Effect of cyanidin 3- O-β-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-β-glucopyranoside is a natural antioxidant compound distributed in several fruits and vegetables. Aim. To evaluate the effect of cyanidin-3- O-β-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 μmol/L). Incubation with ferric nitrilotriacetate induced an increased intracellular hydroperoxide formation, which was completely inhibited by cyanidin-3- O-β-glucopyranoside at a concentration of 50 μmol/L. Similarly, cyanidin-3- O-β-glucopyranoside was able to inhibit ferric nitrilotriacetate-induced hepatic stellate cells proliferation, evaluated by an ELISA method, with a maximal effect at 50 μmol/L. Incubation of hepatic stellate cells with cyanidin-3- O-β-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-β-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-β-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.