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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Oncotarget
2017 ; 8
(34
): 56267-56280
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Casticin attenuates liver fibrosis and hepatic stellate cell activation by
blocking TGF-?/Smad signaling pathway
#MMPMID28915589
Zhou L
; Dong X
; Wang L
; Shan L
; Li T
; Xu W
; Ding Y
; Lai M
; Lin X
; Dai M
; Bai X
; Jia C
; Zheng H
Oncotarget
2017[Aug]; 8
(34
): 56267-56280
PMID28915589
show ga
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
(CCl(4)) or underwent bile duct ligation (BDL) to induce liver fibrosis, followed
by treatment with casticin or vehicle. In addition, transforming growth
factor-?1(TGF-?1)-activated LX-2 cells were used. In vivo experiments showed that
treatment with casticin alone had no toxic effect while significantly attenuating
CCl(4)-or BDL-induced liver fibrosis, as indicated by reductions in the density
of fibrosis, hydroxyproline content, expression of ?-SMA and collagen ?1(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-?1/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.