洋葱是一种用途广泛、营养丰富的食品，广泛应用于世界各地的各种美食中。为了从红洋葱 (Allium cepa L.) 皮中寻找对健康有益的生物活性物质，我们进行了全面的化学研究。结果，从红洋葱皮中提取出总共 44 种化合物，包括三种之前未鉴定的查尔酮 (1-3)。在这些分离物中，查耳酮1-4对A2A腺苷受体(A2AAR)表现出高亲和力，查耳酮2对A2AAR表现出最佳的结合亲和力，IC50值为33.5 nM，A2AAR对A1AR、A2BAR和A3AR具有良好的选择性，并且在 cAMP 功能测定中具有高效力（IC50 为 913.9 nM）。重要的是，IL-2 生物测定和细胞介导的细胞毒性测定表明查耳酮 2 可以促进 T 细胞活化。此外，通过分子对接阐明了查耳酮2与hA2AAR的结合机制。这项工作强调了红洋葱中的活性查耳酮可能有潜力被开发为用于癌症免疫治疗的 A2AAR 拮抗剂。

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 (Allium cepa L.) skin, a comprehensive chemical investigation was undertaken. Consequently, a total of 44 compounds, including three previously unidentified chalcones (1-3) were extracted from red onion skin. Of these isolates, chalcones 1-4 showed high affinity to A2A adenosine receptor (A2AAR), and chalcone 2 displayed the best binding affinity to A2AAR, with the IC50 value of 33.5 nM, good A2AAR selectivity against A1AR, A2BAR, and A3AR, and high potency in the cAMP functional assay (IC50 of 913.9 nM). Importantly, the IL-2 bioassay and the cell-mediated cytotoxicity assay demonstrated that chalcone 2 could boost T-cell activation. Furthermore, the binding mechanism of chalcone 2 with hA2AAR was elucidated by molecular docking. This work highlighted that the active chalcones in red onion might have the potential to be developed as A2AAR antagonists used in cancer immunotherapy.