title: The effects of Tao-Hong-Si-Wu on hepatic necroinflammatory activity and fibrosis in a murine model of chronic liver disease.
abstract: BACKGROUND
  Tao-Hong-Si-Wu decoction (THSWD) is a traditional Chinese herbal medicine that has been used for centuries in the treatment of Chinese patients with chronic liver disease. Recently, THSWD has been reported to alter vascular endothelial growth factor (VEGF) induced angiogenesis, raising the possibility that in addition to its anti-inflammatory properties; THSWD might also inhibit hepatic blood flow associated fibrosis.
  
  
  OBJECTIVE
  To document the effects of THSWD on hepatic necroinflammatory disease activity, fibrosis and VEGF signaling in a murine model of chronic liver disease.
  
  
  METHODS
  Sixty adult mice were equally divided into six study groups. Five groups were exposed to subcutaneous carbon tetrachloride (0.1 ml/10 g BW) for six weeks. Three of the five groups were treated with different concentrations of THSWD (4.25, 8.50, 17.00 g/kg), one with 0.1mg/kg of Colchicine (positive control), and one with physiologic saline (negative control). Mice in the sixth group were not exposed to CCl4 and remained untreated (healthy controls). Liver enzymes/function tests, hyaluronic acid and laminin levels were measured in serum, and hepatic histology, VEGF, Flt-1 and kinase insert domain-containing receptor (KDR), Akt and phosphorylated Akt (pAkt) expression were documented in liver tissue at the end of treatment.
  
  
  RESULTS
  Hepatic necroinflammatory disease activity and fibrosis were significantly attenuated in THSWD treated mice in a dose dependent manner. These beneficial results were similar and often exceeded those achieved with Colchicine. In addition, VEGF, Flt-1, KDR, Akt and pAkt mRNA and protein expression were reduced in TSHWD treated mice.
  
  
  CONCLUSIONS
  In this animal model of chronic liver disease, THSWD decreased hepatic necroinflammatory disease and fibrosis. Inhibition of VEGF expression and downstream signaling were associated with these findings. Further studies with this and other TCMs as treatment for chronic liver disease are warranted.
authors.affiliation: Department of Traditional Chinese Medicine, Medical College, Xiamen University, Xiamen 361102, People's Republic of China. Electronic address: xishengyan@xmu.edu.cn.
authors.forename: Shengyan
authors.initials: S
authors.lastname: Xi
authors.affiliation: Department of Traditional Chinese Medicine, Medical College, Xiamen University, Xiamen 361102, People's Republic of China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Infection, Dongfeng Hospital, Hubei University of Medicine, Shiyan 442000, People's Republic of China.
authors.forename: Xueqiang
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Internal Medicine, John Buhler Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada R3E 3P4.
authors.forename: Gerald Y
authors.initials: GY
authors.lastname: Minuk
authors.affiliation: Department of Traditional Chinese Medicine, Medical College, Xiamen University, Xiamen 361102, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Traditional Chinese Medicine, Medical College, Xiamen University, Xiamen 361102, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: College of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0T5.
authors.forename: Yuewen
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Department of Internal Medicine, John Buhler Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada R3E 3P4.
authors.forename: Yangxinzi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Traditional Chinese Medicine, Medical College, Xiamen University, Xiamen 361102, People's Republic of China.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada R3E 0T5.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Yang
authors.affiliation: Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, People's Republic of China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Yue
authors.affiliation: Department of Traditional Chinese Medicine, Medical College, Xiamen University, Xiamen 361102, People's Republic of China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008517:Phytotherapy; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; C519463:Taohong Siwu decoction II; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D002251:Carbon Tetrachloride; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; Flt-1; Hepatic fibrosis; Hepatic function; Hepatic necroinflammatory activity; Kinase insert domain-containing receptor; Phosphorylated Akt; Tao-Hong-Si-Wu decoction; Vascular endothelial growth factor