Although many advances have been made in understanding the pathogenesis of
liver fibrosis, few options are available for treatment.
Casticin, one of the major
flavonoids in Fructus Viticis extracts, has shown hepatoprotective potential, but its effects on
liver fibrosis are not clear. In this study, we investigated the antifibrotic activity of
casticin and its underlying mechanism in vivo and in vitro. Male mice were injected intraperitoneally with
carbon tetrachloride (CCl4) or underwent bile duct
ligation (BDL) to induce
liver fibrosis, followed by treatment with
casticin or vehicle. In addition, transforming growth factor-β1(TGF-β1)-activated LX-2 cells were used. In vivo experiments showed that treatment with
casticin alone had no toxic effect while significantly attenuating CCl4-or BDL-induced
liver fibrosis, as indicated by reductions in the density of
fibrosis,
hydroxyproline content, expression of α-SMA and
collagen α1(I)
mRNA. Moreover,
casticin inhibited LX2 proliferation, induced apoptosis in a time- and dose-dependent manner in vitro. The underlying molecular mechanisms for the effect of
casticin involved inhibition of hepatic stellate cell (HSC) activation and reduced the expression of
matrix metalloproteinase (MMP)-2, MMP-9,
tissue inhibitor of metalloproteinases (TIMP)-1 and
TIMP-2 resulting from blocking TGF-β1/Smad signaling, as well as increased the apoptosis of HSCs. The results suggest that
casticin has potential benefits in the attenuation and treatment of
liver fibrosis.