Hsuan-Miao Liu
Department and Institute of Pharmacology, National Yang-Ming University, Taipei 112 Taiwan
Title: Anti-inflammation properties of Ger-Gen-Chyn-Lian-Tang regulates hepatic fibrosis in a hypoxia- and angiogenesis-signaling in cholestasis mice
Biography
Biography: Hsuan-Miao Liu
Abstract
Angiogenesis plays an important role in liver inflammation and fibrogenesis. GGCLT, a mixed product of herbal remedy which could have a beneficial effect in hepatic fibrosis. This work addressed a novel mechanism by which GGCLT may be potentially against angiogenesis in chronic liver injuries. Common bile duct-ligated (BDL) fibrosis mice were treated with vehicle, GGCLT (10, 30 or 100mg/kg), separately (twice daily for two weeks). Primary hepatic stellate cells (HSCs) were pre-incubated with GGCLT before taurolithocholic acid (TLCA) stimulation. Real-time polymerase chain reaction, immunoblotting and immunohistochemistry stain analysis were used to measure specific markers. Treatment of GGCLT has resulted in dosage-dependent reduction of TLCA-induced expression of HIF-1α and VEGF in the HSCs (p < 0.05). GGCLT significantly reduced ductular proliferation, portal inflammation, hepatic fibrosis and decreased hepatic α-SMA contents. Alanine aminotransferase, PAI-1, OPN and VEGFR1 levels were decreased in the GGCLT treated mice when compared to BDL groups. Furthermore, GGCLT treatment has reduced macrophage-mediated STAT3 phosphorylation and mRNA levels of inflammatory markers IL-6, IL-1β, TNF-α and the p65 subunit of NF-κB (p < 0.05). In conclusion, the hypoxia-angiogenesis signaling promotes liver cholestasis by enhancing HSCs activation and inflammatory response. Our studies demonstrate that GGCLT exhibits anti-inflammatory properties that are comparable to cholestasis both in vivo and in vitro and that these effects are mediated via the angiogenesis signaling pathway.