Licorice extract inhibits the cGAS-STING pathway and protects against non-alcoholic steatohepatitis

by Selleckchem | May 08 2023

Background: Inflammation and fibrosis are typical symptoms of non-alcoholic steatohepatitis (NASH), which is one of the most common chronic liver diseases. The cGAS-STING signaling pathway has been implicated in the progression of NASH, and targeting this pathway may represent a new therapeutic strategy. Licorice is a widely used herb with anti-inflammatory and liver-protective properties. In this study, we assessed the effect of licorice extract on the cGAS-STING pathway.

Methods: Bone marrow-derived macrophages (BMDMs) were treated with licorice extract and then stimulated with HT-DNA, 2'3'-cGAMP, or other agonists to activate the cGAS-STING pathway. Quantitative real-time PCR and western blot were conducted to analyze whether licorice extract could affect the cGAS-STING pathway. Methionine and choline-deficient diet (MCD) was used to induce NASH in mice, which were treated with licorice extract (500 mg/kg) by gavage and/or c-176 (15 mg/kg) by intraperitoneal injection every 2 days. After 6 weeks of treatment, histological analysis of liver tissue was performed, along with measurements of plasma biochemical parameters.

Results: Licorice extract inhibits cGAS-STING pathway activation. Mechanistically, it might function by inhibiting the oligomerization of STING. Treatment with licorice extract reduced inflammation and fibrosis in MCD diet-induced NASH mice models. Furthermore, we found that the therapeutic effect of combination treatment with licorice extract and C-176 (STING inhibitor) on the pathology and fibrosis of MCD diet-induced NASH models was similar to that of licorice extract or C-176 administered alone.

Conclusion: Licorice extract can inhibit the cGAS-STING pathway and improve hepatic inflammation and fibrosis in NASH mice models. It strongly suggests that licorice extract may be a candidate therapeutic for NASH.

Comments：

This study suggests that licorice extract has potential therapeutic effects on non-alcoholic steatohepatitis (NASH), a chronic liver disease characterized by inflammation and fibrosis. The study investigated the effect of licorice extract on the cGAS-STING signaling pathway, which is known to contribute to the progression of NASH. The researchers found that licorice extract can inhibit the activation of this pathway, possibly by inhibiting the oligomerization of STING.

The study also used a mouse model of NASH induced by a methionine and choline-deficient diet (MCD) to test the therapeutic effects of licorice extract on liver inflammation and fibrosis. The researchers found that treatment with licorice extract reduced inflammation and fibrosis in the liver tissue of the mice. Moreover, the study found that the combination treatment with licorice extract and C-176 (a STING inhibitor) had similar therapeutic effects to licorice extract or C-176 administered alone.

Overall, this study suggests that licorice extract may be a promising candidate therapeutic for NASH by inhibiting the cGAS-STING pathway and improving hepatic inflammation and fibrosis. However, further research is needed to confirm these findings and determine the optimal dosage and administration of licorice extract for treating NASH in humans.