Linarin prevents LPS­induced acute lung injury by suppressing oxidative stress and inflammation via inhibition of TXNIP/NLRP3 and NF­κB pathways.

Acute lung injury (ALI) is an important cause of morbidity and mortality for critically ill patients, and linarin (LR) may be a potential treatment for ALI as it reportedly has antioxidant, anti­inflammatory and apoptotic­regulating activity. In the present study, the authors report that saline and LR (12.5, 25 and 50 mg/kg) were applied to male C57BL/6 mice via gavage. Then, mice were intratracheally injected with either saline or lipopolysaccharide (LPS). LR­pretreatment attenuated LPS­induced ALI and platelet activation and reduced CD41 expression levels and neutrophil platelet aggregates. Additionally, LPS­triggered pulmonary myeloperoxidase activity and neutrophil infiltration in lung tissues, and this was eliminated by LR dose­dependently. Furthermore, LPS­induced oxidative stress and pro­inflammatory cytokine release were downregulated by LR by inhibiting thioredoxin­interacting protein and nuclear factor­κB signaling pathways, including their downstream and upstream signals, such as xanthine oxidase, NLR family WHAT, pyrin domain­containing 3 (NLRP3), apoptosis­associated speck­like protein containing a C­terminal caspase recruitment domain (ASC), caspase­1, IκB kinase­α (IKK­α) and IκBα. Moreover, in LPS­induced mice, the mitogen­activated protein kinase pathway was inactivated by LR. In vitro, LR reduced LPS­induced inflammation and oxidative stress, which was linked to reduction of ROS. In conclusion, LR pretreatment may be protective against LPS­induced ALI.