Embelin ameliorated sepsis-induced disseminated intravascular coagulation intensities by simultaneously suppressing inflammation and thrombosis

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  • Dong Wang, University of Chinese Academy of Sciences
  • ,
  • Yongshuai Yang, University of Chinese Academy of Sciences
  • ,
  • Yu Wang, Fujian Agriculture and Forestry University
  • ,
  • Valérie Proulle, Hôpitaux Universitaires Paris Sud
  • ,
  • Peter A. Andreasen
  • ,
  • Wanjin Hong, Agency for Science, Technology and Research
  • ,
  • Zhuo Chen, University of Chinese Academy of Sciences
  • ,
  • Mingdong Huang, Fuzhou University, University of Chinese Academy of Sciences
  • ,
  • Peng Xu, Fuzhou University, Agency for Science Technology and Research

Disseminated intravascular coagulation (DIC), an acute syndrome of systemic thrombus formation in microvasculatures throughout the body, can be induced by severe infections, e.g. sepsis. Anticoagulants are clinically used to alleviate the intensities of DIC. However, anticoagulants only reduce the thrombus formation but have negligible effects on the inflammatory conditions. We previously reported embelin, a natural product, as an inhibitor of plasminogen activator inhibitor-1 (PAI-1), suggesting the potent antithrombotic property. In this study, we used three thrombotic mice models to confirm the antithrombotic property of embelin. By combining the anti-inflammatory and the antithrombotic properties, we proposed embelin as a potent therapeutic agent for sepsis-induced DIC, which involves both inflammation and thrombosis. In a lipopolysaccharides-induced septic mice model, embelin not only significantly ameliorated the inflammation levels, but also effectively reduced the pulmonary hemorrhages and the micro-thrombi formations in lung. In contrast, low-molecular-weight-heparin, an anticoagulant, only moderately ameliorated the pulmonary hemorrhages and thrombotic obstructions, but had non-measurable effect on the inflammatory conditions. In addition, embelin alleviated the dysregulation of the global coagulation in septic mice, but did not affect the global coagulation in normal mice. Our current study demonstrates the antithrombotic property of embelin and the potency of the treatment or prevention of syndromes combining inflammation and thrombosis, e.g. sepsis-induced DIC.

OriginalsprogEngelsk
Artikelnummer110528
TidsskriftBiomedicine and Pharmacotherapy
Vol/bind130
Antal sider10
ISSN0753-3322
DOI
StatusUdgivet - okt. 2020

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