Linarin prevents LPS-induced acute lung injury by suppressing oxidative stress and inflammation via inhibition of TXNIP/NLRP3 and NF-κB 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, anti-inflammatory and apoptotic-regulating 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). LR-pretreatment attenuated LPS-induced ALI and platelet activation and reduced CD41 expression levels and neutrophil platelet aggregates. Additionally, LPS-triggered pulmonary myeloperoxidase activity and neutrophil infiltration in lung tissues, and this was eliminated by LR dose-dependently. Furthermore, LPS-induced oxidative stress and pro-inflammatory cytokine release were downregulated by LR by inhibiting thioredoxin-interacting protein and nuclear factor-kappa B signaling pathways, including their downstream and upstream signals, such as xanthine oxidase, NLR family WHAT, pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), caspase-1, I kappa B kinase-alpha (IKK-alpha) and IB. Moreover, in LPS-induced mice, the mitogen-activated protein kinase pathway was inactivated by LR. In vitro, LR reduced LPS-induced inflammation and oxidative stress, which was linked to reduction of ROS. In conclusion, LR pretreatment may be protective against LPS-induced ALI.