Isoacteoside Protects Against Sepsis-Induced Acute Lung Injury by Regulating the SIRT1/Nrf2/NF-κB/NLRP3 Signaling Pathways

Sepsis-related acute lung injury is a severe inflammatory pulmonary disorder. Isoacteoside is a phenylethanoid derived from Monochasma savatieri Franch. ex Maxim., Orobanchaceae, and possesses anti-oxidative and anti-inflammatory properties. This study aims to investigate the protective effects of isoacteoside against septic acute lung injury. A mouse model of acute lung injury was established using lipopolysaccharide-treated mice. Histological analysis of lung tissues was conducted by hematoxylin and eosin staining. Enzyme-linked immunosorbent assay was performed to detect the concentrations of proinflammatory cytokines. The levels of antioxidants and lipid peroxidative parameters were evaluated. Results showed that isoacteoside ameliorated lipopolysaccharide-induced lung injury and pulmonary edema of mice. Moreover, isoacteoside impeded lipopolysaccharide-evoked inflammatory cell infiltration into the lung. Isoacteoside attenuated lipid peroxidative markers and enhanced endogenous antioxidants in lung tissues. Isoacteoside also upregulated tight junction expression in lipopolysaccharide-treated lung tissues. Mechanistically, isoacteoside activated the sirtuins 1/nuclear factor erythroid 2 related factor 2 antioxidant signaling and inhibited the activation of nuclear factor-κB/nucleotide-binding oligomeric domain-like receptor protein 3 pathway and the release of proinflammatory cytokines. Additionally, these protective effects of isoacteoside against acute lung injury were reversed by sirtuins 1 inhibitor. Graphical abstract: [Figure not available: see fulltext.]