Exploring the Immunomodulatory Properties of Red Onion ( L.) Skin: Isolation, Structural Elucidation, and Bioactivity Study of Novel Onion Chalcones Targeting the A Adenosine Receptor.

Onions are versatile and nutritious food widely used in various cuisines around the world. In our ongoing pursuit of bioactive substances with health benefits from red onion ( L.) skin, a comprehensive chemical investigation was undertaken. Consequently, a total of 44 compounds, including three previously unidentified chalcones (-) were extracted from red onion skin. Of these isolates, chalcones - showed high affinity to A adenosine receptor (AAR), and chalcone displayed the best binding affinity to AAR, with the IC value of 33.5 nM, good AAR selectivity against AAR, AAR, and AAR, and high potency in the cAMP functional assay (IC of 913.9 nM). Importantly, the IL-2 bioassay and the cell-mediated cytotoxicity assay demonstrated that chalcone could boost T-cell activation. Furthermore, the binding mechanism of chalcone with hAAR was elucidated by molecular docking. This work highlighted that the active chalcones in red onion might have the potential to be developed as AAR antagonists used in cancer immunotherapy.