Abstract
Chronic hepatitis C virus (HCV) infection is the leading risk factor for hepatocellular carcinoma (HCC) and chronic liver disease worldwide. Green tea, in addition to being consumed as a healthy beverage, contains phenolic catechins that have been used as medicinal substances. In the present study, we illustrated that the epicatechin isomers (+)-epicatechin and (-)-epicatechin concentration-dependently inhibited HCV replication at nontoxic concentrations by using in vitro cell-based HCV replicon and JFH-1 infectious systems. In addition to significantly suppressing virus-induced cyclooxygenase-2 (COX-2) expression, our results revealed that the anti-HCV activity of the epicatechin isomers occurred through the down-regulation of COX-2. Furthermore, both the epicatechin isomers additively inhibited HCV replication in combination with either interferon-α or viral enzyme inhibitors [2'-C-methylcytidine (NM-107) or telaprevir]. They also had prominent anti-inflammatory effects by inhibiting the gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and inducible nitrite oxide synthase as well as the COX-2 in viral protein-expressing hepatoma Huh-7 cells. Collectively, (+)-epicatechin and (-)-epicatechin may serve as therapeutic supplements for treating HCV-related diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antiviral Agents / pharmacology*
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Carcinoma, Hepatocellular / drug therapy*
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / pathology
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Carcinoma, Hepatocellular / virology
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Catechin / pharmacology*
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Cell Line, Tumor
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Cyclooxygenase 2 / genetics*
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Cyclooxygenase 2 / metabolism
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Deoxycytidine / analogs & derivatives
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Deoxycytidine / pharmacology
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Gene Expression / drug effects
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Hepacivirus / drug effects*
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Hepacivirus / physiology
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Hepatitis C, Chronic / drug therapy*
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Hepatitis C, Chronic / genetics
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Hepatitis C, Chronic / pathology
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Hepatitis C, Chronic / virology
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Humans
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Inflammation / prevention & control
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Interferon-alpha / pharmacology
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Interleukin-1beta / antagonists & inhibitors
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Interleukin-1beta / genetics
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Nitric Oxide Synthase Type II / antagonists & inhibitors
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Nitric Oxide Synthase Type II / genetics
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Oligopeptides / pharmacology
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RNA, Viral / antagonists & inhibitors*
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Stereoisomerism
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Tea / chemistry
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / genetics
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Virus Replication / drug effects
Substances
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4-amino-1-(3,4-dihydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)pyrimidin-2(1H)-one
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Antiviral Agents
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Interferon-alpha
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Interleukin-1beta
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Oligopeptides
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RNA, Viral
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Tea
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Tumor Necrosis Factor-alpha
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Deoxycytidine
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telaprevir
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Catechin
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NOS2 protein, human
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Nitric Oxide Synthase Type II
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Cyclooxygenase 2
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PTGS2 protein, human