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.
Unidad Operativa Centro de Contención Biológica (UOCCB), Administración Nacional de Laboratorios e Institutos de Salud (ANLIS), Argentina.
Antiviral Res. 2019 Apr;164:1-11. doi: 10.1016/j.antiviral.2019.01.018. Epub 2019 Jan 31.
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease and bronchiolitis in children worldwide. No vaccine or specific, effective treatment is currently available. β-escin is one of the main bioactive constituents of Aesculus hippocastanum L. (Hippocastanaceae) seed extract (AH), and both β-escin and AH have demonstrated a beneficial role in clinical therapy because of their anti-edematous, anti-inflammatory and antioxidative effects. Besides, we have reported that β-escin and AH show virucidal, antiviral and immunomodulatory activities against the enveloped viruses HSV-1, VSV and Dengue virus in vitro. In this study, we demonstrate that β-escin and AH have virucidal and antiviral activities against RSV, as well as NF-κB, AP-1 and cytokine modulating activities in RSV infected epithelial and macrophage cell lines in vitro. Besides, in a murine model of pulmonary RSV infection, AH treatment improves the course of acute disease, evidenced by decreased weight loss, reduced RSV lung titers, and attenuated airway inflammation. In contrast, even though β-escin showed, similarly to AH, antiviral and immunomodulatory properties in vitro, it neither reduces viral titers nor attenuates lung injury in vivo. Thus, our data demonstrate that AH restrains RSV disease through antiviral and immunomodulatory effect.
呼吸道合胞病毒(RSV)是全球儿童下呼吸道疾病和细支气管炎的主要病因。目前尚无疫苗或特效治疗方法。β-七叶皂苷是欧洲七叶树(七叶树科)种子提取物(AH)的主要生物活性成分之一,由于其具有抗水肿、抗炎和抗氧化作用,β-七叶皂苷和 AH 已在临床治疗中显示出有益作用。此外,我们已经报道β-七叶皂苷和 AH 在体外对单纯疱疹病毒 1 型(HSV-1)、水疱性口炎病毒(VSV)和登革热病毒等包膜病毒具有杀病毒、抗病毒和免疫调节活性。在这项研究中,我们证明β-七叶皂苷和 AH 对 RSV 具有杀病毒和抗病毒活性,以及对 RSV 感染的上皮细胞和巨噬细胞系中 NF-κB、AP-1 和细胞因子调节活性的作用。此外,在 RSV 肺部感染的小鼠模型中,AH 治疗可改善急性疾病的病程,表现为体重减轻减少、RSV 肺部滴度降低以及气道炎症减轻。相比之下,尽管β-七叶皂苷在体外表现出与 AH 相似的抗病毒和免疫调节特性,但它既不能降低病毒滴度,也不能减轻体内肺损伤。因此,我们的数据表明 AH 通过抗病毒和免疫调节作用来抑制 RSV 疾病。