Clinical Study: Coptis and Rhubarb Combination (San Huang Xie Xin Tang) Extract Could Be a Treatment for Patients with Hepatitis C Virus-Induced Liver Diseases


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




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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