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.

Rheum officinale Baill. is an important traditional Chinese medicinal herb, its dried roots and rhizomes being widely utilized to cure diverse diseases. However, previous studies mainly focused on the active compounds and their pharmacological effects, and the molecular mechanism underlying the biosynthesis of these ingredients in R. officinale is still elusive. Here, we performed comparative transcriptome analyses to elucidate the differentially expressed genes (DEGs) in the root, stem, and leaf of R. officinale. A total of 236,031 unigenes with N50 of 769 bp was generated, 136,329 (57.76%) of which were annotated. A total of 5884 DEGs was identified after the comparative analyses of different tissues; 175 and 126 key enzyme genes with tissue-specific expression were found in the anthraquinone, catechin/gallic acid biosynthetic pathway, respectively, and some of these key enzyme genes were verified by qRT-PCR. The phylogeny of the PKS III family in Polygonaceae indicated that probably only PL_741 PKSIII1, PL_11549 PKSIII5, and PL_101745 PKSIII6 encoded PKSIII in the polyketide pathway. These results will shed light on the molecular basis of the tissue-specific accumulation and regulation of secondary metabolites in R. officinale, and lay a foundation for the future genetic diversity, molecular assisted breeding, and germplasm resource improvement of this essential medicinal plant.

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