PMID- 27793764 OWN - NLM STAT- MEDLINE DCOM- 20170202 LR - 20220310 IS - 1879-3169 (Electronic) IS - 0378-4274 (Linking) VI - 264 DP - 2016 Dec 15 TI - Cyanidin-3-O-glucoside inhibits NF-kB signalling in intestinal epithelial cells exposed to TNF-alpha and exerts protective effects via Nrf2 pathway activation. PG - 51-58 LID - S0378-4274(16)33288-X [pii] LID - 10.1016/j.toxlet.2016.10.014 [doi] AB - Chronic intestinal inflammatory disorders, such as Inflammatory Bowel Diseases (IBDs), are characterized by excessive release of proinflammatory mediators, intestinal barrier dysfunction and excessive activation of NF-kB cascade. Previous studies shown that TNF-alpha plays a central role in intestinal inflammation of IBDs and supported beneficial effects of flavonoids against chronic inflammatory diseases. In this study, we employed an in vitro model of acute intestinal inflammation using intestinal Caco-2 cells exposed to TNF-alpha. The protective effects of cyanidin-3-glucoside (C3G), an anthocyanin widely distributed in mediterranean diet, were then evaluated. Caco-2 cells exposure to TNF-alpha activated NF-kB proinflammatory pathway and induced IL6 and COX-2 expression. Cells pretreatment for 24h with C3G (20-40muM) prevented TNF-alpha-induced changes, and improved intracellular redox status. Our results demonstrated that C3G, also without any kind of stimulus, increased the translocation of the transcription factor Nrf2 into the nucleus so activating antioxidant and detoxifying genes. In conclusion, C3G exhibited protective effects through the inhibition of NF-kB signalling in Caco-2 cells and these beneficial effects appear to be due to its ability to activate cellular protective responses modulated by Nrf2. These data suggest that anthocyanins could contribute, as complementary or preventive approaches, to the management of chronic inflammatory diseases. CI - Copyright A(c) 2016 Elsevier Ireland Ltd. All rights reserved. FAU - Ferrari, Daniela AU - Ferrari D AD - Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Italy. Electronic address: dani841984@libero.it. FAU - Speciale, Antonio AU - Speciale A AD - Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Italy. Electronic address: specialea@unime.it. FAU - Cristani, Mariateresa AU - Cristani M AD - Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Italy. Electronic address: mcristani@unime.it. FAU - Fratantonio, Deborah AU - Fratantonio D AD - Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Italy. Electronic address: dfratantonio2@unl.edu. FAU - Molonia, Maria Sofia AU - Molonia MS AD - Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Italy. Electronic address: mmolonia@unime.it. FAU - Ranaldi, Giulia AU - Ranaldi G AD - Council for Agricultural Research and Economics, Food and Nutrition Research Centre, (CREA - NUT), Rome, Italy. Electronic address: giulia.ranaldi@crea.gov.it. FAU - Saija, Antonella AU - Saija A AD - Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Italy. Electronic address: asaija@unime.it. FAU - Cimino, Francesco AU - Cimino F AD - Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Italy. Electronic address: fcimino@unime.it. LA - eng PT - Journal Article DEP - 20161025 PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (Anthocyanins) RN - 0 (Antioxidants) RN - 0 (Glucosides) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NF-kappa B) RN - 0 (NFE2L2 protein, human) RN - 0 (Prostaglandins) RN - 0 (Thromboxanes) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (cyanidin-3-O-beta-glucopyranoside) RN - EC 1.14.99.1 (Cyclooxygenase 2) SB - IM MH - Anthocyanins/*pharmacology MH - Antioxidants/metabolism MH - Caco-2 Cells MH - Cyclooxygenase 2/metabolism MH - Epithelial Cells/*drug effects MH - Glucosides/*pharmacology MH - Humans MH - Intestinal Mucosa/cytology/drug effects/metabolism MH - NF-E2-Related Factor 2/*agonists MH - NF-kappa B/*antagonists & inhibitors MH - Prostaglandins/metabolism MH - Signal Transduction/drug effects MH - Thromboxanes/metabolism MH - Tumor Necrosis Factor-alpha/*pharmacology OTO - NOTNLM OT - 12303203) OT - Anthocyanin OT - Caco-2 cells OT - Cyanidin OT - Cyanidin 3-O-glucoside (PubChem CID OT - Inflammatory bowel diseases OT - NF-kB OT - Nrf2 OT - Wedelolactone (PubChem CID: 5281813) EDAT- 2016/10/30 06:00 MHDA- 2017/02/06 06:00 CRDT- 2016/10/30 06:00 PHST- 2016/09/07 00:00 [received] PHST- 2016/10/21 00:00 [revised] PHST- 2016/10/24 00:00 [accepted] PHST- 2016/10/30 06:00 [pubmed] PHST- 2017/02/06 06:00 [medline] PHST- 2016/10/30 06:00 [entrez] AID - S0378-4274(16)33288-X [pii] AID - 10.1016/j.toxlet.2016.10.014 [doi] PST - ppublish SO - Toxicol Lett. 2016 Dec 15;264:51-58. doi: 10.1016/j.toxlet.2016.10.014. Epub 2016 Oct 25.