title: Caffeic acid phenethyl ester inhibits liver fibrosis in rats.
abstract: OBJECTIVE
  To investigate the hepatoprotective effects and antioxidant activity of caffeic acid phenethyl ester (CAPE) in rats with liver fibrosis.
  
  
  METHODS
  A total of 75 male Sprague-Dawley rats were randomly assigned to seven experimental groups: a normal group (n = 10), a vehicle group (n = 10), a model group (n = 15), a vitamin E group (n = 10), and three CAPE groups (CAPE 3, 6 and 12 mg/kg, n = 10, respectively). Liver fibrosis was induced in rats by injecting CCl4 subcutaneously, feeding with high fat forage, and administering 30% alcohol orally for 10 wk. Concurrently, CAPE (3, 6 and 12 mg/kg) was intraperitoneally administered daily for 10 wk. After that, serum total bilirubin (TBil), aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured to assess hepatotoxicity. To investigate antioxidant activity of CAPE, malondialdehyde (MDA), glutathione (GSH) levels, catalase (CAT) and superoxide dismutase (SOD) activities in liver tissue were determined. Moreover, the effect of CAPE on α-smooth muscle actin (α-SMA), a characteristic hallmark of activated hepatic stellate cells (HSCs), and NF-E2-related factor 2 (Nrf2), a key transcription factor for antioxidant systems, was investigated by immunohistochemistry.
  
  
  RESULTS
  Compared to the model group, intraperitoneal administration of CAPE decreased TBil, ALT, and AST levels in liver fibrosis rats (P < 0.05), while serum TBil was decreased by CAPE in a dose-dependent manner. In addition, the liver hydroxyproline contents in both the 6 and 12 mg/kg CAPE groups were markedly lower than that in the model group (P < 0.05 and P < 0.001, respectively). CAPE markedly decreased MDA levels and, in turn, increased GSH levels, as well as CAT and SOD activities in liver fibrosis rats compared to the model group (P < 0.05). Moreover, CAPE effectively inhibited α-SMA expression while increasing Nrf2 expression compared to the model group (P < 0.01).
  
  
  CONCLUSIONS
  The protective effects of CAPE against liver fibrosis may be due to its ability to suppress the activation of HSCs by inhibiting oxidative stress.
authors: Mei Li, Xiu-Fang Wang, Juan-Juan Shi, Ya-Ping Li, Ning Yang, Song Zhai, Shuang-Suo Dang, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710004, Shannxi Province, China.
authors: Mei
authors: M
authors: Li
authors: Mei Li, Xiu-Fang Wang, Juan-Juan Shi, Ya-Ping Li, Ning Yang, Song Zhai, Shuang-Suo Dang, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710004, Shannxi Province, China.
authors: Xiu-Fang
authors: XF
authors: Wang
authors: Mei Li, Xiu-Fang Wang, Juan-Juan Shi, Ya-Ping Li, Ning Yang, Song Zhai, Shuang-Suo Dang, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710004, Shannxi Province, China.
authors: Juan-Juan
authors: JJ
authors: Shi
authors: Mei Li, Xiu-Fang Wang, Juan-Juan Shi, Ya-Ping Li, Ning Yang, Song Zhai, Shuang-Suo Dang, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710004, Shannxi Province, China.
authors: Ya-Ping
authors: YP
authors: Li
authors: Mei Li, Xiu-Fang Wang, Juan-Juan Shi, Ya-Ping Li, Ning Yang, Song Zhai, Shuang-Suo Dang, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710004, Shannxi Province, China.
authors: Ning
authors: N
authors: Yang
authors: Mei Li, Xiu-Fang Wang, Juan-Juan Shi, Ya-Ping Li, Ning Yang, Song Zhai, Shuang-Suo Dang, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710004, Shannxi Province, China.
authors: Song
authors: S
authors: Zhai
authors: Mei Li, Xiu-Fang Wang, Juan-Juan Shi, Ya-Ping Li, Ning Yang, Song Zhai, Shuang-Suo Dang, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an 710004, Shannxi Province, China.
authors: Shuang-Suo
authors: SS
authors: Dang
mesh_terms: D000428:Alcohol Drinking; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D002109:Caffeic Acids / Q000494:pharmacology*; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019610:Cytoprotection; D059305:Diet, High-Fat; D004305:Dose-Response Relationship, Drug; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D002109:Caffeic Acids; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D002251:Carbon Tetrachloride; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol
keywords: Caffeic acid phenethyl ester; Liver fibrosis; NF-E2-related factor 2; Oxidative stress; α-smooth muscle actin