Tanshinone IIA protects against lipopolysaccharide-induced lung injury through targeting Sirt1

OBJECTIVES: This study was designed to investigate the effects and the mechanism of Tanshinone IIA (TIIA) on endotoxic shock-induced lung injury in a mouse model. METHODS: Mice were administered intraperitoneally with TIIA (10 mg/kg) 0.5 h before lipopolysaccharide (LPS) challenge and then received additional injections every 24 h during the 3-day experimental period. The physiological indexes, the survival rate and the parameters for lung injury were examined. The protein levels of Sirt1, and the acetylation and activation of NF-κB p65 were determined. The expression and secretion of pro-inflammatory factors were evaluated, respectively. KEY FINDINGS: Treatment with TIIA significantly improved physiological indexes and increased the survival rate of mice in response to LPS challenge. TIIA treatment displayed an obvious up-regulation of Sirt1 protein, in accompany with reduced acetylation and activation of NF-κB p65 following LPS stimulation. In addition, TIIA attenuated LPS-induced lung injury and prevented the expression and secretion of pro-inflammatory factors. However, the protective effects of TIIA were abolished by Sirt1 inhibitor. CONCLUSIONS: Tanshinone IIA prevents LPS-induced secretion of pro-inflammatory cytokines thus exerts protective effects against acute lung injury, probably via modulation of Sirt1/NF-κB signalling pathway.