Background

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.

Objective

This study investigated the effects of allylpyrocatechol in a mouse model of sepsis-induced lung injury.

Results

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.

Conclusion

The findings suggest that Allylpyrocatechol protects mice against lung injury via SIRT1-mediated suppression of HMGB1 nuclear translocation and p-p65 activation.

中文翻译：

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烯丙基邻苯二酚通过SIRT1介导的p65抑制和HMGB1的核质易位改善脓毒症所致的肺损伤

背景

败血症是致命的临床疾病。烯丙基邻苯二酚是具有生物活性的黄酮类化合物，已显示出令人振奋的抗炎和抗氧化活性。烯丙基邻苯二酚对败血症诱导的肺损伤的作用尚未完全确立。

客观的

这项研究调查了丙烯基邻苯二酚在败血症诱导的肺损伤小鼠模型中的作用。

结果

RAW264.7巨噬细胞用于体外研究。通过盲肠结扎穿刺（CLP）建立脓毒症的小鼠模型。PaO ₂ / FiO ₂结合肺组织的组织学测量比率，通过湿组织：干组织的比率确定水肿。进行ELISA分析IL-6，TNF-α，NOx和HMGB1的水平。测量丙二醛（MDA）水平以确定脂质过氧化状态。通过蛋白质印迹分析研究蛋白质表达。进行了分子对接研究以研究SIRT1与烯丙基邻苯二酚的亲和力。观察到，在体外用细菌脂多糖（LPS）处理的巨噬细胞和在体内CLP败血症的小鼠中，烯丙基邻苯二酚可抑制HMGB1的产生并抑制促炎反应。此外，它改善了LPS处理的巨噬细胞和CLP小鼠中SIRT1水平的降低，减轻了败血症引起的肺水肿，减少了脂质过氧化，改善了肺组织的组织学发现，CLP小鼠中的₂ / FiO ₂比。烯丙基邻苯二酚会导致CLP小鼠肺中IL-6，一氧化氮，TNF-α和HMGB1的血清水平显着降低，以及诱导型一氧化氮合酶SIRT1和HMGB1的核易位。分子对接分析表明SIRT1与烯丙基邻苯二酚有亲和力。

结论

研究结果表明，烯丙基邻苯二酚通过SIRT1介导的HMGB1核易位抑制和p-p65激活来保护小鼠免受肺损伤。