PMID- 33210080
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220418
IS  - 2572-5017 (Electronic)
IS  - 2572-5017 (Linking)
VI  - 4
IP  - 5
DP  - 2020
TI  - Traditional Chinese Medicine Fuzheng Huayu Prevents Development of Liver Fibrosis 
      in Mice.
PG  - 561-580
LID - 10.26502/acbr.50170125 [doi]
AB  - AIM: To investigate the therapeutic effect of FZHY on hepatic fibrosis in mice 
      and to determine the mechanism of its action. METHODS: Wild type mice were 
      subjected to toxic (carbon tetrachloride, CCl(4)) or cholestatic (bile duct 
      ligation, BDL). Upon induction of liver fibrosis, mice were treated with FZHY 
      (4.0g/kg, 2w, oral gavage) or vehicle (PBS). Livers were analyzed by Sirius Red 
      staining, immunostaining and RT-PCR for profibrogenic and pro-inflammatory genes. 
      The effect of FZHY on hepatocytes, inflammatory responses, activation of 
      fibrogenic myofibroblasts, and ROS production was assessed. RESULTS: FZHY 
      strongly inhibited the development of CCl(4)- and BDL-induced liver fibrosis in 
      mice. Liver fibrosis was significantly improved in FZHY-treated mice, as 
      demonstrated by reduced content of hepatic hydroxyproline and Sirius Red positive 
      area. Moreover, the number of SMA (+)and Desmin(+) myofibroblasts was 
      significantly reduced in the livers of FZHY-treated mice, and correlated with 
      downregulation of the mRNA levels of alpha-SMA, collagen-alpha1(I), tissue inhibitor of 
      matrix metalloproteinase-1 (TIMP-1), TGF-beta1 and its receptor TGF-betaRI, and 
      platelet-derived growth factor-beta (PDGF-beta), suggesting that FZHY inhibits 
      activation of fibrogenic myofibroblasts. Furthermore, administration of FZHY 
      markedly decreased recruitment of F4/80(+) inflammatory macrophages to the livers 
      of CCl(4)- and BDL-injured mice, and this effect was associated with 
      downregulation of monocyte chemoattractant protein-1(MCP-1) and macrophage 
      inflammatory protein-1 (MIP-1) mRNA. In addition, the lipid peroxidation products 
      4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) were reduced, demonstrating 
      that treatment with FZHY can effectively block ROS production in livers of 
      CCl(4)- and BDL-injured mice. CONCLUSIONS: Traditional Chinese Medicine FZHY has 
      a variety of anti-fibrotic effects, including strong anti-oxidant, 
      anti-inflammatory and anti-fibrotic effects on myeloid cells and hepatocytes. 
      Although FZHY compound does not seem to directly affect HSCs, it regulates HSC 
      activation via inhibition of macrophage recruitment to fibrotic liver.
FAU - Jiang, Chunyan
AU  - Jiang C
AD  - Beijing Friendship Hospital, Capital Medical University, Beijing, China.
AD  - Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
FAU - Iwaisako, Keiko
AU  - Iwaisako K
AD  - Department of Medical Life Systems, Faculty of Life and Medical Sciences, 
      Doshisha University, Kyotanabe, Japan.
AD  - Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
FAU - Cong, Min
AU  - Cong M
AD  - Beijing Friendship Hospital, Capital Medical University, Beijing, China.
AD  - Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
FAU - Diggle, Karin
AU  - Diggle K
AD  - Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
FAU - Hassanein, Tarek
AU  - Hassanein T
AD  - Southern California Liver Center, Coronado, CA, USA.
FAU - Brenner, David A
AU  - Brenner DA
AD  - Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
FAU - Kisseleva, Tatiana
AU  - Kisseleva T
AD  - Department of Surgery, University of California, San Diego, La Jolla, CA, USA.
LA  - eng
GR  - R37 AI043477/AI/NIAID NIH HHS/United States
GR  - U01 AA018663/AA/NIAAA NIH HHS/United States
GR  - U01 AA029019/AA/NIAAA NIH HHS/United States
GR  - F32 DK009920/DK/NIDDK NIH HHS/United States
GR  - R01 AA028550/AA/NIAAA NIH HHS/United States
GR  - U01 AA022614/AA/NIAAA NIH HHS/United States
GR  - R01 DK101737/DK/NIDDK NIH HHS/United States
GR  - R56 DK088837/DK/NIDDK NIH HHS/United States
GR  - R01 DK111866/DK/NIDDK NIH HHS/United States
GR  - R01 DK099205/DK/NIDDK NIH HHS/United States
GR  - P50 AA011999/AA/NIAAA NIH HHS/United States
GR  - R01 AI043477/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20201020
PL  - United States
TA  - Arch Clin Biomed Res
JT  - Archives of clinical and biomedical research
JID - 101768967
PMC - PMC7671588
MID - NIHMS1639383
OTO - NOTNLM
OT  - Fuzheng Huayu
OT  - Liver fibrosis
OT  - Reactive oxygen species
OT  - Toxic and cholestatic liver injury
OT  - Traditional Chinese medicine
EDAT- 2020/11/20 06:00
MHDA- 2020/11/20 06:01
PMCR- 2020/11/17
CRDT- 2020/11/19 05:51
PHST- 2020/11/19 05:51 [entrez]
PHST- 2020/11/20 06:00 [pubmed]
PHST- 2020/11/20 06:01 [medline]
PHST- 2020/11/17 00:00 [pmc-release]
AID - 10.26502/acbr.50170125 [doi]
PST - ppublish
SO  - Arch Clin Biomed Res. 2020;4(5):561-580. doi: 10.26502/acbr.50170125. Epub 2020 
      Oct 20.