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首页> 美国卫生研究院文献>Biomarker Research >Application of multi-target phytotherapeutic concept in malaria drug discovery: a systems biology approach in biomarker identification
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Application of multi-target phytotherapeutic concept in malaria drug discovery: a systems biology approach in biomarker identification

机译：多目标植物治疗概念在疟疾药物发现中的应用：系统生物学方法在生物标志物识别中的应用

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There is an urgent need for new anti-malaria drugs with broad therapeutic potential and novel mode of action, for effective treatment and to overcome emerging drug resistance. Plant-derived anti-malarials remain a significant source of bioactive molecules in this regard.The multicomponent formulation forms the basis of phytotherapy. Mechanistic reasons for the poly-pharmacological effects of plants constitute increased bioavailability, interference with cellular transport processes, activation of pro-drugs/deactivation of active compounds to inactive metabolites and action of synergistic partners at different points of the same signaling cascade. These effects are known as the multi-target concept. However, due to the intrinsic complexity of natural products-based drug discovery, there is need to rethink the approaches toward understanding their therapeutic effect.This review discusses the multi-target phytotherapeutic concept and its application in biomarker identification using the modified reverse pharmacology - systems biology approach. Considerations include the generation of a product library, high throughput screening (HTS) techniques for efficacy and interaction assessment, High Performance Liquid Chromatography (HPLC)-based anti-malarial profiling and animal pharmacology. This approach is an integrated interdisciplinary implementation of tailored technology platforms coupled to miniaturized biological assays, to track and characterize the multi-target bioactive components of botanicals as well as identify potential biomarkers. While preserving biodiversity, this will serve as a primary step towards the development of standardized phytomedicines, as well as facilitate lead discovery for chemical prioritization and downstream clinical development.
机译：迫切需要具有广泛治疗潜力和新颖作用方式，有效治疗和克服新出现的耐药性的新型抗疟疾药物。在这方面，植物来源的抗疟疾仍然是生物活性分子的重要来源。多组分制剂构成了植物疗法的基础。植物具有多种药理作用的机制原因包括：提高生物利用度，干扰细胞运输过程，激活前药/使活性化合物失活为非活性代谢物以及在同一信号传导级联的不同点上协同伙伴的作用。这些效果被称为多目标概念。然而，由于基于天然产物的药物发现的内在复杂性，有必要重新考虑了解其治疗效果的方法。本综述讨论了多靶点治疗药物的概念及其在使用改良逆向药理学系统进行生物标志物鉴定中的应用生物学方法。考虑因素包括产品库的生成，用于功效和相互作用评估的高通量筛选（HTS）技术，基于高效液相色谱（HPLC）的抗疟疾分析和动物药理学。这种方法是量身定制的技术平台的综合跨学科实施，结合了小型化的生物测定方法，可以跟踪和表征植物药的多目标生物活性成分，并识别潜在的生物标志物。在保护生物多样性的同时，这将是开发标准化植物药的第一步，并有助于发现铅以进行化学优先排序和下游临床开发。

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