Abstract
The nature of blood–brain barrier permeation of most herbal medicines is unknown. To screen blood–brain barrier drug candidates from natural product library, an ECV304/C6 coculture model was established. The permeability parameters and morphological analysis showed that the cultured ECV304 cell monolayer was of integrity and vitality. A library of widely used medicinal plant rhubarb extract was screened using ECV304/C6 coculture model, and then separated and elucidated with liquid chromatography–mass spectroscopy analytical technique. There were three peaks present in the chromatography obtained from the sample of drug candidates that permeated over ECV304 cell monolayer, in which rhein, emodin, and physcion were deduced and identified. Quantitative structure activity relationship analysis showed that the identified three compounds were consistent with the “rule of 5” for drug-like molecules. This result demonstrated that the combination of ECV304/C6 coculture model with chromatography–mass spectroscopy analysis should be an attractive and great potential method for blood–brain barrier drug candidates screening from rhubarb extracts.
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The authors thank the National Nature Science fund of China for financial support (U1404307, 31401672).
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Yuan, JF., Ji, HH., Qiu, ZJ. et al. ECV304/C6 coculture model of the BBB coupled with LC–MS analysis for drug screening from Rhubarb extract. Med Chem Res 25, 1935–1944 (2016). https://doi.org/10.1007/s00044-016-1618-7
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DOI: https://doi.org/10.1007/s00044-016-1618-7