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World J Hepatol. Dec 27, 2014; 6(12): 870-879
Published online Dec 27, 2014. doi: 10.4254/wjh.v6.i12.870
Functional foods effective for hepatitis C: Identification of oligomeric proanthocyanidin and its action mechanism
Yo-ichi Ishida, Masahiko Takeshita, Hiroaki Kataoka
Yo-ichi Ishida, Department of Molecular and Cellular Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588, Japan
Masahiko Takeshita, Research Division, Minami Nippon Dairy Co-op., Ltd., Miyakonojo, Miyazaki 885-0003, Japan
Hiroaki Kataoka, Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan
Author contributions: Ishida Y contributed to the investigation of the action mechanism of oligomeric proanthocyanidin, drafting of the manuscript, and literature review; Takeshita M contributed to the discovery of oligomeric proanthocyanidin as an anti-HCV agent and approved the final version of this manuscript; Kataoka H contributed to the management of the study, critically reviewed and approved the final version of this manuscript.
Supported by The Collaboration of Regional Entities for the Advancement of Technological Excellence from Japan Science and Technology Agency
Correspondence to: Hiroaki Kataoka, MD, PhD, Professor, Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. mejina@med.miyazaki-u.ac.jp
Telephone: +81-985-852809 Fax: +81-985-856003
Received: August 26, 2014
Revised: October 3, 2014
Accepted: October 23, 2014
Published online: December 27, 2014
Processing time: 108 Days and 20.1 Hours
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.