title: Demethyleneberberine Protects against Hepatic Fibrosis in Mice by Modulating NF-κB Signaling.
abstract: Demethyleneberberine (DMB) is an essential metabolite of Berberine (BBR) in vivo. Recent reports have revealed multiple novel therapeutic applications of BBR. However, the pharmacological activities of DMB remain to be elucidated. This study aimed to demonstrate the hepatoprotective and anti-fibrotic effects of DMB both in vitro and in vivo. Here we showed that DMB protects against thioacetamide (TAA)-induced hepatic fibrosis in mice and exhibits a higher safety profile as compared to BBR. Flow cytometry and Western blotting analysis showed that DMB is able to suppress the activation of hepatic stellate cells (HSCs) and induce cell apoptosis through the nuclear factor-κB (NF-κB) cascade. Immunohistochemical (IHC) and quantitative polymerase chain reaction (qPCR) analysis indicated that DMB also has inhibitory effects on collagen synthesis and is able to increase collagen degradation by blocking the transforming growth factor β 1 (TGF-β1)-Smad signaling and reducing the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of MMP (TIMPs). These findings indicate that DMB has the potential to attenuate hepatic fibrosis via suppressing HSC activation.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, Nanjing 210009, China. yongchenwang@g.ucla.edu.|Divisions of Molecular Medicine and Cardiology, Departments of Anesthesiology and Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095, USA. yongchenwang@g.ucla.edu.
authors.forename: Yongchen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Nanjing First Hospital, Nanjing Medical University, Nanjing 210009, China. zhaozheng0322@126.com.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, Nanjing 210009, China. benbobo2012@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, Nanjing 210009, China. qiangxiaoyan0228@126.com.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Qiang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, Nanjing 210009, China. zhoucuisong2009@163.com.
authors.forename: Cuisong
authors.initials: C
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, Nanjing 210009, China. liruiyan_1979@126.com.
authors.forename: Ruiyan
authors.initials: R
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, Nanjing 210009, China. njuchenhuan@163.com.
authors.forename: Huan
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, Nanjing 210009, China. ybzhang@cpu.edu.cn.|Department of Biochemistry, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China. ybzhang@cpu.edu.cn.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism; D013853:Thioacetamide / Q000633:toxicity; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000199:Actins; D016328:NF-kappa B; D020011:Protective Agents; D051785:Smad Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse; D013853:Thioacetamide; D001599:Berberine; C477155:demethyleneberberine; D003094:Collagen; D020782:Matrix Metalloproteinases
keywords: Demethyleneberberine; NF-κB; cell apoptosis; hepatic fibrosis; hepatic stellate cells