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‑κB 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, IκB kinase‑α (IKK‑α) and IκBα. 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.