title: The anti-inflammatory and antioxidant effects of bergamot juice extract (BJe) in an experimental model of inflammatory bowel disease.
abstract: OBJECTIVE
  The beneficial properties of the flavonoid fraction of bergamot juice (BJe) have been raising interest and have been the subject of recent studies, considering the potentiality of its health promoting substances. Flavonoids have demonstrated radical-scavenging and anti-inflammatory activities. The aim of the present study was to examine the effects of BJe in mice subjected to experimental colitis.
  
  
  METHODS
  Colitis was induced in mice by intracolonic instillation of dinitrobenzene sulfonic acid (DNBS). BJe was administered daily orally (at 5, 10 and 20 mg/kg).
  
  
  RESULTS
  Four days after DNBS administration, colon nuclear factor NF-κB translocation and MAP kinase phospho-JNK activation were increased as well as cytokine production such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β. Neutrophil infiltration, by myeloperoxidase (MPO) activity, in the mucosa was associated with up-regulation of adhesion molecules (ICAM-1 and P-selectin). Immunohistochemistry for nitrotyrosine and poly ADP-ribose (PAR) also showed an intense staining in the inflamed colon. Treatment with BJe decreased the appearance of diarrhea and body weight loss. This was associated with a reduction in colonic MPO activity. BJe reduced nuclear NF-κB translocation, p-JNK activation, the pro-inflammatory cytokines release, the appearance of nitrotyrosine and PAR in the colon and reduced the up-regulation of ICAM-1 and P-selectin. In addition, colon inflammation was also associated with apoptotic damage. Treatment with BJe caused a decrease of pro-apoptotic Bax expression and an increase of anti-apoptotic Bcl-2 expression.
  
  
  CONCLUSIONS
  The results of this study suggested that administration of BJe induced, partly specified, anti-inflammatory mechanisms, which potentially may be beneficial for the treatment of IBD in humans.
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166 Messina, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Impellizzeri
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166 Messina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bruschetta
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166 Messina, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166 Messina, Italy.
authors.forename: Akbar
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166 Messina, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Campolo
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166 Messina, Italy; Manchester Biomedical Research Centre, Manchester Royal Infirmary, School of Medicine, University of Manchester, UK. Electronic address: salvator@unime.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.affiliation: Department of Biological and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D'Alcontres, 31-98166 Messina, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.affiliation: Department of Drug Sciences and Products for Health, University of Messina, SS. Annunziata, Messina 98168, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Navarra
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001557:Benzenesulfonates; D001628:Beverages / Q000032:analysis; D002957:Citrus / Q000737:chemistry*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; C494827:Bax protein, mouse; D001557:Benzenesulfonates; D053583:Interleukin-1beta; D016328:NF-kappa B; D019007:P-Selectin; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; C007488:dinitrobenzenesulfonic acid; D018799:Intercellular Adhesion Molecule-1; D011064:Poly Adenosine Diphosphate Ribose; C002744:3-nitrotyrosine; D014443:Tyrosine; D009195:Peroxidase
keywords: Apoptosis; Citrus bergamia; Colitis; Cytokines; Inflammation; Oxidative stress