Linarin prevents LPS‑induced acute lung injury by suppressing oxidative stress and inflammation via inhibition of TXNIP/NLRP3 and NF‑κB pathways

Abstract

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.

Lycorine attenuates lipopolysaccharide-induced acute lung injury through the HMGB1/TLRs/NF-κB pathway

“…Consistent with the previous studies, the present study showed that LPS treatment resulted in the accumulation of oxidative stress and MDA in the lungs and cells, indicating that inflammatory response and oxidative stress play a crucial role in the induction of lung injury. It has been reported that drugs that inhibit inflammation and oxidation effectively attenuated lung damage, including astaxanthin, cordycepin, and linarin (Bi et al 2017 ; Han et al 2018 ; Lei et al 2018 ). Lycorine has been reported to be an effective inhibitor of tumor development and also had many other benefits, including reducing LPS-induced bone loss in mice and inhibiting intervertebral disc degeneration (Park et al 2019 ; Wang et al 2018 ).…”

Releasing Behavior of Lipopolysaccharide from Gelatin Modulates Inflammation, Cellular Senescence, and Bone Formation in Critical-Sized Bone Defects in Rat Calvaria

“…LPS is believed to enhance the generation of reactive oxygen species (ROS), including H 2 O 2 and O 2 − , resulting in oxidative stress [41,42]. Inflammation caused by the increased production of ROS [43,44] is likely to promote cellular senescence [13].…”

Separation of acteoside and linarin from Buddlejae Flos by high‐speed countercurrent chromatography and their anti‐inflammatory activities

“…Ateoside and LIN are essential to the known medicinal activities of Buddlejae Flos. A variety of pharmacological effects of AC [12‐16] and LIN [17‐24] have been reported, such as antioxidant, anti‐inflammatory, anti‐hepatotoxic, neuroprotection, anti‐acetylcholinesterase, and osteogenic. Lipopolysaccharide (LPS) is the main component of the Gram‐negative bacterial cell wall and it can induce inflammatory response [15].…”