Lycorine destabilizes lipid rafts to inhibit inflammation via LXRα signal in the lung of mice

Abstract

Background and Purpose: Lycorine is an alkaloid that was in the bulb of the genus Lycoris. It has properties of anti-inflammatory. This study aimed to investigate the molecular mechanism by which lycorine can reduce acute lung injury (ALI). Experimental Approach: ALI model was established by intranasal injection of lipopolysaccharide (LPS). In vitro, A549 cells were treated with LPS and pretreated with lycorine for 1 hour. Key Results: The results showed that lycorine reduced histopathological changes in lung, myeloperoxidase (MPO) activity, and the production of inflammatory cytokines such as TNF-α, IL-1β, and IL-6 in mice. Lycorine dose-dependently inhibited the production of TNF-α, IL-1β, and IL-6. It also inhibited the transmission of TLR4/NF-κB passway in LPS-stimulated A549 cells. Lycorine increased cholesterol efflux through the activated LXRα-ABCA1/ABCG pathway. Lycorine has a good binding ability with LXRα. After adding the LXRα inhibitor, the anti-inflammatory effect of lycorine was eliminated. Conclusion and Implications: Lycorine can reduce ALI that was induced by lipopolysaccharide. The anti-inflammatory mechanism of lycorine is related to the up-regulation of the LXRα-ABCA1/ABCG pathway, which inhibits TLR4-mediated inflammation by increasing cholesterol efflux and reducing TLR4 transport to lipid rafts.