Although hepatitis C virus (HCV) affects approximately 130–170 million people worldwide, no vaccines are available. HCV is an important cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma, leading to the need for liver transplantation. In this study, curcumin, a constituent used in traditional Chinese medicine, has been evaluated for its anti-HCV activity and mechanism, using a human hepatoma cell line containing the HCV genotype 1b subgenomic replicon. Below the concentration of 20% cytotoxicity, curcumin dose-dependently inhibited HCV replication by luciferase reporter gene assay, HCV RNA detection and HCV protein analysis. Under the same conditions, curcumin also dose-dependently induced heme oxygenase-1 with the highest induction at 24 h. Hemin, a heme oxygenase-1 inducer, also inhibited HCV protein expression in a dose-dependent manner. The knockdown of heme oxygenase-1 partially reversed the curcumin-inhibited HCV protein expression. In addition to the heme oxygenase-1 induction, signaling molecule activities of AKT, extracellular signal-regulated kinases (ERK) and nuclear factor-κB (NF-κB) were inhibited by curcumin. Using specific inhibitors of PI3K-AKT, MEK-ERK and NF-κB, the results suggested that only PI3K-AKT inhibition is positively involved in curcumin-inhibited HCV replication. Inhibition of ERK and NF-κB was likely to promote HCV protein expression. In summary, curcumin inhibited HCV replication by heme oxygenase-1 induction and AKT pathway inhibition. Although curcumin also inhibits ERK and NF-κB activities, it slightly increased the HCV protein expression. This result may provide information when curcumin is used as an adjuvant in anti-HCV therapy.

No abstract

Hepatic fibrosis is an over-accumulation of extracellular matrix (ECM). It is a result of an imbalance between collagen synthesis and degradation. Matrix metalloproteinase (MMP) has degradative activity against collagen, but tissue inhibitors of metalloproteinase (TIMP) control the active forms of MMP by blocking the active site of MMP. In our study, we established the bile duct ligated model (BDL) in rats to evaluate anti-fibrotic potential of Chinese medicine sho-saiko-to (TJ-9). We assessed the drug's potential in inhibiting collagen accumulation, suppressing procollagen alpha1 types (I) and (III), and TIMP-1 mRNA expression. After administration of TJ-9, hyperbilirubinemia reduced approximately four-fold when compared with BDL-untreated group. TJ-9 also significantly reduced the collagen content and fibrogenic score, as well as downregulated elevated procollagen alpha1 types (I) and (III) and TIMP-1 mRNA level. Finally, we concluded that (1) TJ-9 significantly reduced cholestasis in rats with BDL, (2) TJ-9 markedly reduced the collagen content by 50%, and (3) TJ-9 exerted its antifibrogenic effect by downregulation of the mRNA expression of procollagen alpha1 types (I) and (III), and TIMP-1 in liver tissue.

No abstract