Combinations of 1,8-cineol and oseltamivir for the treatment of influenza virus A (H3N2) infection in mice
Combinations of 1,8-cineol and oseltamivir for the treatment of influenza virus A (H3N2) infection in mice
复制标题
1,8-桉树脑和奥司他韦组合治疗小鼠甲型流感病毒（H3N2）感染
DOI：
10.1002/jmv.24755
复制
发表时间：
2017-07-01
影响因子：
12.7
通讯作者：
Xu, Pei-ping
中科院分区：
文献类型：
--
作者：
Lai, Yan-ni;Li, Yun;Xu, Pei-ping
由于现有的治疗策略缺乏有效性，因此需要开发新的抗流感病毒的方法。在先前的研究中，1，8-桉叶油素发挥其抑制核因子（NF）-κ B（流感中细胞因子和趋化因子产生的主要调节剂）和抗炎活性。这些事实支持并有助于建立1，8-桉叶油素可能与抗病毒药物对流感病毒感染具有协同作用的假设。在小鼠A型流感病毒（维多利亚/3/75，H3 N2）模型中检查了1，8-桉叶油素与奥司他韦的联合作用。我们最初测试了1，8-桉树脑（30、60和120 mg/kg/天）和奥司他韦（0.1、0.2和0.4 mg/kg/天）的组合。此外，选择0.4 mg/kg/天的奥司他韦与120 mg/kg的1，8-桉叶醇组合用于进一步的组合研究。在0.1、0.2和0.4 mg/kg/d剂量下，奥司他韦的保护率分别为30%、40%和60%。1，8-桉叶油素（30、60和120 mg/kg/d）和奥司他韦（0.1、0.2和0.4 mg/kg/d）联合治疗增加了存活者数量，联合治疗后的平均存活时间（MST）大于单药治疗。使用MacSynergy方法的药物相互作用的三维分析显示了这些药物组合的强协同效应。存活率、MST、肺参数（肺指数、病毒滴度和病理学）和肺中的细胞因子（IL-10、TNF-α、IL-1 β和IFN-κ）表达证明了组合的高有效性。联合治疗与更长的MST和更多的细胞因子水平降低比单独奥司他韦。这些数据表明，1，8-桉叶油醇和奥司他韦的组合对甲型流感病毒（H3 N2）感染具有协同作用。
It is need for development of new means against influenza virus due to the lack of efficacy of available therapeutic strategies. In previous research, 1,8-cineol exert its inhibition of nuclear factor (NF)-kappa B, the main regulator of cytokine and chemokine production in influenza, and anti-inflammatory activity. These fact supports and helps establish the hypothesis that 1,8-cineol may have synergism with an antiviral on influenza virus infection. The combined effect of 1,8-cineol with oseltamivir in a mouse type A influenza virus (Victoria/3/75, H3N2) model were examined. We initially tested combinations of 1,8-cineol (30, 60, and 120 mg/kg/day) and oseltamivir (0.1, 0.2, and 0.4 mg/kg/day). In addition, the 0.4 mg/kg/day of oseltamivir combined with 120 mg/kg of 1,8-cineol was selected for further combination studies. Oseltamivir was 30%, 40%, and 60% protective at 0.1, 0.2, and 0.4 mg/kg/d. Combinations of 1,8-cineol (30, 60, and 120 mg/kg/d) and oseltamivir (0.1, 0.2, and 0.4 mg/kg/d) increased the number of survivors and mean survival time (MST) following combination treatment was greater than monotherapy alone. Three dimensional analysis of drug interactions using the MacSynergy method showed a strong synergistic effect of these drug combinations. Survival, MST, lung parameters (lung index, viral titers, and pathology), and cytokines (IL-10, TNF-alpha, IL-1 beta, and IFN-kappa) expression in lung demonstrated the high effectiveness of the combination. Combined treatment was associated with longer MST and more reduced cytokine levels than oseltamivir alone. These data demonstrate that combinations of 1,8-cineol and oseltamivir have synergistic effect against influenza A virus (H3N2) infection.