuating tissue oxidative injuries and nonspecific pulmonary inflammation.