Program in Molecular Cell Biology, Department of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou 310058, China.
Anal Chem. 2011 Sep 1;83(17):6518-26. doi: 10.1021/ac201670e. Epub 2011 Aug 12.
Natural products have always been a major source of therapeutic agents; however, the development of traditional herbal products has been currently hampered by the 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.
天然产物一直是治疗药物的主要来源；然而，传统草药产品的开发目前受到缺乏适合高通量筛选和评估作用机制的分析方法的阻碍。细胞过程，如增殖、凋亡和毒性，是实时协调的。监测这些事件及其被天然产物的干扰，可以提供关于涉及细胞生理相关性的丰富信息。在这里，我们报告了一种新颖的基于细胞的表型分析策略，该策略使用电子阻抗读数实时监测细胞对中药的反应。该方法的实用性用于筛选具有历史记载可治愈人类疾病的天然草药，并根据其作用机制将其分为七个簇。结果表明，具有相似细胞机制的草药会产生相似的时间/剂量依赖性细胞反应谱 (TCRP)。通过比较中国药用冬虫夏草产生的 TCRP 与类似化学化合物的 TCRP，我们探讨了使用草药 TCRP 预测细胞作用机制、草药鉴定和生物活性鉴定的潜力。此外，我们还将这种新型 TCRP 技术与基于高效液相色谱 (HPLC) 的方法进行了比较，用于草药溯源鉴定和生物活性成分的鉴定。总之，我们的研究结果表明，使用 TCRP 替代现有的光谱技术可以使我们以更方便和更具生理相关性的方式分析天然产物。
