Digitoflavone (DG) attenuates LPS-induced acute lung injury through reducing oxidative stress and inflammatory response dependent on the suppression of TXNIP/NLRP3 and NF-κB

Acute lung injury is a severe disease with a high rate of mortality. Digitoflavone (DG) was suggested to possess bioactivities to reduce oxidative stress, inflammation and to regulate apoptosis. In our study, the normal saline, a low dose of DG (12.5 mg/kg), a medium dose of DG (25 mg/kg) and a high dose of DG (50 mg/kg) were administered to male C57BL/6 mice by gavage. And then, the mice were intratracheally injected with either normal saline or lipopolysaccharide (LPS). We found that DG ameliorated LPS-induced lung injury and platelets activation, accompanied with reduced CD41 expression and neutrophil platelet aggregates (NPAs). Further, pulmonary myeloperoxidase (MPO) activity and neutrophil infiltration in the lung tissues induced by LPS were abolished by DG dose-dependently. Additionally, LPS-triggered oxidative stress and secretion of pro-inflammatory cytokines were reduced by DG administration through suppressing thioredoxin-interacting protein (TXNIP) and nuclear factor-kappa B (NF kappa B) signaling pathways, and their down-streaming and up-streaming signals, including xanthine oxidase (XO), NLR family, pyrin domain-containing 3 (NLRP3), ASC, Caspase-1, as well as I kappa B kinase-alpha (IKK-alpha), and I kappa B alpha. Moreover, mitogen-activated protein kinases (MAPKs) pathway was also inactivated by DG in LPS-induced mice. The in vitro study further confirmed that DG ameliorated LPS-induced inflammation and oxidative stress, which was associated with reduction of ROS. In conclusion, our data suggested that DG treatment could be considered as a promising therapy for treating acute lung injury. (C) 2017 Published by Elsevier Masson SAS.