Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Laboratorio de Virología, Buenos Aires, Argentina.
CONICET - Universidad de Buenos Aires, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Buenos Aires, Argentina.
J Pharm Pharmacol. 2018 Nov;70(11):1561-1571. doi: 10.1111/jphp.13002. Epub 2018 Aug 30.
β-Escin, one of the constituents of Aesculus hippocastanum L. (Hippocastanaceae) seed extract (AH), inhibits NF-κB activation, which plays an important role in HSV-1 replication. The aim was to examine the antiherpetic activity of β-escin and AH, as well as their effect on the activation of NF-κB and AP-1 and cytokine secretion in epithelial cells and macrophages.
Cell viability was evaluated using MTT assay, and antiviral and virucidal activity was determined by plaque assay. The effect on NF-κB and AP-1 signalling pathways activation was determined by a luciferase reporter assay, and cytokine production was measured by ELISA.
β-Escin and AH had virucidal and anti-HSV-1 activities, and the antiviral activity was discovered for other enveloped viruses (VSV and Dengue). Moreover, β-escin and AH significantly reduced NF-κB and AP-1 activation and cytokine production in macrophages stimulated with HSV-1 and TLRs ligands. However, an enhanced activation of these pathways and an increase in the levels of pro-inflammatory cytokines in β-escin and AH-treated HSV-1-infected epithelial cells were found.
This study demonstrates virucidal and broad-spectrum antiviral activities for β escin and AH. Besides, β-escin and AH modulate cytokine production depending on the stimuli (viral or non-viral) and the cell type under study.
β-七叶皂苷是欧洲七叶树(七叶树科)种子提取物(AH)的成分之一,可抑制 NF-κB 的激活,NF-κB 在 HSV-1 复制中起着重要作用。本研究旨在检测 β-七叶皂苷和 AH 的抗疱疹病毒活性及其对上皮细胞和巨噬细胞中 NF-κB 和 AP-1 激活以及细胞因子分泌的影响。
使用 MTT 法评估细胞活力,通过噬斑试验测定抗病毒和杀病毒活性。通过荧光素酶报告基因测定法确定 NF-κB 和 AP-1 信号通路激活的影响,通过 ELISA 测定细胞因子的产生。
β-七叶皂苷和 AH 具有杀病毒和抗 HSV-1 的活性,并且对其他包膜病毒(VSV 和登革热)也具有抗病毒活性。此外,β-七叶皂苷和 AH 可显著降低 HSV-1 和 TLR 配体刺激的巨噬细胞中 NF-κB 和 AP-1 的激活和细胞因子的产生。然而,在 β-七叶皂苷和 AH 处理的感染 HSV-1 的上皮细胞中,这些途径的激活增强,促炎细胞因子的水平增加。
本研究表明β-七叶皂苷和 AH 具有杀病毒和广谱抗病毒活性。此外,β-七叶皂苷和 AH 根据刺激物(病毒或非病毒)和研究的细胞类型调节细胞因子的产生。