CGX, a multiple herbal drug, improves cholestatic liver fibrosis in a bile duct ligation-induced rat model.

ETHNOPHARMACOLOGIC RELEVANCE: CGX is a modification of a traditional herbal medicine that has been used for various liver disorders as a meaning of "cleaning the liver". The cholestatic liver disorders become prevalent. BACK GROUND AND AIM: This study aimed to investigate the anti-hepatic fibrosis effects of CGX and its underlying mechanisms in a rat model of bile duct ligation (BDL).

MATERIALS AND METHODS: BDL was conducted in SD rats except shame operation group. The rats were orally administrated with distilled water, CGX (25 or 50 mg/kg) or ursodeoxycholic acid (UDCA, 25 mg/kg) for two weeks. The pharmaceutical effects and mechanisms were analyzed in histopathology, biochemistry, oxidative stress/antioxidant biomarkers and hepatic fibrogenic cytokines levels.

RESULTS: BDL markedly elevated white blood cell (WBC) counts as well as changed subset proportions such as increased neutrophils and decreased lymphocytes in peripheral blood. BDL drastically elevated the serum levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin, and hepatic tissue levels of hydroxyproline and malondialdehyde (MDA), while it reduced the total glutathione (GSH) content and the activities of GSH-redox system enzymes such as GSH-peroxidase, GSH-reductase and GSH-S-transferase. These alterations were significantly attenuated by CGX treatment (mainly 50 mg/kg). CGX treatment normalized both the accumulation of collagen in hepatic tissue and the increased levels of profibrogenic cytokine including transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor-BB (PDGF-BB). Moreover, CGX treatment enhanced interferon-gamma (IFN-γ) expression compare to the BDL group at the protein and gene level.

CONCLUSION: These results suggest that CGX exerts anti-hepatofibrotic effect in rat BDL model, and the responsible mechanisms involve the inhibition of hepatic fibrogenic cytokines and oxidative stress.