Ruscogenin alleviates LPS-induced pulmonary endothelial cell apoptosis by suppressing TLR4 signaling.

Acute lung injury (ALI) or its most advanced form, acute respiratory distress syndrome (ARDS) is a severe inflammatory pulmonary process triggered by varieties of pathophysiological factors, among which apoptosis of pulmonary endothelial cells plays a critical role in the progression of ALI/ARDS. Ruscogenin (RUS) has been found to exert significant protective effect on ALI induced by lipopolysaccharides (LPS), but there is little information about its role in LPS-induced pulmonary endothelial cell apoptosis. The aim of the present study was to investigate the underlying mechanism in which RUS attenuates LPS-induced pulmonary endothelial cell apoptosis. Mice were challenged with LPS (5 mg/kg) by intratracheal instillation for 24 h to induce apoptosis of pulmonary endothelial cells in model group. RUS (three doses: 0.1, 0.3, and 1 mg/kg) was administrated orally 1 h prior to LPS challenge. The results showed that RUS could attenuate LPS-induced lung injury and pulmonary endothelial apoptosis significantly. And we observed that RUS inhibited the activation of TLR4/MYD88/NF-κB pathway in pulmonary endothelium after LPS treatment. In murine lung vascular endothelial cells (MLECs) we further confirmed that RUS (1 μmol/L) markedly ameliorated MLECs apoptosis by suppressing TLR4 signaling. By using TLR4 knockout mice we found that TLR4 was essential for the RUS-mediated eff ;ect on LPS-stimulated pulmonary endothelial apoptosis. Collectively, our results indicate that RUS plays a protective role against LPS-induced endothelial cell apoptosis via regulating TLR4 signaling, and may be a promising agent in the management of ALI.

Wu Y ，Wang Y ，Gong S ，Tang J ，Zhang J ，Li F ，Yu B ，Zhang Y ，Kou J ... -  《-》

Ruscogenin attenuates particulate matter-induced acute lung injury in mice via protecting pulmonary endothelial barrier and inhibiting TLR4 signaling pathway.

Wang YW ，Wu YH ，Zhang JZ ，Tang JH ，Fan RP ，Li F ，Yu BY ，Kou JP ，Zhang YY ... -  《-》

Ruscogenin attenuates sepsis-induced acute lung injury and pulmonary endothelial barrier dysfunction via TLR4/Src/p120-catenin/VE-cadherin signalling pathway.

Sepsis-associated acute lung injury (ALI) occurs with the highest morbidity and carries the highest mortality rates among the pathogenies of ALI. Ruscogenin (RUS) has been found to exhibit anti-inflammation property and rescue lipopolysaccharide-induced ALI, but little is known about its role in sepsis-triggered ALI. The aim of this study was to investigate the potential role of RUS in sepsis-induced ALI and the probable mechanism. Mice model of cecal ligation and puncture (CLP) was replicated, and three doses of RUS (0.01, 0.03 and 0.1 mg/kg) were administrated 1 h before CLP surgeries. RUS significantly extended the survival time and attenuated the lung pathological injury, oedema and vascular leakage in sepsis-induced ALI mice. RUS efficiently decreased the level of MPO in lung tissue and the WBC, NEU counts in BALF. In addition, RUS rescued the expression of VE-cadherin and p120-catenin and suppressed the TLR4/Src signalling in lung tissue. RUS attenuated sepsis-induced ALI via protecting pulmonary endothelial barrier and regulating TLR4/Src/p120-catenin/VE-cadherin signalling pathway.

Wang Y ，Xue L ，Wu Y ，Zhang J ，Dai Y ，Li F ，Kou J ，Zhang Y ... -  《-》

MicroRNA-27a alleviates LPS-induced acute lung injury in mice via inhibiting inflammation and apoptosis through modulating TLR4/MyD88/NF-κB pathway.

Ju M ，Liu B ，He H ，Gu Z ，Liu Y ，Su Y ，Zhu D ，Cang J ，Luo Z ... -  《-》

Ulinastatin Protects Against LPS-Induced Acute Lung Injury By Attenuating TLR4/NF-κB Pathway Activation and Reducing Inflammatory Mediators.

Cao C ，Yin C ，Shou S ，Wang J ，Yu L ，Li X ，Chai Y ... -  《-》