engleski

Resolution of liver fibrosis by isoquinoline alkaloid berberine in CCl4-intoxicated mice is mediated by up-regulation of MMP-2 expression

Liver fibrosis is a result of chronic liver injury and represents a widespread medical problem. The aim of this study was to investigate the antifibrotic activity of isoquinoline alkaloid berberine in carbon tetrachloride (CCl4)-induced damage in mice. The hepatoprotective activity of bereberine was compared to the reference drug silymarin. Hepatic fibrosis was induced by intraperitoneal (i.p.) administration of CCl4 (2 ml/kg, 20% v/v in olive oil) twice a week for 8 weeks. Berberine in doses of 3 and 9 mg/kg and silymarin in dose of 50 mg/kg were given i.p. once daily for next 2 weeks. CCl4-intoxication induced elevation of serum transaminases and oxidative stress in the livers. Hepatic fibrosis was evidenced by massive deposition of collagen, which coincided with increased expression of the tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 in the livers and activation of hepatic stelate cells (HSCs). The high-dose berberine (9 mg/kg) ameliorated oxidative stress, decreased the TNF-α and TGF-β1 expression, increased the matrix metalloproteinase (MMP)-2 levels and stimulated elimination of fibrotic deposits. Berberin in dose of 9 mg/kg exhibited stronger therapeutic activity against hepatic fibrosis than silymarin 50 mg/kg. The results of this study suggest that berberine could be used for treatment of liver fibrosis through down-regulation of hepatic fibrogenic potential and stimulation of degradation of collagen deposits by MMP-2.

liver fibrosis; berberine; tumor necrosis factor-α; transforming growth factor-β1; α-smooth muscle actin; matrix metalloproteinase

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