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

• Published in: International immunopharmacology 2017-09, Vol.50, p.77-86
• Main Authors: Chao, Wei, Deng, Jeng-Shyan, Huang, Shyh-Shyun, Li, Pei-Ying, Liang, Yu-Chia, Huang, Guan-Jhong
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Acute lung injury; Acute Lung Injury - drug therapy; Acute Lung Injury - immunology; AKT protein; Alveoli; Animal diseases; Animal tissues; Animals; Bronchus; Butanones - chemistry; Butanones - therapeutic use; Catalase; Cell number; Chemical compounds; Cyclooxygenase-2; Cytokines - metabolism; DBL; Down-Regulation; Extracellular Signal-Regulated MAP Kinases - metabolism; Gelatinase A; Gelatinase B; Glutathione; Glutathione peroxidase; Immune system; Inflammation Mediators - metabolism; Injuries; Interleukin 6; Leukocytes; Lipopolysaccharides; Lipopolysaccharides - immunology; Lung - drug effects; Lung - immunology; Lung - pathology; Lungs; Male; MAP kinase; MAPK; Matrix metalloproteinase; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Metalloproteinase; Mice; Mice, Inbred ICR; MMPs; Molecules; Nitric oxide; Nitric Oxide - metabolism; Peroxidase; Phellinus linteus; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; PI3K/AKT; Plant Extracts - chemistry; Plant Extracts - therapeutic use; Pneumonia - drug therapy; Pneumonia - immunology; Protein kinase; Proteins; Reactive Oxygen Species - metabolism; Rodents; Signal Transduction; Superoxide dismutase; Toll-like receptors; Tumor necrosis factor-TNF
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2017.06.014

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. •3, 4-dihydroxybenzalacetone (DBL) from Phellinus linteus attenuates the inflammatory effects of acute lung injury.•The mechanism was through DBL inhibiting TLR4, PI3K/AKT expressions, and then suppressing MAPKs and NFκB activation.•DBL inhibited activities of MMP-2 and MMP-9 in BALF and decreased these two protein expressions in lung tissues.•DBL decreased oxidative stress via upregulating anti-oxidative enzymes such as SOD, catalase, and GPx.