Shaoyao Gancao decoction promotes splenic immune homeostasis mediating cGAS-STING signaling pathway to delay autoimmune hepatitis progression

Abstract

Ethnopharmacological relevance

Shaoyao Gancao Decoction (SGD), a classic Chinese herbal formula from the “Treatise on Cold Damage (Shang Han Lun),” is widely used for treating liver disease. However, the efficacy and mechanisms by which SGD delays liver fibrosis progression in autoimmune hepatitis (AIH) require further investigation.

Aim of the study: This study aimed to investigate the mechanisms underlying the SGD-mediated delay of liver fibrosis progression in AIH through the spleen.

Materials and methods

SGD was administered via gavage to mice for 15 days before establishing the concanavalin A (ConA)-induced AIH model. The key factors were identified using bioinformatics analysis. The intervention effects and mechanisms of SGD on AIH were clarified using liver function assay, enzyme-linked immunosorbent assay (ELISA), and histopathological, real-time quantitative PCR (RT-qPCR), immunofluorescence (IF), and Western blot analyses. Hepatic stellate cells (HSCs) were co-cultured with splenic mononuclear cells in a Transwell chamber system.

Results

SGD pretreatment alleviated liver injury, spleen injury, and abnormal liver function in AIH mice. Interleukin-1β (IL-1β) and IL-12 were identified as key factors in SGD intervention of AIH. SGD pretreatment promoted immune homeostasis in the spleen and liver. Additionally, SGD reduced HSC proliferation and activation. Further, SGD decreased cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), nuclear factor kappa-B (NF-κB), and transforming growth factor-β1 (TGF-β1) expression in the liver and HSCs.

Conclusions

SGD promoted splenic immune homeostasis, which inhibited the hepatic cGAS-STING signaling pathway, thereby attenuating HSC activation and ultimately delaying liver fibrosis progression in AIH.