Kinetic Cellular Phenotypic Profiling: Prediction, Identification, and Analysis of Bioactive Natural Products
Kinetic Cellular Phenotypic Profiling: Prediction, Identification, and Analysis of Bioactive Natural Products
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动力学细胞表型分析：生物活性天然产物的预测、鉴定和分析
DOI：
10.1021/ac201670e
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发表时间：
2011-09-01
影响因子：
7.4
通讯作者：
Ke, Yuehai
中科院分区：
文献类型：
--
作者：
Fu, Huiying;Fu, Wenqing;Ke, Yuehai
天然产物一直是治疗药物的主要来源；然而，由于缺乏适合于高通量筛选和评估作用机制的分析方法，传统草药产品的发展目前受到阻碍。细胞过程，如增殖、凋亡和毒性，实时得到很好的协调。监测这些事件及其对天然产物的干扰可以提供有关细胞生理关联的高度丰富的信息。在这里，我们报告了一种新的基于细胞的表型分析策略，它使用电子阻抗读数来实时监测细胞对中药(TCM)的反应。这种方法的效用被用来筛选历史上已有文献记载用于治疗人类疾病的天然草药，并根据其作用机制将其分类为七类。结果表明，具有相似细胞机制的草药产生类似的时间/剂量依赖的细胞反应曲线(TCRP)。通过比较中草药冬虫夏草产生的TCRPs与类似化合物的TCRPs，我们探索了草药TCRPs在预测细胞作用机制、草药鉴定和生物活性鉴定方面的潜在用途。此外，我们进一步比较了这一新的TCRP技术与基于高效液相色谱(HPLC)的草药溯源认证和生物活性成分鉴定方法。总之，我们的发现表明，使用TCRP作为现有光谱技术的替代方法，可以让我们以更方便和更具生理相关性的方式分析天然产品。
Natural products have always been a major source of therapeutic agents; however, the development of traditional herbal products has been currently hampered by lack of analytic methods suitable for both high-throughput screening and evaluating the mechanism of action. Cellular processes such as proliferation, apoptosis, and toxicity are well-orchestrated in real time. Monitoring these events and their perturbation by natural products can provide high-rich information about cell physiological relevancies being involved. Here, we report a novel cell-based phenotypic profiling strategy that uses electronic impedance readouts for real-time monitoring of cellular responses to traditional Chinese medicines (TCMs). The utility of this approach was used to screen natural herbs that have been historically documented to cure human diseases and that have been classified into seven clusters based on their mechanisms of action. The results suggest that herbal medicines with similar cellular mechanisms produce similar time/dose-dependent cell response profiles (TCRPs). By comparing the TCRPs produced by the Chinese medicinal Cordyceps sinensis with similar TCRPs of chemical compounds, we explored the potential use of herbal TCRPs for predicting cellular mechanisms of action, herbal authentications, and bioactive identification. Additionally, we further compared this novel TCRP technology with high-performance liquid chromatography (HPLC)-based methods for herbal origin-tracing authentication and identification of bioactive ingredients. Together, our findings suggest that using TCRP as an alternative to existing spectroscopic techniques can allow us to analyze natural products in a more convenient and physiologically relevant manner.