PMID- 32866517
OWN - NLM
STAT- MEDLINE
DCOM- 20201123
LR  - 20221207
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 261
DP  - 2020 Nov 15
TI  - Matrine promotes hepatic oval cells differentiation into hepatocytes and 
      alleviates liver injury by suppression of Notch signalling pathway.
PG  - 118354
LID - S0024-3205(20)31107-3 [pii]
LID - 10.1016/j.lfs.2020.118354 [doi]
AB  - AIMS: Recent studies have shown that the hyperactive Notch pathway is involved in 
      cirrhosis and hepatocellular carcinoma (HCC) development by regulating 
      differentiation of hepatic oval cells (HOCs) into cancer cells. The aim of this 
      study was to investigate whether matrine can alleviate liver injury and promote 
      HOC differentiation into hepatocytes by suppression of Notch pathway. MAIN 
      METHODS: We evaluated the expression of Notch-1, Jagged-1, and Hes-1 in HCC 
      tissue by immunohistochemistry. Stem cell characteristics of HOCs were evaluated 
      by CCK-8, cell cycle, and apoptosis. The expression of Notch pathway, HOC markers 
      and albumin (ALB) was detected by immunohistochemistry, QRT-PCR and western 
      blotting. The effects of matrine in protecting liver in vivo were investigated in 
      a rat Solt-Farber precancerous model. KEY FINDINGS: We found an abnormal 
      activated Notch pathway in HCC tissue, and the hyperactive Notch pathway was 
      strongly associated with poor liver function in patients with cirrhosis with HCC. 
      Using siNotch-1 to inhibit Notch pathway confirmed that Notch pathway could 
      maintain stem cell characteristics of HOCs. Matrine inhibited stem cell 
      characteristics of HOCs, the expression of Notch pathway and HOC markers but 
      upregulated ALB. Matrine in combined with siNotch-1 RNA decreased the more 
      potently inhibited HOC markers and Notch pathway. In rat Solt-Farber precancerous 
      model, prophylactic application of matrine alleviated liver injury, downregulated 
      Notch pathway and HOC markers, and upregulated ALB in a dose-dependent manner. 
      SIGNIFICANCE: Matrine could promote the differentiation of HOCs into hepatocytes 
      by inhibiting the Notch signalling pathway and alleviate liver injury.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Shi, Jianfei
AU  - Shi J
AD  - Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei 
      Medical University, ShiJiaZhuang, PR China.
FAU - Han, Guangjie
AU  - Han G
AD  - Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei 
      Medical University, ShiJiaZhuang, PR China.
FAU - Wang, Jinfeng
AU  - Wang J
AD  - Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei 
      Medical University, ShiJiaZhuang, PR China.
FAU - Han, Xin
AU  - Han X
AD  - Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei 
      Medical University, ShiJiaZhuang, PR China.
FAU - Zhao, Man
AU  - Zhao M
AD  - Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei 
      Medical University, ShiJiaZhuang, PR China.
FAU - Duan, Xiaoling
AU  - Duan X
AD  - Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei 
      Medical University, ShiJiaZhuang, PR China.
FAU - Mi, Lili
AU  - Mi L
AD  - Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei 
      Medical University, ShiJiaZhuang, PR China.
FAU - Li, Ning
AU  - Li N
AD  - Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei 
      Medical University, ShiJiaZhuang, PR China.
FAU - Yin, Xiaolei
AU  - Yin X
AD  - Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei 
      Medical University, ShiJiaZhuang, PR China.
FAU - Shi, Huacun
AU  - Shi H
AD  - Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei 
      Medical University, ShiJiaZhuang, PR China.
FAU - Li, Cuizhen
AU  - Li C
AD  - Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei 
      Medical University, ShiJiaZhuang, PR China.
FAU - Xu, Jinsheng
AU  - Xu J
AD  - Department of Nephrology, The Fourth Hospital of Hebei Medical University, 
      ShiJiaZhuang, PR China. Electronic address: xjs5766@126.com.
FAU - Yin, Fei
AU  - Yin F
AD  - Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei 
      Medical University, ShiJiaZhuang, PR China. Electronic address: 
      yinfei_4y@sina.com.
LA  - eng
PT  - Journal Article
DEP - 20200828
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Alkaloids)
RN  - 0 (Quinolizines)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Notch)
RN  - 0 (Matrines)
SB  - IM
MH  - Alkaloids/*pharmacology
MH  - Animals
MH  - Apoptosis/drug effects
MH  - *Cell Differentiation/drug effects
MH  - Cell Survival/drug effects
MH  - Disease Models, Animal
MH  - Fatty Liver/pathology/physiopathology
MH  - Female
MH  - Hepatocytes/drug effects/metabolism/*pathology
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Liver/drug effects/*injuries/*pathology/physiopathology
MH  - Liver Function Tests
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Proportional Hazards Models
MH  - Quinolizines/*pharmacology
MH  - RNA, Small Interfering/metabolism
MH  - Rats, Sprague-Dawley
MH  - Receptors, Notch/*metabolism
MH  - *Signal Transduction
MH  - Matrines
OTO - NOTNLM
OT  - Cirrhosis
OT  - Differentiation
OT  - Hepatic oval cells (HOCs)
OT  - Hepatocellular carcinoma (HCC)
OT  - Matrine
OT  - Notch signalling pathway
OT  - Rat Solt-Farber model
EDAT- 2020/09/01 06:00
MHDA- 2020/11/24 06:00
CRDT- 2020/09/01 06:00
PHST- 2020/05/06 00:00 [received]
PHST- 2020/08/16 00:00 [revised]
PHST- 2020/08/24 00:00 [accepted]
PHST- 2020/09/01 06:00 [pubmed]
PHST- 2020/11/24 06:00 [medline]
PHST- 2020/09/01 06:00 [entrez]
AID - S0024-3205(20)31107-3 [pii]
AID - 10.1016/j.lfs.2020.118354 [doi]
PST - ppublish
SO  - Life Sci. 2020 Nov 15;261:118354. doi: 10.1016/j.lfs.2020.118354. Epub 2020 Aug 
      28.