Ishida Yo-Ichi, Takeshita Masahiko, Kataoka Hiroaki
Yo-ichi Ishida, Department of Molecular and Cellular Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo 204-8588, Japan.
World J Hepatol. 2014 Dec 27;6(12):870-9. doi: 10.4254/wjh.v6.i12.870.
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.
丙型肝炎病毒(HCV)是病毒性肝炎的主要病因,目前全球约有1.7亿人感染该病毒。HCV感染会导致慢性肝炎的高发病率(>75%),最终发展为肝硬化和肝细胞癌。聚乙二醇化α干扰素和广谱抗病毒药物利巴韦林联合使用可清除HCV;然而,这种治疗方法的疗效和耐受性仍然较差,且常伴有严重的副作用。虽然最近开发了一些新型的抗HCV直接作用抗病毒药物,但高昂的医疗成本限制了成本敏感型国家获得该疗法的机会。为了寻找新的天然抗HCV药物,我们利用HCV复制子细胞系统在体外筛选了当地农产品对HCV复制的抑制活性。我们在蓝莓叶提取物中发现了一种有效的HCV RNA表达抑制剂,随后鉴定出低聚原花青素为活性成分。对低聚原花青素作用机制的进一步研究表明,它是一种异质性核糖核蛋白(hnRNPs)如hnRNP A2/B1的抑制剂。在这篇综述中,我们概述了对HCV感染有效的功能性食品和成分、低聚原花青素的化学结构特征及其作用机制。