Aim: To explore the protective effect and the relevant mechanisms of Fufang Biejia Ruangan Pills (FFBJRGP) on hepatic fibrosis in vivo and in vitro.
Methods: Hepatic fibrosis was induced by carbon tetrachloride composite factors. Adult Wistar rats were randomly divided into four groups: normal control group; hepatic fibrosis model group; FFBJRGP-treated group at a daily dose of 0.55 g/kg; and colchicine-treated group at a daily dose of 0.1 g/kg. The effects of FFBJRGP on liver function, serum levels of hyaluronic acid (HA), type IV collagen (CIV), type III procollagen (PC III), laminin (LN), histopathology, and expression of transforming growth factor (TGF-β1) and Smad3 in hepatic fibrosis were evaluated in vivo. The effects of FFBJRGP on survival rate, hydroxyproline content and cell cycle distribution were further detected in vitro.
Results: Compared with the hepatic fibrosis model group, rats treated with FFBJRGP showed a reduction in hepatic collagen deposition and improvement in hepatic lesions. Compared with those of the model group, the activities of alanine aminotransferase (62.0 ± 23.7 U/L) and aspartate aminotransferase (98.8 ± 40.0 U/L) in the FFBJRGP-treated group were decreased (50.02 ± 3.7 U/L and 57.2 ± 30.0 U/L, respectively, P < 0.01). Compared with those in the model group, the levels of PCIII (35.73 ± 17.90 μg/mL), HA (563.82 ± 335.54 ng/mL), LN (89.57 ± 7.59 ng/mL) and CIV (29.20 ± 6.17 ng/mL) were decreased to 30.18 ± 9.41, 456.18 ± 410.83, 85.46 ± 7.51 and 28.02 ± 9.45 ng/mL, respectively. Reverse-transcriptase polymerase chain reaction and Western blotting also revealed that expression of TGF-β1 and Smad3 were down-regulated in vivo. Cell proliferation was inhibited, the level of hydroxyproline was decreased compared with the control group (P < 0.01), and the cell cycle was redistributed when exposed to FFBJRGP in vitro.
Conclusion: FFBJRGP inhibits hepatic fibrosis in vivo and in vitro, which is probably associated with downregulation of fibrogenic signal transduction of the TGF-β-Smad pathway.
Keywords: Fufang Biejia Ruangan Pill; Hepatic fibrosis; Transforming growth factor-Smad signaling.