Black ginseng protects against Western diet‐induced nonalcoholic steatohepatitis by modulating the TLR4/NF‐κB signaling pathway in mice

Black ginseng (BG) shows beneficial effects on liver injury, but the related mechanism has not been fully revealed. This study attempted to investigate the protective effects and associated mechanisms of BG against nonalcoholic steatohepatitis (NASH). Twelve ginsenosides in BG were annotated by ultrahigh performance liquid chromatography combined with high resolution mass spectrometry (UHPLC-HRMS). The Western diet (WD) together with the low-dose CCl4 was given to mice to create the NASH model. Histopathological examination and liver/serum biochemical analysis revealed that the NASH mice displayed severe steatosis and liver damage compared with control mice. After BG administration, the serum and liver triglycerides (TG) concentrations and the serum level of low-density lipoprotein (LDL) were dramatically reduced. Besides, the BG treatment greatly decreased the serum values of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), and the hepatic expression of fibrotic-related genes, such as alpha-smooth muscle actin (α-SMA) and collagen type I alpha 1 (Col1α1). We further discovered that BG administration could block the protein expression of toll-like receptor 4 (TLR4) and the phosphorylation of nuclear factor-kappa B p65 (NF-κB p65), indicating that BG exerted a liver protective effect via regulating the TLR4/NF-κB pathway. This study demonstrated the therapeutic efficacy and the associated mechanism of BG in the treatment of NASH, giving evidence for BG as a potential functional food to prevent NASH. PRACTICAL APPLICATIONS: BG is a type of processed ginseng product that has been used as diet supplementation and has shown favorable effects on liver injury. However, the pharmacological impact of BG on NASH has not been studied in depth. The present study showed that BG could effectively reduce WD-induced liver fibrosis and inflammation through the TLR4/NF-κB axis, which indicated that BG has the potential to be utilized as a functional herb to attenuate liver injury.