title: Kinetic cellular phenotypic profiling: prediction, identification, and analysis of bioactive natural products.
abstract: 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.
authors.affiliation: Program in Molecular Cell Biology, Department of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou 310058, China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Fu
authors.forename: Wenqing
authors.initials: W
authors.lastname: Fu
authors.forename: Mingjiao
authors.initials: M
authors.lastname: Sun
authors.forename: Qiyang
authors.initials: Q
authors.lastname: Shou
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Zhai
authors.forename: Hongqiang
authors.initials: H
authors.lastname: Cheng
authors.forename: Li
authors.initials: L
authors.lastname: Teng
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Mou
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Li
authors.forename: Shuying
authors.initials: S
authors.lastname: Wan
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhang
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Xu
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.forename: Jiucun
authors.initials: J
authors.lastname: Wang
authors.forename: Jenny
authors.initials: J
authors.lastname: Zhu
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.forename: Xiao
authors.initials: X
authors.lastname: Xu
authors.forename: Guiyuan
authors.initials: G
authors.lastname: Lv
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Wensheng
authors.initials: W
authors.lastname: Guo
authors.forename: Yuehai
authors.initials: Y
authors.lastname: Ke
mesh_terms: D000818:Animals; D001688:Biological Products / Q000032:analysis*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D032661:Cordyceps / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008516:Medicine, Chinese Traditional; D051379:Mice; D051381:Rats; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D001688:Biological Products