Decursinol angelate attenuates lipopolysaccharide- induced acute lung injury by regulating AKT/NF-ΚB pathway

Purpose: To investigate the effect of decursinol angelate in acute lung injury induced by lipopolysaccharide treatment.Methods: Human bronchial epithelial cells (BEAS-2B cells) and human pulmonary artery endothelial cells (HPAECs) were exposed to lipopolysaccharide to induce cell injury and then treated with 20, 40, or 60 mu M decursinol angelate. Cell viability was quantified using a cell counting assay, while cell apoptosis was evaluated by western blot and flow cytometry. Colorimetric and enzyme-linked immunosorbent assay (ELISA) was used to measure oxidative stress. Expressions of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta, and interleukin-6 were evaluated using quantitative real-time-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Phosphorylation levels of p65, I Kappa B alpha, AKT, and phosphatidylinositol 3-kinase were assessed by western blot, while the entry of p65 into the nucleus was investigated by indirect immunofluorescence assay. Results: Treatment with 40 or 60 mu M decursinol angelate increased cell viability after lipopolysaccharide-induced damage. B-cell lymphoma 2 (Bcl2) and Bax expression were regulated, and the rate of apoptosis was inhibited. The concentration of superoxide dismutase and glutathione was elevated, and the density of malondialdehyde and myeloperoxidase decreased significantly. Inflammation was also suppressed by decursinol angelate by regulating TNF-alpha, interleukin-1 beta, and interleukin-6 expressions. Furthermore, decursinol angelate significantly decreased the phosphorylation of p65, I Kappa B alpha, AKT, and phosphatidylinositol 3-kinase. Finally, decursinol angelate inhibited p65 entry into the cell nucleus.Conclusion: Decursinol angelate alleviates cell damage and apoptosis, reduces oxidative stress, and attenuates inflammation after lipopolysaccharide-induced acute lung injury by inhibiting AKT/NF-Kappa B signaling pathway. Thus, decursinol angelate is a potential candidate for the treatment of lung injury.