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3. A natural small molecule inhibitor corilagin blocks HCV replication and modulates oxidative stress to reduce liver damage.

Author

Reddy BU, Mullick R, Kumar A, Sharma G, Bag P, Roy CL, Sudha G, Tandon H, Dave P, Shukla A, Srinivasan P, Nandhitha M, Srinivasan N, and Das S

Subjects
Animals, Antiviral Agents isolation & purification, Antiviral Agents pharmacology, Cell Line, Cell Survival drug effects, Cells, Cultured, Disease Models, Animal, Gene Expression, Genes, Reporter, Glucosides isolation & purification, Hepatitis C complications, Hepatitis C pathology, Humans, Hydrolyzable Tannins isolation & purification, Liver drug effects, Liver Cirrhosis, Mice, NADPH Oxidase 4 metabolism, Oxidative Stress drug effects, Plant Extracts isolation & purification, Plant Extracts pharmacology, Rats, Reactive Oxygen Species metabolism, Signal Transduction drug effects, Transforming Growth Factor beta metabolism, Viral Nonstructural Proteins antagonists & inhibitors, Viral Nonstructural Proteins metabolism, Virus Replication drug effects, Glucosides pharmacology, Hepacivirus drug effects, Hepacivirus physiology, Hepatitis C metabolism, Hepatitis C virology, Hydrolyzable Tannins pharmacology, Liver metabolism, Liver virology
Abstract

Hepatitis C virus (HCV) infection causes chronic liver disease, which often leads to hepatocellular carcinoma. Earlier, we have demonstrated anti-HCV property of the methanolic extract of Phyllanthus amarus, an age-old folk-medicine against viral hepatitis. Here, we report identification of a principal bioactive component 'corilagin', which showed significant inhibition of the HCV key enzymes, NS3 protease and NS5B RNA-dependent-RNA-polymerase. This pure compound could effectively inhibit viral replication in the infectious cell culture system, displayed strong antioxidant activity by blocking HCV induced generation of reactive oxygen species and suppressed up-regulation of NOX4 and TGF-β mRNA levels. Oral administration of corilagin in BALB/c mice demonstrated its better tolerability and systemic bioavailability. More importantly, corilagin could restrict serum HCV RNA levels, decrease collagen deposition and hepatic cell denaturation in HCV infected chimeric mice harbouring human hepatocytes. Taken together, results provide a basis towards developing a pure natural drug as an alternate therapeutic strategy for restricting viral replication and prevent liver damage towards better management of HCV induced pathogenesis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Published
2018
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