PMID- 25407538
OWN - NLM
STAT- MEDLINE
DCOM- 20150608
LR  - 20240109
IS  - 1472-6882 (Electronic)
IS  - 1472-6882 (Linking)
VI  - 14
DP  - 2014 Nov 18
TI  - Fuzheng Huayu recipe alleviates hepatic fibrosis via inhibiting TNF-alpha induced 
      hepatocyte apoptosis.
PG  - 449
LID - 10.1186/1472-6882-14-449 [doi]
LID - 449
AB  - BACKGROUND: What was the relationship of Fuzheng Huayu recipe (FZHY) inhibiting 
      hepatocyte apoptosis and HSC activation at different stage of liver fibrosis? In 
      order to answer this question, the study was carried out to dynamically observe 
      FZHY's effect on hepatocyte apoptosis and HSC activation and further explored 
      underling mechanism of FZHY against hepatocyte apoptosis. METHODS: Mice were 
      randomly divided into four groups: normal, model, FZHY, and N-acetylcystein (NAC) 
      groups. Acute hepatic injury and liver fibrosis in mice were induced by CCl4. 
      Three days before the first CCl4 injection, treatment with FZHY powder or NAC 
      respectively was started. In vitro, primary hepatocytes were pretreated with FZHY 
      medicated serum or Z-VAD-FMK and then incubated with ActD and TNF-alpha. Primary HSCs 
      were treated with DNA from apoptotic hepatocytes incubated by Act D/TNF-alpha or FZHY 
      medicated. Liver sections were analyzed for HE staining and immunohistochemical 
      evaluation of apoptosis. Serum ALT and AST, Alb content and TNF-alpha expression in 
      liver tissue were detected. Hyp content was assayed and collagen deposition was 
      visualized. Expressions of alpha-SMA and type I collagen were analyzed by 
      immunofluorescence and immunoblotting. Flow cytometry, immunofluorescence, and 
      DNA ladder for hepatocyte apoptosis and immunoblotting for TNF-R1, Bcl-2 and Bax 
      were also analyzed. RESULTS: Mice showed characteristic features of massive 
      hepatocytes apoptosis in early stage of liver injury and developed severe hepatic 
      fibrosis in later phase. FZHY treatment significantly alleviated acute liver 
      injury and hepatocyte apoptosis, and inhibited liver fibrosis by decreasing alpha-SMA 
      expression and hepatic Hyp content. In vitro, primary hepatocytes were induced by 
      TNF-alpha and Act D. The anti-apoptotic effect of FZHY was generated by reducing 
      TNFR1 expression and balancing the expressions of Bcl-2 and Bax. Meanwhile, the 
      nuclear DNA from apoptotic hepatocytes stimulated HSC activation in a dose 
      dependent manner, and the DNA from apoptotic hepatocytes treated with FZHY or 
      Z-VAD-FMK reduced HSC activation and type I collagen expression. CONCLUSION: 
      These findings suggested that FZHY suppressed hepatocyte apoptosis through 
      regulating mediators in death receptor and mitochondrial pathways, and the effect 
      of FZHY on hepatocyte apoptosis might play an important role in inhibiting liver 
      fibrosis.
FAU - Tao, Yan-yan
AU  - Tao YY
FAU - Yan, Xiu-chuan
AU  - Yan XC
FAU - Zhou, Tao
AU  - Zhou T
FAU - Shen, Li
AU  - Shen L
FAU - Liu, Zu-long
AU  - Liu ZL
FAU - Liu, Cheng-hai
AU  - Liu CH
AD  - Institute of Liver Diseases, Shuguang Hospital affiliated to Shanghai University 
      of Traditional Chinese Medicine, 528 Zhangheng Road, Pudong New Area, Shanghai 
      201203, China. chenghailiu@hotmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141118
PL  - England
TA  - BMC Complement Altern Med
JT  - BMC complementary and alternative medicine
JID - 101088661
RN  - 0 (Acta2 protein, mouse)
RN  - 0 (Actins)
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (Bax protein, mouse)
RN  - 0 (Drugs, Chinese Herbal)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Tnfrsf1a protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 0 (benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone)
RN  - 0 (fuzheng huayu)
RN  - 114100-40-2 (Bcl2 protein, mouse)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
RN  - RMB44WO89X (Hydroxyproline)
SB  - IM
MH  - Actins/metabolism
MH  - Amino Acid Chloromethyl Ketones/pharmacology
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Carbon Tetrachloride
MH  - Chemical and Drug Induced Liver Injury/*drug therapy/metabolism
MH  - Drugs, Chinese Herbal/pharmacology/*therapeutic use
MH  - Enzyme Inhibitors/pharmacology
MH  - Hepatic Stellate Cells/drug effects
MH  - Hepatocytes/drug effects/metabolism
MH  - Hydroxyproline/metabolism
MH  - Liver/cytology/*drug effects/metabolism
MH  - Liver Cirrhosis/chemically induced/*drug therapy/metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - *Phytotherapy
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type I/metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - bcl-2-Associated X Protein/metabolism
PMC - PMC4289302
EDAT- 2014/11/20 06:00
MHDA- 2015/06/09 06:00
PMCR- 2014/11/18
CRDT- 2014/11/20 06:00
PHST- 2014/04/08 00:00 [received]
PHST- 2014/09/19 00:00 [accepted]
PHST- 2014/11/20 06:00 [entrez]
PHST- 2014/11/20 06:00 [pubmed]
PHST- 2015/06/09 06:00 [medline]
PHST- 2014/11/18 00:00 [pmc-release]
AID - 1472-6882-14-449 [pii]
AID - 2067 [pii]
AID - 10.1186/1472-6882-14-449 [doi]
PST - epublish
SO  - BMC Complement Altern Med. 2014 Nov 18;14:449. doi: 10.1186/1472-6882-14-449.