Green Tea Phenolic Epicatechins Inhibit Hepatitis C Virus Replication via Cycloxygenase-2 and Attenuate Virus-Induced Inflammation

• Published in: PloS one Vol. 8; no. 1; p. e54466
• Main Authors: Lin, Ying-Ting, Wu, Yu-Hsuan, Tseng, Chin-Kai, Lin, Chun-Kuang, Chen, Wei-Chun, Hsu, Yao-Chin, Lee, Jin-Ching
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.01.2013; Public Library of Science (PLoS)
• Subjects: Amino acids; Anemia; Antibiotics; Antiviral Agents - pharmacology; Biology; Biotechnology; Cancer therapies; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - virology; Catechin; Catechin - pharmacology; Cats; Cell Line, Tumor; Cellular signal transduction; Chronic infection; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Cyclooxygenase-2; Cyclooxygenases; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacology; Enzyme inhibitors; Epicatechin; Gene expression; Gene Expression - drug effects; Genetic aspects; Green tea; Health aspects; Health risks; Hepacivirus - drug effects; Hepacivirus - physiology; Hepatitis; Hepatitis C; Hepatitis C virus; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - genetics; Hepatitis C, Chronic - pathology; Hepatitis C, Chronic - virology; Hepatocellular carcinoma; Hepatoma; Humans; IL-1β; Infections; Inflammation; Inflammation - prevention & control; Inhibition; Interferon; Interferon-alpha - pharmacology; Interleukin; Interleukin-1beta - antagonists & inhibitors; Interleukin-1beta - genetics; Interleukins; Isomers; Life sciences; Liver; Liver diseases; Medicine; Natural products; Nitric Oxide Synthase Type II - antagonists & inhibitors; Nitric Oxide Synthase Type II - genetics; Oligopeptides - pharmacology; Phenolic compounds; Phenols; Product development; Prostate; Proteins; Replication; Risk factors; RNA polymerase; RNA, Viral - antagonists & inhibitors; Stereoisomerism; Tea; Tea - chemistry; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - genetics; Tumor necrosis factor-α; Viral infections; Virus replication; Virus Replication - drug effects; Viruses; United States > US; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0054466

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.