Functional foods effective for hepatitis C: Identification of oligomeric proanthocyanidin and its action mechanism

Abstract

Hepatitis C virus (HCV) is a major cause of viral hepatitis and currently infects approximately 170 million people worldwide. An infection by HCV causes high rates of chronic hepatitis (> 75%) and progresses to liver cirrhosis and hepatocellular carcinoma ultimately. HCV can be eliminated by a combination of pegylated α-interferon and the broad-spectrum antiviral drug ribavirin; however, this treatment is still associated with poor efficacy and tolerability and is often accompanied by serious side-effects. While some novel direct-acting antivirals against HCV have been developed recently, high medical costs limit the access to the therapy in cost-sensitive countries. To search for new natural anti-HCV agents, we screened local agricultural products for their suppressive activities against HCV replication using the HCV replicon cell system in vitro. We found a potent inhibitor of HCV RNA expression in the extracts of blueberry leaves and then identified oligomeric proanthocyanidin as the active ingredient. Further investigations into the action mechanism of oligomeric proanthocyanidin suggested that it is an inhibitor of heterogeneous nuclear ribonucleoproteins (hnRNPs) such as hnRNP A2/B1. In this review, we presented an overview of functional foods and ingredients efficient for HCV infection, the chemical structural characteristics of oligomeric proanthocyanidin, and its action mechanism.

Keywords: Hepatitis C virus, Blueberry leaves, Functional foods, Oligomeric proanthocyanidin, Heterogeneous nuclear ribonucleoproteins

Core tip: An infection by hepatitis C virus (HCV) causes chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. While the combination of pegylated α-interferon and ribavirin is used for the elimination of HCV, a new anti-HCV drug is required due to the poor efficacy and serious side-effects associated with this combination therapy. We searched for new anti-HCV agents from natural products and then identified oligomeric proanthocyanidin from blueberry leaves. Further investigations suggested that several heterogeneous nuclear ribonucleoproteins may be the candidate proteins involved in the proanthocyanidin-mediated inhibition of HCV subgenomic expression. Oligomeric proanthocyanidin isolated from blueberry leaves may have potential usefulness as an anti-HCV compound.