College of Life Sciences, Northwest A&F University, Yangling, 712100 Shaanxi, China.
Integr Biol (Camb). 2013 Feb;5(2):351-71. doi: 10.1039/c2ib20204b.
Given the imminent threat of influenza pandemics and continuing emergence of new drug-resistant influenza virus strains, novel strategies for preventing and treating influenza disease are urgently needed. Herbal medicine, used for thousands of years in combinational therapies (Herb Formula), plays a significant role in stimulating the host immune system in vivo, and meanwhile, in fighting against the pandemic by directly inhibiting influenza virus in vitro. Such potential Janus functions may spark interest in therapeutic manipulation of virus diseases. Unfortunately, the molecular mechanism of the Janus functions of the medicinal herbs in the treatment of influenza remains unclear. In this work, to illustrate the therapeutic concept of Janus functions in the treatment of influenza, we have introduced a novel systems pharmacology model that integrates pharmacokinetic screening, targeting and network analysis of two representative herbs Lonicera japonica and Fructus Forsythiae that are efficient in the treatment of influenza, inflammation and other diseases. 50 Chemicals with favorable pharmacokinetic profiles have been identified for the two herbs, and the ligand-target network was constructed by complementing the literature-based experimental data deposited in DrugBank. The annotation of these chemicals was assigned using a novel drug targeting approach, and mapped to target-disease and drug-target-pathway networks. The overall data suggest that the medicinal herbs function by indirectly suppressing the virus proliferation via regulating the immune systems in hosts, and also, by directly inhibiting virus proliferation through targeting viral proteins essential for the viral life cycle. For the first time, we have demonstrated the mechanism of medicinal herbs in prevention and treatment of virus diseases via the Janus functions on a systematic level.
鉴于流感大流行的迫在眉睫的威胁和新出现的抗药性流感病毒株，迫切需要新的预防和治疗流感的策略。草药在组合疗法（草药配方）中使用了数千年，在体内刺激宿主免疫系统方面发挥着重要作用，同时通过直接抑制体外流感病毒在对抗大流行方面发挥作用。这种潜在的两面神功能可能会引起人们对病毒疾病治疗干预的兴趣。不幸的是，草药在治疗流感方面的两面神功能的分子机制尚不清楚。在这项工作中，为了说明治疗流感的两面神功能的治疗概念，我们引入了一种新的系统药理学模型，该模型整合了两种治疗流感、炎症和其他疾病的有代表性的草药金银花和连翘的药代动力学筛选、靶向和网络分析。已经为这两种草药鉴定了 50 种具有良好药代动力学特征的化学物质，并通过补充 DrugBank 中基于文献的实验数据构建了配体-靶标网络。这些化学物质的注释使用新的药物靶向方法进行分配，并映射到靶标-疾病和药物-靶标-途径网络。总体数据表明，草药通过间接调节宿主免疫系统来抑制病毒增殖，还通过靶向病毒蛋白来直接抑制病毒增殖，这些蛋白对病毒生命周期至关重要。我们首次在系统水平上证明了草药在预防和治疗病毒疾病方面的两面神功能的机制。
