Two flavonoids extracts from Glycyrrhizae radix inhibit in vitro hepatitis C virus replication

Two flavonoids extracts from Glycyrrhizae radix inhibit in vitro hepatitis C virus replication
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DOI:
10.1111/j.1872-034x.2008.00398.x
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发表时间:
2009-01-01
影响因子:
4.2
通讯作者:
Watanabe, Mamoru
Watanabe, Mamoru
中科院分区:
医学2区
文献类型:
--
作者:
Sekine-Osajima, Yuko;Sakamoto, Naoya;Watanabe, Mamoru

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传统草药在中国和其他亚洲国家已经使用了几千年。在这项研究中,我们使用Feo复制子系统筛选草药及其纯化化合物,以确定它们对HCV体外复制的影响。我们使用表达嵌合萤火虫荧光素酶报告基因和新霉素磷酸转移酶(Feo)基因的丙型肝炎病毒复制子系统,筛选草药及其纯化提取物抑制丙型肝炎病毒(HCV)复制的活性。我们测试了以下草药的提取物和13种纯化化合物:甘草;生地黄基数;Paeoniae基数;细毛蒿;大黄。从甘草酸根中分离得到的两种化合物异异黄酮原素和甘草香豆素能显著抑制HCV的复制,并呈剂量依赖性。剂量效应分析表明,异异黄酮原素和甘油三酯素的50%有效浓度分别为6.2 +/- 1.0 μ g/mL和15.5 +/- 0.8 μ g/mL。MTS实验没有显示在这些有效浓度下对细胞生长和活力有任何影响,表明这两种化合物的作用是针对HCV复制的。这两种化合物不影响HCV ires依赖性翻译,也没有显示出与干扰素- α的协同作用。两种纯化的草药提取物,异黄酮素和甘草香豆素,特异性抑制体外HCV复制。进一步阐明其作用机制,评价其体内效应和安全性,可能成为一种新的抗hcv治疗方法。
Traditional herbal medicines have been used for several thousand years in China and other Asian countries. In this study we screened herbal drugs and their purified compounds, using the Feo replicon system, to determine their effects on in vitro HCV replication.We screened herbal drugs and their purified extracts for the activities to suppress hepatitis C virus (HCV) replication using an HCV replicon system that expressed chimeric firefly luciferase reporter and neomycin phosphotransferase (Feo) genes. We tested extracts and 13 purified compounds from the following herbs: Glycyrrhizae radix; Rehmanniae radix; Paeoniae radix; Artemisiae capillari spica; and Rhei rhizoma.The HCV replication was significantly and dose-dependently suppressed by two purified compounds, isoliquiritigenin and glycycoumarin, which were from Glycyrrhizae radix. Dose-effect analyses showed that 50% effective concentrations were 6.2 +/- 1.0 mu g/mL and 15.5 +/- 0.8 mu g/mL for isoliquiritigenin and glycycoumarin, respectively. The MTS assay did not show any effect on cell growth and viability at these effective concentrations, indicating that the effects of the two compounds were specific to HCV replication. These two compounds did not affect the HCV IRES-dependent translation nor did they show synergistic action with interferon-alpha.Two purified herbal extracts, isoliquiritigenin and glycycoumarin, specifically suppressed in vitro HCV replication. Further elucidation of their mechanisms of action and evaluation of in vivo effects and safety might constitute a new anti-HCV therapeutics.