Effects and underlying mechanisms of ginsenoside Rb1 in improving non-alcoholic steatohepatitis via modulation of the gut-liver axis

Abstract Objective To investigate the therapeutic effects of ginsenoside Rb1 on non-alcoholic steatohepatitis (NASH) and its mechanisms through modulating gut microbiota and repairing intestinal barriers in liver inflammation and metabolic disorders. Methods A model NASH mouse was established by high-fat, high-cholesterol diet (HFHCD) feeding. After modeling, the NASH mice were treated with Rb1 via intraperitoneal injection. An in vitro NASH model was induced with oleic acid+cholesterol in HepG2 cells. Serum biochemistry, histopathological observation (HE, Oil Red O, Masson, Sirius Red staining), and Western blotting (inflammatory and tight junction proteins) were performed. Gut microbiota was analyzed with 16S rRNA gene sequencing. The correlations between key microbiota and metabolic phenotypes were analyzed using Spearman correlation analysis and SHapley Additive exPlanations (SHAP) analysis. Results Rb1 significantly reduced serum levels of total cholesterol (TC), triglyceride (TG), alanine transaminase (ALT), aspartate aminotransferase (AST) and low-density lipid-cholesterol (LDL-C) in the NASH mice (P