San-Huang-Xie-Xin-Tang Extract Suppresses Hepatitis C Virus

Replication and Virus-Induced Cyclooxygenase-2 Expression

 

J.-C. Lee, C.-k. Tseng, S.-F. Wu, F.-R. Chang, C.-C. Chiu and Y.-C. Wu

 

 

Abstract

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Chronic hepatitis C virus (HCV) infection is associated with chronic inflammation of liver, which leads to the development of cirrhosis and hepatocellular carcinoma (HCC). Because of severe side effects and only a 50–70% cure rate in genotype 1 HCV-infected patients upon current standard treatment with pegylated interferon-a plus ribavirin, new therapeutic regimens are still needed. San-Huang-Xie-Xin-Tang (SHXT) is a transitional Chinese herbal formula, composed of Rhei rhizoma, Scutellaria radix and Coptidis rhizome, and possesses anti-inflammatory effect. Here, we describe a (+)-catechin-containing fraction extracted from SHXT, referred as SHXT-frC, exhibited effective inhibition of HCV replication, with selectivity index value (SI; CC50/EC50) of 84, and displayed synergistic anti-HCV effects when combined with interferon-α, HCV protease inhibitor telaprevir or polymerase inhibitor 2’-C-methylcytidine. The activation of factor-ĸB (NF-ĸB) and cyclooxygenase-2 (COX-2) signaling pathway has particular relevance to HCV-associated HCC. SHXT-frC treatment also caused a concentration-dependent decrease in the induction of COX-2 and NF-ĸB expression caused by either HCV replication or HCV NS5A protein. Collectively, SHXT-frC could be an adjuvant treatment for patients with HCV-induced liver diseases.

 

Copyright © 2011 Journal of Viral Hepatitis. All rights reserved.

1.              Introduction

2.              Material and Methods

1.           Materials and reagents

2.           Extraction and isolation

3.           Chromatographic analysis of SHXT-frC and isolation of SHXT-frC-C and SHXT-frC-R

4.           Cell culture

5.           Plasmid construction

6.           Northern blotting analysis

7.           Quantification of hepatitis C virus RNAs

8.           Hepatitis C virus JFH-1 infection assay

9.           Western blotting assay

10.       Cytotoxicity assay

11.       Analysis of drug synergism

12.       Transfection and luciferase activity assay

13.       Intracellular prostaglandin E₂ (PGE₂) measurements

14.       Statistical analysis

3.              Results

1.           Chromatographic analysis of SHXT-frC

2.           Antiviral effect of SHXT-frC, SHXT-frC-C and SHXT-frC-R on hepatitis C virus replicon cells

3.           Inhibition of hepatitis C virus RNA replication in combination of SHXT-frC with INF-α or hepatitis C virus enzyme inhibitors

4.           SHXT-frC attenuates cyclooxygenase-2 and NF-ĸB activation in subgenomic hepatitis C virus-replicating cells

5.           SHXT-frC attenuates COX-2 and NF-ĸB activation in hepatitis C virus NS5A-expressing cells

4.              Discussion

5.              Acknowledgements

6.              References

 

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