PMID- 27376272
OWN - NLM
STAT- MEDLINE
DCOM- 20170329
LR  - 20181113
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 17
IP  - 7
DP  - 2016 Jun 30
TI  - Demethyleneberberine Protects against Hepatic Fibrosis in Mice by Modulating 
      NF-kappaB Signaling.
LID - 10.3390/ijms17071036 [doi]
LID - 1036
AB  - 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-kappaB (NF-kappaB) 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 beta 1 (TGF-beta1)-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.
FAU - Wang, Yongchen
AU  - Wang Y
AD  - State Key Laboratory of Natural Medicines, Department of Biochemistry, China 
      Pharmaceutical University, Nanjing 210009, China. yongchenwang@g.ucla.edu.
AD  - 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.
FAU - Zhao, Zheng
AU  - Zhao Z
AD  - Department of Pharmacy, Nanjing First Hospital, Nanjing Medical University, 
      Nanjing 210009, China. zhaozheng0322@126.com.
FAU - Yan, Yan
AU  - Yan Y
AD  - State Key Laboratory of Natural Medicines, Department of Biochemistry, China 
      Pharmaceutical University, Nanjing 210009, China. benbobo2012@163.com.
FAU - Qiang, Xiaoyan
AU  - Qiang X
AD  - State Key Laboratory of Natural Medicines, Department of Biochemistry, China 
      Pharmaceutical University, Nanjing 210009, China. qiangxiaoyan0228@126.com.
FAU - Zhou, Cuisong
AU  - Zhou C
AD  - State Key Laboratory of Natural Medicines, Department of Biochemistry, China 
      Pharmaceutical University, Nanjing 210009, China. zhoucuisong2009@163.com.
FAU - Li, Ruiyan
AU  - Li R
AD  - State Key Laboratory of Natural Medicines, Department of Biochemistry, China 
      Pharmaceutical University, Nanjing 210009, China. liruiyan_1979@126.com.
FAU - Chen, Huan
AU  - Chen H
AD  - State Key Laboratory of Natural Medicines, Department of Biochemistry, China 
      Pharmaceutical University, Nanjing 210009, China. njuchenhuan@163.com.
FAU - Zhang, Yubin
AU  - Zhang Y
AD  - State Key Laboratory of Natural Medicines, Department of Biochemistry, China 
      Pharmaceutical University, Nanjing 210009, China. ybzhang@cpu.edu.cn.
AD  - Department of Biochemistry, China Pharmaceutical University, 24 Tongjia Xiang, 
      Nanjing 210009, China. ybzhang@cpu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20160630
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Actins)
RN  - 0 (NF-kappa B)
RN  - 0 (Protective Agents)
RN  - 0 (Smad Proteins)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (alpha-smooth muscle actin, mouse)
RN  - 075T165X8M (Thioacetamide)
RN  - 0I8Y3P32UF (Berberine)
RN  - 25459-91-0 (demethyleneberberine)
RN  - 9007-34-5 (Collagen)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Berberine/*analogs & derivatives/pharmacology
MH  - Cell Line
MH  - Collagen/genetics/metabolism
MH  - Disease Models, Animal
MH  - Hepatic Stellate Cells/cytology/drug effects/metabolism
MH  - Liver Cirrhosis/chemically induced/metabolism/pathology
MH  - Male
MH  - Matrix Metalloproteinases/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred ICR
MH  - NF-kappa B/*metabolism
MH  - Protective Agents/*pharmacology
MH  - Rats
MH  - Signal Transduction/*drug effects
MH  - Smad Proteins/metabolism
MH  - Thioacetamide/toxicity
MH  - Tissue Inhibitor of Metalloproteinases/genetics/metabolism
MH  - Transforming Growth Factor beta1/metabolism
PMC - PMC4964412
OTO - NOTNLM
OT  - Demethyleneberberine
OT  - NF-kappaB
OT  - cell apoptosis
OT  - hepatic fibrosis
OT  - hepatic stellate cells
EDAT- 2016/07/05 06:00
MHDA- 2017/03/31 06:00
PMCR- 2016/07/01
CRDT- 2016/07/05 06:00
PHST- 2016/05/12 00:00 [received]
PHST- 2016/06/17 00:00 [revised]
PHST- 2016/06/23 00:00 [accepted]
PHST- 2016/07/05 06:00 [entrez]
PHST- 2016/07/05 06:00 [pubmed]
PHST- 2017/03/31 06:00 [medline]
PHST- 2016/07/01 00:00 [pmc-release]
AID - ijms17071036 [pii]
AID - ijms-17-01036 [pii]
AID - 10.3390/ijms17071036 [doi]
PST - epublish
SO  - Int J Mol Sci. 2016 Jun 30;17(7):1036. doi: 10.3390/ijms17071036.