1. Academic Validation
  2. Piperlongumin Improves Survival in the Mouse Model of Sepsis: Effect on Coagulation Factors and Lung Inflammation

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

  • Inflammation. 2022 Jul 13;1-16. doi: 10.1007/s10753-022-01709-x.
Zhendong Fang 1 2 3 Xianwei Zhang 1 2 3 Yueyue Huang 1 2 3 Hongmin Zhou 1 2 3 Yilun Lu 1 2 3 Yuanyuan Sun 1 2 3 Fanrong Ye 1 2 3 Songzan Qian 1 2 3 Lingling Pan 1 2 3 Wenjing Chen 1 2 3 Hao Jiang 1 2 3 Jingye Pan 4 5 6 7
Affiliations

Affiliations

  • 1 Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 2 Key Laboratory of Intelligent Treatment and Life Support for Critical Diseases of Zhejiang Provincial, Wenzhou, China.
  • 3 Wenzhou Key Laboratory of Critical Care and Artificial Intelligence, Wenzhou, China.
  • 4 Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. wmupanjingye@126.com.
  • 5 Key Laboratory of Intelligent Treatment and Life Support for Critical Diseases of Zhejiang Provincial, Wenzhou, China. wmupanjingye@126.com.
  • 6 Wenzhou Key Laboratory of Critical Care and Artificial Intelligence, Wenzhou, China. wmupanjingye@126.com.
  • 7 The Project of Application Technology Collaborative Innovation Center of Wenzhou Institutions of Higher-Learning-Collaborative Innovation Center of Intelligence Medical Education, Wenzhou, China. wmupanjingye@126.com.
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.

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