Glycyrrhizin mitigates acute lung injury by inhibiting the NLRP3 inflammasome in vitro and in vivo

Glycyrrhiza glabra L. is a widely used traditional Chinese medicine with antipyretic, detoxification, antibacterial and therapeutic effects against various diseases, including liver diseases. Glycyrrhizin (GL), the most significant active ingredient of Glycyrrhiza glabra L., exerts anti-inflammatory activity. However, the anti-inflammatory effect of GL remains to be determined.Consequently, this research was carried out to discover the effects and mechanism of action of GL on ALI.Cell experiments established an in vitro model of LPS-induced RAW 264.7 macrophages to verify the mechanism. The levels of NO, PEG2, and inflammatory cytokines were estimated by ELISA. The expression levels of proteins related to the NF-κB signalling pathway and NLRP3 inflammasome were determined by Western blotting. The nuclear translocation of NF-κB p65 and ASC was tested through immunofluorescence analysis. The inhibitory effect of NLRP3 inhibitor MCC950 on macrophage was evaluated. Male BALB/C mice were selected to establish the ALI model. The experiment was randomly divided into five groups: control, ALI, GLL, GLH, and DEX. Pathological alterations were explored by H&E staining. The weight ratios of lung W/D, MPO, and inflammatory cytokines were evaluated by ELISA. The expression levels of proteins related to the NF-κB signalling pathway or NLRP3 inflammasome were analysed by Western blotting.Here, we demonstrate that GL attenuates inflammation, nitric oxide, IL-18, IL-1β, TNF-α, IL-6, and PGE2 levels and alveolar epithelial barrier permeability in macrophages and mice challenged with LPS. In addition, GL inhibits NLRP3 inflammasome initiation and activation and NF-κB signalling pathway activation.This research demonstrates that GL may alleviate ALI inflammation by interfering with the NF-κB/NLRP3 inflammasome signalling pathway.