Metformin

Metformin upregulates BAX activation with facilitation of BIM, BAD and PUMA, downregulates Bcl-2 and Bcl-xl, also induces cytochrome c release from mitochondria into the cytoplasm, directly triggering caspase-9-mediated mitochondrial apoptosis.^[4]

The human hepatic stellate cells (HSCs) LX-2 is maintained in RPMI 1640 medium, rat HSCs T6, human hepatocyte L02 and rat hepatocyte BRL-3A were maintained in DMEM, which are both supplemented with 10% (v/v) FBS and 1% (v/v) penicillin/streptomycin sulfate at 37 ℃ in a humidified 5% CO₂ incubator. Metformin and AICAR solutions are filtered through 0.22 μm millipore membrane filter units. CCK8 assay is used to detect the effects of different concentration of metformin and AICAR on the proliferation of hepatic stellate cells. T6 cells and LX-2 cells are treated with different concentration of metformin and AICAR for 24 h, and the expression of collagen and α - SMA protein are detected by Western blot. Cells are treated with 10 mM metformin and 0.5 mM AICAR for 24 h, and the expression of collagen and α - SMA protein are detected by Western blot. The mRNA levels of collagen I and α - SMA are detected by RT-qPCR.

Metformin shows therapeutic effect of metformin in mouse model of liver fibrosis associated with nonalcoholic steatohepatitis (NASH) in which hepatic function, NASH lesions and fibrosis are improved.^[4]