Green tea phenolic epicatechins inhibit hepatitis C virus replication via cycloxygenase-2 and attenuate virus-induced inflammation.
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.
Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
Ying-Ting
YT
Lin
Yu-Hsuan
YH
Wu
Chin-Kai
CK
Tseng
Chun-Kuang
CK
Lin
Wei-Chun
WC
Chen
Yao-Chin
YC
Hsu
Jin-Ching
JC
Lee
D000998:Antiviral Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000821:virology; D002392:Catechin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000821:virology; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D016898:Interferon-alpha / Q000494:pharmacology; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics; D009842:Oligopeptides / Q000494:pharmacology; D012367:RNA, Viral / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013662:Tea / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects
C577202:4-amino-1-(3,4-dihydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)pyrimidin-2(1H)-one; D000998:Antiviral Agents; D016898:Interferon-alpha; D053583:Interleukin-1beta; D009842:Oligopeptides; D012367:RNA, Viral; D013662:Tea; D014409:Tumor Necrosis Factor-alpha; D003841:Deoxycytidine; C486464:telaprevir; D002392:Catechin; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human