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Huang Qi Decoction Prevents BDL-Induced Liver Fibrosis Through Inhibition of Notch Signaling Activation
- Source :
- The American Journal of Chinese Medicine. 45:85-104
- Publication Year :
- 2017
- Publisher :
- World Scientific Pub Co Pte Ltd, 2017.
-
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.
- Subjects :
- Liver Cirrhosis
0301 basic medicine
medicine.medical_specialty
JAG1
Notch signaling pathway
Pharmacology
Biology
Smad7 Protein
Transforming Growth Factor beta1
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cholestasis
Fibrosis
Internal medicine
medicine
Animals
RNA, Messenger
Biliary Tract
Ligation
Cell Proliferation
Common Bile Duct
Receptors, Notch
Membrane Proteins
Epithelial Cells
Epithelial cell adhesion molecule
General Medicine
Astragalus propinquus
Epithelial Cell Adhesion Molecule
medicine.disease
Actins
Rats
Disease Models, Animal
030104 developmental biology
Endocrinology
Liver
Complementary and alternative medicine
chemistry
Biliary tract
Intercellular Signaling Peptides and Proteins
Keratins
Jagged-1 Protein
030211 gastroenterology & hepatology
Collagen
Signal transduction
Drugs, Chinese Herbal
Signal Transduction
Subjects
Details
- ISSN :
- 17936853 and 0192415X
- Volume :
- 45
- Database :
- OpenAIRE
- Journal :
- The American Journal of Chinese Medicine
- Accession number :
- edsair.doi.dedup.....48932f2b1238652027a07ab4f34c5245