Effects of standardized bilberry fruit extract (Mirtoselect®) on resolution of CCl4-induced liver fibrosis in mice

Bilberry (Vaccinium myrtillus L) has been traditionally used in the treatment of various liver disorders. The aim of this study was to investigate the effects of bilberry fruit extract (BE) on carbon tetrachloride (CCl4)-induced hepatic fibrosis. Male Balb/C mice were treated with CCl4 dissolved in olive oil (20% v/v, 2 ml/kg) intraperitoneally (i.p.), twice a week for 7 weeks. BE (1, 5, and 10 mg/kg) was given to mice for next 15 days, 72 h after the last dose of CCl4. The CCl4 administration increased oxidative stress as well as the expression of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta 1 (TGF-beta 1) in the liver. Furthermore, increased alpha-smooth muscle actin (alpha-SMA) expression and hydroxyproline levels indicated activation of hepatic stellate cells (HSCs) and enhanced collagen production. BE 10 mg/kg markedly attenuated oxidative stress, decreased TNF-alpha, TGF-beta 1, and alpha-SMA expression, and eliminated hepatic collagen deposits. These results indicate that BE, in a dose dependent manner, induces the resolution of liver fibrosis by decreasing oxidative stress and inactivating HSCs via down-regulation of fibrogenic cytokines, TGF-beta 1 and TNF-alpha. (C) 2010 Elsevier Ltd. All rights reserved.