In Vitro Antiviral Activity of Mentha cordifolia Plant Extract in HIV-1 Latently Infected Cells Using an Established Human Cell Line

In Vitro Antiviral Activity of Mentha cordifolia Plant Extract in HIV-1 Latently Infected Cells Using an Established Human Cell Line
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DOI:
10.1089/aid.2021.0053
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发表时间:
2021-06-18
影响因子:
1.5
通讯作者:
Okamoto,Takashi
Okamoto,Takashi
中科院分区:
医学4区
文献类型:
--
作者:
de Paz-Silava,Sheriah Laine M.;Victoriano-Belvis,Ann Florence B.;Okamoto,Takashi

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耐药性的出现要求针对人类免疫缺陷病毒(HIV)的新的治疗策略。目前,针对基因表达的研究越来越多--这是扩增新病毒和新病毒株的关键步骤。此外,天然产品也被认为是新的抗病毒药物的潜在候选者。我们筛选了从菲律宾药用植物薄荷(Mc)中提取的提取物。在这项研究中,我们证明了Mc硫酸铵提取物具有抗逆转录病毒活性。用Mc提取物预先处理HIV1潜伏感染细胞(OM10.1),再用肿瘤坏死因子α激活。在处理的细胞中,病毒在细胞培养上清液和全细胞裂解液中的复制都受到抑制。病毒产生水平,以病毒p24蛋白浓度衡量,在非细胞毒性浓度下被非常显著地抑制,与没有添加肿瘤坏死因子α的水平相似。然而,荧光素酶分析表明,Mc并不抑制HIV-1长末端重复序列驱动的基因表达。免疫印迹和免疫荧光显示,IκBα降解和p65核转位也没有受到影响。这些观察结果表明,Mc具有抗HIV-1的抗病毒成分,并值得进一步研究,以探索其在基因表达的后期阶段的作用靶点。我们的研究介绍了一种针对艾滋病毒生命周期步骤的先导化合物的潜在来源。
Emergence of drug resistance demands new therapeutic strategies against the human immunodeficiency virus (HIV). Currently, there is an increasing research focus on targeting gene expression—the crucial step wherein new viruses and new viral strains are amplified. Moreover, natural products are also being considered as potential candidates for new antivirals. We screened the extract obtained from a Philippine medicinal plant,Mentha cordifolia(Mc). In this study, we demonstrated that Mc ammonium sulfate extract has antiretroviral activity against HIV. HIV-1 latently infected cells (OM10.1) were pretreated with Mc extract and activated with TNFα. In treated cells, viral replication was inhibited in both cell culture supernatant and whole cell lysates. The level of viral production, as measured by the viral p24 protein concentration, was very much inhibited under noncytotoxic concentrations to the similar level without addition of TNFα. Luciferase assays, however, showed that Mc does not inhibit the HIV-1 long terminal repeat-driven gene expression. IκBα degradation and p65 nuclear translocation was also not affected as visualized through Western blot and immunofluorescence. These observations demonstrated that Mc possessed an antiviral component against HIV-1 and warrant further work to explore its target of action at a later step of gene expression. Our study introduces a potential source of a lead compound that targets steps in the HIV life cycle.