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.
Modern pharmacological studies and clinical practices have demonstrated that free radicals produced by normal organ activities will cause chain reactions after exceeding a certain amount in the body, and a series of biological reactions will eventually lead to the occurrence of a variety of diseases, such as cancer, atherosclerosis, hypertension, cataracts, arthritis, and rheumatoid arthritis (Moreno-Ortega et al., 2020;Raja et al., 2020;Wu et al., 2020). Therefore, antioxidant research has become the forefront of medical research and a hot spot for disease prevention and treatment.
This study aimed to investigate the therapeutic effect of black ginseng (BG) on non-alcoholic fatty liver disease (NAFLD) using network pharmacology combined with the molecular docking strategy. The saponin composition of BG was analyzed by liquid chromatography-mass spectrometry (LC/MS) instrument. Then the network pharmacology was applied to explore the potential targets and related mechanisms of BG in the treatment of NAFLD. After screening out key targets, molecular docking was used to predict the binding modes between ginsenoside and target. Finally, a methionine and choline deficiency (MCD) diet-induced NAFLD mice model was established to further confirm the therapeutic effect of BG on NAFLD. Twenty-four ginsenosides were annotated based on the MS and tandem MS information. Ten proteins were screened out as key targets closely related to BG treatment of NAFLD. The molecular docking showed that most of the ginsenosides had good binding affinities with AKT1. The validation experiment revealed that BG administration could reduce serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and improve the MCD diet-induced histological changes in liver tissue. Moreover, BG could upregulate the phosphorylation level of AKT in the liver of NAFLD mice, thereby exerting the therapeutic effect on NAFLD. Further studies on the active ginsenosides as well as their synergistic action on NAFLD will be required to reveal the underlying mechanisms in-depth. This study demonstrates that network pharmacological prediction in conjunction with molecular docking is a viable technique for screening the active chemicals and related targets of BG, which can be applied to other herbal medicines.
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