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Updated: Mar 8, 2026
Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
Huang Qi Decoction Prevents BDL-Induced Liver Fibrosis Through Inhibition of Notch Signaling Activation
Xiao Zhang1,2,3, Ying Xu1,2, Jia-Mei Chen1,2
1* Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (TCM), Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases, China.
Abstract:
Notch signaling has been demonstrated to be involved in ductular reactions and fibrosis. Previous studies have shown that Huang Qi Decoction (HQD) can prevent the progression of cholestatic liver fibrosis (CLF). However, whether HQD affects the Notch signaling pathway is unclear. In this study, CLF was established by common bile duct ligation (BDL) in rats. At the end of the first week, the rats were randomly divided into a model group (i.e., BDL), an HQD group, and a sorafenib positive control group (SORA) and were treated for 3 weeks. Bile duct proliferation and liver fibrosis were determined by tissue staining. Activation of the Notch signaling pathway was evaluated by analyzing expressions of Notch-1, -2, -3, and -4, Jagged (JAG) 1, and Delta like (DLL)-1, -3, and -4. The results showed that HQD significantly reduced the deposition of collagen and the Hyp content of liver tissue and inhibited the activation of HSCs compared with the BDL group. In addition, HQD significantly decreased the protein and mRNA expressions of TGF-[Formula: see text]1 and [Formula: see text]-SMA. In contrast, HQD significantly enhanced expression of the Smad 7 protein. HQD also reduced biliary epithelial cell proliferation, and reduced the mRNA levels of CK7, CK8, CK18, SRY-related high mobility group-box gene (SOX) 9, epithelial cell adhesion molecule (EpCAM) and the positive areas of CK19 and OV6. In addition, the mRNA and protein expressions of Notch-3, -4, JAG1, and DLL-1, -3 were significantly reduced in the HQD compared to the BDL group. These results demonstrated that HQD may prevent biliary liver fibrosis through inhibition of the Notch signaling pathway, and it may be a potential treatment for cholestatic liver disease.
Insights
Huang Qi Decoction (HQD) effectively treats cholestatic liver fibrosis (CLF) by inhibiting Notch signaling. This traditional Chinese medicine reduces liver fibrosis and biliary epithelial cell proliferation, offering a potential therapeutic for CLF.
Area of Science:
- Hepatology
- Molecular Biology
- Pharmacology
Background:
- Cholestatic liver fibrosis (CLF) involves ductular reactions and fibrosis, with Notch signaling playing a key role.
- Huang Qi Decoction (HQD) is a traditional Chinese medicine with potential antifibrotic properties.
- The effect of HQD on Notch signaling in CLF remains largely unexplored.
Purpose of the Study:
- To investigate whether HQD affects the Notch signaling pathway in a rat model of CLF.
- To evaluate the therapeutic potential of HQD in mitigating liver fibrosis and related cellular changes.
Main Methods:
- CLF was induced in rats via common bile duct ligation (BDL).
- Rats were treated with HQD or sorafenib for 3 weeks.
- Liver fibrosis, bile duct proliferation, and Notch signaling pathway components (Notch-1-4, JAG1, DLL-1, -3, -4) were assessed via tissue staining and gene/protein expression analysis.
Main Results:
- HQD significantly reduced collagen deposition, hydroxyproline content, and hepatic stellate cell activation.
- HQD decreased TGF-β1 and α-SMA expression while increasing Smad 7 expression.
- HQD inhibited biliary epithelial cell proliferation and downregulated key markers (CK7, CK8, CK18, SOX9, EpCAM, CK19, OV6).
- HQD treatment significantly reduced the expression of Notch-3, Notch-4, JAG1, DLL-1, and DLL-3.
Conclusions:
- HQD demonstrates significant antifibrotic effects in CLF by inhibiting hepatic stellate cell activation and biliary epithelial cell proliferation.
- HQD exerts its therapeutic effects, at least in part, through the inhibition of the Notch signaling pathway.
- HQD represents a promising therapeutic agent for treating cholestatic liver disease.
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