title: Effect of cyanidin 3-O-beta-glucopyranoside on hepatic stellate cell proliferation and collagen synthesis induced by oxidative stress.
abstract: BACKGROUND
  Reactive oxygen species play a role in the pathogenesis of hepatic fibrosis, mainly through the activation of hepatic stellate cells. Cyanidin-3-O-beta-glucopyranoside is a natural antioxidant compound distributed in several fruits and vegetables.
  
  
  OBJECTIVE
  To evaluate the effect of cyanidin-3-O-beta-glucopyranoside on hepatic stellate cells proliferation and collagen synthesis induced by a pro-oxidant agent.
  
  
  RESULTS
  Oxidative stress was induced by incubation of hepatic stellate cells with a ferric nitrilotriacetate complex (100 micromol/L). Incubation with ferric nitrilotriacetate induced an increased intracellular hydroperoxide formation, which was completely inhibited by cyanidin-3-O-beta-glucopyranoside at a concentration of 50mumol/L. Similarly, cyanidin-3-O-beta-glucopyranoside was able to inhibit ferric nitrilotriacetate-induced hepatic stellate cells proliferation, evaluated by an ELISA method, with a maximal effect at 50mumol/L. Incubation of hepatic stellate cells with cyanidin-3-O-beta-glucopyranoside inhibited ferric nitrilotriacetate-induced extracellular signal-regulated kinase 1/2 activation, evaluated by western blot, whereas it did not affect p70S6 kinase and AKT expression. Finally, cyanidin-3-O-beta-glucopyranoside reduced ferric nitrilotriacetate-induced Na(+)/H(+) exchange activation, evaluated by a spectrofluorimetric method, and collagen type I synthesis, evaluated by northern blot.
  
  
  CONCLUSIONS
  Cyanidin-3-O-beta-glucopyranoside is able to modulate hepatic stellate cells proliferation and type I collagen synthesis induced by a pro-oxidant agent, thus suggesting a potential role for this antioxidant compound in the prevention of fibrosis in chronic liver diseases.
authors.affiliation: Department of Gastroenterology, University of Ancona, Polo Didattico, III Piano, Via Tronto 10, 60020 Torrette, Ancona, Italy. a.disario@univpm.it
authors.forename: E
authors.initials: E
authors.lastname: Bendia
authors.forename: A
authors.initials: A
authors.lastname: Benedetti
authors.forename: G S
authors.initials: GS
authors.lastname: Baroni
authors.forename: C
authors.initials: C
authors.lastname: Candelaresi
authors.forename: G
authors.initials: G
authors.lastname: Macarri
authors.forename: L
authors.initials: L
authors.lastname: Trozzi
authors.forename: A
authors.initials: A
authors.lastname: Di Sario
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D015152:Blotting, Northern; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D008099:Liver / Q000166:cytology*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects*; D013050:Spectrometry, Fluorescence
chemical_list: D000872:Anthocyanins; D017923:Sodium-Hydrogen Exchangers; C462279:cyanidin-3-O-beta-glucopyranoside; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3