Beta-naphthoflavone Regulates Inflammation and Coagulation of Sepsis by Raising Nrf2/Ho-1 and Involving AKT/NF-κB Signaling Pathways

Abstract BACKGROUND During sepsis, macrophages are activated by various irritants, such as Gram-negative bacteria LPS, which leads to the transcription of inflammatory and coagulation factors, including iNOS,COX-2,IL-1β,TNF-α and TF,PAI-1.Although inflammatory responses play a key role in the host's defense against infection, overactivation of innate immune cells can lead to severe sepsis. In the course of sepsis development, a variety of factors induce inflammatory response while activating coagulation function. Activation of the coagulation system is considered to be a host immune response against infection, however, overactivation of coagulation can cause harm to the host body, resulting in sepsis induced coagulopathy (SIC).METHODSIn this study, we aimed to evaluate the anti-inflammatory and anticoagulatory effects of BNF on sepsis by constructing in vivo (cecal ligation and puncture (CLP)-induced sepsis) and in vitro (LPS-induced mouse macrophage RAW264.7) sepsis models; the mechanisms behind these effects were also studied. Various aspects of sepsis, including inflammation, coagulation, and lung function, were monitored in the sepsis models.RESULTS Results indicated that the administration of BNF in sepsis mice caused reduced expression of pro-inflammatory factors, inhibited activation of coagulation, and lesser lung damage. The levels of LPS-induced macrophages, which lead to inflammation and coagulation, were also reduced. These effects are caused by participation in the Akt/NF-κB/Nrf2/HO-1 signaling pathway.CONCLUSIONThe results demonstrated that BNF treatment reduced the inflammatory response and coagulation dysfunction caused by sepsis in in vivo and in vitro models.Thus, BNF can be adopted as a novel therapeutic option to reduce sepsis mortality;However, further clinical studies are needed to confirm these effects on human sepsis.