Piperlongumin Improves Survival in the Mouse Model of Sepsis: Effect on Coagulation Factors and Lung Inflammation

Abstract

Excessive inflammation and coagulation contribute to high morbidity and mortality in sepsis. Many studies have indicated the role of piperlongumine (PL) in anti-inflammation, but its effect on coagulation remains uncertain. Here, we explore whether PL could moderate coagulation indicators and alleviate lung inflammation during sepsis. RAW264.7 cells were induced by lipopolysaccharide (LPS) and treated with PL. Inflammatory and coagulation indicators, cell function and signaling, were evaluated in cells. Cecal ligation and puncture (CLP) mice were treated with PL by gavage. The harvested lungs and plasma were used to assess inflammation and coagulation indicators. As a result, PL increased the survival rate and reduced the concentrations of tissue factor (TF), plasminogen activator inhibitor 1 (PAI-1), thrombin-antithrombin complex (TAT), D-dimer, interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α in CLP mice, with fibrinogen in reverse. Moreover, the PL alleviated inflammation, fibrin deposition, and lung injury in the lungs of CLP mice. In vitro, PL downregulated the expression of TF, PAI-1, IL-6, TNF-α, and IL-1β in RAW264.7 cells induced by LPS. Furthermore, PL inhibited the phosphorylation of the AKT/mTOR signaling pathway's key proteins and suppressed the nuclear translocation of p-STAT3 in LPS-stimulated RAW264.7 cells. In conclusion, this study suggests that PL may modulate coagulation indicators and improve lung inflammation through AKT/mTOR signaling pathway in sepsis.

Keywords: AKT/mTOR.; coagulation indicators; lung inflammation; piperlongumine; sepsis.