Green tea phenolic epicatechins inhibit hepatitis C virus replication via cycloxygenase-2 and attenuate virus-induced inflammation.
Green tea phenolic epicatechins inhibit hepatitis C virus replication via cycloxygenase-2 and attenuate virus-induced inflammation.
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DOI：
10.1371/journal.pone.0054466
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lee JC
中科院分区：
文献类型：
--
作者：
Lin YT;Wu YH;Tseng CK;Lin CK;Chen WC;Hsu YC;Lee JC
慢性丙型肝炎病毒（HCV）感染是全球范围内肝细胞癌（HCC）和慢性肝病的主要危险因素。绿色茶，除了作为健康饮料消费外，还含有已用作药用物质的酚类儿茶素。在本研究中，我们通过使用体外基于细胞的HCV复制子和JFH-1感染系统，说明表儿茶素异构体（+）-表儿茶素和（−）-表儿茶素在无毒浓度下浓度依赖性地抑制HCV复制。除了显著抑制病毒诱导的环氧合酶-2（考克斯-2）表达外，我们的研究结果表明，表儿茶素异构体的抗HCV活性通过下调考克斯-2而发生。此外，两种表儿茶素异构体与干扰素-α或病毒酶抑制剂[2′-C-甲基胞苷（NM-107）或特拉匹韦]联合使用时，均可叠加抑制HCV复制。它们还通过抑制表达病毒蛋白的肝癌Huh-7细胞中肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β和诱导型一氧化氮合酶以及考克斯-2的基因表达而具有显著的抗炎作用。总的来说，（+）-表儿茶素和（-）-表儿茶素可以作为治疗HCV相关疾病的治疗补充剂。
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.