Antiviral activities of Indonesian medicinal plants in the East Java region against hepatitis C virus.

Antiviral activities of Indonesian medicinal plants in the East Java region against hepatitis C virus.
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DOI:
10.1186/1743-422x-10-259
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发表时间:
2013-08-13
期刊:
影响因子:
4.8
通讯作者:
Hotta H
Hotta H
中科院分区:
医学3区
文献类型:
--
作者:
Wahyuni TS;Tumewu L;Permanasari AA;Apriani E;Adianti M;Rahman A;Widyawaruyanti A;Lusida MI;Fuad A;Soetjipto;Nasronudin;Fuchino H;Kawahara N;Shoji I;Deng L;Aoki C;Hotta H

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丙型肝炎病毒(HCV)是肝脏疾病的主要原因,也是世界范围内大量发病率和死亡率的潜在原因。HCV感染的总体患病率为2%,代表全球1.2亿人。目前使用聚乙二醇干扰素和利巴韦林的标准治疗仅对50%的HCV基因型1感染患者有效,并且与显著的副作用相关。因此,开发新的治疗HCV的药物仍具有重要意义。从天然产物(包括药用植物)中获得的抗病毒物质是潜在的良好研究目标。在这项研究中,我们评估了印尼药用植物的抗HCV活性。对东爪哇地区17种药用植物的21个样品的乙醇提取物进行了测试。使用Huh7.5细胞和9种不同基因型(1a至7a、1b和2b)的HCV株,通过细胞培养法测定抗HCV活性。检测的21个样本中有4个显示出抗丙型肝炎病毒的抗病毒活性:香椿叶(TSL)对HCV J6/JFH 1-P47和-P1株的半数抑制浓度(IC_(50))分别为13.9和2.0 μ g/ml;多腺黑鳞草茎(MMS)的IC 50分别为17.1和6.2 μg/ml,以及Ficus fistulosa叶(FFL)的IC 50分别为15.0和5.7 μg/ml。添加时间实验表明,TSL和MLL在进入步骤和进入后步骤都有抑制作用,而MMS和FFL主要在进入步骤。TSL和MLL对所有基因型的11株HCV株均有相同程度的抑制作用。另一方面,与其他HCV基因型相比,FFL对HCV基因型1a株的抑制活性明显较弱,MMS对基因型2b和7a的HCV株的抑制活性较低。TSL、MLL、MMS和FFL的乙醇提取物对所有测试的HCV基因型显示出抗病毒活性,除了一些基因型对FFL和MMS显示出较低程度的显著抗性。这些植物提取物可能是开发抗HCV药物的良好候选物。
Hepatitis C virus (HCV) is a major cause of liver disease and a potential cause of substantial morbidity and mortality worldwide. The overall prevalence of HCV infection is 2%, representing 120 million people worldwide. Current standard treatment using pegylated interferon and ribavirin is effective in only 50% of the patients infected with HCV genotype 1, and is associated with significant side effects. Therefore, it is still of importance to develop new drugs for treatment of HCV. Antiviral substances obtained from natural products, including medicinal plants, are potentially good targets to study. In this study, we evaluated Indonesian medicinal plants for their anti-HCV activities. Ethanol extracts of 21 samples derived from 17 species of medicinal plants explored in the East Java region were tested. Anti-HCV activities were determined by a cell culture method using Huh7.5 cells and HCV strains of 9 different genotypes (1a to 7a, 1b and 2b). Four of the 21 samples tested showed antiviral activities against HCV: Toona sureni leaves (TSL) with 50% inhibitory concentrations (IC50) of 13.9 and 2.0 μg/ml against the HCV J6/JFH1-P47 and -P1 strains, respectively, Melicope latifolia leaves (MLL) with IC50 of 3.5 and 2.1 μg/ml, respectively, Melanolepis multiglandulosa stem (MMS) with IC50 of 17.1 and 6.2 μg/ml, respectively, and Ficus fistulosa leaves (FFL) with IC50 of 15.0 and 5.7 μg/ml, respectively. Time-of-addition experiments revealed that TSL and MLL inhibited both at the entry and post-entry steps while MMS and FFL principally at the entry step. TSL and MLL inhibited all of 11 HCV strains of all the genotypes tested to the same extent. On the other hand, FFL showed significantly weaker inhibitory activities against the HCV genotype 1a strain, and MMS against the HCV strains of genotypes 2b and 7a to a lesser extent, compared to the other HCV genotypes. Ethanol extracts of TSL, MLL, MMS and FFL showed antiviral activities against all the HCV genotypes tested with the exception that some genotype(s) showed significant resistance to FFL and to MMS to a lesser extent. These plant extracts may be good candidates for the development of anti-HCV drugs.