In this study, we investigated the anti-angiogenic effect of the Chinese herbal decoction
Danggui Buxue Tang (DBT;
Radix Astragali and Radix Angelicae sinensis in 5 : 1 ratio) in a rat model of
liver fibrosis, in order to elucidate its mechanisms of action against
liver fibrosis.
Liver fibrosis was induced with CCl(4) and high-fat food for 6 weeks, and the rats were treated with oral doses of DBT (6 g raw herbs/kg/d) and
N-Acetyl-L-cysteine (NAC; 0.1 g/kg/d). The results showed that both DBT and NAC attenuated
liver fibrosis and neo-angiogenesis. Furthermore, DBT and NAC improved SOD activity but decreased MDA content and
8-OH-dG in fibrotic livers, with DBT being more effective than NAC. DBT decreased the expression of
VEGF, Ang1 and TGF-β1 and their signaling mediators, whereas NAC had no effect on
VEGF and VEGFR2 expression. Both DBT and NAC reduced HIF-1α gene and
protein expression in fibrotic livers, with DBT being more effective. These data clearly demonstrate that the anti-fibrotic properties of DBT are related to its ability to inhibit angiogenesis and its anti-angiogenic mechanisms are associated with improving oxidative stress, regulating the expression and signaling of angiogenic factors, and especially modulating HIF-1α in fibrotic livers.