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马齿苋作为丙型肝炎病毒NS3丝氨酸蛋白酶的潜在候选抑制剂。

Portulaca oleracea L. as a Prospective Candidate Inhibitor of Hepatitis C Virus NS3 Serine Protease.

作者信息

Noreen Sobia, Hussain Ishtiaq, Tariq Muhammad Ilyas, Ijaz Bushra, Iqbal Shahid, Ashfaq Usman Ali, Husnain Tayyab

机构信息

1Department of Chemistry, University of Sargodha, Sargodha, Pakistan.

2Center of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore, Pakistan.

出版信息

Viral Immunol. 2015 Jun;28(5):282-9. doi: 10.1089/vim.2014.0079. Epub 2015 Apr 14.

DOI:10.1089/vim.2014.0079
PMID:25871297
Abstract

Hepatitis C virus (HCV) infection is a worldwide health problem affecting about 300 million individuals. HCV causes chronic liver disease, liver cirrhosis, hepatocellular carcinoma, and death. Many side effects are associated with the current treatment options. Natural products that can be used as anti-HCV drugs are thus of considerable potential significance. NS3 serine protease (NS3-SP) is a target for the screening of antiviral activity against HCV. The present work explores plants with anti-HCV potential, isolating possible lead compounds. Ten plants, used for medicinal purposes against different infections in rural areas of Pakistan, were collected. The cellular toxicity effects of methanolic extracts of the plants on the viability of Huh-7 cells were studied through the Trypan blue dye exclusion method. Following this, the anti-HCV potential of phytoextracts was assessed by infecting liver cells with HCV-3a-infected serum inoculum. Only the methanolic extract of Portulaca oleracea L. (PO) exhibited more than 70% inhibition. Four fractions were obtained through bioassay-guided extraction of PO. Subsequent inhibition of all organic extract fractions against NS3 serine protease was checked to track the specific target in the virus. The results showed that the PO methanolic crude and ethyl acetate extract specifically abridged the HCV NS3 protease expression in a dose-dependent fashion. Hence, PO extract and its constituents either alone or with interferon could offer a future option to treat chronic HCV.

摘要

丙型肝炎病毒(HCV)感染是一个全球性的健康问题,影响着约3亿人。HCV可导致慢性肝病、肝硬化、肝细胞癌和死亡。目前的治疗方案有许多副作用。因此,可用作抗HCV药物的天然产物具有相当大的潜在意义。NS3丝氨酸蛋白酶(NS3-SP)是筛选抗HCV抗病毒活性的靶点。本研究探索具有抗HCV潜力的植物,分离可能的先导化合物。收集了巴基斯坦农村地区用于治疗不同感染的10种药用植物。通过台盼蓝染料排除法研究了这些植物甲醇提取物对Huh-7细胞活力的细胞毒性作用。在此之后,用HCV-3a感染的血清接种物感染肝细胞,评估植物提取物的抗HCV潜力。只有马齿苋(PO)的甲醇提取物表现出超过70%的抑制作用。通过对PO进行生物测定指导的提取得到了四个馏分。随后检查所有有机提取物馏分对NS3丝氨酸蛋白酶的抑制作用,以追踪病毒中的特定靶点。结果表明,PO甲醇粗提物和乙酸乙酯提取物以剂量依赖的方式特异性地减少了HCV NS3蛋白酶的表达。因此,PO提取物及其成分单独或与干扰素联合使用可能为治疗慢性HCV提供未来的选择。

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