Published online Jun 7, 2020. doi: 10.3748/wjg.v26.i21.2810
Peer-review started: February 17, 2020
First decision: March 30, 2020
Revised: March 30, 2020
Accepted: April 27, 2020
Article in press: April 27, 2020
Published online: June 7, 2020
Liver fibrosis is a common health problem worldwide and there is still a lack of effective medicines. The Chinese herbal medicine, Gan Shen Fu Fang (GSFF) is composed of salvianolic acid B and diammonium glycyrrhizinate. In this study, we observed the effects of GSFF on liver fibrosis in vivo and in vitro in an attempt to provide some hope for the treatment.
To observe the effects of GSFF on liver fibrosis in vivo and in vitro and investigate the mechanism from the perspective of the inflammatory response and extracellular signal-regulated kinase (ERK) phosphorylation.
Common bile duct-ligated rats were used for in vivo experiments. Hepatic stellate cells-T6 (HSC-T6) cells were used for in vitro experiments. Hematoxylin and eosin staining and Masson staining, biochemical assays, hydroxyproline (Hyp) assays, enzyme-linked immunoasorbent assay and western blotting were performed to evaluate the degree of liver fibrosis, liver function, the inflammatory response and ERK phosphorylation. The CCK8 assay, immunofluorescence and western blotting were applied to test the effect of GSFF on HSC-T6 cell activation and determine whether GSFF had an effect on ERK phosphorylation in HSC-T6 cells.
GSFF improved liver function and inhibited liver fibrosis in common bile duct-ligated rats after 3 wk of treatment, as demonstrated by histological changes, hydroxyproline assays and collagen I concentrations. GSFF alleviated inflammatory cell infiltration and reduced the synthesis of pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interlukin-1β] and NF-κB. In addition, GSFF decreased ERK phosphorylation. In vitro, GSFF inhibited the viability of HSC-T6 cells with and without transforming growth factor β1 (TGF-β1) stimulation and decreased the synthesis of collagen I. GSFF had the greatest effect at a concentration of 0.5 μmol/L. GSFF inhibited the expression of α-smooth muscle actin (α-SMA), a marker of HSC activation, in HSC-T6 cells. Consistent with the in vivo results, GSFF also inhibited the phosphorylation of ERK and downregulated the expression of NF-κB.
GSFF inhibited liver fibrosis progression in vivo and HSC-T6 cell activation in vitro. These effects may be related to an alleviated inflammatory response and downregulated ERK phosphorylation.
Core tip: Liver fibrosis results from various kinds of chronic liver diseases and there is no specific treatment so far. Inflammatory response and extracellular signal-regulated kinase cascade play an important role in liver fibrosis development and progression. In this study, we observed the effects of herbal medicine, Gan Shen Fu Fang (GSFF) on liver fibrosis in vivo and in vitro. The results indicate that GSFF alleviates liver fibrosis progression in vivo and inhibits HSC-T6 activation in vitro, which may be related with inhibited inflammatory response and downregulated extracellular signal-regulated kinase phosphorylation. GSFF may provide hope for liver fibrosis treatment.