PMID- 29497376
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 9
DP  - 2018
TI  - The Flavonoid Quercetin Ameliorates Liver Inflammation and Fibrosis by Regulating 
      Hepatic Macrophages Activation and Polarization in Mice.
PG  - 72
LID - 10.3389/fphar.2018.00072 [doi]
LID - 72
AB  - At present, there are no effective antifibrotic drugs for patients with chronic 
      liver disease; hence, the development of antifibrotic therapies is urgently 
      needed. Here, we performed an experimental and translational study to investigate 
      the potential and underlying mechanism of quercetin treatment in liver fibrosis, 
      mainly focusing on the impact of quercetin on macrophages activation and 
      polarization. BALB/c mice were induced liver fibrosis by carbon tetrachloride 
      (CCl(4)) for 8 weeks and concomitantly treated with quercetin (50 mg/kg) or 
      vehicle by daily gavage. Liver inflammation, fibrosis, and hepatic stellate cells 
      (HSCs) activation were examined. Moreover, massive macrophages accumulation, M1 
      macrophages and their related markers, such as tumor necrosis factor (TNF)-alpha, 
      interleukin (IL)-1beta, IL-6, and monocyte chemotactic protein-1 (MCP-1) in livers 
      were analyzed. In vitro, we used Raw 264.7 cells to examine the effect of 
      quercetin on M1-polarized macrophages activation. Our results showed that 
      quercetin dramatically ameliorated liver inflammation, fibrosis, and inhibited 
      HSCs activation. These results were attributed to the reductive recruitment of 
      macrophages (F4/80(+) and CD68(+)) into the liver in quercetin-treated fibrotic 
      mice confirmed by immunostaining and expression levels of marker molecules. 
      Importantly, quercetin strongly inhibited M1 polarization and M1-related 
      inflammatory cytokines in fibrotic livers when compared with vehicle-treated 
      mice. In vitro, studies further revealed that quercetin efficiently inhibited 
      macrophages activation and M1 polarization, as well as decreased the mRNA 
      expression of M1 macrophage markers such as TNF-alpha, IL-1beta, IL-6, and nitric oxide 
      synthase 2. Mechanistically, the inhibition of M1 macrophages by quercetin was 
      associated with the decreased levels of Notch1 expression on macrophages both in 
      vivo and in vitro. Taken together, our data indicated that quercetin attenuated 
      CCl(4)-induced liver inflammation and fibrosis in mice through inhibiting 
      macrophages infiltration and modulating M1 macrophages polarization via targeting 
      Notch1 pathway. Hence, quercetin holds promise as potential therapeutic agent for 
      human fibrotic liver disease.
FAU - Li, Xi
AU  - Li X
AD  - Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai, China.
FAU - Jin, Qianwen
AU  - Jin Q
AD  - Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan 
      University, Shanghai, China.
AD  - Shanghai Institute of Liver Diseases, Shanghai, China.
FAU - Yao, Qunyan
AU  - Yao Q
AD  - Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan 
      University, Shanghai, China.
AD  - Shanghai Institute of Liver Diseases, Shanghai, China.
FAU - Xu, Beili
AU  - Xu B
AD  - Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan 
      University, Shanghai, China.
AD  - Shanghai Institute of Liver Diseases, Shanghai, China.
FAU - Li, Lixin
AU  - Li L
AD  - Shanghai Institute of Liver Diseases, Shanghai, China.
FAU - Zhang, Shuncai
AU  - Zhang S
AD  - Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan 
      University, Shanghai, China.
AD  - Shanghai Institute of Liver Diseases, Shanghai, China.
FAU - Tu, Chuantao
AU  - Tu C
AD  - Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan 
      University, Shanghai, China.
AD  - Shanghai Institute of Liver Diseases, Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20180209
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC5819566
OTO - NOTNLM
OT  - Notch1
OT  - hepatic fibrosis
OT  - hepatic stellate cells (HSCs)
OT  - macrophages
OT  - polarization
OT  - quercetin
EDAT- 2018/03/03 06:00
MHDA- 2018/03/03 06:01
PMCR- 2018/02/09
CRDT- 2018/03/03 06:00
PHST- 2017/09/11 00:00 [received]
PHST- 2018/01/22 00:00 [accepted]
PHST- 2018/03/03 06:00 [entrez]
PHST- 2018/03/03 06:00 [pubmed]
PHST- 2018/03/03 06:01 [medline]
PHST- 2018/02/09 00:00 [pmc-release]
AID - 10.3389/fphar.2018.00072 [doi]
PST - epublish
SO  - Front Pharmacol. 2018 Feb 9;9:72. doi: 10.3389/fphar.2018.00072. eCollection 
      2018.