Effect of cyanidin 3-O-beta-glucopyranoside on hepatic stellate cell proliferation and collagen synthesis induced by oxidative stress.
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.
Bendia
E
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Department of Gastroenterology, University of Ancona, Polo Didattico, III Piano, Via Tronto 10, 60020 Torrette, Ancona, Italy. a.disario@univpm.it
Benedetti
A
A
Baroni
G S
GS
Candelaresi
C
C
Macarri
G
G
Trozzi
L
L
Di Sario
A
A
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
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