title: Yiguanjian decoction and its ingredients inhibit angiogenesis in carbon tetrachloride-induced cirrhosis mice.
abstract: BACKGROUND
  Cirrhosis is associated with angiogenesis and disruption of hepatic vascular architecture. Yiguanjian (YGJ) decoction, a prescription from traditional Chinese medicine, is widely used for treating liver diseases. We studied whether YGJ or its ingredients (iYGJ) had an anti-angiogenic effect and explored possible mechanisms underlying this process.
  
  
  METHODS
  Cirrhosis was induced with carbon tetrachloride (CCl4) (ip) in C57BL/6 mice for 6 weeks. From week 4 to week 6, cirrhotic mice were randomly divided into four groups: sorafenib-treated, YGJ-treated and iYGJ-treated mice and placebo. Serum biochemistries, hydroxyproline (Hyp) content and histopathological changes of hepatic tissues were measured as were α-smooth muscle actin (α-SMA), collagen I, CD31, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR) 2 and hypoxia-inducible factor (HIF)-1α.
  
  
  RESULTS
  Both YGJ and iYGJ improved serum biochemistries. Changes of histopathology showed that YGJ and iYGJ reduced hepatic tissue necroinflammatory and collagen fiber deposition in cirrhosis mice. Compared to the CCl4 treated animals, Hyp, α-SMA, collagen I, CD31, VEGF, VEGFR, and HIF-1α expression decreased in YGJ and iYGJ groups.
  
  
  CONCLUSIONS
  YGJ and iYGJ inhibited liver angiogenesis in cirrhotic mice treated with CCl4 by inhibiting the HIF-1α/VEGF signaling pathway, suggesting that anti-angiogenic effects of YGJ and iYGJ are associated with improving the hepatic hypoxic microenvironment.
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. zhouyaning103@sina.com.
authors.forename: Ya-Ning
authors.initials: YN
authors.lastname: Zhou
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. ypmu8888@126.com.
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Mu
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. fuwenweispu@sina.com.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Fu
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. ningbingbing1986@163.com.
authors.forename: Bing-Bing
authors.initials: BB
authors.lastname: Ning
authors.affiliation: Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. duguangli2002@126.com.
authors.forename: Guang-Li
authors.initials: GL
authors.lastname: Du
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. cjm0102@126.com.
authors.forename: Jia-Mei
authors.initials: JM
authors.lastname: Chen
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. mysun248@hotmail.com.
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Sun
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. 394787336@qq.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. yyhuliver@163.com.|E-institute of Shanghai Municipal Education Commission, Shanghai, 201203, China. yyhuliver@163.com.
authors.forename: Yi-Yang
authors.initials: YY
authors.lastname: Hu
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. chenghailiu@hotmail.com.|E-institute of Shanghai Municipal Education Commission, Shanghai, 201203, China. chenghailiu@hotmail.com.
authors.forename: Cheng-Hai
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. xulieming@126.com.
authors.forename: Lie-Ming
authors.initials: LM
authors.lastname: Xu
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. liuliver@vip.sina.com.|E-institute of Shanghai Municipal Education Commission, Shanghai, 201203, China. liuliver@vip.sina.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
mesh_terms: D000199:Actins; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D002251:Carbon Tetrachloride; D003094:Collagen / Q000009:adverse effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006909:Hydroxyproline / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008103:Liver Cirrhosis / Q000188:drug therapy; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D011897:Random Allocation; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D020533:Angiogenesis Inhibitors; D004365:Drugs, Chinese Herbal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; C576320:yiguanjian decoction; D003094:Collagen; D002251:Carbon Tetrachloride; D040301:Vascular Endothelial Growth Factor Receptor-2; D006909:Hydroxyproline