title: Effect of Total Flavone of Haw Leaves on Nuclear Factor Erythroid-2 Related Factor and Other Related Factors in Nonalcoholic Steatohepatitis Rats.
abstract: OBJECTIVE
  To investigate the effect of total flavone of haw leaves (TFHL) on the expression of nuclear factor erythroid-2 related factor (Nrf2) and other related factors in nonalcoholic steatohepatitis (NASH) rats induced by high-fat diet and then to further discuss the mechanism of TFHL's prevention against NASH.
  
  
  METHODS
  High-fat diet was fed to 40 rats to establish the NASH model. Then model rats were intragastrically administrated with 40, 80, 160 mg/(kg•day) TFHL, respectively. The pathological changes of liver tissues in NASH rats were detected by oil red O and hematoxylin-eosin (HE) stainings. The expression of Nrf2 in rat liver was examined through immunohistochemistry. The level of 8-iso-prostaglandin F2α in serum was detected through enzyme linked immunosorbent assay (ELISA). The mRNA and protein levels of Nrf2 and other related factors in liver tissue were measured by real-time reverse transcriptionpolymerase chain reaction and western blot.
  
  
  RESULTS
  Lipid deposition, hepatic steatosis, focal necrosis in lobular inflammation and ballooning degeneration were emerged in livers of NASH rats. The 8-iso-prostaglandin F2α in the serum of NASH rats increased significantly compared with the control group (P<0.05). The mRNA of Nrf2, hemeoxyenase1 (HO-1) and the mRNA and protein levels of quinine oxidoreductase (NQO1) in NASH rats liver tissue showed a striking increase, while the mRNA levels of Keap1, r-glutamylcysteine synthethase (rGCS) and glutathione S-transferase (GST) were significantly decreased compared with the control group (P<0.05). After TFHL treatment, 8-iso-prostaglandin F2α level in serum significantly decreased, and Nrf2 mRNA and protein levels in hepatocytes nucleus enhanced compared with the model group (P<0.05 or 0.01). Meanwhile the Keap1 mRNA, the mRNA and protein levels of HO-1, NQO1 antibody, rGCS antibody, GST increased after TFHL treatment (P<0.05 or 0.01).
  
  
  CONCLUSIONS
  Nrf2 and other related factors were involved in development of NASH, and they also served as an important part in its occurrence. By regulating expression of Nrf2 and other related factors, TFHL may play a role in antioxidative stress and prevention of NASH.
authors.affiliation: Laboratory Animal Research Center, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: De-Jun
authors.initials: DJ
authors.lastname: Wang
authors.affiliation: Laboratory Animal Research Center, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: Yue-Qin
authors.initials: YQ
authors.lastname: Cai
authors.affiliation: Drug Safety Evaluation Center, Zhejing Academy of Medical Sciences, Hangzhou, 310053, China.
authors.forename: Shui-Zhen
authors.initials: SZ
authors.lastname: Pan
authors.affiliation: Laboratory Animal Research Center, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: Li-Zong
authors.initials: LZ
authors.lastname: Zhang
authors.affiliation: Drug Safety Evaluation Center, Zhejing Academy of Medical Sciences, Hangzhou, 310053, China.
authors.forename: Yun-Xiang
authors.initials: YX
authors.lastname: Chen
authors.affiliation: Laboratory Animal Research Center, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: Fang-Ming
authors.initials: FM
authors.lastname: Chen
authors.affiliation: Laboratory Animal Research Center, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Jin
authors.affiliation: The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: Mao-Xiang
authors.initials: MX
authors.lastname: Yan
authors.affiliation: The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Li
authors.affiliation: The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310053, China. zhiych123@163.com.
authors.forename: Zhi-Yun
authors.initials: ZY
authors.lastname: Chen
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D027825:Crataegus / Q000737:chemistry*; D015237:Dinoprost / Q000378:metabolism; D047309:Flavones / Q000494:pharmacology / Q000627:therapeutic use*; D008055:Lipids / Q000737:chemistry; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008517:Phytotherapy; D018515:Plant Leaves / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D047309:Flavones; D008055:Lipids; D051267:NF-E2-Related Factor 2; D012333:RNA, Messenger; D015237:Dinoprost; C043562:flavone
keywords: nonalcoholic steatohepatitis; nuclear factor erythroid-2 related factor; total flavone of Haw leaves