title: Prevention of oxidative stress, inflammation and mitochondrial dysfunction in the intestine by different cranberry phenolic fractions.
abstract: Cranberry fruit has been reported to have high antioxidant effectiveness that is potentially linked to its richness in diversified polyphenolic content. The aim of the present study was to determine the role of cranberry polyphenolic fractions in oxidative stress (OxS), inflammation and mitochondrial functions using intestinal Caco-2/15 cells. The combination of HPLC and UltraPerformance LC®-tandem quadrupole (UPLC-TQD) techniques allowed us to characterize the profile of low, medium and high molecular mass polyphenolic compounds in cranberry extracts. The medium molecular mass fraction was enriched with flavonoids and procyanidin dimers whereas procyanidin oligomers (DP > 4) were the dominant class of polyphenols in the high molecular mass fraction. Pre-incubation of Caco-2/15 cells with these cranberry extracts prevented iron/ascorbate-mediated lipid peroxidation and counteracted lipopolysaccharide-mediated inflammation as evidenced by the decrease in pro-inflammatory cytokines (TNF-α and interleukin-6), cyclo-oxygenase-2 and prostaglandin E2. Cranberry polyphenols (CP) fractions limited both nuclear factor κB activation and Nrf2 down-regulation. Consistently, cranberry procyanidins alleviated OxS-dependent mitochondrial dysfunctions as shown by the rise in ATP production and the up-regulation of Bcl-2, as well as the decline of protein expression of cytochrome c and apoptotic-inducing factor. These mitochondrial effects were associated with a significant stimulation of peroxisome-proliferator-activated receptor γ co-activator-1-α, a central inducing factor of mitochondrial biogenesis and transcriptional co-activator of numerous downstream mediators. Finally, cranberry procyanidins forestalled the effect of iron/ascorbate on the protein expression of mitochondrial transcription factors (mtTFA, mtTFB1, mtTFB2). Our findings provide evidence for the capacity of CP to reduce intestinal OxS and inflammation while improving mitochondrial dysfunction.
authors: Marie-Claude
authors: MC
authors: Denis
authors: ‡Institute of Nutrition and Functional Foods (INAF), Université Laval, Quebec, Quebec G1V 0A6, Canada.
authors: Yves
authors: Y
authors: Desjardins
authors: §Department of Biochemistry, Université de Montréal, Montreal, Quebec H3T 1C5, Canada.
authors: Alexandra
authors: A
authors: Furtos
authors: *Research Centre, CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada, H3T 1C5.
authors: Valérie
authors: V
authors: Marcil
authors: ‡Institute of Nutrition and Functional Foods (INAF), Université Laval, Quebec, Quebec G1V 0A6, Canada.
authors: Stéphanie
authors: S
authors: Dudonné
authors: *Research Centre, CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada, H3T 1C5.
authors: Alain
authors: A
authors: Montoudis
authors: *Research Centre, CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada, H3T 1C5.
authors: Carole
authors: C
authors: Garofalo
authors: Edgard
authors: E
authors: Delvin
authors: André
authors: A
authors: Marette
authors: Emile
authors: E
authors: Levy
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000975:Antioxidants / Q000737:chemistry*; D017209:Apoptosis; D044946:Biflavonoids / Q000737:chemistry; D018938:Caco-2 Cells; D002392:Catechin / Q000737:chemistry; D015232:Dinoprostone / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D007422:Intestines / Q000187:drug effects*; D015227:Lipid Peroxidation; D008928:Mitochondria / Q000187:drug effects*; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D010936:Plant Extracts / Q000627:therapeutic use*; D044945:Proanthocyanidins / Q000737:chemistry; D029799:Vaccinium macrocarpon / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D044946:Biflavonoids; D005227:Fatty Acids; D010936:Plant Extracts; D044945:Proanthocyanidins; C017674:procyanidin; D000255:Adenosine Triphosphate; D002392:Catechin; D015232:Dinoprostone