The Effects of Silibinin on Gene Expression of NOX1, NOX2, and the Production of Reactive Oxygen Species in TGF-Β-Treated Liver Stellate Cells

Abstract

Background: Liver fibrosis is a chronic disease caused by viral infections (such as hepatitis B and C viruses), alcohol abuse, and metabolic and genetic disorders that leads to excessive accumulation of extracellular matrix proteins, including collagen. The progression of liver fibrosis can leads to cirrhosis and liver cancer. In this study, the role of silibinin in the prevention of liver fibrosis progression was investigated.Methods: LX2 cells were cultured in DMEM medium with 10% Fetal Bovine Serum (FBS). In the first stage, cells were treated with TGF-β at a concentration of 2 ng / ml (fibrotic group) for cell damage and fibrotic conditions for 24 hours, then at concentrations of 10, 20, 40, 60 and 80 μM of silibinin (The treatment groups) were treated for 24 hours and the mRNA expression of αSMA, collagen1α, NOX1 and NOX2 genes and the rate of intracellular reactive oxygen species (ROS) production were measured.Findings: The results showed that the mRNA expression of αSMA, collagen1α, NOX1 and NOX2 genes at concentrations of 60 and 80 μM silibinin was significantly reduced compared to the TGF-β group. Also, the rate of intracellular ROS production at 60 and 80 μM concentrations of silibinin was significantly reduced compared to the TGF-β group (P < 0.05).Conclusion: According to our study, silibinin inhibits the activation of Hepatic stellate cells (HSCs) by reducing the expression of genes involved in the progression of hepatic fibrosis and reduces liver damage caused by excessive production of collagen and reactive oxygen species in vitro. The findings from this study indicate that silybinin may be a potential therapeutic agent in the treatment of liver fibrosis.

Keywords

• liver fibrosis
• silibinin
• reactive oxygen species
• transforming growth factor beta