Hydroxysafflor yellow A suppresses liver fibrosis induced by carbon tetrachloride with high-fat diet by regulating PPAR-γ/p38 MAPK signaling.

CONTEXT: One approach to protect against liver fibrosis is the use of herb-derived natural compounds, such as hydroxysafflor yellow A (HSYA). The antifibrosis effect of HYSA against liver fibrosis has been investigated; however, its mechanisms have not yet been entirely revealed.

OBJECTIVES

To study the protective effects of HSYA on liver fibrosis induced by carbon tetrachloride (CCl4) and a high-fat diet (HFD), and to determine the mechanism of action of HSYA.

MATERIALS AND

METHODS

CCl4 and HFD were used to mimic liver fibrosis in rats, and serum biochemical indicators were determined. The antifibrosis effects of HSYA were evaluated and its mechanisms were investigated by histopathological analysis, immunohistochemical staining, enzyme-linked immunosorbent assays, real-time-PCR, and western blotting.

RESULTS

HSYA reduced CCl4- and HFD-mediated liver fibrosis and ameliorated serum biochemical indicator, downregulated the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) (0.31 ± 0.03 protein, 0.59 ± 0.02 mRNA) and transformin growth factor-β1 (TGF-β1) (0.81 ± 0.02 protein, 0.58 ± 0.04 mRNA), and upregulated the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) (1.57 ± 0.13 protein, 2.48 ± 0.19 mRNA) and matrix metallopeptidases-2 (MMP-2) (2.31 ± 0.16 protein, 2.79 ± 0.22 mRNA) (p < 0.01, versus model group). These effects were significantly attenuated by PPAR-γ antagonist GW9662 via blocking the phosphorylation of p38 MAPK.

DISCUSSION AND

CONCLUSION

These data demonstrate a novel role for HSYA in inhibiting CCl4- and HFD-mediated liver fibrosis, and reveal that PPAR-γ and p38 MAPK signaling play pivotal roles in the prevention of liver fibrosis induced by CCl4 and HFD.