title: Huang Qi Decoction Prevents BDL-Induced Liver Fibrosis Through Inhibition of Notch Signaling Activation.
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.
authors.affiliation: * Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (TCM), Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases, China.|‡ Shanghai Key Laboratory of TCM, Shanghai, P.R. China.|§ Longhua Hospital Affiliated to Shanghai University of TCM, Shanghai, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: * Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (TCM), Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases, China.|‡ Shanghai Key Laboratory of TCM, Shanghai, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: * Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (TCM), Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases, China.|‡ Shanghai Key Laboratory of TCM, Shanghai, P.R. China.
authors.forename: Jia-Mei
authors.initials: JM
authors.lastname: Chen
authors.affiliation: * Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (TCM), Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases, China.|‡ Shanghai Key Laboratory of TCM, Shanghai, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Liu
authors.affiliation: † E-institute of Shanghai Municipal Education Commission, Shanghai University of TCM, Shanghai, P.R. China.
authors.forename: Guang-Li
authors.initials: GL
authors.lastname: Du
authors.affiliation: * Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (TCM), Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases, China.|‡ Shanghai Key Laboratory of TCM, Shanghai, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: * Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (TCM), Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases, China.|‡ Shanghai Key Laboratory of TCM, Shanghai, P.R. China.
authors.forename: Gao-Feng
authors.initials: GF
authors.lastname: Chen
authors.affiliation: * Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (TCM), Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases, China.|‡ Shanghai Key Laboratory of TCM, Shanghai, P.R. China.
authors.forename: Shi-Li
authors.initials: SL
authors.lastname: Jiang
authors.affiliation: * Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (TCM), Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases, China.|‡ Shanghai Key Laboratory of TCM, Shanghai, P.R. China.
authors.forename: Cheng-Hai
authors.initials: CH
authors.lastname: Liu
authors.affiliation: * Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (TCM), Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases, China.|‡ Shanghai Key Laboratory of TCM, Shanghai, P.R. China.
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Mu
authors.affiliation: * Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (TCM), Institute of Liver Diseases, Key Laboratory of Liver and Kidney Diseases, China.|† E-institute of Shanghai Municipal Education Commission, Shanghai University of TCM, Shanghai, P.R. China.|‡ Shanghai Key Laboratory of TCM, Shanghai, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
mesh_terms: D000199:Actins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000818:Animals; D027885:Astragalus propinquus; D001659:Biliary Tract / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002779:Cholestasis / Q000209:etiology / Q000517:prevention & control; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D003135:Common Bile Duct / Q000601:surgery; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D000071858:Epithelial Cell Adhesion Molecule / Q000187:drug effects / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000072100:Jagged-1 Protein / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D007633:Keratins / Q000187:drug effects / Q000235:genetics; D008026:Ligation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000209:etiology / Q000517:prevention & control; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects*; D051381:Rats; D051880:Receptors, Notch / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051906:Smad7 Protein / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; C512923:Dlk1 protein, rat; D004365:Drugs, Chinese Herbal; D000071858:Epithelial Cell Adhesion Molecule; D036341:Intercellular Signaling Peptides and Proteins; C000606275:Jag1 protein, rat; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D012333:RNA, Messenger; D051880:Receptors, Notch; D051906:Smad7 Protein; C497808:Smad7 protein, rat; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D007633:Keratins; D003094:Collagen; C027492:Huang Qi
keywords: Bile Duct Ligation; Hepatic Progenitor; Huang Qi Decoction; Liver Fibrosis; Notch Signaling Pathway