Purpurogallin通过抑制AKT/mTOR/STAT3信号通路改善脓毒症凝血功能障碍和肝损伤

Abstract

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. In sepsis, activation of the coagulation cascade can lead to disseminated intravascular coagulation (DIC) and increase patient mortality. Purpurogallin (PPG) is a natural phenolic compound that has not been investigated for its role in sepsis-induced coagulopathy. The aim of this study was to explore the potential relationship between PPG and coagulation dysfunction during sepsis. Lipopolysaccharide (LPS)-induced septic mice and RAW264.7 cells were treated with PPG. In vivo, PPG markedly improved survival in septic mice, improved plasma coagulation parameters, reduced hepatic microthrombosis, and increased hepatic blood flow. PPG alleviated liver pathological injury and fibrin deposition. In vitro, PPG attenuated the coagulation and inflammatory indicators of RAW264.7 cells. Mechanistically, PPG suppressed phosphorylation of AKT, mTOR and STAT3. In summary, PPG improves survival, ameliorates coagulation abnormalities and hepatic injury in septic mice by inhibiting the activation of AKT/mTOR/STAT3 signaling pathway.