Suppression of NLRP3 and NF-κB signaling pathways by α-Cyperone via activating SIRT1 contributes to attenuation of LPS-induced acute lung injury in mice

alpha-Cyperone is the volatile oil component in Cyperus rotundas L. The previous reports had shown the inhibition of alpha-Cyperone on NF-kappa B signaling in LPS-stimulated RAW264.7 cells. However, it is still unclear whether alpha-Cyperone could suppress inflammatory response in acute lung injury (ALI) induced by LPS. The aim of this study is to investigate the suppression of alpha-Cyperone on LPS-induced ALI in mice. In this study, we established the LPS-induced ALI model and compared different doses of alpha-Cyperone with the control group and LPS group. Accordingly, the following indexes would be compared, including lung wet/dry ratio, MPO activity, inflammatory cell number, histopathological changes, levels of inflammatory cytokines, NF-kappa B and NLRP3 signaling pathways activation. The results demonstrated that alpha-Cyperone had the effect on reducing the wet/dry ratio and MPO activity. Furthermore, the increase of inflammatory cells and inflammatory cytokines could be inhibited by alpha-Cyperone. Meanwhile, alpha-Cyperone could downregulate NF-kappa B and NLRP3 signaling pathways. Finally, we found alpha-Cyperone could up-regulate the expression of SIRT1 and SIRT1 inhibitor could reverse the protective effects of alpha-Cyperone on ALI. In conclusion, alpha-Cyperone showed the protective effect on LPS-induced ALI in mice by suppressing the NF-kappa B and NLRP3 signaling pathways, mainly via up-regulating SIRT1. This provides a potential drug for the treatment of LPS-induced ALI.