title: Palmitate-induced endothelial dysfunction is attenuated by cyanidin-3-O-glucoside through modulation of Nrf2/Bach1 and NF-κB pathways.
abstract: Free fatty acids (FFA), commonly elevated in diabetes and obesity, have been shown to impair endothelial functions and cause oxidative stress, inflammation, and insulin resistance. Anthocyanins represent one of the most important and interesting classes of flavonoids and seem to play a role in preventing cardiovascular diseases. Herein, we investigated the in vitro protective effects of cyanidin-3-O-glucoside (C3G) on cell signaling pathways in human umbilical vein endothelial cells (HUVECs) exposed to palmitic acid (PA), the most prevalent saturated FFA in circulation. Our data reported a significant augmentation of free radicals and oxidative stress in HUVECs exposed to PA for 3h, while C3G pretreatment improved intracellular redox status altered by FFA. Moreover, C3G significantly inhibited NF-κB proinflammatory pathway and adhesion molecules induced by PA, and these effects were attributed to the activation of Nrf2/EpRE pathway. In fact, C3G induced Nrf2 nuclear localization and activation of cellular antioxidant and cytoprotective genes at baseline and after PA exposure in endothelial cells. Our data confirm the hypothesis that natural Nrf2 inducers, such as C3G, might be a potential therapeutic strategy to protect vascular system against various stressors preventing several pathological conditions.
authors.affiliation: Department of Drug Sciences and Health Products, University of Messina, Viale Annunziata, 98168 Messina, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Fratantonio
authors.affiliation: Department of Drug Sciences and Health Products, University of Messina, Viale Annunziata, 98168 Messina, Italy. Electronic address: specialea@unime.it.
authors.forename: A
authors.initials: A
authors.lastname: Speciale
authors.affiliation: Department of Drug Sciences and Health Products, University of Messina, Viale Annunziata, 98168 Messina, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Ferrari
authors.affiliation: Department of Drug Sciences and Health Products, University of Messina, Viale Annunziata, 98168 Messina, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cristani
authors.affiliation: Department of Drug Sciences and Health Products, University of Messina, Viale Annunziata, 98168 Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Saija
authors.affiliation: Department of Drug Sciences and Health Products, University of Messina, Viale Annunziata, 98168 Messina, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Cimino
mesh_terms: D000872:Anthocyanins / Q000494:pharmacology*; D061745:Antioxidant Response Elements; D000975:Antioxidants / Q000494:pharmacology; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004727:Endothelium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics / Q000378:metabolism*; D005960:Glucosides / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010168:Palmitates / Q000009:adverse effects*; D015398:Signal Transduction
chemical_list: D000872:Anthocyanins; D000975:Antioxidants; C102108:BACH1 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D051856:Fanconi Anemia Complementation Group Proteins; D005960:Glucosides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D010168:Palmitates; C462279:cyanidin-3-O-beta-glucopyranoside; D005978:Glutathione
keywords: Cellular adaptive response; Cyanidin; Endothelial dysfunction; Nrf2; Oxidative stress