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Int. J. Mol. Sci. 2016, 17(7), 1036; doi:10.3390/ijms17071036

Demethyleneberberine Protects against Hepatic Fibrosis in Mice by Modulating NF-κB Signaling

1
State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, Nanjing 210009, China
2
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
3
Department of Pharmacy, Nanjing First Hospital, Nanjing Medical University, Nanjing 210009, China
4
Department of Biochemistry, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, China
*
Author to whom correspondence should be addressed.
Academic Editors: Amedeo Lonardo and Giovanni Targher
Received: 12 May 2016 / Revised: 17 June 2016 / Accepted: 23 June 2016 / Published: 30 June 2016
(This article belongs to the Section Bioactives and Nutraceuticals)
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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. View Full-Text
Keywords: hepatic fibrosis; hepatic stellate cells; cell apoptosis; Demethyleneberberine; NF-κB hepatic fibrosis; hepatic stellate cells; cell apoptosis; Demethyleneberberine; NF-κB
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Wang, Y.; Zhao, Z.; Yan, Y.; Qiang, X.; Zhou, C.; Li, R.; Chen, H.; Zhang, Y. Demethyleneberberine Protects against Hepatic Fibrosis in Mice by Modulating NF-κB Signaling. Int. J. Mol. Sci. 2016, 17, 1036.

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