Allylpyrocatechol ameliorates sepsis-induced lung injury via SIRT1-mediated suppression of p65 and nucleocytoplasmic translocation of HMGB1

Sepsis is a deadly clinical condition. Allylpyrocatechol is bioactive flavonoid that has shown promising anti-inflammatory and antioxidant activity. The effects of allylpyrocatechol on sepsis-induced lung injury have not been fully established. This study investigated the effects of allylpyrocatechol in a mouse model of sepsis-induced lung injury. RAW264.7 macrophages were used for in vitro studies. A mouse model of sepsis was established by cecal ligation and puncture (CLP). The PaO2/FiO2 ratio was measured in conjunction with lung tissue histology, and edema was determined by the wet:dry tissue ratio. ELISA was performed to analyze levels of IL-6, TNF-α, NOx, and HMGB1. Malondialdehyde (MDA) levels were measured to determine lipid peroxidation status. Protein expression was investigated via Western blotting analyses. Molecular docking studies were done to study the affinity of SIRT1 with Allylpyrocatechol. It was observed that Allylpyrocatechol inhibited the production of HMGB1 and suppressed pro-inflammatory responses in macrophages treated with bacterial lipopolysaccharide (LPS) in vitro, and in CLP sepsis mice in vivo. Moreover, it ameliorated the reduction of SIRT1 levels in both LPS-treated macrophages and CLP mice, alleviated sepsis-induced lung edema, reduced lipid peroxidation, improved lung tissue histology findings, reduced mortality, and improved the PaO2/FiO2 ratio in CLP mice. Allylpyrocatechol caused significant reductions in serum levels of IL-6, nitric oxide, TNF-α, and HMGB1, as well as nuclear translocation of inducible nitric oxide synthase, SIRT1, and HMGB1 in lungs of CLP mice. Molecular docking analysis suggested affinity of SIRT1 with Allylpyrocatechol. The findings suggest that Allylpyrocatechol protects mice against lung injury via SIRT1-mediated suppression of HMGB1 nuclear translocation and p-p65 activation.