西亚试剂优势供应上万种化学试剂产品，欢迎各位新老客户咨询、选购！
中国
联系我们
联系方式：400-990-3999 / 邮箱：sales@xiyashiji.com
西亚试剂 —— 品质可靠，值得信赖
Proanthocyanidin from Blueberry Leaves Suppresses Expression of Subgenomic Hepatitis C Virus RNA*
Masahiko Takeshita, Yo-ichi Ishida, Ena Akamatsu, Yusuke Ohmori?, Masayuki Sudoh?, Hirofumi Uto||, Hirohito Tsubouchi||, and Hiroaki Kataoka**1
From the From the Research Division, Minami Nippon Dairy Co-op Co., Ltd., Miyazaki 885-0073, , the Miyazaki Prefectural Industrial Support Foundation, Miyazaki 880-0303, , the ?Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd., Kanagawa 247-8530, , the ||Department of Digestive Disease and Life-style Related Disease, Health Research Human and Environmental Sciences, Kagoshima University, Graduate School of Medicine and Dental Sciences, Kagoshima 890-8520, and , the **Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan
ABSTRACT
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma. While searching for new natural anti-HCV agents in agricultural products, we found a potent inhibitor of HCV RNA expression in extracts of blueberry leaves when examined in an HCV subgenomic replicon cell culture system. This activity was observed in a methanol extract fraction of blueberry leaves and was purified by repeated fractionations in reversed-phase high-performance liquid chromatography. The final purified fraction showed a 63-fold increase in specific activity compared with the initial methanol extracts and was composed only of carbon, hydrogen, and oxygen. Liquid chromatography/mass-ion trap-time of flight analysis and butanol-HCl hydrolysis analysis of the purified fraction revealed that the blueberry leaf-derived inhibitor was proanthocyanidin. Furthermore, structural analysis using acid thiolysis indicated that the mean degree of polymerization of the purified proanthocyanidin was 7.7, consisting predominantly of epicatechin. Proanthocyanidin with a polymerization degree of 8 to 9 showed the greatest potency at inhibiting the expression of subgenomic HCV RNA. Purified proanthocyanidin showed dose-dependent inhibition of expression of the neomycin-resistant gene and the NS-3 protein gene in the HCV subgenome in replicon cells. While characterizing the mechanism by which proanthocyanidin inhibited HCV subgenome expression, we found that heterogeneous nuclear ribonucleoprotein A2/B1 showed affinity to blueberry leaf-derived proanthocyanidin and was indispensable for HCV subgenome expression in replicon cells. These data suggest that proanthocyanidin isolated from blueberry leaves may have potential usefulness as an anti-HCV compound by inhibiting viral replication.
