Study on the mechanism of anti-hepatic fibrosis of Glycyrrhiza Uralensis-Salvia miltiorrhiza prescription based on serum and urine metabolomics and network pharmacology.

Hepatic fibrosis (HF) is a kind of chronic epidemic liver disease. Glycyrrhiza Uralensis and Salvia Miltiorrhiza (GUSM), traditional Chinese medicine, has the obvious clinical treatment of liver fibrosis. This study aimed to investigate the mechanisms of GUSM against HF by an integrated strategy combining untargeted metabolomics with network pharmacology. The results showed that GUSM prescription can improve the morphology and structure of liver tissue, inhibit the proliferation of collagen fibers and reducing the inflammatory response of the liver and so on. Endogenous metabolites and HF-related potential biomarkers in serum and urine were detected by ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS). The metabolic pathways were enriched by MetaboAnalyst. GUSM prescription showed an antifibrotic effect on rats by regulating metabolic pathways, mainly pentose and glucuronate interconversions and arachidonic acid metabolism. Network pharmacology was then applied to find 42 overlapping targets of GUSM-HF. Quercetin was found to be the main active component and STAT3 was the main active target in GUSM prescription. Molecular docking showed high affinities between quercetin and STAT3. Therefore, GUSM has protective effects on HF by regulating the metabolism and different signaling pathways. The work also shows that the metabolomic and network pharmacology methods are promising tools to gain insight into the efficacy and mechanism research of traditional Chinese medicines.