Label-free pharmacological profiling based on dynamic mass redistribution for characterization and authentication of hazardous natural products

• Published in: Journal of hazardous materials 2017-07, Vol.333, p.265-274
• Main Authors: Song, Hui-Peng, Wang, Hong, Zhao, Xiaoai, He, Ling, Zhong, Huailing, Wu, Si-Qi, Li, Ping, Yang, Hua
• Format: Article
• Language: English
• Subjects: Animals; Biological Products - chemistry; Biological Products - toxicity; Biosensing Techniques; Cell Line; CHO Cells; Chromatography, High Pressure Liquid - methods; Cricetulus; Datura - chemistry; Dynamic mass redistribution; Hazardous herbs; Hazardous Substances - chemistry; Hazardous Substances - toxicity; Humans; Hyoscyamine - analysis; Hyoscyamine - toxicity; Molecular Docking Simulation; Pharmacological profiling; Proof of Concept Study; Receptor; Receptor, Muscarinic M2 - antagonists & inhibitors; Scopolamine Hydrobromide - analysis; Scopolamine Hydrobromide - toxicity
• ISSN: 0304-3894; 1873-3336
• DOI: 10.1016/j.jhazmat.2017.03.025

[Display omitted] •Dynamic mass redistribution (DMR) profiling was proposed to characterize toxic herbs.•Qualitative DMR profiling has obvious advantages over the classic method.•Quantitative DMR profiling is powerful in discovery of toxic marker compounds.•The proposed method is high-throughput, cost-saving and easily operated.•DMR profiling is universal for discovery of most receptor-targeted toxicants. Natural products are becoming increasingly popular in multiple fields involving medicines, foods and beverages. However, due to the frequent occurrence of poisoning incidents, their toxicity and safety have caused a serious concern. Here we report a method of biosensor-based two-phase pharmacological profiling (BTPP) for discovery, monitor and control of receptor-targeted natural products. BTPP uses a resonant waveguide grating biosensor for label-free and non-invasive detection of intracellular dynamic mass redistribution (DMR), a phenomenon caused by protein relocalization after receptors receiving stimulation from toxicants. The method can not only facilitate the identification of hazardous materials but also quantify their bioactivity by EC50. As a proof of concept, the method was successfully applied to recognize Daturae Flos (DF), an herb that can antagonize muscarinic acetylcholine M2 receptor and further cause poisoning, from other easily confused species. BTPP combined with high performance liquid chromatography revealed that scopolamine and hyoscyamine in DF were the key marker compounds. Moreover, the method accurately picked out 2 M2 receptor antagonists from 25 natural compounds, displaying its potential in high-throughput screening. This study provides a systematic illustration about the establishment, applicability and advantages of BTPP, which contributes to the safety assessment of natural products in related fields.