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从马占相思茎中提取的 3-羟基卡鲁里苷 C 抗丙型肝炎病毒活性。

Anti-hepatitis C virus activity of 3-hydroxy caruilignan C from Swietenia macrophylla stems.

机构信息

Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Taichung, Taiwan.

出版信息

J Viral Hepat. 2012 May;19(5):364-70. doi: 10.1111/j.1365-2893.2011.01558.x. Epub 2011 Nov 24.

Abstract

Chronic hepatitis C virus (HCV) infection ultimately leads to chronic hepatitis, hepatic cirrhosis and hepatocellular carcinoma (HCC). As the standard treatment is not completely efficacious, a safer and more effective agent against HCV infection needs to be developed. In this report, we demonstrated that 3-hydroxy caruilignan C (3-HCL-C) isolated from Swietenia macrophylla stems exhibited high anti-HCV activity at both protein and RNA levels at nontoxic concentrations, with an EC(50) value of 10.5 ± 1.2 μm. Combinations of 3-HCL-C and interferon-α (IFN-α), an HCV NS5B polymerase inhibitor (2'-C-methylcytidine; NM-107) or an HCV NS3/4A protease inhibitor (Telaprevir; VX-950) increased the suppression of HCV RNA replication. The results suggested that 3-HCL-C may be a potential anti-viral agent. We then demonstrated that 3-HCL-C interfered with HCV replication by inducing IFN-stimulated response element transcription and IFN-dependent anti-viral gene expression.

摘要

慢性丙型肝炎病毒(HCV)感染最终会导致慢性肝炎、肝硬变和肝细胞癌(HCC)。由于标准治疗并非完全有效,因此需要开发针对 HCV 感染更安全、更有效的药物。在本报告中,我们证明了从桃花心木茎中分离得到的 3-羟基卡鲁里烷 C(3-HCL-C)在非毒性浓度下在蛋白质和 RNA 水平上均表现出很高的抗 HCV 活性,EC(50)值为 10.5±1.2μm。3-HCL-C 与干扰素-α(IFN-α)、HCV NS5B 聚合酶抑制剂(2'-C-甲基胞苷;NM-107)或 HCV NS3/4A 蛋白酶抑制剂(特拉匹韦;VX-950)的联合使用增加了对 HCV RNA 复制的抑制作用。结果表明,3-HCL-C 可能是一种有潜力的抗病毒药物。然后,我们证明 3-HCL-C 通过诱导 IFN 刺激反应元件转录和 IFN 依赖性抗病毒基因表达来干扰 HCV 复制。

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