Abstract
Inflammation plays a major role in the pathogenesis of acute lung injury (ALI), but the mechanism remains unclear. Current anti-inflammatory therapy has poor efficacy on ALI. The aim of this study was to investigate the protective mechanism of curcumin against ALI. In in vivo experiments, curcumin significantly alleviated lung inflammation, histopathological injury and MPO activity, serum concentrations of CCL7, IL-6 and TNF-α, and mortality in mice compared to the model group. RAW264.7 cells cultured in the presence of lipopolysaccharide and adenosine triphosphate showed significantly lower viability, higher pyroptotic percentage and inflammation, but supplement of curcumin increased the cell viability, reduced pyroptosis and inflammation. Additionally, the expressions of NF-κB and pyroptosis related proteins were notably increased, while Sirtuin 1 (SIRT1) was decreased in both in vivo and in vitro ALI models. The results suggested that curcumin remarkably inhibited the expression of NF-κB and pyroptosis related proteins and increased the expression of SIRT1. However, EX527, a SIRT1 inhibitor, blocked the protective effect of curcumin against ALI. In conclusion, curcumin has protective effect against ALI. It may inhibit inflammatory process by inhibiting the activation of NLRP3 inflammasome-dependent pyroptosis through the up-regulation of SIRT1.
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