Targeted Affinity Screening Approach for Bioactive Compounds in Curcuma longa Utilizing a Cell-Functionalized...

Selective discovery of receptor-binding ligands from complex natural matrices remains a significant analytical challenge for bioactive compound identification and lead discovery. Herein, a three-dimensional biomimetic screening strategy was established. Cells with high α1A-adrenergic receptor (AR) expression were employed as the screening tool and incorporated into a three-dimensional agarose network to prepare a biomimetic α1A AR stationary phase. This screening strategy involves the incorporation of a large number of cells into a three-dimensional network, followed by analysis and identification based on the specific interactions between membrane receptors and their ligands. Importantly, the native cellular architecture and membrane receptor integrity were preserved within the biomimetic microenvironment. Screening of Curcuma longa extracts using the proposed strategy led to the identification of ar-turmerone, curcumin, and curcumin III as α1A AR-binding candidates. Subsequent bioassays demonstrated their prostate relaxation and antiproliferative activities. This work establishes a biomimetic strategy for receptor-guided ligand screening from complex natural products and expands the toolbox of cell-based bioanalytical platforms for ligand discovery.