1. Immobilized cells on microcarriers for efficient and biomimetic screening of active compounds acting on FGFR4 from Fructus evodiae.
- Author
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Wei F, Gou X, and Wang S
- Subjects
- Humans, HEK293 Cells, Evodia chemistry, Limonins pharmacology, Limonins chemistry, Plant Extracts pharmacology, Plant Extracts chemistry, Biomimetics methods, Fruit chemistry, Collagen, Drug Evaluation, Preclinical methods, Receptor, Fibroblast Growth Factor, Type 4 metabolism, Receptor, Fibroblast Growth Factor, Type 4 antagonists & inhibitors, Quinazolines pharmacology, Quinazolines chemistry, Cells, Immobilized metabolism
- Abstract
Cell membrane coating strategies have been increasingly researched in new drug discovery from complex herb extracts. However, these systems failed to maintain the functionality of the coated cells because cell membranes, not whole cells were used. Original source cells can be used as a vector for active compound screening in a manner that mimics in vivo processes. In this study, we established a novel approach to fabricate high-density fibroblast growth factor receptor 4 (FGFR4)-HEK293 cells on microcarriers covered with collagen through cell culture and covalent immobilization between proteins. This method enables the efficient screening of active compounds from herbs. Two compounds, evodiamine and limonin, were obtained from Fructus evodiae, which were proven to inhibit the FGFR4 target. Enhanced immobilization effects and negligible damage to FGFR4-HEK293 cells treated with paraformaldehyde were successfully confirmed by immunofluorescence assays and transmission electron microscopy. A column was prepared and used to analyze different compounds. The results showed that the method was selective, specific, and reproducible. Overall, the high density of cells immobilized on microcarriers achieved through cell culture and covalent immobilization represents a promising strategy for affinity screening. This approach highlights the potential of the affinity screening method to identify active compounds from an herbal matrix against designed targets and its prospects for use in drug discovery from herbs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Fen Wei reports financial support was provided by National Natural Science Foundation of China. Sicen Wang reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2024
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