HEALTH NEWS

Study Title:

Blueberry Leaf and Hepatitis C

Study 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.

From press release:

A chemical found in blueberry leaves has shown a strong effect in blocking the replication of the Hepatitis C virus, opening up a new avenue for treating chronic HCV infections, which affect 200 million people worldwide and can eventually lead to cirrhosis and liver cancer.

Among the areas of especially high Hepatitis C incidence is the Miyazaki prefecture of southern Japan, a trend that led Hiroaki Kataoka and colleagues at the University of Miyazaki and elsewhere in Japan on a search for better treatment options. Currently, there is no vaccine for HCV, and though a combination drug regimen can clear HCV infection, this treatment is only about 60% effective on average and poses risks of severe side effects.

Kataoka and colleagues believed that since HCV is localized in the liver and can take 20 years or more to develop into disease, a dietary supplement might help slow or stop disease progression. So they screened nearly 300 different agricultural products for potential compounds that suppress HCV replication and uncovered a strong candidate in the leaves of rabbit-eye blueberry (native to the southeastern US).

They purified the compound and identified it as proanthocyandin (a polyphenol similar to the beneficial chemicals found in grapes and wine). While proanthocyandin can be harmful, Kataoka and colleagues noted its effective concentration against HCV was 100 times less than the toxic threshold, and similar chemicals are found in many edible plants, suggesting it should be safe as a dietary supplement. In the meantime, the researchers now hope to explore the detailed mechanisms of how this chemical stops HCV replication.

Study Information

Takeshita M, Ishida Y, Akamatsu E, Ohmori Y, Sudoh M, Uto H, Tsubouchi H, Kataoka H.
Proanthocyanidin from blueberry leaves suppresses expression of subgenomic hepatitis C virus RNA.
J Biol Chem.
2009 August
Research Division, Minami Nippon Dairy Co-op Co., Ltd., Miyazaki 885-0073.