Sophocarpine attenuates septic liver injury through suppression of the NLRP3 inflammasome via autophagy-mediated degradation.

Abstract

Septic liver injury remains a challenge in sepsis treatment. Nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 (NLRP3) inflammasome activation has been suggested to be a major cause of hepatocyte cell death in liver diseases. However, insufficient research has been performed to explore the underlying mechanisms associated with this. In the present study, sophocarpine, a pharmaceutical monomer originally isolated from Sophora flavescens, was suggested to attenuate septic liver injury in a mouse cecal ligation and puncture (CLP) model. By utilizing western blotting, ELISA, H&E staining and immunohistochemistry, the results demonstrated that sophocarpine treatment reversed CLP-induced elevations in serum aspartate transaminase, alanine transaminase, interleukin (IL)-6 and IL-1β levels. Additionally, sophocarpine appeared to have suppressed the activation of the NLRP3 inflammasome, as indicated by observed reductions in liver IL-1β, NLRP3, caspase 1-p20 and gasdermin D-p30 protein levels. Further investigation suggested that sophocarpine-induced autophagy was essential for this suppression of NLRP3 inflammasome activation, the inhibition of which reversed the protective effects of sophocarpine on CLP-induced liver injury. Collectively, results from the present study suggested a protective role for sophocarpine against septic liver injury, where sophocarpine may suppress NLRP3 inflammasome activation by autophagy-mediated degradation.