Glycyrrhiza Uralensis Polysaccharides Inhibits the cGAS-STING Signaling Pathway and Ameliorates Cecum Ligation and Puncture-induced Sepsis ​

Abstract

Sepsis is a disease of multiple organ dysfunction caused by infection. It threatens human health and is one of the major human mortality problems. Recent researches have shown that cGAS-STING pathway is involved in the development and progression of sepsis. Here, we report that Glycyrrhiza Uralensis Polysaccharides (GUP), one of the major components of licorice, has a protective effect against cecal ligation and puncture (CLP) sepsis in mice. We found that GUP reduced pathological changes in CLP sepsis-inducing tissues and the expression of genes downstream (IFN-β and TNF-α) of cGAS-STING pathway. Moreover, GUP significantly reduced the expression of IFN-β, IL-6 and TNF-α mediated by a mouse-specific activators of STING (DMXAA) in mice. In vitro studies, GUP inhibited the activation of the cGAS-STING pathway as evidenced by inhibition of the expression of related downstream genes, such as IFN-β, IL-6, TNF-α and interferon-stimulated genes (CXCL10). Mechanistically, GUP inhibited the activation of cGAS-STING pathway by inhibiting the interaction of STING with TBK1 and TBK1 with IRF3. In conclusion, our studies suggest that GUP is an effective inhibitor of the cGAS-STING pathway, which may be a potential medicine for the treatment of inflammatory diseases mediated by the cGAS-STING pathway.