The Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Viruses. 2021 May 27;13(6):1004. doi: 10.3390/v13061004.
Chemodietary agents are emerging as promising adjuvant therapies in treating various disease conditions. However, there are no adjuvant therapies available to minimize the neurotoxicity of currently existing antiretroviral drugs (ARVs). In this study, we investigated the anti-HIV effect of a chemodietary agent, Cucurbitacin-D (Cur-D), in HIV-infected macrophages using an in-vitro blood-brain barrier (BBB) model. Since tobacco smoking is prevalent in the HIV population, and it exacerbates HIV replication, we also tested the effect of Cur-D against cigarette smoke condensate (CSC)-induced HIV replication. Our results showed that Cur-D treatment reduces the viral load in a dose-dependent (0-1 μM) manner without causing significant toxicity at <1 μM concentration. Further, a daily dose of Cur-D (0.1 μM) not only reduced p24 in control conditions, but also reduced CSC (10 μg/mL)-induced p24 in U1 cells. Similarly, Cur-D (single dose of 0.4 μM) significantly reduced the CSC (single dose of 40 μg/mL)-induced HIV replication across the BBB model. In addition, treatment with Cur-D reduced the level of pro-inflammatory cytokine IL-1β. Therefore, Cur-D, as an adjuvant therapy, may be used not only to suppress HIV in the brain, but also to reduce the CNS toxicity of currently existing ARVs.
化学饮食因子作为有前途的辅助疗法，正在被用于治疗各种疾病。然而，目前还没有辅助疗法可以减轻现有的抗逆转录病毒药物（ARV）的神经毒性。在这项研究中，我们使用体外血脑屏障（BBB）模型，研究了化学饮食因子葫芦素-D（Cur-D）对感染 HIV 的巨噬细胞中的抗 HIV 作用。由于吸烟在 HIV 人群中很普遍，并且会加剧 HIV 的复制，因此我们还测试了 Cur-D 对香烟烟雾冷凝物（CSC）诱导的 HIV 复制的影响。我们的结果表明，Cur-D 治疗以剂量依赖性方式（0-1 μM）降低病毒载量，而在 <1 μM 浓度下不会引起明显毒性。此外，Cur-D 的每日剂量（0.1 μM）不仅降低了对照条件下的 p24，而且还降低了 U1 细胞中 CSC（10 μg/mL）诱导的 p24。同样，Cur-D（单次剂量 0.4 μM）也显著降低了穿过 BBB 模型的 CSC（单次剂量 40 μg/mL）诱导的 HIV 复制。此外，Cur-D 治疗降低了促炎细胞因子 IL-1β的水平。因此，Cur-D 作为辅助疗法，不仅可以抑制大脑中的 HIV，还可以降低目前现有的 ARV 的 CNS 毒性。
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