Positive effects of Ger-Gen-Chyn-Lian-Tang on cholestatic liver fibrosis in bile duct ligation-challenged mice

pose of this study was to investigate whether Ger-Gen-Chvn-Lian-Tang (GGCLT) resses oxidative stress, inflammation, and angiogenesis during experimental liver fibrosis through x>xia-inducible factor-la (HIF-la)-mediated pathway. Male C57BL/6 mice were randomly assigned to a sham-control or bile duct ligation (BDL) group with or without treatment with GGCLT at 30,100, and 300 mg/kg. Plasma alanine aminotransferase (ALT) levels were analyzed using a diagnostic kit. Liver histopathologv and hepatic status parameters were measured. Compared to control mice, the BDL mice exhibited an enlargement in liver HIF-la levels, which was suppressed bv 100 and 300 mg/kg GGCLT treatments (control: BDL: BDL + GGCLT-100: BDL + GGCLT-300 = 0.95 ± 0.07 1,95|± |0,12: 1.43|± |0,05: 1.12|± |0.10 fold; p|<|0.05). GGCLT restrained the induction of hepatic hydroxyproline and malondialdehyde levels in the mice challenged with BDL, further increasing the hepatic glutathione levels. Furthermore, in response to increased hepatic inflammation and fibrogenesis, significant levels of ALT, nuclear factor kappa B, transforming growth factor-0, ot-smooth muscle actin, matrix metalloproteinase-2 (MMP-2), MMP-9, and procolIagen-III were found in BDL mice, which were attenuated with GGCLT In addition, GGCLT reduced the induction of angiogenesis in the liver after BDL by inhibiting vascular endothelial growth factor (VEGF) and VEGF receptors 1 and 2. In conclusion, the anti-liver fibrosis effect of GGCLT, which suppresses hepatic oxidative stress and angiogenesis, may be dependent on an HIF-la-mediated pathway.