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.