Effect of cyanidin 3-O-β-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. Aim. To evaluate the effect of cyanidin-3-O-beta-glucopyranoside on hepatic stellate cells proliferation and collagen synthesis induced by a pro-oxidant agent. Methods/results. Oxidative stress was induced by incubation of hepatic stellate cells with a ferric nitrilotriacetate complex (100 mu mol/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 50 mu mol/L. Similarly, cyanidin-3-O-beta-lucopyranoside was able to inhibit ferric nitrilotriacetate-induced hepatic stellate cells proliferation, evaluated by an ELISA method, with a maximal effect at 50 mu mol/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. Conclusion. 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. (c) 2005 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.