title: Label-free pharmacological profiling based on dynamic mass redistribution for characterization and authentication of hazardous natural products.
abstract: 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 M2receptor 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 M2receptor 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.
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hui-Peng
authors.initials: HP
authors.lastname: Song
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA 94305 USA.
authors.forename: Xiaoai
authors.initials: X
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ling
authors.initials: L
authors.lastname: He
authors.affiliation: U-Pharm Laboratories LLC, 239 New Rd, Suite A-107, Parsippany, NJ 07054 USA.
authors.forename: Huailing
authors.initials: H
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Si-Qi
authors.initials: SQ
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: liping2004@126.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: 104yang104@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D001688:Biological Products / Q000737:chemistry* / Q000633:toxicity; D015374:Biosensing Techniques; D016466:CHO Cells; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003412:Cricetulus; D032302:Datura / Q000737:chemistry*; D015386:Hazardous Substances / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D064692:Hyoscyamine / Q000032:analysis / Q000633:toxicity; D062105:Molecular Docking Simulation; D000075082:Proof of Concept Study; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors; D012601:Scopolamine / Q000032:analysis / Q000633:toxicity
chemical_list: D001688:Biological Products; D015386:Hazardous Substances; D043585:Receptor, Muscarinic M2; D012601:Scopolamine; D064692:Hyoscyamine
keywords: Dynamic mass redistribution; Hazardous herbs; Pharmacological profiling; Receptor