PMID- 27055862 OWN - NLM STAT- MEDLINE DCOM- 20180104 LR - 20180131 IS - 1464-5157 (Electronic) IS - 0265-6736 (Linking) VI - 32 IP - 5 DP - 2016 Aug TI - Punicalagin induces Nrf2 translocation and HO-1 expression via PI3K/Akt, protecting rat intestinal epithelial cells from oxidative stress. PG - 465-73 LID - 10.3109/02656736.2016.1155762 [doi] AB - PURPOSE: 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. MATERIALS AND METHODS: IEC-6 cells were pretreated with PUN for 6 h and exposed to 42 degrees 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. RESULTS: 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. CONCLUSIONS: 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. FAU - Xu, Lei AU - Xu L AD - a Beijing Key Laboratory for Dairy Cow Nutrition , College of Animal Science and Technology, Beijing University of Agriculture , Beijing ; FAU - He, ShaSha AU - He S AD - b College of Veterinary Medicine , China Agricultural University (CAU) , Beijing , China. FAU - Yin, Peng AU - Yin P AD - b College of Veterinary Medicine , China Agricultural University (CAU) , Beijing , China. FAU - Li, DeYin AU - Li D AD - a Beijing Key Laboratory for Dairy Cow Nutrition , College of Animal Science and Technology, Beijing University of Agriculture , Beijing ; FAU - Mei, Chen AU - Mei C AD - a Beijing Key Laboratory for Dairy Cow Nutrition , College of Animal Science and Technology, Beijing University of Agriculture , Beijing ; FAU - Yu, XiaoHong AU - Yu X AD - a Beijing Key Laboratory for Dairy Cow Nutrition , College of Animal Science and Technology, Beijing University of Agriculture , Beijing ; FAU - Shi, YaRan AU - Shi Y AD - a Beijing Key Laboratory for Dairy Cow Nutrition , College of Animal Science and Technology, Beijing University of Agriculture , Beijing ; FAU - Jiang, LinShu AU - Jiang L AD - a Beijing Key Laboratory for Dairy Cow Nutrition , College of Animal Science and Technology, Beijing University of Agriculture , Beijing ; FAU - Liu, FengHua AU - Liu F AD - a Beijing Key Laboratory for Dairy Cow Nutrition , College of Animal Science and Technology, Beijing University of Agriculture , Beijing ; LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160407 PL - England TA - Int J Hyperthermia JT - International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group JID - 8508395 RN - 0 (Antioxidants) RN - 0 (Hydrolyzable Tannins) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Nfe2l2 protein, rat) RN - 0 (Reactive Oxygen Species) RN - 31C4KY9ESH (Nitric Oxide) RN - 65995-63-3 (punicalagin) RN - EC 1.14.14.18 (Heme Oxygenase (Decyclizing)) RN - EC 1.14.14.18 (Hmox1 protein, rat) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Antioxidants/*pharmacology MH - Cell Line MH - Cell Survival MH - Epithelial Cells/*drug effects/metabolism MH - Heme Oxygenase (Decyclizing)/metabolism MH - Hot Temperature/*adverse effects MH - Hydrolyzable Tannins/*pharmacology MH - Intestines/*cytology MH - NF-E2-Related Factor 2/metabolism MH - Nitric Oxide/metabolism MH - Oxidative Stress/drug effects MH - Phosphatidylinositol 3-Kinases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Rats MH - Reactive Oxygen Species/metabolism MH - Superoxide Dismutase/metabolism OTO - NOTNLM OT - Cytoprotection OT - Nrf2 OT - oxidative stress OT - punicalagin EDAT- 2016/04/09 06:00 MHDA- 2018/01/05 06:00 CRDT- 2016/04/09 06:00 PHST- 2016/04/09 06:00 [entrez] PHST- 2016/04/09 06:00 [pubmed] PHST- 2018/01/05 06:00 [medline] AID - 10.3109/02656736.2016.1155762 [doi] PST - ppublish SO - Int J Hyperthermia. 2016 Aug;32(5):465-73. doi: 10.3109/02656736.2016.1155762. Epub 2016 Apr 7.