Research Papers:

Casticin attenuates liver fibrosis and hepatic stellate cell activation by blocking TGF-β/Smad signaling pathway

Ling Zhou, Xiaoying Dong, Linlin Wang, Lanlan Shan, Ting Li, Wanfu Xu, Yan Ding, Mingqiang Lai, Xiaojun Lin, Meng Dai, Xiaochun Bai, Chunhong Jia _ and Hang Zheng

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Oncotarget. 2017; 8:56267-56280. https://doi.org/10.18632/oncotarget.17453

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Ling Zhou1,*, Xiaoying Dong1,*, Linlin Wang1, Lanlan Shan2, Ting Li3, Wanfu Xu4, Yan Ding2, Mingqiang Lai5, Xiaojun Lin5, Meng Dai2, Xiaochun Bai5, Chunhong Jia5 and Hang Zheng1

1Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China

2Department of Health Management, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China

3Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China

4Department of Gastroenterology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China

5Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China

*These authors contributed equally to this work

Correspondence to:

Chunhong Jia, email: [email protected]

Hang Zheng, email: [email protected]

Keywords: casticin, CCl4, liver fibrosis, hepatic stellate cell, TGF-β/Smad

Received: May 24, 2016     Accepted: April 14, 2017     Published: April 27, 2017


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.

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