Herb medicine Gan-fu-kang attenuates liver injury in a rat fibrotic model

Aim of the studyTo verify therapeutic effects of Gan-fu-kang (GFK), a traditional Chinese medicine compound, in a rat model and to investigate the underlying mechanisms.Materials and methodsLiver fibrosis was established by 12 weeks of carbon tetrachloride (CCl4) treatment (0.5 mg/kg, twice per week) followed by 8 weeks of “recovery” in rats. Rats randomly received GFK (31.25, 312.5 and 3125 mg/kg/day, p.o.) or vehicle from weeks 9 to 20, and were sacrificed at the end of week 20 for histological, biochemical, and molecular biological examinations. In a separate set of experiments, rats received 12 weeks of CCl4 treatment, concomitant with GFK (312.5 mg/kg/day, p.o.) during the same period in some subjects, but were then sacrificed immediately. An additional group of rats receiving no CCl4 treatment served as normal controls.Results and conclusions(1) CCl4 treatment resulted in severe liver damage and fibrosis. (2) In the main block of the 20-week study, GFK attenuated liver damage and fibrosis. (3) In the 12-week study, GFK produced prevention effect against hepatic injury. (4) GFK suppressed the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), type I collagen, platelet-derived growth factor-BB (PDGF-BB)/PDGF receptor-β chains (PDGFRβ) and mitogen-activated protein kinases (MAPKs)/active protein-1 (AP-1) signal pathways. Taken together, these results indicated that GFK could attenuate liver injuries in both settings. Our findings also suggest that the AP-1 pathway is the likely molecular substrate for the observed GFK effects.