title: Punicalagin induces Nrf2 translocation and HO-1 expression via PI3K/Akt, protecting rat intestinal epithelial cells from oxidative stress.
abstract: Oxidative stress plays a central role in heat stress-induced gastrointestinal injury. Punicalagin (PUN), a major polyphenol abundant in pomegranate fruit, husk and juice, exhibits antioxidative effects. In this study we used a heat stress model to investigate the intestinal protection effect of PUN and the underlying mechanisms.
  
  
  
  IEC-6 cells were pretreated with PUN for 6 h and exposed to 42 °C for 6 h. Intracellular reactive oxygen species levels, malondialdehyde, nitrogen oxide, and superoxide dismutase activity were measured. IEC-6 cells were treated with PUN at different times and doses, the protein levels of haeme oxygenase-1 (HO-1) were evaluated. The nuclear translocation of the transcription factor NF-erythroid 2-related factor (Nrf2) and the phosphorylation level of PI3K/Akt were also investigated.
  
  
  
  PUN significantly decreased the heat stress-induced cell death and apoptosis. Heat stress increased reactive oxygen species, malondialdehyde and nitrogen oxide production, while it decreased superoxide dismutase activity. These effects were markedly inversed when the cells were pretreated with PUN. Furthermore, PUN treatment induced the expression of HO-1 and increased Nrf2 nuclear translocation in a time- and dose-dependent manner. The Nrf2-related cytoprotective effects of PUN were via the PI3K/Akt signalling pathway, as LY294002, a specific PI3K/Akt inhibitor, suppressed the PUN-induced nuclear translocation of Nrf2, the HO-1 up-regulation and the protective effect of PUN against oxidative stress.
  
  
  
  PUN protects IEC-6 cells against oxidative stress by up-regulating the expression of HO-1 via a mechanism that involves PI3K/Akt activation and Nrf2 translocation.
authors.affiliation: a Beijing Key Laboratory for Dairy Cow Nutrition , College of Animal Science and Technology, Beijing University of Agriculture , Beijing ;
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: b College of Veterinary Medicine , China Agricultural University (CAU) , Beijing , China.
authors.forename: ShaSha
authors.initials: S
authors.lastname: He
authors.affiliation: b College of Veterinary Medicine , China Agricultural University (CAU) , Beijing , China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yin
authors.affiliation: a Beijing Key Laboratory for Dairy Cow Nutrition , College of Animal Science and Technology, Beijing University of Agriculture , Beijing ;
authors.forename: DeYin
authors.initials: D
authors.lastname: Li
authors.affiliation: a Beijing Key Laboratory for Dairy Cow Nutrition , College of Animal Science and Technology, Beijing University of Agriculture , Beijing ;
authors.forename: Chen
authors.initials: C
authors.lastname: Mei
authors.affiliation: a Beijing Key Laboratory for Dairy Cow Nutrition , College of Animal Science and Technology, Beijing University of Agriculture , Beijing ;
authors.forename: XiaoHong
authors.initials: X
authors.lastname: Yu
authors.affiliation: a Beijing Key Laboratory for Dairy Cow Nutrition , College of Animal Science and Technology, Beijing University of Agriculture , Beijing ;
authors.forename: YaRan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: a Beijing Key Laboratory for Dairy Cow Nutrition , College of Animal Science and Technology, Beijing University of Agriculture , Beijing ;
authors.forename: LinShu
authors.initials: L
authors.lastname: Jiang
authors.affiliation: a Beijing Key Laboratory for Dairy Cow Nutrition , College of Animal Science and Technology, Beijing University of Agriculture , Beijing ;
authors.forename: FengHua
authors.initials: F
authors.lastname: Liu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006358:Hot Temperature / Q000009:adverse effects*; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D007422:Intestines / Q000166:cytology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D047348:Hydrolyzable Tannins; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C115642:punicalagin; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D013482:Superoxide Dismutase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Cytoprotection; Nrf2; oxidative stress; punicalagin